VA/DoD CLINICAL PRACTICE GUIDELINE FOR 

THE NON-SURGICAL MANAGEMENT OF HIP & 

KNEE OSTEOARTHRITIS

Department of Veterans Affairs

Department of Defense

QUALIFYING STATEMENTS

The Department of Veterans Affairs and the Department of Defense guidelines are based upon the best 

information available at the time of publication. They are designed to provide information and assist 

decision-making. They are not intended to define a standard of care and should not be construed as one.

Neither should they be interpreted as prescribing an exclusive course of management.

This Clinical Practice Guideline is based on a systematic review of both clinical and epidemiological 

evidence. Developed by a panel of multidisciplinary experts, it provides a clear explanation of the logical 

relationships between various care options and health outcomes while rating both the quality of the 

evidence and the strength of the recommendations.

Variations in practice will inevitably and appropriately occur when clinicians take into account the needs of 

individual patients, available resources, and limitations unique to an institution or type of practice. Every 

healthcare professional making use of these guidelines is responsible for evaluating the appropriateness of 

applying them in the setting of any particular clinical situation. 

These guidelines are not intended to represent TRICARE policy. Further, inclusion of recommendations for 

specific testing and/or therapeutic interventions within these guidelines does not guarantee coverage of 

civilian sector care. Additional information on current TRICARE benefits may be found at www.tricare.mil 

or by contacting your regional TRICARE Managed Care Support Contractor. 

Version 1.0 – 2014
Prepared by:

THE NON-SURGICAL MANAGEMENT OF HIP & KNEE OSTEOARTHRITIS

Working Group

With support from:

The Office of Quality and Performance, VA, Washington, DC

& 

Office of Evidence Based Practice, US Army Medical Command

Version 1.0 – 2014
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Table of Contents

Executive Summary ............................................................................................................................................................... 5

Background............................................................................................................................................................................ 7

Methods................................................................................................................................................................................. 8

Scope and Structure .............................................................................................................................................................. 9

Guideline Working Group ................................................................................................................................................... 14

Recommendations .............................................................................................................................................................. 15

Algorithm............................................................................................................................................................................. 17

Module A: Diagnosis & Evaluation...................................................................................................................................... 18

A1. History & Physical Examination ............................................................................................................... 18

A2. Plain Radiography..................................................................................................................................... 19

A3. Magnetic Resonance Imaging (MRI)........................................................................................................ 20

A4. Routine Use of Laboratories and Synovial Fluid Analysis........................................................................ 21

Module B: Core Non-Surgical Treatment Principles........................................................................................................... 22

B1. Patient Education ..................................................................................................................................... 22

B2. Comprehensive Management Plan ......................................................................................................... 22

B3. Weight Reduction in Patients with Knee or Hip Osteoarthritis and Elevated BMI ................................ 24

Module C: Physical Therapy Approaches........................................................................................................................... 26

C1. Manual Physical Therapy ......................................................................................................................... 26

C2. Aquatic Therapy ....................................................................................................................................... 26

C3. Walking Aids............................................................................................................................................. 28

Module D: Pharmacologic Therapies.................................................................................................................................. 30

D1. Acetaminophen and Non-steroidal Anti-inflammatory Drugs................................................................ 30

D2. Topical Capsaicin ...................................................................................................................................... 36

D3. Other Pain Management Pharmacotherapies ........................................................................................ 38

D4. Intra-articular Injections (Corticosteroids and Hyaluronic Acid) ............................................................ 40

Module E: Complementary & Alternative Medicine.......................................................................................................... 43

E1. Nutritional Supplements/Nutraceuticals/Dietary Supplements ............................................................ 43

E2. Acupuncture and Chiropractic Care......................................................................................................... 45

Module F. Referrals for Surgical Consultation.................................................................................................................... 47

Appendix A: Guideline Development Process.................................................................................................................... 50

Introduction .................................................................................................................................................................... 50

Methodology................................................................................................................................................................... 50

Appendix B: Evidence Table................................................................................................................................................ 83
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Appendix C: Patient History and Physical Examination ..................................................................................................... 88

Knee History.................................................................................................................................................................... 88

Knee Physical Examination ............................................................................................................................................. 88

Hip History....................................................................................................................................................................... 88

Hip Physical Examination................................................................................................................................................ 88

Appendix D: Pharmacologic Therapies............................................................................................................................... 89

Tramadol ......................................................................................................................................................................... 89

Non-Tramadol Opioids.................................................................................................................................................... 92

Corticosteroids versus Placebo ...................................................................................................................................... 93

Hyaluronate/Hylan (HA) ................................................................................................................................................. 94

Corticosteroids versus Hyaluronate/Hylan .................................................................................................................... 96

Corticosteroid Injection prior to Hip or Knee Arthroplasty ........................................................................................... 97

Appendix E: Nutraceuticals and Dietary Supplements .................................................................................................... 103

Appendix F: Participants List............................................................................................................................................. 108

Appendix G: References.................................................................................................................................................... 110
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Executive Summary

According to the Centers for Disease Control and Prevention (CDC), 13.9 percent of adults age 25 years 

and older and 33.6 percent of adults age 65 years and older are affected by osteoarthritis (OA). 

Arthritis appears to be a significant burden among Veterans of the United States (US) Armed Forces. 

[1] Research suggests that military service-related overuse and injuries may be a contributing factor 

for the increased risk of developing OA. One study examined the incidence of OA among active duty 

US Service Members between 1999 and 2008 where they concluded that rates of OA were 

“significantly higher in military populations than in comparable age groups in the general population.”

Severe OA of the hip and knee causes debilitating pain and is a common cause of mobility impairment 

in elderly patients. [2] 

The Department of Veterans Affairs (VA) and Department of Defense (DoD) have an obligation to 

ensure that all patients with OA receive a full range of high quality care. This clinical practice guideline 

(CPG) recommends a framework that includes a structured evaluation and diagnosis of Veterans and 

Service Members who may be suffering from hip and knee OA. Additionally, the CPG provides 

treatment options, including pharmacological, non-pharmacological, complementary and alternative 

medicine, as well as options for referral for surgical consultation. 

Topics discussed in this CPG include:

• Diagnosis and evaluation of OA

• Comparative effectiveness of pharmacological therapies for OA

• Comparative effectiveness of non-pharmacologic therapies

• Comparative effectiveness of complementary and alternative medicine

• Referrals for surgical consultation

OA is typically diagnosed based on the patient’s medical history and a physical examination. Patients 

with OA may have morning joint stiffness that usually resolves within 30 minutes. As the disease 

progresses, prolonged joint stiffness and joint enlargement may also become evident. Although 

radiographs are not required to make a diagnosis of knee OA, they can be used to confirm the 

diagnosis and to rule out fracture, osteonecrosis, malignancy, or other conditions. Primary care 

providers could consider radiographs such as the weight-bearing tunnel or Rosenberg view to aid in 

differential diagnosis and guide the overall treatment plan. 

A management plan for a patient with OA involves a partnership between the patient and primary 

care provider to develop an individualized course of treatment that can provide optimal results. 

Decisions regarding pharmacological therapy should be based on a risk benefit assessment, patient 

preference, and resource utilization. This process will allow selection of pharmacologic agents with 

proven benefit to be used in conjunction with non-pharmacologic interventions. Non-pharmacologic 

therapies (i.e., physical therapy (including aquatic therapy, land-based strength therapy, and manual 

physical therapy), as well as acupuncture and chiropractic care) should also be considered during the 

development of a patient’s management plan. Lastly, the primary care provider may consider referral 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 6 of 126

for surgical evaluation for OA patients that do not find relief through pharmacologic and/or nonpharmacologic therapies. 

The goal of this guideline is to assist primary care providers in developing a comprehensive care 

program for patients with OA in order to achieve maximum functionality and independence, as well as 

improve patient and family quality of life. 
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Background

Public Health Burden of Osteoarthritis to the U.S. Population

Arthritis, of which osteoarthritis is the most common type, is the most frequent cause of disability 

among adults in the United States. In 2005, The National Arthritis Data Work Group estimated that 27 

million US adults, ages 18 or older, had one or more type of clinical OA, representing more than ten

percent of the US adult population. Consequently, clinical OA affects quality of life (QoL) in many 

patients through pain and functional limitations. [3] The economic burden of direct and indirect costs 

associated with OA is also significant, likely exceeding $60 billion annually. [2]

Veterans and Service Members

Most information on OA is reported on elderly populations with less data about the prevalence of OA

in younger and physically active populations. While OA is clearly considered a disease that affects older 

patients, increasing in prevalence with advancing age, recently many studies document that OA is also 

a common problem in patients younger than the age of 65. Occupational physical demands and 

traumatic joint injury have been associated with the development of OA. Studies also suggest that 

physical activity involving repetitive joint loading may be associated with incidence of OA. [2] The 

active duty U.S. Service Members population provides an excellent opportunity to examine the 

prevalence of OA in a young and physically active group that is regularly exposed to repetitive joint 

loading during physical activity and occupational tasks.

A total of 108,266 patients with incident cases of OA and 13,768,885 person-years of follow-up were 

documented in the Defense Medical Surveillance System during a 10-year study period. On average, 

10,827 incident cases of OA were diagnosed each year of the study among 1,376,889 active duty US 

Service Members. The overall incidence rate for OA during the study period within the military 

population was 7.86 (95% CI 7.82–7.91) cases per 1,000 person-years. Females experienced a slightly 

higher incidence rate for OA when compared to males. The adjusted incidence rate for OA was ∼20 

percent higher in women when compared to men (rate ratio 1.19, 95% CI 1.17-1.21). Age was a 

significant factor among older Service Members (>40 years) who experienced a much greater 

incidence of OA compared to younger Service Members (<20 years) (rate ratio 18.61, 95 % CI 17.57-

19.57). [2]

Occupational risk factors including military rank and branch of military service were associated with 

variation in the incidence of OA in a current study. Junior and senior enlisted Service Members and 

those serving in the Army experienced the highest incidence rates for OA. Scher et al. [4] reported 

similar findings for the incidence rate of primary hip OA in a military population. It is likely that Service 

Members in these occupational groups engage in regular hip and knee bending and medium, heavy, or 

very heavy physical demands on a regular basis. They also engage in physical activities involving 

significant joint loading, particularly in the lower extremity. When comparing rates of OA in military 

versus general populations, rates of OA are significantly higher in the military population compared to

the general population of the same age group. [2]
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Methods

The recommendations presented in this CPG are based on a systematic appraisal of the published 

evidence on non-surgical interventions for managing OA. In areas where the evidence is particularly 

lacking, expert opinion served as the basis for the recommendation. Published evidence was identified 

through extensive searches of the following databases: MEDLINE, PreMEDLINE, EMBASE, (via the OVID 

SP platform using the one-search and de-duplication features), the Cochrane Database of Systematic 

Reviews, the Database of Abstracts of Reviews of Effects, and the Health Technology Assessment 

Database. Searches were designed to identify unique reviews, trials, and technology assessments. 

Searches of the World Wide Web were also performed to capture relevant grey literature that has not 

been indexed to the databases listed above. The searches covered the time period of January 2002 

through December 2012. 

In general, full-text clinical studies or systematic reviews published in peer-reviewed journals were 

considered as evidence in this CPG. Stand-alone abstracts, letters, editorials, and non-English language 

papers were excluded from the searches. Other study selection criteria varied depending on the 

context of the study (e.g., diagnostic study, intervention study, or referral study). For instance, 

intervention studies must have been prospective, randomized or nonrandomized comparative trials 

with an independent, concurrent control group that enrolled at least 25 patients per treatment arm. 

Diagnostic studies, on the other hand, could have been either prospective or retrospective, but must 

have linked use of diagnostic technologies with improvement in clinical outcomes and enrolled at least 

10 patients. Diagnostic studies that only considered diagnostic test properties (i.e., sensitivity or 

specificity) were not included as evidence in this report.

This guideline focuses primarily on the following patient-centered outcomes: pain, function, and 

harms. The evidence from each included study was abstracted into evidence tables and narratively 

synthesized. The methodological quality of the included systematic reviews and independent clinical 

studies was assessed using the U.S. Preventive Services Task Force (USPSTF) method. Each study was 

assigned a rating of Good, Fair, or Poor based on sets of criteria that varied depending on study design. 

Detailed lists of criteria and definitions of Good, Fair, or Poor ratings for different study designs appear 

in the USPSTF procedure manual. [5] The strength of the evidence was assessed along the following 

criteria: methodological quality, consistency of findings across studies, directness of the evidence (e.g., 

head-to-head comparisons provide the most direct evidence), and precision (i.e., the degree of 

certainty around an outcome’s effect size). 

Overall, the evidence base for this guideline consisted of 155 studies. The majority of the evidence 

addressed pharmacological or non-pharmacological interventions for OA of the knee. Fewer studies 

addressed interventions for OA of the hip. All the evidence addressing pharmacological and nonpharmacological interventions came from head-to-head comparative trials that compared one 

intervention to another or one intervention to a placebo or sham condition. Inconsistencies in the 

evidence are discussed in the text describing the basis of a recommendation. Very few studies 

considered the contribution of diagnostic methods, such as various imaging modalities and laboratory 

tests, to improve clinical outcomes of adults with OA of the hips and/or knees. 
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Finally, the evidence addressing the association of various indications (e.g., patient signs and 

symptoms, imaging findings) for referral to surgery (partial or total joint replacement) was mostly 

indirect. Ideally, studies addressing indications for referral to surgery would be randomized or nonrandomized prospective controlled trials of patients with OA of the hip or knee (advanced enough to 

be considered surgical candidates) that assigned patients with similar diagnostic imaging findings or 

signs and/or symptoms to either more intensive non-surgical treatment such as joint injections or 

total/partial joint replacement surgery. However, the literature searches did not identify any such 

studies. 

Scope and Structure

The Veterans Affairs (VA) and Department of Defense (DoD) Evidence-Based Practice Working Group 

(EBPWG) was established and first chartered in 2004, with a mission to advise the “...Health Executive 

Council on the use of clinical and epidemiological evidence to improve the health of the population 

across the Veterans Health Administration (VHA) and Military Health System,” by facilitating the 

development of clinical practice guidelines for the VA and DoD populations. This Clinical Practice 

Guideline (CPG) is intended to provide primary care clinicians with a framework by which to evaluate 

the individual needs and preferences of patients with OA, leading to improved clinical outcomes. It is 

designed to be adapted by individual facilities in consideration of local needs and resources. The 

algorithm serves as a guide that providers can use to determine best interventions and timing of care 

for their patients in order to optimize quality of care and clinical outcomes. 

Although this CPG represents the practice on the date of its publication, medical practice is evolving 

and this evolution requires continuous updating based on published information. New technology and 

more research will improve patient care in the future. This CPG can assist in identifying and prioritizing 

areas for research, and optimizing the allocation of resources. Future studies examining the results of 

clinical practice guidelines may lead to the development of new practice-based evidence.

Target Audience

This CPG is designed for primary care providers in an ambulatory care setting. The modules can also be 

used to coordinate and standardize care within specialty teams. 

Population

This CPG applies to any adult patient eligible for care in the VHA or DoD healthcare delivery systems 

who has chronic joint complaints in the absence of acute trauma. Such patients should be screened

for, and if necessary, be treated for hip and knee OA as described in this guideline. 

Intervention

The interventions reviewed and discussed in this CPG are physical therapy, pharmacologic, and surgical 

approaches. In this context, physical therapy approaches are described as any traditional, manual, 

land-based, and aquatic therapy that can be used as mono- or adjunctive to pharmacologic and 

surgical interventions. Pharmacologic approaches include all medications currently indicated for the 

management of osteoarthritis. As this CPG is intended for non-surgical management of OA, the 

discussion on surgical approaches is limited to considerations for patient referral. This CPG did not 
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consider or review the evidence for behavioral therapies (i.e., cognitive behavioral therapy) for the 

management of OA.

Patient-Centered Care

Guideline recommendations are patient-centered. Regardless of setting, or the availability of 

professional expertise, any patient in the healthcare system should be provided with the interventions 

that are recommended in this guideline and found to be appropriate to the patient’s specific 

condition. 

Treatment and care should take into account a patient’s needs and preferences. Good communication 

between healthcare professionals and the patient is essential. It should be supported by evidencebased information tailored to the patient’s needs. The information that patients are given about 

treatment and care should be culturally appropriate and available to people who do not speak or read 

English or who have limited literacy skills. It should also be accessible to people with additional needs 

such as physical, sensory or learning disabilities.

Care of Service Members in transition between facilities, services, or from the DoD health care system 

to the VHA should have a transition plan and be managed according to best practice guidance. Health 

care teams should work jointly to provide assessment and services to patients within this transitioning 

patient population. Management should be reviewed throughout the transition process, and there 

should be clarity about who is the lead clinician to ensure continuity of care.

This guideline is structured by six modules addressing the following components of care: 

Module A: Diagnosis and Evaluation – Any adult eligible for care in the VHA or DoD healthcare 

delivery system who has chronic joint complaints in the absence of acute trauma

should be evaluated for OA. 

Module B: Core Non-Surgical Treatment Principles – As part of a shared decision making 

process, a plan should be developed to determine the effectiveness of selected nonpharmacologic and/or pharmacologic interventions and to monitor for adverse 

events. The close monitoring for efficacy and adverse events will determine if a 

program or intervention should be modified, continued, or terminated. Overarching 

principles such as the utilization of shared-decision making and patient-centeredness 

should be incorporated in the care and management of patients with OA. 

Module C: Physical Therapy Approaches – Patients with diagnosed OA should be referred to a 

physical therapist for management of resultant pain, impairments, functional 

limitations, and disability. Reducing risk for falls and improving functional mobility 

should be a primary focus.

Module D: Pharmacologic Therapies – The patient and health care provider should develop an 

individualized course of pharmacologic treatment that has optimal effectiveness for 

each patient with OA. This process involves a complete medical assessment of the 
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patient that will allow an understanding of the risk and benefits that may be 

anticipated with pharmacologic therapies.

Module E: Complementary and Alternative Medicine – Patients with diagnosed OA may explore 

the use of dietary supplemental and alternative therapies, such as acupuncture and 

chiropractic care, to alleviate pain. 

Module F: Referrals for Surgical Consultation – Patients are referred for surgical consultation 

when the OA leads to a significant impact on their QoL and /or they are not 

responding to nonsurgical treatment. 

Strength of Recommendations

In order for the clinician to be aware of the evidence base behind the recommendations and the 

weight that should be given to each recommendation, the recommendations are keyed according to 

the level of confidence with which each recommendation is made. The graded recommendations are 

based on two main dimensions: 1) net benefit of an intervention and 2) certainty of evidence 

associated with that net benefit. When evidence is limited, the level of confidence also incorporates 

clinical consensus with regard to a particular clinical decision. The strength of recommendation is 

based on the level of the evidence and graded using the USPSTF rating system (see Table 1. Strength of 

Recommendation Rating). The discussion following the recommendations for each annotation includes 

the quality of the evidence that has been considered and the strength of recommendations (SR). 

Table 1. Strength of Recommendation Rating (SR) [5] 

Grade Definition Suggestions for Practice

A The USPSTF recommends the service. There is high 

certainty that the net benefit is substantial.

Offer or provide this 

service.

B 

The USPSTF recommends the service. There is high 

certainty that the net benefit is moderate or there is 

moderate certainty that the net benefit is moderate to 

substantial.

Offer or provide this 

service.

C 

The USPSTF recommends selectively offering or providing 

this service to individual patients based on professional 

judgment and patient preferences. There is at least 

moderate certainty that the net benefit is small.

Offer or provide this service 

for selected patients 

depending on individual 

circumstances.

D 

The USPSTF recommends against the service. There is 

moderate or high certainty that the service has no net 

benefit or that the harms outweigh the benefits.

Discourage the use of this 

service.

I Statement

The USPSTF concludes that the current evidence is 

insufficient to assess the balance of benefits and harms of 

the service. Evidence is lacking, of poor quality, or 

conflicting, and the balance of benefits and harms cannot 

be determined.

If the service is offered, 

patients should understand 

the uncertainty about the 

balance of benefits and 

harms.
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Grade of EO for Expert Opinion: To grade the recommendations for the guideline, the Working Group 

members used a variation of the USPSTF grading framework to provide a grade of EO for “Expert 

Opinion.” Given that evidence-based clinical practice guidelines have to be used in real practice

settings for Veterans and Service Members, a grade of I for insufficient evidence may not provide 

useful guidance for supporting clinical decisions. In particular, we considered certain instances in 

which evidence suggests a Substantial or Moderate net benefit, but the certainty/strength of that 

evidence is Low. In those instances, rather than concluding that the evidence is insufficient to support 

a clinical decision, we relied on Expert Opinion to support a recommendation. A grade of EO does not 

imply that the evidence is strong (it is still Low). Rather, it suggests that the magnitude of net benefit 

(Substantial or Moderate) is of sufficient clinical importance to make a recommendation, even if it is 

based on Low certainty (weak evidence). The final CPG document represents a synthesis of current 

scientific knowledge and clinical practice regarding the non-surgical management of hip and knee OA. 

It attempts to be as free as possible of bias toward any theoretical or empirical approach to treatment. 

Recommendations with grades A or B typically employ the terms “should” or “should consider”, 

respectively, as it indicates that the certainty of the evidence and magnitude of net benefits is high. 

Recommendations with a grade C typically use the phrase “may” or “may consider” and 

recommendations with a grade D use a negative phrase such as “do not”. Recommendations with 

insufficient evidence are stated as such with no positive or negative implication, while expert opinion 

recommendations may use any of these phrases. It is important to note that these are merely 

guidelines and should not be accepted as the rule. For example, some recommendations in this CPG 

with a C grade, may use the term “should” rather than the more common, “may”. Careful 

consideration was given by the Champions regarding the terminology used in each recommendation 

and may not necessarily follow the guidelines as described above. 

This CPG is the product of many months of diligent effort and consensus building among 

knowledgeable individuals from the VHA and the DoD. An experienced moderator facilitated the 

multidisciplinary Working Group. The draft document was discussed in a face-to-face group meeting. 

The content and validity of each section was thoroughly reviewed in a series of conference calls. The 

final document is the product of those discussions and has been approved by all members of the 

Working Group. The list of participants is included in Appendix G of the guideline.

Algorithm

One of the key components of the OA CPG is an algorithm intended to facilitate clinical decision 

making at the point of care. A clinical algorithm provides a graphical representation of a guideline, 

using standardized symbols to illustrate each recommendation. The use of the algorithm was chosen 

based on evidence that such a format improves data collection, diagnostic and therapeutic decisionmaking, and changes patters of resources use. This format allows the provider to follow a systematic

approach to critical information needed at the major decision points in the clinical process, and 

includes:

• An ordered sequence of steps of care
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• Recommended observations

• Decisions to be considered

• Actions to be taken

Rounded rectangles represent a clinical state or condition.

Hexagons represent a decision point in the guideline, formulated as a 

question that can be answered “Yes” or “No”. 

Rectangles represent an action in the process of care.

Ovals represent a link to another section within the guideline.

A clinical algorithm diagrams a guideline into a step-by-step decision tree, using standardized symbols 

to display each step, as developed by the Society for Medical Decision-Making committee. [6] In this 

format, arrows connect the numbered boxes, indicating the order in which the steps should be 

followed. Standardized symbols (below) are used to display each step in the algorithm and arrows 

connect the numbered boxes indicating the order in which the steps should be followed. 
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Guideline Working Group

VA

Grant W. Cannon, MD, MACP, FACR

William C. McMaster, MD, FAAOS, FACS

DoD

LTC Jess D. Edison, MD, FACP, FACR

LTC Anthony Johnson, MD, FAAOS

Francine Goodman, PharmD, BCPS MAJ Ethan Brooks, DSc, PA-C

Linda Kaiser, RN, DNP, GNP-BC, NP-C CDR Pierre A. Bruneau, MD, FAAOS

Catherine Kelley, PharmD Maj Heidi L. Clark, MS, RD

Anita Manns, RN, MBA, NP-C, DNP MAJ Angelique N. Collamer, MD.

Jiby Mathew, MSN, APRN, FNP-c Corinne K.B. Devlin, MSN, RN, FNP-BC

John Seiverd, PT, DPT, CCCE Wanda E. Friday, RN, BSN, MSM, CCM

Jennifer Wood Silva, LCSW, BCD David Parish, DC

MAJ Jeffrey D Rumfield, CCRN, MPH, PH.D(c)

James Sall, PhD, FNP-BC

LCDR Robert Selvester, MD

LCDR Carter H. Sigmon, MD, MHA

Office of Quality, Safety and Value

Carla Cassidy, MSN, ANP

M. Eric Rodgers, PhD, FNP, BC

Rene Sutton, BS, HCA

Office of Evidence Based Practice

Ernest Degenhardt, COL USA (Ret.), MSN, RN, 

ANP, FNP 

James Sall, PhD, FNP-BC

The Lewin Group 

Cliff Goodman, PhD 

Erin Gardner, BS

Hillary Kleiner, MPH

Sneha Rangarao, MPH

Mariam Siddiqui, BS 

Paul Wallace, MD

ECRI Institute

James Reston, PhD

Stacey Uhl, MS

* Bolded names are members of the Editorial Panel. All of the Work Group members’ contact

information is available in Appendix F. 
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Recommendations

Recommendations GRADE

Diagnosis and Evaluation

1. Clinicians should conduct a history and physical examination for all patients, with an

emphasis on the musculoskeletal examination. EO

2. Clinicians may use plain radiography to confirm the clinical diagnosis of hip and

knee osteoarthritis. C 

3. Clinicians should not use magnetic resonance imaging (MRI) as an evaluative tool to

diagnose, confirm, or manage the treatment of osteoarthritis. D 

4. Clinicians should avoid routine use of laboratory examinations or synovial fluid

analysis to diagnose osteoarthritis of the hip and/or knee. EO

Core Non-Surgical Treatment Principles

5. The decision to prescribe any intervention should be based on consideration of

assessment findings, risk vs. benefit analysis, pain severity, functional status, patient

preference, and resource utilization.

EO

6. For patients with osteoarthritis of the hip and/or knee, clinicians should attempt

the core non-surgical therapies prior to referral to surgery. C 

7. For patients with osteoarthritis of the hip and/or knee, clinicians should refer for

physical therapist services early on, as part of a comprehensive management plan. B 

8. Clinicians should refer overweight or obese patients (defined by a BMI > 25 kg/m2)

with osteoarthritis of the knee to a weight management program to lose a

minimum of five percent body weight and maintain this new level of weight.

C 

9. Clinicians should refer overweight or obese patients (defined by a BMI > 25 kg/m2)

with osteoarthritis of the hip to a weight management program to lose a minimum

of five percent body weight and maintain this new level of weight.

EO

Physical Therapy Approaches

10. For patients with osteoarthritis of the knee, the addition of manual physical therapy

as an adjunct to traditional physical therapy and supervised exercise can improve

pain, function, and walking distance.

B 

11. For patients with osteoarthritis of the hip, the addition of manual physical therapy

as an adjunct to traditional physical therapy and supervised exercise can improve

pain, function, and range of motion.

B 

12. For adults with osteoarthritis of the knee who do not tolerate land-based

therapeutic exercise, clinicians should consider adjunctive aquatic physical therapy. C 

13. For patients with osteoarthritis of the knee or hip, the prescription and training of

ambulation or walking aids should be carried out by a physical therapist or the

referring provider.

EO

Pharmacologic Therapies

14. In patients with no contraindications to pharmacologic therapy, clinicians should

consider acetaminophen or oral non-steroidal anti-inflammatory drugs (NSAIDs) as

first line treatment.

B 

15. Clinicians should ensure that patients receive no more than four grams of

acetaminophen daily from all sources of prescribed and non-prescribed

medications.

A 

16. In patients requiring treatment with oral NSAIDs and who are at risk for serious

upper gastrointestinal (GI) adverse events, clinicians should consider the addition A 
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Recommendations GRADE

of a proton-pump inhibitor (PPI) or misoprostol. 

17. Clinicians should consider the balance of benefit and potential harm in prescribing

oral NSAIDs in patients at risk for or with known cardiovascular disease or renal

injury/disease.

B 

18. In patients with mild to moderate pain associated with osteoarthritis of the knee,

topical capsaicin can be considered as first line or adjunctive therapy. C 

19. There is insufficient evidence to recommend for or against the use of topical

capsaicin for the hip as first line or adjunctive therapy. I 

20. For patients with persistent moderate or moderately severe osteoarthritis pain,

clinicians may offer duloxetine or tramadol as an alternative or adjunct to oral

NSAIDs.

B 

21. For patients with persistent severe osteoarthritis pain who have contraindications,

inadequate response, or intolerable adverse effects with non-opioid therapies and

tramadol, clinicians may consider prescribing non-tramadol opioids.

C 

22. For patients with symptomatic osteoarthritis of the knee, clinicians may consider

intra-articular corticosteroid injection. C 

23. There is insufficient evidence to recommend for or against the use of intra-articular

hyaluronate/hylan injection in patients with osteoarthritis of the knee; however, it

may be considered for patients who have not responded adequately to

nonpharmacologic measures and who have an inadequate response, intolerable

adverse events, or contraindications to other pharmacologic therapies.

I 

24. For patients with moderate to severe osteoarthritis of the hip, clinicians may

consider imaging/ultrasound directed corticosteroid injection to reduce pain. C 

25. Intra-articular injection of hyaluronate/hylan is not recommended for patients with

osteoarthritis of the hip. EO

Complementary and Alternative Therapies

26. In patients with hip and/or knee osteoarthritis, there is insufficient evidence to

recommend for or against the use of dietary supplements for relief of pain and

improved function.

I 

27. In patients with hip and/or knee osteoarthritis, clinicians should not prescribe

chondroitin sulfate, glucosamine, and/or any combination of the two, to treat joint

pain or improve function.

D 

28. In adults with hip and/or knee osteoarthritis, there is insufficient evidence to

recommend for or against referral for short term trial needle acupuncture or

chiropractic therapy for relief of pain and improved function.

I 

Referrals for Surgical Consultation

29. For patients with osteoarthritis of the hip and/or knee, who experience joint

symptoms (such as pain, stiffness, and reduced function) with substantial impact on

their quality of life (individualized based upon patient assessment), and who have

not benefited from the core non-surgical therapies, clinicians may offer referral for

joint replacement surgery.

B 

30. In patients with osteoarthritis of the hip and/or knee considered for surgical

consultations, clinicians should obtain weight-bearing plain radiographs within 6

months prior to the referral to surgical consultation.

B 

31. In candidates for joint replacement of the hip and/or knee, joint injections should

not be given into the involved joint if surgery is anticipated within three months. EO
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Algorithm
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Module A: Diagnosis & Evaluation

A1. History & Physical Examination

Background

The diagnosis of OA can usually be made solely on the basis of a patient history and physical

examination. This section emphasizes the key patient history and physical features of this condition in 

the hip and knee. OA is a clinical syndrome characterized by joint pain, joint stiffness, and limitation of 

range of motion, decreased physical functioning, and decreased quality of life (QoL). Pain is typically 

worse after activity and generally without morning stiffness which, if present, lasts usually less than 30 

minutes.

Recommendation

1. Clinicians should conduct a history and physical examination for all patients, with an emphasis

on the musculoskeletal examination. [EO]

Discussion

A thorough physical examination coupled with a detailed history is required for the diagnosis of OA. [7] 

Symptoms may be symmetric or asymmetric. Patients with OA may have morning joint stiffness that 

usually resolves within 30 minutes. Joint stiffness may also occur with mild to moderate activity. As the 

disease progresses, prolonged joint stiffness and joint enlargement may also become evident. A late 

manifestation of the disease may be crepitus or a grating sensation in the joint. Any limitations in joint 

movement may be due to a flexion contracture or a mechanical obstruction. Common physical 

examination findings include pain and crepitus with active motion, joint line tenderness, deformity, 

restricted painful movements and occasional effusions. Patients that are asymptomatic are not 

included in this guideline. Other conditions should be considered in symptomatic patients without 

radiographic evidence for OA. [8] Laboratory evaluation is not generally needed or helpful in the 

diagnosis of OA, but may be useful to rule out other conditions. Radiographs may provide objective 

findings consistent with OA, but are not a requirement for making the diagnosis. (See Appendix C. 

Patient History and Physical Examination.)

OA has multiple risk factors and includes both biomechanical and systemic components. 

Biomechanical risk factors include obesity, joint injury, occupational or recreational overuse, and 

muscle weakness. Systemic risk factors include age, gender, genetics, and bone density. Obesity is the 

most common modifiable risk factor for the development of OA. Evidence suggests an increased 

susceptibility to both hip and knee OA with increasing body mass index (BMI). 

A history of acute joint injury, including fractures of the articular cartilage or subchondral bone, joint 

dislocations, ligamentous injury, and meniscus injuries are linked to the subsequent development of 

post-traumatic OA. The musculature surrounding joints, particularly the quadriceps muscle at the 

knee, assists in both joint stability and function. Quadricep weakness from diffuse OA is common and 

has been identified as an independent risk factor in the development of knee OA. 

Occupational or recreational overuse is of particular concern to the VA/DoD population. Specific 

activities which require kneeling or squatting along with heavy lifting are associated with high rates of 
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both hip and knee OA. Additionally, repetitive or high-intensity training or sport activities that involve 

twisting or pivoting moments at the knee or hip, as well as participation in contact sports involving 

direct joint impact, have been implicated in the development of OA. 

Knee deformity such as genu varum or genu valgum resulting in an altered mechanical axis has been 

found to increase the risk of developing knee OA. Furthermore, osseous deformities found about the 

hip in the form of cam or pincer lesions found in femoroacetabular impingement (FAI) may be 

associated with an increased risk of hip OA. 

Age and gender also play significant roles in both susceptibility and symptom severity with OA. The 

prevalence of OA increases significantly with age with studies demonstrating a ten-fold increase in OA

between the ages of 30 and 65 years. While males are more likely to develop OA at an earlier age 

(younger than 45), by the age of 55, females are ten percent more likely to have OA than their male 

counterparts. Although the precise genetics of OA is complex and not completely understood, several 

epidemiologic studies demonstrate a genetic contribution to the development of OA. Genome studies 

have demonstrated both sex-specific and site-specific genes that may contribute to OA. A family 

history of OA, therefore, represents an independent risk factor in the development of the disease. [9-

24] 

It is also important for primary care providers to recognize presence of certain red flags that suggest 

an alternative diagnosis and should prompt an immediate evaluation. [25] Severe local inflammation, 

erythema, and progressive pain unrelated to usage suggest an alternative diagnosis such as septic 

arthritis, crystalline arthritis, inflammatory arthritis, mechanical derangement, or serious bone 

pathology. Additionally, mechanical symptoms such as catching or locking may also serve as red flags 

suggesting an alternative diagnosis. The presence of any of these symptoms should prompt an 

immediate evaluation outside the scope of this guideline. Likewise, the involvement of other joints 

outside the hip or knee expands the differential diagnosis beyond OA. 

A2. Plain Radiography

Background

Radiography can be useful in confirming a suspect diagnosis of OA and may eliminate other potential 

diagnoses from consideration. 

Recommendation

2. Clinicians may use plain radiography to confirm the clinical diagnosis of hip and knee

osteoarthritis. [C]

Discussion

In adults with non-traumatic knee pain, the consensus of the working group is to obtain a weightbearing anterior-posterior (AP) knee as well as a weight-bearing flexed knee view in 30 degrees of 

flexion (also known as a tunnel or Rosenberg view), in addition to a lateral and merchant view (also 

known as a sunrise or skyline view). Although radiographs are not required to make a diagnosis of
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knee OA, they can be used to confirm the diagnosis and to rule out fracture, osteonecrosis, 

malignancy, or other red flags. [26,27] 

In adults with non-traumatic hip or groin pain, the consensus of the working group is to obtain a 

weight-bearing (standing) AP pelvis radiograph and non-weight bearing frog lateral of the affected hip. 

Plain radiographs may be used to confirm the diagnosis and to rule out fracture, osteonecrosis, 

malignancy, (either primary or metastatic) or other red flags.

Common radiographic findings of hip and knee OA include joint space narrowing, increased 

subchondral sclerosis, marginal osteophyte formation, subchondral cysts and joint subluxation. 

Weight-bearing radiographs of the knee especially the Rosenberg view are the most sensitive for 

detecting early joint space narrowing.

A3. Magnetic Resonance Imaging (MRI)

Background

Magnetic resonance imaging (MRI) has a very limited role in the evaluation of OA. A review of the 

literature failed to provide any evidence of utility or benefit in the diagnosis or management of OA.

Recommendation

3. Clinicians should not use magnetic resonance imaging (MRI) as an evaluative tool to diagnose,

confirm, or manage the treatment of osteoarthritis. [D]

Discussion

The diagnosis of OA can be made by a thorough physical examination and plain radiographs may be 

used to confirm the diagnosis. The literature review did not demonstrate any evidence of improved 

outcomes in OA patients who underwent an MRI examination as part of their evaluation. Some studies 

have shown a utility of MRI for identifying articular cartilage degeneration. However, given the 

heterogeneity of MRI sequences and findings, as well as the lack of studies evaluating MRI for 

monitoring disease progression and improving clinical outcomes, a definitive conclusion regarding its 

global clinical utility for guiding diagnosis and treatment is not possible. Consequently, MRI is not 

recommended as an evaluative tool to diagnose or confirm OA. In patients with OA who have 

concomitant signs and symptoms of loose body, meniscal pathology or an injury or incident with a 

sudden onset of pain and effusion, MRI may be indicated. Meniscal and loose body findings may 

include locking, where the knee is stuck in flexion, usually due to a flipped meniscal fragment or a 

loose body. If there is radiographic evidence for OA and no mechanical symptoms or acute injury 

suggesting a concomitant internal derangement, MRI is not recommended as it may lead to an 

erroneous diagnosis and exaggerated patient expectations. Advanced imaging, including MRI, is only 

useful if other underlying, more severe conditions are presumed. Therefore, as a tool for routine 

diagnosis for OA, MRI is not recommended. [28] 
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A4. Routine Use of Laboratories and Synovial Fluid Analysis

Background

The literature review revealed little evidence of benefit from laboratory evaluation of blood, urine, or 

synovial fluid in the evaluation of OA. These relatively few available studies found that laboratory tests 

or synovial fluid analysis may be of benefit only when considering an alternative diagnosis or when red 

flags are present. 

Recommendation

4. Clinicians should avoid routine use of laboratory examinations or synovial fluid analysis to

diagnose osteoarthritis of the hip and/or knee. [EO]

Discussion

Laboratory tests on blood, urine, or synovial fluid are not required for the diagnosis of hip and knee 

OA. Literature review found no evidence of laboratory studies improving outcomes in OA. Laboratory 

and synovial fluid evaluation may be useful to confirm or exclude coexistent inflammatory disease or 

other conditions in patients with suggestive symptoms or signs. [25] 
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Module B: Core Non-Surgical Treatment Principles

The following management principles must be considered when developing and implementing a 

comprehensive treatment plan consisting of non-surgical interventions for OA. 

B1. Patient Education

Background

The development of an individualized evaluation and management plan is recommend for patients 

with OA. Dicussions between the patient and provider should allow for a patient-centered evaluation 

and management plan to address the patients needs. Patient education is a critical piece within the 

patient-provider relationship that empowers and enabes patients to make well informed, shared 

decisions related to their care. Furthermore, evidence suggests that patient compliance with physical 

exercise, energy conservation, and joint protection is increased by patient education. [29]

Recommendation

5. The decision to prescribe any intervention should be based on consideration of assessment

findings, risk vs. benefit analysis, pain severity, functional status, patient preference, and

resource utilization. [EO]

Discussion

The development of a management plan in patients with OA requires a partnership between the 

patient and their health care providers to develop an individualized course of treatment that can 

provide the optimal program for each patient with OA. This process involves a complete medical 

assessment of the patient that will allow an understanding of the risks and benefits that may be 

anticipated. The decision for any pharmacologic and non-pharmacologic intervention should be based 

on consideration of patient history, assessment findings, a risk benefit analysis, patient preference, 

and resource utilization. This process will allow selection of pharmacologic agents with proven benefit

to be used in conjunction with non-pharmacologic interventions. Once a therapy is selected, a plan 

should be developed to determine the effectiveness of the therapy and monitor for adverse events. 

The close monitoring for efficacy and adverse events will determine if a program should be continued 

or terminated.

B2. Comprehensive Management Plan

Background

As part of a comprehensive, core treatment and management plan for patients with OA of the hip or 

knee, consideration should be given to the least invasive interventions prior to referral for surgical 

intervention. Physical therapists are highly educated and skilled, licensed providers who prescribe safe 

and appropriate therapeutic exercises and interventions. Physical therapists should be involved early 

in the development of a comprehensive plan to manage symptoms, reduce fall risk, and maximize

patient function.
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Recommendation

6. For patients with osteoarthritis of the hip and/or knee, clinicians should attempt the core nonsurgical therapies prior to referral for surgery. [C]

7. For patients with osteoarthritis of the hip and/or knee, clinicians should refer for physical

therapist services early on, as part of a comprehensive management plan. [B]

Discussion

Clinicians should attempt the core non-surgical therapies prior to the referral for surgery. A typical 

treatment program should consist of patient education on their condition, activity and lifestyle

modification, to include a therapeutic exercise program targeting the quadriceps and the gluteus 

medius as well a weight reduction program (as appropriate), judicious use of topical or oral NSAIDs 

and/or acetaminophen and the use of an appropriate walking aid or assistive device. This plan should 

be based upon a patient-centered, shared decision making process.

Exercise in general has been a longstanding recommendation within numerous scholarly publications 

as one of the core elements in a comprehensive management plan for patients with OA of the hip or 

knee. Despite this support from the literature, patients and some health care providers commonly 

think that exercise may make symptoms from OA worse and/or should be avoided. Although it is true 

that some forms of high impact or high intensity physical activity should be avoided, the literature has 

shown that the correct type, frequency, and duration of the appropriate exercises can be beneficial for 

reducing pain, improving function and improving flexibility in patients with hip or knee OA. Thus, 

education and skilled intervention are key factors in the effective management of OA.

As part of an overall comprehensive management plan, physical therapy can augment the medical 

plan and pharmacologic interventions by providing patients with a safe and effective therapeutic 

exercise program, interventions to normalize gait and joint kinematics, patient education related to 

lifestyle and activity modifications, reducing risk for falls, and a comprehensive home program 

designed to make patients independent with self management strategies.

Upon clinical examination, patients with moderate to severe OA of the hip or knee commonly exhibit 

weakness within regional muscles surrounding or local to the affected joint. The literature indicates 

that, although the exact pathogenesis of OA is unknown, weakness often precedes or accompanies the 

osteoarthritic process. Whether this weakness is a result of a neurogenic mechanism (autogenic 

inhibition from pain), age related decrease of muscle volume (sarcopenia), or disuse is unclear. 

However, a combination of these contributing factors is most likely. Regardless of the cause of the 

weakness, in cases where hip or knee OA progresses it typically leads to disuse, decreased shock 

absorbing capabilities, and decreased load transfer capabilities (contralaterally and ipsilaterally), as 

well as overall deconditioning (decreased aerobic capacity). It is also well documented within the 

literature that muscle weakness within key muscle groups (namely quadriceps and gluteus medius) 

leads to further disuse and atrophy of the surrounding/adjacent and regional muscle groups and 

accelerates the joint stiffness and progression (such as degradation of hyaline cartilage, etc.) 

associated with hip and knee OA. Weakness has been identified as a biomechanical risk factor for the 

development of OA and specifically quadriceps weakness as a primary risk factor for knee OA.
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According to Barbour et al, the direct annual medical costs associated with falls among older adults is 

nearly $30 billion. While falls are common among older adults, research also suggests that falls are 

common among middle aged adults. Poor neuromuscular function and weakness is common among 

persons with arthritis. Decreased gait speed and impaired balance are risk factors for falling and 

common among those with arthritis. The single most effective strategy to effectively reduce falls 

involves exercise or physical therapy to improve gait, balance, and lower body strength. Research has 

shown this combination to reduce risk of falls by 14% to 37%. Effective programs should focus on 

improving balance, be progressively more challenging, and involve at least 50 hours of practice. [30] 

Early intervention which provides a tailored therapeutic exercise program to focus on regaining 

quadriceps and gluteal strength, flexibility, range of motion, and aerobic conditioning is in line with 

nationally accepted guidelines and appears to be key to improving pain and function. For these 

reasons, it is recommended and imperative that clinicians refer for physical therapist services early on 

in the management of patients diagnosed with OA of the hip and/or knee. Referring patients with OA 

to a physical therapist to provide skilled services promotes patient compliance, safety (as some 

patients require close monitoring and may need ongoing screening for medical referral), decreased fall 

risk, and appropriate exercise prescription. [31-34] 

B3. Weight Reduction in Patients with Knee or Hip Osteoarthritis and Elevated BMI 

Background

Obesity is a well-recognized risk factor for the development of hip and knee OA. The Work Group

recommends permanent weight reduction in overweight patients with knee or hip OA. This position is 

supported in knee OA by several randomized controlled trials and systematic reviews. Furthermore, 

patients with BMI greater than 30 kg/m2 have an increased rate of surgical complications such as

infection, most notably in patients with knee OA. 

Recommendations

8. Clinicians should refer overweight or obese patients (defined by a BMI > 25 kg/m2

) with

osteoarthritis of the knee to a weight management program to lose a minimum of five percent

body weight and maintain this new level of weight. [C]

9. Clinicians should refer overweight or obese patients (defined by a BMI > 25 kg/m2

) with

osteoarthritis of the hip to a weight management program to lose a minimum of five percent

body weight and maintain this new level of weight. [EO]

Discussion

It is well-established in previously published guidelines that weight reduction is a cornerstone of nonpharmacologic therapy for the management of hip or knee OA. A review of the literature revealed two 

well-designed RCTs in which patients with knee OA self-reported improvements in pain and disability 

after losing weight. [35,36] It is also noted that patients who engaged in exercise or weight loss 

programs experienced the greatest benefit. 

Although the literature is sparse on the effect of weight loss in patients with hip OA, it is our expert 

opinion that weight loss in patients with hip OA would be beneficial. Providers may refer to the 
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VA/DoD Clinical Practice Guideline for Screening and Management of Overweight and Obesity1 for 

current evidence based recommendation on the treatment of obesity. 

1 See the VA/DoD Clinical Practice Guideline for Screening and Management of Overweight and 

Obesity available at: 

http://www.healthquality.va.gov/guidelines/CD/obesity/VADoDCPGManagementOfOverweightAnd

ObesityFinal.pdf 
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Module C: Physical Therapy Approaches

C1. Manual Physical Therapy 

Background

Manual physical therapy techniques are hands-on interventions that aim to restore or normalize the 

joint mechanics and integrity of the surrounding tissues. These techniques are provided by a skilled, 

licensed physical therapist who has completed training, residency, fellowship, or certification in 

orthopedic manual physical therapy. These techniques include, but are not limited to, soft tissue 

mobilization (STM), joint manipulation/mobilization, range of motion (ROM), manual stretching, and 

massage. Such physical therapists are skilled to provide a thorough evaluation of the body system to 

identify and treat movement related dysfunctions that may be causing, aggravating, or contributing to 

joints affected with OA.

Recommendations

10. For patients with OA of the knee, the addition of manual physical therapy as an adjunct to

traditional physical therapy and supervised exercise can improve pain, function, and walking

distance. [B]

11. For patients with OA of the hip, the addition of manual physical therapy as an adjunct to

traditional physical therapy and supervised exercise can improve pain, function, and range of

motion. [B]

Discussion

After review of the literature, there is not enough evidence to support manual physical therapy over 

traditional physical therapy/ therapeutic exercise alone. This absence of evidence comparing the two 

therapies precludes a preference or recommendation be made for one over the other. However, 

combining the two interventions appears to be beneficial and should be considered for OA of the hip 

and knee, with stronger evidence to support offering the combination as a promising intervention for 

OA of the knee. The literature reviewed focused not on replacing traditional therapeutic exercise with 

manual physical therapy, but rather focused on the comparative effectiveness of a therapeutic 

exercise program, plus the combination/addition of manual physical therapy. [31-33] 

The benefits of the adjunctive manual physical therapy combined with supervised therapeutic exercise 

were the same for the hip and knee; however, the quality and strength of the evidence differed.

Within some of the studies reviewed, the addition of manual physical therapy added a skilled, handson component of interventions that were administered during a treatment session before or after 

patients completed the prescribed therapeutic exercises. [31] 

C2. Aquatic Therapy 

Background

No comparative studies were discovered for manual physical therapy as compared to aquatic physical 

therapy. However, some general guidelines and recommendations may be drawn from the evidence 

regarding the efficacy of each intervention as an effective option to be considered.
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Recommendation

12. For adults with osteoarthritis of the knee who do not tolerate land-based therapeutic exercise,

clinicians should consider adjunctive aquatic physical therapy. [C]

Discussion

Some evidence suggests that aquatic therapy leads to less discomfort and is better tolerated than 

traditional, land based physical therapy. Examples of reported discomfort with land based therapeutic 

exercise includes: increased blood pressure, swelling of the knee, and increased pain/discomfort 

during exercise. The improved tolerance associated with aquatic or pool based physical therapy is 

possibly due to the overall intensity and reduced full weight bearing associated aquatic therapy as 

compared with land based therapeutic exercise. Intensity and impact on the affected joints during 

therapeutic exercise should be considered. Low to no impact activities are indicated and are typically 

better tolerated. The heated water typically provided in therapy pools may also provide a temporary 

analgesic affect for arthritic joints, as pain and temperature both travel on the lateral spinothalamic 

tract and it is theorized that this interferes with the afferent pain signal transmission. 

For OA of the knee, evidence supports both traditional therapeutic exercise and aquatic physical 

therapy as equally effective in terms of pain reduction and functional improvement for OA of the 

knees. However, patient reported complaints (e.g., knee swelling) occur more often in patients

undergoing land based therapeutic exercises. Even though there is sufficient evidence to support 

aquatic physical therapy and land-based physical therapy in terms of improving pain and function in 

patients with knee OA, there is limited evidence to distinguish between the two therapies. This makes 

aquatic physical therapy a viable consideration for those patients who have not or will likely not 

tolerate land based physical therapy and therapeutic exercise. [31,37-42] 

For OA of the hip, there is little evidence to recommend or discourage either treatment modality 

(traditional land based versus aquatic therapy) in terms of pain reduction, increased function or harms. 

Despite the lack of certainty in the literature, therapeutic exercises that target local muscle 

(particularly quadriceps and gluteus medius) strengthening and overall aerobic fitness should be 

included in the core treatment plan. These key muscles are joint stabilizers and promote shock 

absorption and load transferring forces to be distributed appropriately throughout the body system. 

[32,33,39] 

When it comes to aquatic physical therapy, there is tremendous value in engaging the patient in a 

patient centered decision making process. Patient preferences, fears/apprehension about the pool 

environment, and facility or local area resources should be considered when deciding whether or not 

to refer for aquatic physical therapist services. Clinicians should educate patients that participation in 

physical therapist prescribed exercise is safe and beneficial.

Aquatic physical therapy is provided by a skilled, licensed physical therapist who has experience or 

certification in evaluating individuals and developing a customized plan of care to be carried out in a 

therapeutic pool. This includes screening for contraindications, monitoring high risk individuals, and 

knowing when to appropriately refer for medical intervention.
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No evidence was identified within the literature for a head to head comparison of manual physical 

therapy versus aquatic physical therapy. Despite lack of comparative effectiveness, the evidence does 

support either therapy as a beneficial and viable intervention for pain reduction and improvement of 

function in patients with hip or knee OA. [34,43-52] 

C3. Walking Aids 

Background

In patients with OA of the hips or knees, the goals of treatment are to control pain, and the resultant 

disability, while providing education on the disease process and/or its treatment. Walking aids, such as 

walkers, crutches and canes, are prescribed to reduce the load on affected joint(s) - thereby reducing

pain while improving balance. The totality of the intended effect is an overall improvement in 

functional mobility. Among the available selection of walking aids, the cane is the most commonly 

prescribed outpatient intervention. Canes may be used on the ipsilateral or contralateral side for 

patients with OA. The rationale is that the cane, by sharing the load of the body weight with the upper 

extremity, increases the support base and balance. 

Recommendations

13. For patients with osteoarthritis of the knee or hip, the prescription and training of ambulation

or walking aids should be carried out by a physical therapist or the referring provider. [EO]

Discussion

The load on weight-bearing structures can be readily reduced if the burden is shared with the arms

through an assistive device. When the hip abductors are weak, using a cane in the opposite hand can 

reduce the forces across the hip joint to less than half the normal, depending on the amount of force 

exerted on the cane. A cane can also unload the medial knee compartment – the most commonly 

affected compartment in knee OA. For patients with OA of the knee, there is no clear evidence that 

either the contralateral or ipsilateral method of cane use is better at reducing muscle strain. However, 

studies suggest that contralateral cane use can effectively diminish pain and improve function and 

some aspects of quality of life in patients with knee OA. [53] Tibial strain rates are significantly 

decreased with both methods although peak ground reaction forces at heel strike are maximally 

decreased when both the cane and the heel strike the ground in cadence. Similarly, an ambulation aid 

placed anteriorly can assist the hip and spinal extensor muscles. [34,51,52,54-62] 

Unfortunately, many patients have difficulty determining the degree of weight-bearing support they 

should apply to their ambulation aids. Furthermore, gait pattern(s) required for cane ambulation also 

decreases the efficiency of walking. Walking aids are associated with a large number of accidents

(frequently falls) requiring urgent medical treatment. Thus, the patient's functional requirements 

should be matched with the proper walking aid and the clinician must consider whether the patient 

has sufficient strength, exercise tolerance, balance, coordination and judgment to master the 

prescribed aid. Before a patient uses an ambulation aid, contractures may need to be overcome or 

muscles strengthened. These factors speak to the skill required to effectively evaluate a patient for the 

most appropriate assistive device and ensure proper fit and training is performed. The upper

extremity muscle groups used most often are the shoulder girdle depressors, elbow extensors, wrist 
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movers and finger flexors. In the lower extremity, the hip extensors, hip abductors and knee extensors 

are particularly important. 

The social meanings that people attribute to walking aids are important factors to consider as they 

affect patient compliance with the use of walking aids. Providers should reach shared decisions with 

patients about the use of walking aids based on awareness of the factors that might influence a 

patient's choice to use the prescribed aids. The prescription of a cane should take into account the 

substantial increase in energy expenditure, especially in the first month of use. When prescribed 

appropriately, energy expenditure is less of a factor for concern by the end of the second month due 

to adaptation. Final selection of an ambulation aid should be made only after the patient has had an 

opportunity to learn how to use the fitted walking aid appropriately, preferably under the supervision 

of a physical therapist and/or the prescribing provider. A physical therapist training a patient to use an 

ambulation aid should include education on safely negotiating carpet, throw rugs and rough ground as 

well as on inclines and stairs. The patient should also be taught how to circumvent obstacles and 

appropriate methods to use the aid while transferring during activities of daily living. [34,51,52,54-62] 
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Module D: Pharmacologic Therapies

For recommendations on specific pharmacologic therapies, the guideline panel did not attempt to 

differentiate agents within a specific drug class when multiple agents are present.

D1. Acetaminophen and Non-steroidal Anti-inflammatory Drugs 

Background

Acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) are both widely available and are 

commonly used by patients who are seeking pain relief from OA. Both acetaminophen and NSAIDs 

have been shown to reduce pain associated with OA of the hip and/or knee when compared to 

placebo. Initial selection of drug therapy and dose will depend upon a number of factors including 

severity of pain, individual patient factors, comorbid conditions (e.g., cardiovascular disease, renal 

impairment and history of gastrointestinal adverse events), previous pharmacologic therapy for OA, 

and patient preference. 

Recommendations 

14. In patients with no contraindications to pharmacologic therapy, clinicians should consider

acetaminophen or oral non-steroidal anti-inflammatory drugs (NSAIDs) as first line treatment.

[B]

15. Clinicians should ensure that patients receive no more than four grams of acetaminophen

daily from all sources of prescribed and non-prescribed medications. [A]

16. In patients requiring treatment with oral NSAIDs and who are at high risk for serious adverse

upper gastrointestinal (GI) events, clinicians should consider the addition of a proton-pump

inhibitor (PPI) or misoprostol. [A]

17. Clinicians should consider the balance of benefit and potential harm in prescribing oral NSAIDs

in patients at risk for or with known cardiovascular disease or renal injury/disease. [B]

Discussion

Oral NSAIDs are commonly prescribed for OA of the hips or knees and are generally well tolerated. 

Their long-term use is limited by adverse effects such as increased cardiovascular events, GI 

perforation, ulceration, and bleeding, and renal impairment. The risks of these complications increase 

with age, drug-drug and drug-disease interactions, and probably duration of use. [63] These risks are 

especially important concerning the typically older population affected by OA who often have 

comorbidities and take multiple medications. Alternative therapies to reduce these risks are limited.

The superiority of NSAIDs over acetaminophen for treating OA pain was more apparent in patients 

with moderate to severe levels of pain at baseline, while differences were negligible in patients with 

more mild disease or with mild symptoms. Therefore, in patients with moderate to severe levels of 

pain at baseline and with no contraindications to treatment with NSAIDs, initial treatment with a 

NSAID can be considered. [64]

Acetaminophen has both analgesic and antipyretic effects but lacks potent anti-inflammatory 

activity. When taken in usual doses (two to four grams per day), acetaminophen is recognized as the 

preferred initial choice for the management of OA in most patients; especially those patients with 
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milder disease or symptoms of OA and in those patients with risks associated with taking NSAIDs 

including presence of renal disease, cardiovascular disease or at risk for cardiovascular disease, 

history of gastrointestinal ulcers, those receiving oral anticoagulants or corticosteroids, and the 

elderly (e.g., greater than 65 years).

Although acetaminophen is a relatively safe analgesic when taken in usual doses (up to a maximum of 

four grams daily), the risk for acute liver injury and liver failure is increased in patients taking doses 

greater than 4,000 mg daily. [65,66] 

The recommendation to use topical NSAID therapy as an alternative to oral NSAIDs is supported by 

evidence from studies that have compared various topical and oral NSAIDs (i.e., ibuprofen, diclofenac, 

piroxicam and others) in patients with knee OA. The results have consistently shown that the topical 

and oral formulations of any given NSAID are similar in terms of improvement in pain and function in 

patients with knee OA. [67] In a meta-analysis of placebo-controlled trials, the number needed for 

treatment (NNT) for at least 50 percent pain relief over 8 to 12 weeks was 6.4 for diclofenac topical 

solution and 11 for the gel formulation. [67] 

Results from two studies showed that oral diclofenac has a higher incidence of adverse GI symptoms, 

whereas topical diclofenac has a higher incidence of local application site reactions, commonly dry 

skin, rash, and pruritus. The absolute risk of adverse GI symptoms of topical diclofenac has been 

shown to be decreased by 12 percent to 17 percent compared with oral diclofenac. [68,69] For topical 

NSAIDs collectively, the reduction in the incidence of gastrointestinal events has been shown to be 36

percent relative to the oral formulations. However, there is insufficient evidence to compare topical 

and oral NSAIDs in terms of serious GI adverse events (perforation, ulcers or bleeding).

Results from single studies suggested other potential safety advantages of topical NSAIDs over oral 

NSAIDs, namely a lower incidence of respiratory events [70] and lower incidence of psychiatric 

disorders. [71] One study showed decreases in hemoglobin by about 30 g/l and increases in serum 

creatinine by 3 ml/min with oral diclofenac relative to the topical formulation. [72] 

In a systematic review focusing on older patients (≥ 60 years of age) with OA, topical NSAIDs seemed 

to be about as effective as oral NSAIDs and to be associated with a lower risk of severe adverse GI

symptoms, defined as “events that produced significant impairment of functioning or incapacitation 

and were a definite hazard to patient’s health.” [73] However, the severe GI adverse events were not 

adequately documented in the review. GI bleeds were the closest to meeting the definition of severe 

adverse GI symptoms, but there was no definite difference between the oral and topical NSAIDs. In 

the absence of direct evidence, providers should take into account the uncertainty of the magnitude of 

net benefit when considering topical NSAIDs in patients at high risk for GI adverse events.

Clinicians should understand the limitations of the available evidence. There is insufficient evidence to 

compare topical and oral NSAIDs in terms of serious GI adverse events (perforation, ulcers, or 

bleeding), cardiovascular events, renal impairment and hepatotoxicity. [74] There is a lack of long-term 

studies. A 52-week, non-controlled observational study of diclofenac solution showed that the agent’s 

longer term adverse event profile was consistent with those in shorter term studies; [75] however, 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 32 of 126

comparative trials extending beyond 12 weeks have not been performed. The effects of dosage size 

(e.g., resulting from oligoarticular versus multiarticular application) on efficacy and safety have also 

not been studied. Overall, there is insufficient evidence to guide choice of topical over oral NSAIDs in 

older and elderly patient subgroups. Similarly, there is insufficient evidence available on the 

comparative safety of topical and oral NSAIDs in patients at high risk for cardiovascular, 

gastrointestinal, renal and hepatic complications. [76] 

The decision to use a topical NSAID (versus oral NSAID with or without PPI) should be based on 

consideration of patient preference, adverse event potential (including GI adverse events), and 

resource utilization. Other factors should also be taken into consideration. Smaller joints close to the 

skin surface (e.g., knees and hands) are more amenable than large joints to topical NSAID effects, and 

the evidence discussed here is applicable to OA of the knee. Topical NSAIDs have not been studied for 

hip OA. Diclofenac is the only NSAID currently approved by FDA in topical formulations (solution and 

gel) for OA. No studies have directly compared the solution and gel formulations in patients with OA. 

Other adverse events associated with topical NSAIDs may be due to components of the formulation 

rather than the NSAID itself (e.g., unpleasant odor from the dimethyl sulfide metabolite of 

dimethylsulfoxide (DMSO) in diclofenac solution). [73] 

Considerations for selecting oral NSAIDs

Non-steroidal anti-inflammatory drugs (NSAIDs) possess anti-inflammatory, analgesic, and antipyretic 

properties that arise from inhibition of the enzyme cyclooxygenase (COX 1 and COX-2). COX 1 is 

produced constitutively in most tissues and is responsible for prostaglandin synthesis important for

the maintenance of the gastric mucosal barrier and platelet aggregation. COX 2 is an inducible isoform 

present at sites of inflammation. In general, inhibition of COX-2 is responsible for the analgesic effect, 

while inhibition of COX-1 is responsible for the adverse GI events and anti-platelet effect of the 

NSAIDs. [77]

The NSAID class is a heterogeneous class of drugs which differ in their relative potencies of COX-1 and 

COX-2 inhibition and consequently, in their adverse event profiles. Although published studies of in 

vitro assays have been done to determine relative potencies of COX-2 versus COX-1 inhibition, 

providers are cautioned against extrapolation of these in vitro findings to conclude relative safety 

between NSAIDs. NSAIDs are commonly referred to as nonselective (e.g., ibuprofen, naproxen, 

diclofenac, indomethacin, etc.), relatively selective (e.g., etodolac, meloxicam and nabumetone) or 

selective (e.g., celecoxib). However, the US Food and Drug Administration (FDA) considers all of these 

agents as members of the NSAID class, including celecoxib, and they all have similar warnings, 

precautions and contraindications for use. (See Appendix C. list of Pharmaceutical Contraindications 

and Boxed Warnings.) Table 2 below displays considerations associated with initiating a NSAID.

Table 2. Considerations when initiating a NSAID (COX-2 selective inhibitor or Nonselective NSAID)

Patient Characteristics No/Low GI Complication Risk High GI Complication Risk

No history or no sufficient 

risk for Cardiovascular or 

Cerebrovascular Disease 

Nonselective NSAID 

(ibuprofen, naproxen, etc.)*

If possible, consider other 

treatment modalities.

NSAID or salsalatea + PPI or 
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Patient Characteristics No/Low GI Complication Risk High GI Complication Risk

(And not receiving low-dose 

ASA)

misoprostol

Hospital admission for UGI 

bleeding (Very high risk): 

Celecoxib + PPI

History of or sufficient risk 

for Cardiovascular or 

Cerebrovascular Disease (On 

ASA or consider adding ASA)

If possible, consider other 

treatment modalities.

Nonselective NSAID (naproxen) 

If possible, consider other 

treatment modalities.

Nonselective NSAID (naproxen) 

plus a PPI or misoprostol

*Generic nonselective NSAID, Adapted from Fendrick 2004, and Scheiman and Fendrick 2005. [78,79]

NSAIDs and risk of serious adverse upper gastrointestinal (GI) events 

There are a number of factors that can contribute to an increase in the risk for NSAID related serious 

upper GI adverse events (GI perforation, ulcer or bleeding). These factors include prior history of 

serious upper GI adverse event or history of ulcers, prior history of NSAID related GI adverse event, 

concomitant use of warfarin or other anticoagulant, advanced age, use of oral corticosteroids and high 

dose NSAIDs. [80] 

There is limited evidence suggesting a lower incidence of endoscopically identified ulcers, for several 

NSAIDs including celecoxib, meloxicam and etodolac versus nonselective NSAIDs. However, the 

correlation between findings of short-term endoscopically identified ulcers and the relative incidence 

of clinical significant serious adverse upper GI events (e.g., perforation, ulcers or bleeding) with longerterm use is not known. In the Celecoxib Long-Term Arthritis Safety Study (CLASS), the incidence of 

complicated ulcers (gastrointestinal bleeding, perforation or obstruction) was not different between 

celecoxib and the combined group of patients treated with either ibuprofen or diclofenac. 

Furthermore, those patients receiving low dose aspirin in combination with celecoxib had a four-fold 

higher rate of complicated ulcers compared to those not receiving low dose aspirin. Therefore, any GI 

safety advantage of the more COX-2 selective NSAIDs may be lost concurrent low dose aspirin is used. 

In patients with a history of ulcers (higher risk patients), rates of complicated and symptomatic ulcers 

were greater with celecoxib alone (2.56 percent) and celecoxib plus low dose aspirin (6.85 percent) at 

48 weeks versus those patients without a prior history of ulcer disease (0.78 percent celecoxib and 

2.19 percent celecoxib + aspirin). [81,82]In a meta-analysis of individual participant data from 280 

clinical trials of NSAIDs versus placebo and 474 trials of NSAIDs versus another NSAID, rates of serious 

vascular and/or GI adverse events were examined. In the meta-analysis, all NSAIDs (including 

celecoxib) increased the risk for any serious upper GI complication including perforation, obstruction 

or bleeding by two- four times when compared to placebo. Higher baseline risk for complicated upper 

GI events appeared to be predictive of a higher rate of events. [83]

There are several options that can be considered for high-risk patients who require treatment with 

NSAIDs to minimize their risk of experiencing NSAID-induced serious upper GI events, including 

addition of a proton-pump inhibitor (PPI) [84] or misoprostol. [85] In patients at greatest risk of 

experiencing a NSAID associated serious upper GI adverse event (e.g., patient with recent 

complicated ulcer with hospital admission); it is recommended that patients and providers consider 

alternative treatment. However, if treatment with NSAIDs is deemed necessary, use of a COX-2 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 34 of 126

selective NSAID combined with a PPI can be considered. [86] Evidence comparing use of a 

nonselective or relatively COX-2 selective NSAID combined with a PPI versus a COX-2 selective NSAID 

plus a PPI in patients at greatest risk are lacking. However, many patients will be at sufficiently high 

risk to warrant avoidance of NSAIDs. 

NSAIDs and risk of cardiovascular events

To date, there are no published, prospective clinical trials examining the cardiovascular risk of NSAIDs, 

including celecoxib. The Prospective Randomized Evaluation of Celecoxib Integrated Safety versus 

Ibuprofen or Naproxen (PRECISION) study is underway and with plans to recruit 20,000 patients with 

OA or rheumatoid arthritis who have or are at risk for cardiovascular disease. In this study, the 

symptomatic benefit, GI, renal and cardiovascular safety will be examined. Results of PRECISION are 

not expected until 2015. There are, however, numerous published observational studies with many 

demonstrating an increased cardiovascular risk with NSAIDs, including celecoxib. A systematic review 

of population based controlled observational studies was done to determine the cardiovascular risk of 

NSAIDs and included 31 case control and 21 cohort studies. Of the NSAIDs most extensively studied, 

the highest risks were seen with rofecoxib (RR 1.45, 95% CI 1.33-1.59) and diclofenac (RR 1.4, 95% CI 

1.27-1.55) and the lowest risk with naproxen (RR 1.09, 95% CI 1.02-1.16) and ibuprofen (RR 1.18, 95% 

CI 1.11-1.25). Cardiovascular risk appeared to increase with higher NSAID doses, including high dose 

ibuprofen but was also apparent with lower doses of rofecoxib, celecoxib and diclofenac. Naproxen 

was reported to be risk neutral at all doses studied. In the less extensively studied NSAIDs, etoricoxib 

(RR 2.05, 95% CI 1.45-2.88), etodolac (RR 1.55, 95% CI 1.28-1.87) and indomethacin (RR 1.3, 95% CI 

1.19-1.41) had the highest risk. However in pair-wise comparisons, cardiovascular risk with etodolac 

was not significantly different than ibuprofen or naproxen. [87] A 2011 meta-analysis of 31 clinical 

trials of NSAIDs in 116,429 patients showed a trend towards an increased risk of myocardial infarction, 

stroke, and cardiovascular death for all NSAIDs (ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, 

lumiracoxib and naproxen) compared to placebo, with some of the differences reaching statistical 

significance. [88] The authors concluded from the data that little evidence suggests cardiovascular 

safety of any of the agents studied, but naproxen appears to have the lowest risk. In a second metaanalysis, individual participant data from randomized clinical trials were used to determine rates of 

adverse cardiovascular and complicated upper GI events in individuals taking NSAIDs, including 

celecoxib and other COX-2 selective inhibitors. [83] Two hundred eighty trials comparing NSAIDs to 

placebo (n=124,513 patients; 68,342 person-years) and 474 trials (n=229,296 patients; 165,456 

person-years) comparing NSAIDs to another NSAID were included. Most trials used higher dose NSAIDs 

(ibuprofen 2400 mg, diclofenac 150 mg or naproxen 1000 mg daily). Major vascular events (e.g., fatal 

or nonfatal MI, fatal or nonfatal stroke, coronary heart disease death, etc.) were increased in patients 

receiving a COX-2 selective inhibitor (RR 1.37, 95% CI 1.14-1.66, p=0.0009) or diclofenac (RR 1.41, 95% 

CI 1.12-1.78, p=0.0036), influenced primarily by an increase in major coronary events. Ibuprofen was 

associated with a higher rate of major coronary events (RR 2.22, 95% CI 1.10-4.48, p=0.0253) but did 

not significantly increase major vascular events (RR 1.44, 95% CI 0.89-1.27). Naproxen did not increase 

major vascular events (RR 0.93, 95% CI 0.69-1.27) or major coronary events (RR 0.84, 95% CI 0.52-

1.35). Risk of any stroke was not increased significantly by any of the NSAIDs studied. Heart failure was 

increased in all NSAID groups versus placebo. Overall, of 1000 patients receiving a COX-2 inhibitor or 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 35 of 126

diclofenac for one year, an additional three had a major vascular event (one of which was death) 

compared to placebo. In analysis of baseline annual risk for major vascular events, an increased risk is 

predicted in those patients with higher cardiovascular risk at baseline. As a result, cardiovascular risk 

or presence of known cardiovascular disease should be considered when prescribing any NSAID and 

NSAIDs avoided in these patients if possible. [83]

NSAIDs and the risk of renal disease 

Use of nonselective or COX-2 selective NSAIDs can result in renal papillary necrosis, acute tubular 

necrosis, renal insufficiency, fluid and electrolyte disturbances, acute renal failure or other renalrelated injury in an estimated one to five percent of patients. [89,90] All available agents approved for 

use in the U.S. include a warning for such events in their prescribing information. The risk for renal 

adverse events is increased in patients who are dependent upon a compensatory increase in the 

production of renal prostaglandins to maintain renal perfusion. Patients at higher risk for renal injury 

from NSAIDs or COX-2s include those with preexisting renal disease, volume depletion (e.g., diuretics 

and vomiting), congestive heart failure, liver dysfunction, cirrhosis with ascites, use of angiotensin 

converting enzyme inhibitors (ACEs) or angiotensin receptor blockers (ARBs) and older patients. 

[91,92] In healthy patients, renal prostaglandins do not play a significant role in maintaining renal 

perfusion.However, in situations of reduced volume, hypotension and reduced renal perfusion, 

production of renal prostaglandins is increased to maintain renal blood flow, glomerular filtration rate 

(GFR) and limit ischemia. Administration of NSAIDs or COX-2s in these patients reduces the 

compensatory vasodilatory renal prostaglandins and can result in reduced renal perfusion; [93] 

reduced GFR and can lead to renal damage. Although there are other mechanisms of NSAID induced 

renal injury, hemo-dynamically mediated acute renal insufficiency is the most common cause, has 

known risk factors and is most frequently reversible once the offending agent is discontinued.

Although use of NSAIDs should generally be avoided in patients with CKD, a discussion of potential 

risks and benefits should be considered on a case-by-case basis in patients with arthritis whose pain is 

not controlled with other non-NSAID modalities. [94]

Although there are no prospective studies specifically examining the risk for renal complications from 

NSAIDs or COX-2 inhibitors in patients at risk, there are several case-control studies that have been 

conducted. [95] [95] [96]. In these studies, heavy or regular use of acetaminophen was associated with 

a higher risk for renal failure or renal impairment compared to no use in patients aged 18-75 years. 

[95,96] Moderate to heavy use of NSAIDs did not increase the risk but the absolute numbers taking 

NSAIDs were very small. Heavy cumulative lifetime use of NSAIDs was associated with a greater risk. 

The use of aspirin was not associated with an increased risk in one study but risk was similar to 

acetaminophen in the other. However, adjustments were not made for important confounders such 

systemic disease in either study that examined use of acetaminophen or aspirin and risk for renal 

failure. 

In a cohort of healthy men, no association was found for use of acetaminophen, aspirin or NSAIDs and 

risk for renal injury. Use of nonselective or selective NSAIDs by an older population of patients was 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 36 of 126

associated with a similar, greater risk for acute renal failure. In this nested case-control study, the 

highest risk was observed within the first 30 days of use; and decreased thereafter. [97]

In a group of patients dependent upon circulating prostaglandins for maintaining renal perfusion and 

GFR, addition of a NSAID to existing therapy with a diuretic plus an ACEI or ARB resulted in a higher 

rate of acute renal failure. [98] Addition of a NSAID to therapy with either a diuretic, ACEI or ARB did 

not increase the risk. Finally, in one cohort and one small prospective study, risk factors for developing 

renal impairment from NSAIDs included older age, renal insufficiency, coronary artery disease, male 

gender, elevated systolic pressure, high-dose NSAIDs and use of diuretics. [99] [100]

D2. Topical Capsaicin 

Background

Topically applied capsaicin has been used for the management of various types of pain including 

neuropathic pain syndromes (e.g., post herpetic neuralgia, diabetic neuropathy, post-mastectomy 

pain, etc.) and pain arising from OA. Although topical capsaicin is generally used as adjunctive therapy, 

it may be used as monotherapy in patients with more mild to moderate OA pain. 

Capsaicin works by reversibly depleting substance P (SP), an endogenous neuropeptide involved in the 

pathogenesis and modulation of pain. Capsaicin is derived from chili peppers and its application 

stimulates release of SP, initially causing a painful and burning sensation. With prolonged exposure 

and continued application, SP is depleted from afferent neurons and transmission of painful stimuli is 

reduced or absent. Adverse events are limited to temporary burning, stinging and pain at the site of 

application. 

Recommendations

18. In patients with mild to moderate pain associated with osteoarthritis of the knee, topical

capsaicin can be considered as first line therapy or adjunctive therapy. [C]

19. There is insufficient evidence to recommend the use of topical capsaicin for the hip as first line

or adjunctive therapy. [I]

Discussion

Limited data show that topical capsaicin, applied three to four times daily, results in minimal 

improvement in pain associated with OA of the knee, but without systemic adverse events. A 

favorable response to treatment may take up to two weeks to occur. Data for OA of the hip are more 

limited as most studies that did include patients with hip OA did not separate the results by affected 

joint. All four studies assessing the benefit of topical capsaicin are small and of short duration (less 

than three months) and three of the four studies are more than ten years old. [101-104] Adverse 

events are local (burning and stinging at the application site) and resolve in most patients with 

continued use. Patients and caregivers should be educated to wash their hands after application of 

capsaicin and to avoid contact with irritated skin, eyes or mucous membranes.

Capsaicin as Monotherapy for Osteoarthritis

There were two published double-blinded, placebo-controlled trials assessing the efficacy and safety 

of topically applied capsaicin for the treatment of pain associated with OA of the knee. In both studies, 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 37 of 126

use of acetaminophen was permitted but not use of NSAIDs or COX-2 inhibitors and patients having 

had recent intra-articular joint injections were excluded. In the study by Kosuwon W, et al., [105] 100

patients with OA of the knee were randomized to receive topical capsaicin gel 0.0125 percent or 

placebo applied three times daily for four weeks and then crossed over to the alternate treatment for 

four weeks; separated by a one week washout period. Improvement in pain was assessed using visual 

analog scale (VAS) and total WOMAC score and subscales to measure changes in pain, stiffness and

function. At four weeks, the mean difference in VAS between capsaicin and placebo was 0.72 (95% CI 

0.17-1.27) in favor of capsaicin. Although the difference was statistically significant, the clinical 

significance of the difference was negligible. Additionally, the authors concluded that the total 

WOMAC and WOMAC subscales were statistically improved in favor of capsaicin versus placebo, the 

differences were small (Mean difference in total WOMAC at 4 weeks: -3.42, 95% CI -2.34 to -4.51). Use 

of acetaminophen as a rescue did not differ between groups. Burning sensation was reported by more 

than 60 percent of patients but no patients stopped treatment because of it. This study was included 

in a Cochrane systematic review of topical herbal therapies for OA. The authors of the Cochrane 

review did not conclude a meaningful difference of capsaicin versus placebo when applied in the 

capsaicin concentration studied. [101] In the second study by Altman et al., [102] 113 patients with at 

least moderate OA pain (knee, ankle, elbow, wrist and shoulder) were randomized to receive capsaicin 

cream 0.025 percent or placebo vehicle applied four times daily for 12 weeks. At least 70 percent of 

patients in each group had knee OA. At 12 weeks, more patients had improved pain (e.g., pain better, 

much better or completely gone) using the physician’s global evaluation versus placebo (81 percent

capsaicin versus 54 percent placebo, p=0.03) and improvements in patient’s global evaluation was 

similar (81 percent capsaicin versus 56 percent placebo, p=0.03). Using VAS, pain was statistically 

improved versus placebo beginning at week four through the end of the 12-week study. Protocol 

violation, involving improper use of acetaminophen (use for OA pain) or use of unauthorized pain 

medications, was similar in both groups. No differences were reported for improvements in health 

assessment questionnaire or morning stiffness between groups. Burning and stinging at the 

application site was reported in 46 percent of patients and resolved in all but three patients by week 

12. [102]

Capsaicin as Adjunctive Therapy for Osteoarthritis

There were two double-blinded, placebo-controlled studies examining the efficacy and safety of 

topical capsaicin as adjunctive therapy in patients with moderate to severe pain arising from OA. 

Concomitant medications for arthritis were not altered during either study. In both trials, capsaicin 

0.025 percent was applied topically four times daily to the front and back and to each side of the knee 

or affected joint for a period of four to six weeks. In the study by Deal et al., [103] 70 patients with OA 

of the knee and 31 patients with rheumatoid arthritis were randomized to capsaicin or placebo vehicle 

for four weeks. Physician’s global improvement of knee pain was significantly better in the capsaicin 

versus placebo group for patients OA (p=0.023). Improvements in pain using VAS statistically favored 

capsaicin at week two but not at week four. Overall change from baseline in VAS was statistically 

significant for the capsaicin group since baseline VAS scores were higher in the capsaicin group versus

placebo (Mean VAS: capsaicin 66.6 versus placebo 50.5, p=0.004). Mild to moderate burning sensation 

was reported by 44 percent of capsaicin users and two capsaicin treated patients withdrew due to 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 38 of 126

adverse events. [103] In the second study by McCleane, the efficacy of capsaicin was compared to 

placebo vehicle, glyceryl trinitrate and capsaicin plus glyceryl trinitrate in 200 patients with OA of the 

knee, hip, shoulder or hand (Results are only provided for 267 patients). [104] Ninety nine patients had 

either hip or knee OA. Improvements in mean VAS pain scores were statistically greater with capsaicin, 

glyceryl trinitrate and the combination from baseline. Change in VAS from baseline was not statistically 

significant for placebo. No difference was observed between the reduction from baseline in VAS pain 

scale between capsaicin and glyceryl trinitrate but the change from baseline with the combination was 

statistically better than either active treatment alone (p<0.05). Results were not separated by affected 

joint (e.g., hip versus knee, etc.). Odds ratio of patients favoring treatments was higher for capsaicin 

(OR=2.4, 95% CI 1.2-5.1) and glyceryl trinitrate (2.1, 95% CI 1.1-4.4) versus placebo. However, the odds 

ratio favoring the combination was the highest (OR=5, 95% CI 3.8-6.4). [104]

D3. Other Pain Management Pharmacotherapies 

Background

OA is associated with significant pain. Several medications with primarily analgesic effects have been 

studied in OA patient and demonstrated to relieve pain. The greatest challenge in deciding whether to 

use these agents is the risk benefit assessment with a particular concern for the risk of chronic pain 

medication treatment. Ongoing communication between the provider and patient with OA should 

always monitor the benefit to the patient of all medications prescribed and continually assess adverse 

events to assure that a benefit is being received by the patient and that this benefit justifies the 

current and/or potential adverse events with these agents. 

Recommendations

20. For patients with persistent moderate or moderately severe osteoarthritis pain, clinicians may

offer duloxetine or tramadol as an alternative or adjunct to oral NSAIDs. [B]

21. For patients with persistent severe osteoarthritis pain who have contraindications, inadequate

response, or intolerable adverse effects with non-opioid therapies and tramadol, clinicians

may consider prescribing non-tramadol opioids. [C]

Discussion

Duloxetine

Duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI) that is FDA-approved for the 

management of chronic musculoskeletal pain such as OA for patients with OA of the knee who have an 

inadequate response or intolerance to NSAIDs. Duloxetine may be considered because it has a 

different mechanism of action and safety profile. Duloxetine may simultaneously treat certain 

concomitant conditions, since it is indicated for other disorders that may commonly accompany 

chronic pain due to OA, such as lower back pain, generalized anxiety disorder and major depressive 

disorder. 

Duloxetine 60 to 120 mg daily resulted in moderate improvement in pain and small increase in 

function in patients with symptomatic knee OA.[106,107] Only the 60-mg dose was approved because 

no incremental benefit and increases in the incidence of adverse events were seen with the higher 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 39 of 126

dose. Another trial showed analgesic and functional benefits in older patients (≥ 65 years of age). [108] 

Compared with NSAIDs alone, adding duloxetine to NSAID therapy has been shown to provide 

moderate additional analgesic and functional benefits. [109] 

Duloxetine therapy can be limited by adverse gastrointestinal, central nervous system and other 

reactions. The most common adverse events in clinical trials were nausea, dry mouth, fatigue, 

somnolence and constipation. [106,109,110] When duloxetine is added on to a NSAID, the incidence 

of adverse events (i.e., nausea, dry mouth, constipation, fatigue, decreased appetite and dizziness) and 

withdrawals due to intolerance is slightly to moderately increased relative to those for NSAID therapy 

alone. (See Appendix D. Pharmacologic Treatment). The decision to use duloxetine should be based on 

consideration of patient preference, adverse event potential (including risks for bleeding, 

hepatotoxicity, urinary retention, suicidality, orthostasis / syncope and serotonin syndrome), and 

resource utilization.

Tramadol

Tramadol is a dual-mechanism analgesic with centrally acting, weak opioid and weak serotoninnorepinephrine reuptake inhibitor properties. The opioid analgesic effects of tramadol result primarily 

from its active metabolite, (+)-O-desmethyltramadol (M1), which is six times more potent than 

tramadol in producing analgesia and 200 times more potent as a mu-receptor agonist. 

Tramadol is a therapeutic option for patients who have inadequate response to acetaminophen, 

NSAIDs (including COX-2 inhibitors and topical NSAIDs), and duloxetine. Tramadol may be preferable 

to NSAIDs, particularly in elderly patients with OA, because it lacks the renal, cardiovascular, and 

gastric ulcerative effects seen with NSAIDs, and lacks the risks of worsening hypertension or 

congestive heart failure. 

Tramadol is available as immediate-release (IR) and extended-release (ER) formulations that may be 

used for chronic pain including OA, although the ER formulation may be preferred for persistent pain 

requiring around-the-clock analgesia. An IR combination tramadol/acetaminophen product is also 

available for short-term (five days or less) treatment of acute pain; however, there is no evidence to 

support its use for breakthrough OA pain.

Patients who do not have an adequate response to nondrug, non-opioid and tramadol therapies have 

recalcitrant OA pain. The last group of pharmaco-therapeutic agents to consider is opioids other than 

tramadol, including more potent opioids as well as tapentadol. These opioids are considered to have 

higher abuse and addiction potential than tramadol. Tapentadol (a schedule II controlled substance) is 

similar to tramadol in that it has weak opioid and SNRI properties. Its analgesic mechanisms, however, 

are attributed to the opioid effects and inhibition of norepinephrine reuptake. There is substantially 

more evidence to support tramadol therapy than there is with other opioids. Tapentadol IR is FDAapproved for treatment of moderate to severe acute pain based on a short-term (ten day) study in 

patients with end-stage OA who were candidates for joint replacement surgery. [111] 

Therapy with opioids other than tramadol is relegated to last-line and ideally short-term treatment in 

patients with severe OA pain because of the well-known risks of opioids, lack of evidence for improved 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 40 of 126

physical function, lack of long-term studies and the emerging reports of adverse events such as 

endocrine dysfunction and sleep-disordered breathing associated with long-term opioid therapy in 

chronic pain.2 Patients should be selectively considered for a trial of opioid therapy. Screening and 

management of risks related to long-term opioid therapy should be integral components of the 

treatment plan. Special attention to be given to regularly reassessing the need to continue opioid 

therapy and considering tapering off opioid therapy if treatment is not beneficial or risks outweigh 

benefits.

D4. Intra-articular Injections (Corticosteroids and Hyaluronic Acid) 

Background

Corticosteroid and hyaluronate/hylan (HA) injectable products are available in numerous formulations 

that are commonly used by healthcare providers for intra-articular injection of the knee and less 

commonly of the hip; and are typically reserved for second or third-line treatment of OA. Intraarticular corticosteroids are commonly used to reduce pain in patients with OA of the knee and less 

commonly of the hip. Available evidence provides support for reducing pain in patients with OA of the 

knee but evidence is limited for hip OA. 

Recommendations

22. For patients with symptomatic osteoarthritis of the knee, clinicians may consider intraarticular corticosteroid injection. [C]

23. There is insufficient evidence to recommend for or against the use of intra-articular

hyaluronate/hylan injection in patients with OA of the knee; however it may be considered for

patients who have not responded adequately to nonpharmacologic measures and who have

an inadequate response, intolerable adverse events, or contraindications to other

pharmacologic therapies. [I]

24. For patients with moderate to severe osteoarthritis of the hip, clinicians may consider

imaging/ultrasound directed corticosteroid injection to reduce pain. [C]

25. Intra-articular injection of hyaluronate/hylan is not recommended for patients with

symptomatic osteoarthritis of the hip. [EO]

Discussion

Corticosteroid injections are generally considered after a therapeutic trial of conservative and 

pharmacologic measures have not resulted in adequate pain relief or the patient has contraindications 

to pharmacologic therapies; as a strategy to delay surgery; or in those patients in whom surgery is 

2 See the VA/DoD Clinical Practice Guideline for Opioid Therapy for Chronic Pain. Available at: 

http://www.healthquality.va.gov/guidelines/Pain/cot/ 
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contraindicated. Pain relief is rapid and relatively short-lived with pain relief occurring within the first 

week and lasting only three to four weeks. 

Local adverse events are the most commonly reported adverse events from steroid injections. These 

include pain on injection, redness, post injection flare and skin discoloration. The rate of joint infection 

is considered to be very low when strict aseptic techniques are followed. [112] Systemic effects include 

rapid suppression of serum cortisol, adrenocorticotropin hormone (ACTH) and inflammatory markers 

(erythrocyte sedimentation rate [ESR], C-reactive protein [CRP] and cytokines, returning to baseline 

levels in one to four weeks. In diabetics, a transient, short-term increase in blood glucose levels has 

been reported. The evidence for an effect on blood pressure is mixed but facial flushing can occur. 

[113] The clinical significance of these changes is unclear and is likely dependent upon the individual 

patient. There has been concern regarding the potential for intra-articular corticosteroid injections 

leading to joint destruction and tissue atrophy but more recent evidence does not support this 

assertion. In a study of patients with OA of the knee, steroid injections were given every three months 

for two years versus saline injections. Radiologic studies did not show a difference in joint 

deterioration between groups over the two year period and local and systemic adverse events were 

not reported. [114,115] 

In a review of various pharmacologic interventions for OA of the knee, trials assessing the effect of 

intra-articular steroid injections compared to placebo showed a benefit in reducing pain in patients 

with moderate OA of the knee. [116] 

If intra-articular steroid injections are administered in the hip, they should be performed using strict 

aseptic techniques and guided by fluoroscopy or ultrasound since the hip joint is more challenging to 

access and if done improperly, may damage the neighboring femoral nerve, artery or other structures 

near the anterior hip joint. [117] 

Evidence is lacking to appropriately identify those patients that may experience the most benefit from 

intra-articular HA/hylan administration for OA of the knee. However, there is some evidence to 

suggest that patients with more severe or advanced disease with significant joint space narrowing may 

be less likely to benefit. [118] Because evidence supports only a modest effect in reducing pain and 

only a limited effect in improving function in patients with OA of the knee, the use of HA/hylan 

products should be reserved for patients who have not responded to conservative measures and in 

whom pharmacologic therapies have not resulted in adequate pain reduction or these therapies are 

contraindicated. Furthermore, use of these agents may be considered as a strategy to delay surgery or 

for those patients that are not surgical candidates. 

At this time, there are no high quality studies that have demonstrated the use of HA intra-articular hip 

injections is an effective practice to delay the need for total hip arthroplasty. Additionally, the 

injections are not currently FDA-approved for use in the hip. Because there is a lack of evidence 

supporting the safe and effective use of intra-articular HA/hylan in patients with OA of the hip, its use 

in these patients cannot be recommended at this time. 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 42 of 126

Seven studies comparing corticosteroids to HA in patients with OA were identified. These studies 

compared corticosteroid to hyaluronate injections and include one systematic review and six 

randomized controlled trials (RCTs). [113,119-122] 

The available evidence demonstrates that the onset of pain relief is more rapid with steroid versus 

HA/hylan injections with greater benefit within the first four weeks post-injection. At four weeks, 

similar benefit was observed and beyond week eight, HA/hylan are more effective than steroids for 

reducing pain in patients with OA of the knee. 

A number of professional organizations have recently updated clinical practice guidelines for patients 

with OA of the knee and have updated recommendations regarding intra-articular injections. (See 

Table 3 below for details.) 

Table 3. Clinical Practice Guidelines for the Management of OA from Professional Organizations

Professional Organization Place in Therapy Comments

American Academy of 

Orthopaedic Surgeons (AAOS)

IACS: Unable to recommend for 

or against

IACS: Inconclusive

IAHA: Cannot recommend IAHA: Strong recommendation, 

citing that the evidence to 

support their recommendation is 

high quality. However, existing 

evidence is mostly of low quality 

as asserted by most authors of 

systematic reviews

American College of 

Rheumatology (ACR)

IACS: Conditionally recommend No details provided

IAHA: No recommendations 

regarding use

No details provided

National Institute for Clinical 

Excellence (NICE)

IACS: Should be considered as an 

adjunct to core treatments for 

the management of moderate to 

severe OA of the knee

IACS: Short term benefit, minimal 

harms

IAHA: Do not recommend use IAHA: Balance between 

effectiveness in reducing painful 

OA (clinical benefit), number of 

injections and potential harms

IACS=intraarticular corticosteroids, IAHA=intraarticular hyaluronic acid

Based on the available evidence and the number of injections per course of HA (depending upon the 

product), it is recommended that clinicians should consider a trial of intra-articular corticosteroid 

injections for adults with osteoarthritis of the knees prior to considering use of intra-articular 

HA/hylan.
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Module E: Complementary & Alternative Medicine

E1. Nutritional Supplements/Nutraceuticals/Dietary Supplements 

Background

Dietary supplements are commonly consumed by patients for diverse health and personal reasons and 

are often incorrectly perceived by consumers to be as effective as drugs without negative side effects. 

Within the United States, there is minimal regulation imposed upon the dietary supplement industry

and supplements are not required to be approved by the FDA before they are sold to comsumers. The 

1994 Dietary Supplement Health and Education Act (DSHEA) requires that the dietary supplement 

manufacturers not make misleading or false claims.3 The DSHEA also requires that the supplement is 

safe before it reaches consumers and in the case of an adverse health event, manufacturers are 

required to report the event to the FDA. However, there are no requirements for supplement 

manufacturers to demonstrate effectiveness of their product. Glucosamine and chondroitin sulfate are 

marketed as nutritional supplements in the US and despite the limited data for benefit, the uptake of 

these agents by US consumers has increased significantly in patients with OA

It is important for healthcare providers to have frank conversations with patients who choose to take 

dietary supplements, so that the patient has realistic expectations and is making an informed choice 

regarding their care and how to spend personal resources. It is also important that healthcare 

providers are aware of the dietary supplements their patients are taking, so that potential drugsupplement interactions can be mitigated and adverse events can be appropriately reported.

Recommendations

26. In patients with hip and/or knee osteoarthritis, there is insufficient evidence to recommend

for or against the use of dietary supplements for relief of pain and improved function. [I]

27. In patients with hip and/or knee osteoarthritis, clinicians should not prescribe chondroitin

sulfate, glucosamine, and/or any combination of the two, to treat joint pain or improve

function. [D]

Discussion

Dietary Supplements

There is insufficient evidence to support the use of dietary supplements for relief of pain and improved 

function in adults with hip and knee OA. Research on the effectiveness of dietary supplements for 

managing pain and improving function in adults with OA is frequently funded by the supplement 

industry, which generates concern regarding potential bias in study design and analysis, reporting and 

publication of results. Aside from potential study design and publication bias, studies assessing dietary 

3

http://www.fda.gov/regulatoryinformation/legislation/federalfooddrugandcosmeticactfdcact/significantamend

mentstothefdcact/ucm148003.htm
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 44 of 126

supplements are commonly of lesser quality and often include a smaller sample size, unclear blinding 

methodology, variable study duration and variable follow up. Additionally, in the studies reviewed, 

there was inconsistency and a great deal of variability in the measurement tools used to assess key 

outcomes (e.g., pain and function). Doses varied among studies of the same supplement, and often 

proprietary blends of components were studied. The majority of the research focused on hip OA 

versus knee OA. All of these factors contributed to challenges in evaluating the quality and consistency 

of the literature for various supplements as it pertained to the management of pain and function in 

those with OA of the hip and knee. This information is provided to support informed dialogue between 

the healthcare provider and patient, particularly for those patients who may be unduly influenced by 

marketing or anecdotal information on claims of dietary supplement effectiveness. (See Appendix E.

Nutraceuticals and Dietary Supplements.)

Patients who choose to utilize dietary supplements should have realistic expectations of their potential 

benefit; knowledge of potential risks; and should balance this with the cost of the dietary 

supplements. Healthcare providers should encourage patients to disclose and discuss their 

supplement use with the medical team and providers should document supplement use in the medical 

record. This may help to avoid a negative drug supplement interaction and potentially lessen adverse 

events associated with dietary supplement use. 

The Human Performance Resource Center (HPRC) is a DoD initiative under the Force Health Protection 

and Readiness Program. [123] Both patients and healthcare providers can access these resources to 

assist in informed decisions regarding any dietary supplement use. Additionally, there is information 

on the site to guide healthcare providers in reporting any adverse events associated with a dietary 

supplement. [124] 

Chondroitin Sulfate and Glucosamine 

Review of the evidence suggests that there were negligible health benefits, (i.e, improved pain and 

function) and an absence of statistically significant effectiveness of glucosamine, chondroitin sulfate, 

or the combination in trial participants. There were seven RCTs on chondroitin sulfate, of which four

showed a statistically significant reduction in pain. Out of these four, two studies showed only short 

term pain reduction. However, three of these four studies allowed the use of rescue medications

during the study period. Additionally, there was a lack of consistency in defining “clinically meaningful” 

across the studies, particularly for pain.

The Cochrane systematic review found no difference in efficacy for glucosamine versus NSAIDs. Similar 

results were found for pain management as there was no difference in efficacy between glucosamine 

and polyherbal supplementation. [125-133] 

For chondroitin sulfate a statistically significant difference in pain was noted in 2 studies, but only 

short-term. Although there appears to be minimal risk of harm in adults treated with glucosamine, 

chondroitin sulfate, or a combination of the two, there is insufficient data to support use for the 

treatment of adults with symptomatic OA of the hip and/or knee.
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 45 of 126

Much of the research on nutritional supplements were funded by industry. The studies found 

statistically significant improvements however the high risk of potential funding bias resulted in lower 

certainty of the evidence. 

E2. Acupuncture and Chiropractic Care 

Background 

Acupuncture is available and is promoted as a pain modifying intervention for patients with OA of the 

hip or knee. Many who suffer from OA of the hip or knee may also experience stiffness, loss of joint 

motion and mobility irrespective of pain. Whether acupuncture is applicable to these various clinical 

complaints adds another dimension to its possible utility. Acupuncture is performed via a variety of 

formats including adding temperature and electric stimulation in addition to the needling itself. A 

number of studies have been published on the effects of needle acupuncture against sham needling. 

There remains concern about the appropriateness of a needling sham and how blinding could be 

adequately controlled. 

Chiropractic care is also often used in the treatment of OA. Unfortunately, there is a paucity of 

research available to make evidence based statements on efficacy. Chiropractic care is not always 

specified for the involved joint, but may be directed solely to the axial skeleton, rather than involving 

the appendicular skeleton. A difference is seen when looking at results for motion, mobility, pain 

control and function. All of these results have varied outcomes.

Recommendation

28. In patients with hip and/or knee osteoarthritis, there is insufficient evidence to recommend

for or against referral for short term trial of needle acupuncture or chiropractic therapy for

relief of pain and improved function. [I]

Discussion

Acupuncture 

In the review of the available literature, including a Cochrane review, the use of acupuncture as an 

adjunct to other treatment modalities did not find an additional effect. When all acupuncture versus

sham controlled trials were combined, patients experienced statistically significant, but clinically 

irrelevant, short term improvement in pain and function over sham treated patients. However, there 

was much heterogeneity among the individual studies’ effect sizes and some studies identified no 

difference in efficacy. When sham controlled trials were limited to those with adequate patient 

blinding, the heterogeneity and the effect sizes decreased. There remains a question concerning 

needling sham as an appropriate control as evidence exists, in non-OA research, that needle insertion 

at non-acupuncture sites may have a physiologic effect. Overall, these acupuncture trials lacked a level 

of certainty over a clinically important improvement over the sham comparator. There clearly is a need 

for further well controlled prospective studies to clarify the value and efficacy of this intervention.

[134-138] Harms were documented in many studies which included local site bleeding or bruising and 

potential infection.
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Chiropractic Care

Chiropractic care is often used in the treatment of OA. Unfortunately, there is a paucity of research 

available to make evidence based statements on efficacy. Chiropractic care is not always specified for 

the involved joint, but may be directed solely to the axial skeleton, rather than involving the 

appendicular skeleton. A difference is also seen when looking at results for motion, mobility, pain 

control and function. All of these results have varied outcomes.

Chiropractic studies on OA of the hip and/or knee were limited to a single systematic review of fair 

quality. While the review identified no harm results, there was not overwhelming evidence for efficacy

in improving function and controlling pain. In light of these findings, it is important that healthcare 

providers consider the cost versus relative research proven benefit when discussing this alternative. 

[139] 

Specificity of application to the involved joint or joints should be considered in the referral, with an 

understanding that appendicular joint issues may involve the axial skeleton as well. There is certainly a 

great need for more research on the application of chiropractic care in the treatment of OA of the hip 

and/or knee. 
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Module F. Referrals for Surgical Consultation

Background

Patients with OA of the hip or knee can be managed in primary care with various modalities until 

mechanical symptoms or intractable pain results in diminished physical ability and impact the quality 

of life (QoL). At that time the primary care provider should engage in frank discussions with the patient 

regarding further treatment options that encompass realistic treatment goals and the patient’s values. 

One of the possible interventions is surgical intervention such as a total knee or hip arthroplasty. If the 

patient is agreeable, then consultation with an orthopedic surgeon is appropriate. Prior to surgical 

consultation, radiologic imaging may be needed to expedite the orthopedic surgery consultation. 

Recommendations

29. For patients with osteoarthritis of the hip and/or knee, who experience joint symptoms (such

as pain, stiffness, and reduced function) with substantial impact on their quality of life

(individualized based upon patient assessment), and who have not benefited from the core

non-surgical therapies, clinicians may offer referral for joint replacement surgery. [B]

30. In patients with osteoarthritis of the hip and/or knee considered for surgical consultations,

clinicians should obtain weight-bearing plain radiographs within 6 months prior to the referral

to surgical consultation. [B]

31. In candidates for joint replacement of the hip and/or knee, joint injections should not be given

into the involved joint if surgery is anticipated within three months. [EO]

Discussion

Considerations for Referrals

In advanced stages of OA of the hip and knee, noninvasive treatments such as medications and 

physical therapy are of limited value. Risk factors may be modifiable; therefore, identifying them prior 

to surgery may lead to beneficial lifestyle modifications that could reduce the risk of a poor surgical 

outcome prior to the patient undergoing surgery. 

Joint replacement can effectively alleviate pain and restore function; however, it is associated with risk 

and does not prolong life. The potential benefits of joint replacement must be weighed against the risk 

of surgical mortality and morbidity and the discomfort and inconvenience associated with recovery. 

[140] A simple decision tree based on WOMAC outcomes can help to determine the appropriate 

application of total hip replacement (THR). It could also be used to evaluate clinical practice or for 

quality control. [141] 

While the studies attempted to identify risk factors associated with poor surgical outcomes, the 

studies could not recommend the preclusion of a surgical referral as a recommendation for the 

treatment of hip and knee OA.

Therefore, appropriate due diligence by the primary care provider should be employed to engage the 

patient in shared decision making about the benefits of intensifying lifestyle modification (weight loss, 

smoking cessation, controlling diabetes and hypertension) and consider adjusting medication for 

depression, as needed, to improve postoperative outcomes and to minimize postsurgical complications. 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 48 of 126

Moreover, the indirect research body of evidence does not recommend precluding a referral for surgery. 

Indeed, it must be noted, not all patients with the previously mentioned modifiable risk factors will 

necessarily have a poor postoperative outcome.

Elderly patients who had knee or hip replacements for severe OA took several weeks to recover, but 

experienced excellent long-term outcomes. Clinicians often do not discuss joint replacement surgery 

with elderly patients who might benefit. [140] Total knee arthroplasty (TKA) has been established as a 

highly successful procedure for treating patients with advanced OA. Several key factors play a crucial 

role in obtaining successful TKAs, and these include well-selected patients, appropriate implants, well 

performed surgical procedures, and adequate postoperative rehabilitation. Patient age, radiographic 

severity of OA, and severity of symptoms including response to other treatment modalities are 

typically considered as the three key factors in selecting the patients for TKA. [142]

There are no systematic reviews or randomized controlled trials concerning the use of advanced 

imaging such as MRI versus plain radiographs. The review of the evidence revealed studies that 

indirectly addressed the role of radiographic imaging. A total of seven studies were reviewed, five 

studies addressed imaging in knee OA and two addressed hip OA. [226-229] [230] 

There is insufficient evidence regarding the use of advanced imaging in OA of the hip. Again, there 

were no studies that compared any advanced imaging to plain radiographs. Although no studies were 

found that evaluated the use of various imaging studies, two of the studies cited required plain 

radiographic documented OA of the hip as inclusion criteria. [143,144] The evidence is lacking to 

support the use of advanced radiologic imaging for the evaluation of OA in adults prior to referral for 

surgical evaluation.

Injection Therapy prior to Referral for Total/Partial Joint Replacement Surgery

Adults with OA of the hips and knees commonly receive intra-articular corticosteroid injections to the 

affected joints. The use of intra-articular knee hyaluronic acid (HA) has also become widespread. HA

injection of the hip joint is less common (and is not FDA approved); however some anecdotal success 

has been reported. Intra-articular injections are often used as a bridge to surgery or as an attempt to 

improve patient function and thus delay the need for a total joint arthroplasty.

Intra-articular use of corticosteroids was first reported in 1951. [145] Since that time, the intraarticular use of corticosteroids to treat knee osteoarthritis has become commonplace. Fluoroscopy or 

ultrasound guided intra-articular hip corticosteroid injections have also become increasing utilized in 

the past decade.

Despite the widespread use of intra-articular corticosteroids for the hip and knee in osteoarthritis, no 

randomized controlled trials or non-randomized prospective controlled studies have addressed their 

efficacy in the delaying of surgical interventions to these joints. Creation of a high quality study 

addressing this question is difficult as the decision to proceed to a major surgical intervention involves 

incorporation of many patient-dependent variables, making standardization complex. The efficacy of 

an intra-articular injection may or may not be the deciding factor to proceed to surgery for any 

individual patient. (See Section D4. Intra-Articular Injections (Corticosteroids and Hyaluronic Acid).) 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 49 of 126

Three studies [146-148] have examined the effect of HA injections in delaying the need for total knee 

replacement surgery. The first study [148] was a retrospective cohort study with an overall poor 

quality rating (USPSTF criteria for cohort studies), as it did not statistically adjust for potential 

confounding variables. The other two studies [146,147] were retrospective case series found to be of 

fair quality. No study compared their treatment arm to a placebo or non-intervention arm. The 

majority of the patients in the three studies were candidates for knee replacement who had been 

unsuccessfully treated with conservative forms of therapy (e.g., anti-inflammatory medication, weight 

reduction, shoe modification and exercise). Mean patient age ranged from 59.4 to 72 years, and all of 

the studies had more females than males.

These studies reported that some patients treated with HA injections did not need to undergo surgery 

and did well with the injection series (58.7 percent in the Anand paper, 75 percent in the Waddell group, 

81 percent for Barrett & Siviero with improved QoL scores in 67.3 percent of knees) [146-148] and 

recommended HA as part of the core treatment program for knee OA prior to a total joint arthroplasty. 

The evidence to support these recommendations is considered weak at this time. [149] As some patients 

have clinical improvement with HA injections and harms are limited, we recommend that clinicians may 

consider a trial of hyaluronic acid intra-articular to the knee prior to surgical referral. 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 50 of 126

Appendix A: Guideline Development Process

Introduction

The methodology used in the development of the clinical practice guideline for non-surgical 

management of osteoarthritis (Version 1.0 - 2014) follows the Guideline for Guidelines, an internal 

working document of the Veterans Health Administration (VHA) and Department of Defense (DoD) 

Evidence-based Practice Working Group (EBPWG). [150] This document provides information 

regarding the process of developing guidelines, including the identification and assembly of the 

Guideline Champions (Champions) and other subject matter experts from within the VA and DoD, 

known as the Work Group, and ultimately, the submission of a new CPG.

The Champions and Work Group members for this CPG were charged with developing evidence-based 

clinical practice recommendations and publishing a guideline document to be used by providers within 

the VA/DoD healthcare system. Specifically, the Champions for this CPG were responsible for 

identifying the key evidence questions of greatest clinical relevance, importance, and interest for 

rehabilitation of a patient with an upper extremity amputation. In addition, Champions assisted in:

a. Conducting the evidence review, including providing direction on inclusion and exclusion

criteria

b. Assessing the level and quality of the evidence

c. Identifying appropriate disciplines to be included as part of the Work Group

d. Directing and coordinating the Work Group

e. Participating throughout the guideline development and review processes

The VA Office of Quality, Safety and Value, in collaboration with the DoD, identified four clinical 

leaders as Champions for the 2014 OA CPG. The Lewin Group (Lewin) and their sub-contractors ECRI 

Institute and Duty First Consulting, held the first conference call for this Guideline in August 2012, with 

participation from the contracting officer’s representatives (COR), leaders from the VA and DoD 

evidence-based guideline development program, and the Champions. During this call, the project 

team discussed the scope of the guideline initiative, the roles and responsibilities of the Champions, 

the project timeline, and the approach for developing evidence questions for a systematic review on 

the nonsurgical management of OA. During this call, the team also identified a list, from which the 

Work Group members were recruited, of clinical specialties and areas of expertise that are important 

and relevant to OA. The specialties areas included are dietetics, family practice, internal medicine, 

nursing, orthopedics, primary care, pharmacy and rheumatology. 

Methodology

The guideline development process for the VA/DoD OA CPG consisted of the following steps:

• Identifying the key evidence questions

• Conducting a systematic review of the literature

• Convening a three and a half day face to face meeting with the CPG Champions and Work

Group members
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• Submitting a final CPG on to the VA/DoD Evidence-Based Practice Working Group

The following is a detailed description of each of these steps.

Key Question Formulation

Following a series of discussions on the highest priority topics related to VA and DoD populations 

regarding OA, the Champions, in consultation with the Work Group, identified a set of 19 key 

questions to guide the systematic review of the literature. The key questions followed the industry 

standard PICOTS framework for evidence questions, as developed by the Agency for Healthcare 

Research and Quality (AHRQ). [151] Table A-1 provides a brief overview of the PICOTS typology. Lewin 

described this method in detail during the biweekly teleconference held with the Champions and 

guided them into identifying and prioritizing topics of interest for this CPG. 

Table A-1. PICOTS Framework [152] 

P Patients, Population 

or Problem

A description of the patients of interest. It includes the condition(s), populations or subpopulations, disease severity or stage, comorbidities, and other patient characteristics or 

demographics.

I Intervention or 

Exposure

Refers to the specific treatments or approaches used with the patient or population. It includes 

doses, frequency, methods of administering treatments, etc.

C Comparison

Describes the interventions or care that is being compared with the intervention(s) of interest 

described above. It includes alternatives such as placebo, drugs, surgery, lifestyle changes, 

standard of care, etc.

O Outcome Describes the specific results of interest. Outcomes can include short, intermediate, and long-term 

outcomes, or specific results such as quality of life, complications, mortality, morbidity, etc.

(T) Timing, if applicable Describes the duration of time that is of interest for the particular patient outcome, benefit, or 

harm to occur (or not occur).

(S) Setting, of applicable Describes the setting or context of interest. Setting can be a location (such as primary, specialty, or 

inpatient care).

The key questions, listed in table A-2, cover the following topics:

• Diagnosis and evaluation of OA

• Comparative effectiveness of drugs for OA

• Comparative effectiveness of non-pharmacologic therapies

• Comparative effectiveness of complementary and alternative medicine

• Surgical referral
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Table A-2. Key Evidence questions for the OA CPG

Key Questions

Diagnostic Questions

1. In adults with clinical symptoms and signs consistent with OA of the hips or knees, which imaging strategies,

including plain radiograph, MRI, and CT contribute to improved clinical outcomes?

2. In adults with clinical symptoms and signs consistent with OA of the hips or knees, do laboratory tests

contribute to improved clinical outcomes?

3. In adults with clinical symptoms and signs consistent with OA of the knees, does synovial fluid analysis

contribute to improved clinical outcomes?

Intervention Questions

4. In adults with OA of the hips or knees, what is the comparative effectiveness of acetaminophen to placebo

with respect to pain, improved function, and harms?

5. In adults with OA of the hips or knees, what is the comparative effectiveness of intra-articular corticosteroids

to intra-articular hyaluronates with respect to pain, improved function, and harms?

6. In adults with OA of the hips or knees, what is the comparative effectiveness of intra-articular hyaluronates

to sham injections with respect to pain, improved function, and harms?

7. In adults with OA of the hips or knees, what is the comparative effectiveness of joint injections to oral

NSAIDs (selective or non-selective) with respect to pain, improved function, and harms?

8. In adults with OA of the hips or knees, what is the comparative effectiveness of topical NSAIDs to oral

NSAIDs (selective or non-selective) with respect to pain, improved function, and harms?

9. In adults with OA of the hips or knees, what is the comparative effectiveness of traditional land-based

strengthening exercises to aquatic therapy with respect to pain, improved function, and harms?

10. In adults with OA of the hips or knees, what is the comparative effectiveness of traditional land-based

strengthening exercises to manual physical therapy with respect to pain, improved function, and harms?

11. In adults with OA of the hips or knees, what is the comparative effectiveness of aquatic therapy to manual

therapy with respect to pain, improved function, and harms?

12. What is the comparative effectiveness of walking aids or devices (e.g., cane ambulation to OA unloader

braces for the knees) used to treat OA of the hips or knees with respect to pain, improved function, and

harms?

13. In adults with OA of the hips or knees, what is the comparative effectiveness of chiropractic care to usual

therapy with respect to pain, improved function, and harms?

14. In adults with OA of the hips or knees, what is the comparative effectiveness of acupuncture to usual

therapy with respect to pain, improved function, and harms?

15. In adults with OA of the hips or knees, what is the comparative effectiveness of nutritional supplements

(e.g., glucosamine) to usual therapy with respect to pain, improved function, and harms?

Referral Questions

16. In patients with clinical symptoms and signs consistent with OA, what imaging findings indicate that referral

for total/partial joint replacement surgery is the best option for achieving optimal clinical outcomes?

17. For adults with OA of the hips or knees, what patient symptoms or signs (e.g., level of pain and/or disability)

indicate that referral for total/partial joint replacement surgery is the best option for achieving optimal

clinical outcomes?

18. In adults with OA of the hips or knees, what patient-centered risk factors would preclude referral for

surgery?

19. For adults with OA of the hips or knees, should a trial of injection therapy (corticosteroids or viscosupplementation) be attempted before referral for total/partial joint replacement surgery?
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 53 of 126

Evidence Review

The methods guiding this systematic review are described below. In part, these methods follow the 

guidelines for conducting a systematic review set forth by the Agency for Healthcare Research and 

Quality (AHRQ) in the Methods Guide for Effectiveness and Comparative Effectiveness Reviews. [153] 

The methods also follow the guidance set forth by the VA/DoD in the Guideline for Guidelines

document. [150] 

A systematic review of the literature consists of several distinct steps. ECRI Institute conducted the 

evidence review for this CPG, by following the process outlined below:

1. Defining the inclusion and exclusion search criteria

2. Developing a search strategy (i.e., search logic using MeSH (Medical Subject Headings)

terminology and key words)

3. Screening the results based on abstracts and titles (i.e., identifying relevant studies and

excluding duplicate records)

4. Reviewing the full text of remaining studies and abstracting relevant data points (i.e.,

population, comparator, results, etc.)

5. Assessing the internal and external validity of abstracted studies

6. Summarizing the evidence

7. Interpreting the results

Criteria for Study Inclusion/Exclusion

The inclusion criteria are listed below in separate categories pertaining to the following: general 

criteria relevant to all studies included in the evidence base; criteria that is specific to studies that 

address the diagnostic questions; criteria specific to studies that address the pharmacological and nonpharmacological intervention questions; and criteria specific to studies that address the referral 

questions. 

General Criteria

• Clinical studies published on or after January 1, 2002, and systematic reviews published on or

after January 1, 2008

• Studies must be published in English

• Publication must be a full-length clinical study or systematic review; abstracts alone were not

included. Similarly, letters, editorials, and other publications that are not full-length, clinical

studies were not accepted as evidence

• Study must have enrolled a patient population in which at least 85 percent of patients had OA

(post-traumatic or idiopathic) of the hips or knees

• Studies must have enrolled adults 18 years or older. In studies that mixed adults and children,

at least 85 percent of the enrolled patients must have been 18 years or older

• Study included 50 percent or more of patients at final follow-up
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• Studies that enrolled adults with osteonecrosis, rheumatoid arthritis, or other inflammatory

joint disease were excluded

Diagnosis/Evaluation Studies 

• Studies must have enrolled ≥ 10 patients

• Studies must have linked use of diagnostic technologies with improvement in clinical

outcomes. This ideally requires a study that compares clinical outcomes after diagnostic

technology evaluation versus clinical evaluation, or compares clinical outcomes linked to

different diagnostic technologies

Intervention Studies 

• Study must have evaluated a treatment for OA of the hips or knees

• Study must have been a prospective, randomized or nonrandomized comparative trial with an

independent, concurrent control group

• Crossover trials were considered only if data from the first treatment period were reported

separately

• Study must have enrolled ≥ 25 patients per treatment arm

• The study must report data on at least one of the included outcomes

• Study must have followed patients for at least four weeks

• All subjective outcomes (e.g., pain, aspects of patient function) must be measured using

validated instruments

Referral Studies

• Study must have enrolled ≥ 10 patients

• Study must have been a clinical study (comparative or not) that investigated indications for

referring patients with OA of the hips or knees for total/partial joint replacement surgery

• Expert opinion papers were not considered as evidence addressing the referral questions

• Study must have reported on the outcomes associated with indications

Additional Criteria for Key Question 18 

• Study must have enrolled at least 100 patients

• Study excluded if it only considered non-modifiable patient risk factors, such as gender or age

• Study excluded if outcomes of pain and function are measured prior to six months follow-up

Search Strategy

MeSH, EMTREE, and Keywords

The search strategies employed combinations of free text keywords as well as controlled vocabulary 

terms including (but not limited to) the concepts shown in the Topic-specific Search Terms table.
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 55 of 126

The strategies below are presented in OVID syntax; the searches were simultaneously conducted 

across EMBASE and Medline. Similar strategies were used to search the databases comprising 

PubMed, and the Cochrane Library (See Tables A-3 through A-12 below). Search sets were structured 

to address specific key questions and/or groups of key questions (i.e., diagnosis/evaluation, 

pharmacologic management, non-pharmacologic management, complementary and alternative 

medicine, and referrals). These search results were further refined to capture specific patient 

outcomes, study designs and publication types. 

Table A-3. Topic-specific Search Terms

Concept Controlled Vocabulary Keywords 

Patient Population

Osteoarthritis MEDLINE (MeSH)

osteoarthritis/ 

osteoarthritis, knee/ 

osteoarthritis, hip/

EMBASE (EMTREE)

osteoarthritis/ 

knee osteoarthritis/

hip osteoarthritis/

arthrit$ 

degenerative joint disease$

osteoarthrit$ 

Knee MEDLINE (MeSH)

exp knee/

exp knee joint/

exp knee injuries/

EMBASE (EMTREE)

exp knee/ 

exp knee injury/

ACL 

anterior cruciate ligament

iliotibial

knee 

knees

menisc$ 

patellofemor$ 

patell$ 

Hip MEDLINE (MeSH)

exp hip/

exp hip joint/

exp hip injuries/

hip fractures/

EMBASE (EMTREE)

exp hip/

exp hip injury/

coxa

coxas

hip 

hips

Terms for Diagnostic/Evaluation Questions

Imaging

(Note that the same 

terms were used for the 

Referrals Question that 

involved imaging)

MEDLINE (MeSH)

exp *diagnostic imaging/

*tomography scanners, x-ray computed/

EMBASE (EMTREE)

exp diagnostic imaging equipment/

exp "imaging and display"/

exp radiodiagnosis/

exp echography/

absorptiometry

arthrography

computed tomography

CT

DEXA

dGEMRIC

diffusion tensor

image$

imaging

magnetic resonance

MR

MRI

neuroimaging

NMR
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 56 of 126

Concept Controlled Vocabulary Keywords 

PET

phonoarthrography

positron emission tomography

radiodiagnos$

radiograph$

ultrasonography

ultrasound

PET

Scan

scans

scanning

scintigraph$

sonograph$

SPECT

spectroscopy

Tc-99m

technetium

tomosynthesis

ultrasonography

ultrasound$

x ray$

xray$

Laboratory Tests 

(including synovial fluid 

analysis)

MEDLINE (MeSH)

exp clinical laboratory techniques/ 

exp hematologic tests/ 

c-reactive protein/ 

synovial fluid/ 

rheumatoid factor/ 

exp serologic tests/ 

exp blood cell count/ 

EMBASE (EMTREE)

exp laboratory diagnosis/ 

exp blood examination/ 

C reactive protein/ 

synovial fluid/

rheumatoid factor/

exp serology/

articular fluid

blood

c-reactive protein

c reactive protein

hematology

hematologic

joint fluid

lab

laboratory

rheumatoid factor

sera

serum

serology

synovial fluid

synovium

Terms for Pharmacologic Management Questions

Acetaminophen MEDLINE (MeSH)

acetaminophen/

EMBASE (EMTREE)

paracetamol/

acetaminophen$ 

paracetamol 

tylenol 

anacin 

acetaco 

datril

panadol 

acamol 

algotropyl 

acetamidophenol

Corticosteroids MEDLINE (MeSH)

exp adrenal cortex hormones/

EMBASE (EMTREE)

Adrenal cortex hormones

betamethasone 

corticosteroid$ 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 57 of 126

Concept Controlled Vocabulary Keywords 

exp corticosteroid/ corticoid$ 

Dexamethasone

cortisone$

glucocorticoid$ 

hydroxycorticosteroid$ 

hydrocortisone

Methylprednisolone

prednisolone 

prednisone 

steroid$ 

Injection Therapy

(Note that the same 

terms were used for the 

Referrals Question that 

involved injections)

MEDLINE (MeSH)

injections/ 

exp injections, intra-articular/

viscosupplementation/

EMBASE (EMTREE)

intraarticular drug administration/ 

injection/ 

viscosupplementation/

inject$

intra-articular inject$

Intra articular inject$

Intraarticular inject$

IACI

viscosupplement$

Intra-articular 

hyaluronates

MEDLINE (MeSH)

viscosupplementation/

hyaluronic acid/

hyaluronic acid/tu 

EMBASE (EMTREE)

viscosupplementation/ 

hyaluronic acid/

hyaluronic acid/dt

Adant 

Amvisc 

Arthrease 

Arthrum H 

Artz 

Biolon 

BioHy 

Durolane 

Etamucine

Euflexxa 

Fermathron 

"gel-one" 

Healon 

Hyalgan 

Hyaluronan 

hyaluronate$ 

hyaluronic 

Hyaluronidate 

"hylan gf-20" 

Hyruan 

Hyvisc 

Luronit 

nuflexxa 

Orthovisc 

Ostenil 

Replasyn 

SLM-10 

supartz 

Suplasyn 

Synject 

synvisc 

viscosupplement$ 

vitrax
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 58 of 126

Concept Controlled Vocabulary Keywords 

Nonsteroidal antiinflammatory drugs MEDLINE (MeSH)

exp anti-inflammatory agents, nonsteroidal/

exp cyclooxygenase inhibitors/

exp cyclooxygenase 2 Inhibitors/

EMBASE (EMTREE)

exp nonsteroid antiinflammatory agent/

exp prostaglandin synthase inhibitor/

exp cyclooxygenase 2 inhibitor/

aleve 

aspirin 

celecoxib 

Celebrex 

(Cox$ OR Cyclooxygenase$ OR Cyclooxygenase$) AND inhibit$

coxib$

diclofenac

ibuprofen 

motrin 

naproxen 

nonsteroidal anti-inflammatory 

NSAID$

rofecoxib 

salicylate$ 

vioxx

Topical NSAIDS

"Deep Relief"

"Fenbid Gel" 

Ibugel 

Ibuleve 

Ibumousse 

Ibuspray 

optifen

pennsaid 

Powergel 

sulidin 

Traxam 

voltaran 

voltarol

Oral Administration MEDLINE (MeSH)

exp administration oral/

EMBASE (EMTREE)

oral drug administration/ 

buccal 

"by mouth"

oral 

"p.o." 

sublingual 

Placebos MEDLINE (MeSH)

placebos/

EMBASE (EMTREE)

placebo/ 

dummy

Inactive

no intervention

no treatment

placebo$ 

sham$ 

Topical Therapy MEDLINE (MeSH)

administration, topical/

administration, cutaneous/

EMBASE (EMTREE)

topical treatment/ 

transdermal drug administration/

aerosol 

balm

cream 

creme 

cutaneous 

dermal 

embrocation

emulsion

epicutaneous

foam 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 59 of 126

Concept Controlled Vocabulary Keywords 

gel 

lotion

liniment

massage 

mousse 

oil

ointment 

patch 

percutaneous 

plaster 

rub

salve

skin 

spray 

topical$ 

transcutaneous 

transdermal 

Terms for Non-pharmacologic Management Questions

Aquatic therapy MEDLINE (MeSH)

pools, swimming/

swimming/

EMBASE (EMTREE)

aquatic exercise/

swimming/

swimming pool/

aquarobic$

aquatic

aquatics

hydrotherapy

pool based

pool therapy

swim$

water

Land-based 

strengthening exercises

MEDLINE (MeSH)

exp exercise/ 

exp exercise movement techniques/

exp exercise therapy/

physical fitness/

EMBASE (EMTREE)

exp exercise/

fitness/

exp kinesiotherapy/ 

exp physical activity/

active stretching 

aerobic activity

aerobic conditioning

aerobics

dance

dancing

endurance training

exercise$

fitness

hip school

kinesiotherapy

land based

motion therapy

muscle strengthening

physical activity

physical conditioning

plyometric training

resistance training

strength training

tai chi

walk$

weight lifting

yoga

Manual physical 

therapy

MEDLINE (MeSH)

exp musculoskeletal manipulations/

manipulation$

manipulative
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 60 of 126

Concept Controlled Vocabulary Keywords 

[note: includes massage]

physical therapists/

physical therapy modalities/

physical therapy department, hospital/

physical therapy specialty/

EMBASE (EMTREE)

manipulative medicine/ 

massage/

muscle training/

orthopedic manipulation/

physiotherapist/

exp physiotherapy/

stretching/

manual techniques

manual therapy

massage

mobilization

mobilisation 

muscle stretching

physical therapy

physiotherap$

rehabilitation

stretching

Walking aids or devices MEDLINE (MeSH)

canes/

crutches/

orthotic devices/

walkers/

EMBASE (EMTREE)

orthopedic shoe/

exp orthosis/

orthotics/

exp walking aid/

brace$

bracing

cane

canes

crutch

crutches

footwear 

inshoe$

joint supports

orthotic

orthotics

orthoses

orthosis

orthopedic shoe$

taping

splint

splints

walker$

walking aid$

walking device$

walking stick$ 

wedge$

Terms for Complementary and Alternative Medicine Questions

Acupuncture MEDLINE (MeSH)

acupressure/

acupuncture/

exp acupuncture therapy/

EMBASE (EMTREE)

exp acupuncture/

acupoint

acupressure

acupuncture$

acustimulation

acu stimulation

electroacupoint

electroacupuncture

electroacustimulation

Chiropractic care MEDLINE (MeSH)

chiropractic/

manipulation, chiropractic/

manipulation, osteopathic/

EMBASE (EMTREE)

chiropractic/

chiropractic practice/

adjustment$

chiropractic$

chiropractor$

manipulation$

manipulative
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 61 of 126

Concept Controlled Vocabulary Keywords 

chiropractor/

Nutritional 

Supplements

MEDLINE (MeSH)

exp dietary supplements/ 

exp glucosamine/ 

exp chondroitin/ 

capsaicin/ 

exp plants, medicinal/

EMBASE (EMTREE)

nutraceutical/ 

diet supplementation/ 

vitamin supplementation/ 

exp plant medicinal product/ 

exp glucosamine/ 

chondroitin/

alliums

black cohosh 

capsaicin$ 

Capsaicine 

chondroitin

Cimicifuga

Creatine

curcuma 

curcumin 

Cyperus 

devils claw

Dietary supplement

eazmov

Feverfew

Fraxinus

garlic 

ginger 

Gitadyl

glucosamine 

Guaiacum

harpagophytum 

herb 

medicinal

Methylsulfonylmethane 

milfoil

Nettle$

nutraceutical$ 

nutritional supplement

omega-3 

Phytodolor

Picrorhiza

Picrorrhiza

plant

Poplar

populus 

quercetin 

remedy

Reumalex

Rose hip

S-adenosylmethionine 

Sarsaparilla 

saussurea

Smilax

solidago

supplement

tanacetum parthenium

Tinospora

Turmeric 

uncaria 

willow
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 62 of 126

Concept Controlled Vocabulary Keywords 

zingiber

Terms for Referral questions

Joint Replacement 

Surgery

MEDLINE (MeSH)

exp arthroplasty/ 

EMBASE (EMTREE)

exp arthroplasty/

arthroplast$

replace

replacement$

resurfac$

surgical

surgery

Outcomes MEDLINE (MeSH)

prognosis/ 

treatment outcome/ 

exp postoperative complications/ 

survival rate/ 

outcome assessment/ 

"outcome assessment (health care)"/

exp "quality of life"/ 

mortality.fs. 

reoperation/ 

adverse effects.fs. 

recovery of function/ 

comorbidity/ 

mortality/ 

morbidity/

EMBASE (EMTREE)

prognosis/ 

treatment outcome/ reoperation/ 

exp postoperative complication/ 

mortality/ 

morbidity/ 

complication.fs. 

convalescence/

appropriate

appropriateness

comorbid

comorbidity

complication$

morbidity 

mortality

prognosis

prognostic

QOL

"quality of life"

survival*

Referral MEDLINE (MeSH)

"referral and consultation"/ 

decision making/

patient selection/ 

"severity of illness index"/ 

risk factors/ 

disability evaluation/ 

risk assessment/

decision trees/

patient care planning/ 

EMBASE (EMTREE)

decision making/ 

patient selection/ 

risk assessment/ 

patient referral/ 

patient care planning/ 

risk factor/ 

exp disability/ 

exp disease severity/

consult

consultation

contraindicate

criteria 

decide

decision

indication

patient selection

patient characteristics

predict

risk

"red flag" 

referral 

refer 

serious 

surgeon 

specialist

urgent

warning 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 63 of 126

OVID Conventions:

$ or * = truncation character (wildcard)

.ab. = limit to abstract

ADJn = search terms within a specified number (n) of words from each other in any order

exp/ = “explodes” controlled vocabulary term (e.g., expands search to all more specific related 

terms in the vocabulary’s hierarchy)

.de. = limit controlled vocabulary heading

.fs. = floating subheading

.hw. = limit to heading word

.mp. = combined search fields (default if no fields are specified)

.pt. = publication type 

.ti. = limit to title 

.tw. = limit to title and abstract fields 

Table A-4. Search Strategy for Diagnosis/Evaluation Key Question 1 (imaging strategies) 

Set # Concept Search Statement

1 Osteoarthritis of 

specific joints

osteoarthritis, knee/ OR osteoarthritis, hip/ OR hip osteoarthritis/ OR knee 

osteoarthritis/

2 Osteoarthritis osteoarthritis/ OR (arthrit$ OR osteoarthrit$ OR degenerative joint).ti.

3 Knee exp knee/ OR exp knee joint/ OR exp knee injuries/ OR exp knee injury/ OR (knee OR 

knees OR menisc$ OR patellofemor$ OR patell$ OR iliotibial OR ACL OR anterior 

cruciate ligament).ti.

4 Hip exp hip/ OR exp hip joint/ OR exp hip injuries/ OR exp hip fractures/ OR exp hip 

injury/ OR (hip OR hips).ti.

5 Combine sets 2 AND (3 OR 4)

6 1 OR 5

7 Diagnostic 

imaging

Controlled 

vocabulary

Exp *diagnostic imaging equipment/ OR exp *"imaging and display"/ OR exp 

*radiodiagnosis/ OR exp *echography/ OR exp *diagnostic imaging/ OR 

*tomography scanners, x-ray computed/

8 Diagnostic 

imaging

Keywords

(absorptiometry OR arthrography OR computed tomography OR CT OR DEXA OR 

dGEMRIC OR diffusion tensor OR image$ OR imaging OR magnetic resonance OR MR 

OR MRI OR neuroimaging OR NMR OR PET OR phonoarthrography OR positron 

emission tomography OR radiodiagnos$ OR radiograph$ OR scan OR scans OR 

scanning OR scintigraph$ OR sonograph$ OR SPECT OR spectroscopy OR Tc-99m OR 

technetium OR tomosynthesis OR ultrasonography OR ultrasound$ OR x-ray$ OR 

xray$).ti.

9 Combine sets 6 AND (7 OR 8)

10 Exclude 

publications that 

are outside of 

scope

9 NOT (spine OR spinal OR vertebr$ OR lumbar$ OR cervic$ OR thorac$ OR surgery 

OR surgical OR psoriatic OR rheumatoid OR rheumatic OR inflammatory OR juvenile 

OR "JRA" OR arthroplast$ OR replace$ OR reconstruct$ OR arthroscop$ OR 

biomarker$ OR implant$ OR injection$ OR marker$ OR osteotom$ OR resurfac$ OR 

sepsis OR septic OR therapeutic ultrasound OR TKA OR ultrasound therapy OR 

urinary).ti.

11 Exclude

unwanted 

publications

10 NOT (book/ OR edited book/ OR case report/ OR case reports/ OR comment/ OR 

conference abstract/ OR conference paper/ OR conference review/ OR editorial/ OR 

letter/ OR news/ OR note/ OR proceeding/ OR (book OR edited book OR case report 

OR case reports OR comment OR conference OR editorial OR letter OR news OR note 

OR proceeding).pt.)
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 64 of 126

Set # Concept Search Statement

12 Keep case series 10 AND (case series OR case control)

13 Combine 11 OR 12

14 Limit to humans limit 13 to humans

15 Limit to english 

language

limit 14 to english language

16 Limit by 

publication date

limit 15 to yr="2002 -Current"

17 Limit to 

comparative 

studies and 

systematic 

reviews

16 AND (comparative study/ OR control groups/ OR controlled clinical trial/ OR 

controlled study/ OR cross-over studies/ OR double-blind method/ OR random 

allocation/ OR randomized controlled trial/ OR sham procedure/ OR single-blind 

method/ OR (compar$ OR versus OR vs).ti. OR (blind$ OR (control ADJ group$) OR 

controlled study OR controlled trial OR crossover OR cross over OR latin square OR 

mask$ OR matched controls OR pooled OR research synthesis OR sham OR ACTRN$ 

OR ISRTCN$ OR (NCT$ NOT NCT)).ti,ab. OR meta-analysis/ OR systematic review/ OR 

(evidence ADJ base$).ti. OR (meta-analysis OR methodologic$ OR pooled OR search$ 

OR systematic literature review OR systematic review).ti,ab.)

18 Limit to studies 

that address 

management or 

outcomes

16 AND (disease course/ OR disease progression/ OR exp disease management/ OR 

exp "outcome assessment (health care)"/ OR predictive value/ OR "predictive value 

of tests"/ OR prognosis/ OR treatment outcome/ OR (adverse OR function$ OR 

harm$ OR pain OR outcome$ OR utility).ti,ab. OR clinical.ti. OR adverse effects.fs. OR 

disease management.fs.)

19 Combine sets 17 OR 18

20 Eliminate overlap Remove duplicates from 19

Table A-5. Search Strategy for Diagnosis/Evaluation Key Questions 2 and 3 (laboratory tests and 

synovial fluid analysis) 

Set # Concept Search Statement

1 Knee or Hip 

osteoarthritis

osteoarthritis, knee/ OR osteoarthritis, hip/ OR hip osteoarthritis/ OR knee 

osteoarthritis/ 

2 Osteoarthritis 

keywords

osteoarthritis/ OR arthrit$.ti. OR osteoarthrit$.ti. OR degenerative joint.ti.

3 Knee joint exp knee/ OR exp knee joint/ OR exp knee injuries/ OR exp knee injury/ OR knee.ti. 

OR knees.ti. OR menisc$.ti. OR patellofemor$.ti. OR patell$.ti. OR iliotibial.ti. OR 

ACL.ti. OR anterior cruciate ligament.ti.

4 Hip exp hip/ OR exp hip joint/ OR exp hip injuries/ OR exp hip fractures/ OR exp hip 

injury/ OR hip.ti. OR hips.ti.

5 Combine 

population sets

1 OR (2 AND (3 OR 4))

6 Laboratory tests exp clinical laboratory techniques/ OR exp hematologic tests/ OR c-reactive protein/ 

OR synovial fluid/ OR rheumatoid factor/ OR exp serologic tests/ OR exp blood cell 

count/ OR exp laboratory diagnosis/ OR exp blood examination/ OR C reactive 

protein/ OR exp serology/

7 Laboratory tests 

(keywords)

"c-reactive protein".ti. OR "c reactive protein".ti. OR ((joint OR articular OR synovial 

OR synovium AND fluid) OR (rheumatoid ADJ factor)).ti. OR lab.ti. OR laboratory.ti. 

OR labs.ti. OR blood.ti. OR hematol$.ti. OR sera.ti. OR serum.ti. OR serolog$.ti. 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 65 of 126

Set # Concept Search Statement

11 Diagnostic test 

hedge

exp diagnosis/ OR di.fs. OR receiver operating characteristic/ OR ROC curve/ OR 

"sensitivity and specificity"/ OR accuracy/ OR diagnostic accuracy/ OR precision OR 

exp "prediction and forecasting"/ OR likelihood OR ((false OR true) adj (positive OR 

negative)) OR predictive value of tests/ OR exp diagnostic errors/ OR exp diagnostic 

error/ OR diagnostic accuracy/ OR positive predictive value OR PPV OR diagnosis.ti. 

OR diagnostic$.ti. OR diagnose$.ti. OR evaluat$.ti. OR assess$.ti. OR test.ti. OR 

testing.ti. OR tests.ti.

12 Combine sets 5 AND (6 OR 7) AND 11

13 Limit to english 

language

limit 12 to english language

14 Limit to Human 

studies

limit 13 to humans

15 Exclude 

unwanted 

publication types

14 NOT (book/ OR edited book/ OR case report/ OR case reports/ OR comment/ OR 

conference abstract/ OR conference paper/ OR conference review/ OR editorial/ OR 

letter/ OR news/ OR note/ OR proceeding/ OR book OR edited book OR case report 

OR case reports OR comment OR conference OR editorial OR letter OR news OR note 

OR proceeding.pt.)

16 Include case 

series

14 AND (case series OR case control)

17 Combine sets 15 OR 16 

18 Limit by 

publication date

limit 17 to yr="2002-Current"

19 Eliminate overlap Remove duplicates from 18

Table A-6. Search Strategy for Pharmacologic Management Key Questions 4, 5, 6, 7, and 8

Set # Concept Search Statement

1 Knee or Hip 

osteoarthritis

osteoarthritis, knee/ OR osteoarthritis, hip/ OR hip osteoarthritis/ OR knee 

osteoarthritis/ 

2 Osteoarthritis 

keywords

osteoarthritis/ OR arthrit$.ti. OR osteoarthrit$.ti. OR degenerative joint.ti.

3 Knee joint exp knee/ OR exp knee joint/ OR exp knee injuries/ OR exp knee injury/ OR knee.ti. 

OR knees.ti. OR menisc$.ti. OR patellofemor$.ti. OR patell$.ti. OR iliotibial.ti. OR 

ACL.ti. OR anterior cruciate ligament.ti.

4 Hip exp hip/ OR exp hip joint/ OR exp hip injuries/ OR exp hip fractures/ OR exp hip 

injury/ OR hip.ti. OR hips.ti.

5 Combine 

population sets

1 OR (2 AND (3 OR 4))

6 Intervention -

Acetaminophen

Acetaminophen/ OR Paracetamol/ OR Acetaminophen$ OR paracetamol$ OR tylenol 

OR anacin OR acetaco OR datril OR panadol OR acamol OR algotropyl OR 

acetamidophenol

7 Intervention -

Placebo

placebos/ OR placebo/ OR placebo$ OR sham$ OR dummy OR inactive OR (no ADJ2 

intervention) OR (no ADJ2 treatment$)

8 Intervention –

corticosteroids

exp adrenal cortex hormones/ OR exp corticosteroid OR "Adrenal cortex hormones" 

OR corticosteroid$ OR corticoid$ OR steroid$ OR glucocorticoid$ OR 

hydroxycorticosteroid$ OR cortisone$ OR hydrocortisone OR Dexamethasone OR 

prednisolone OR prednisone OR hydrocortisone OR betamethasone OR 

Methylprednisolone
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 66 of 126

Set # Concept Search Statement

9 Intervention -

NSAIDS

exp Anti-Inflammatory Agents, Non-Steroidal/ OR exp cyclooxygenase inhibitors/ OR 

exp cyclooxygenase 2 Inhibitors/ OR exp nonsteroid antiinflammatory agent/ OR exp 

prostaglandin synthase inhibitor/ OR exp cyclooxygenase 2 inhibitor/ OR aleve OR 

aspirin OR diclofenac OR naproxen OR NSAID$ OR celecoxib OR Celebrex OR ((Cox$ 

OR Cyclooxygenase$ OR Cyclo-oxygenase$) AND inhibit$) OR coxib$ OR ibuprofen 

OR motrin OR naproxen OR (Nonsteroidal ADJ anti-inflammator$) OR (Non-steroidal 

ADJ anti-inflammator$) OR (Non-steroidal ADJ antiinflammatory) OR rofecoxib OR 

salicylate$ OR vioxx 

10 Intervention –

Topical NSAIDS

Traxam OR "Deep Relief" OR "Fenbid Gel" OR Ibugel OR Ibuleve OR Ibumousse OR 

Ibuspray OR Powergel OR voltaran OR voltarol OR pennsaid OR sulidin OR optifen

11 Intervention -

Hyaluronates

Viscosupplementation/ OR Hyaluronic Acid/ OR Adant OR Amvisc OR Arthrease OR 

Arthrum H OR Artz OR Biolon OR BioHy OR Durolane OR Etamucine OR Euflexxa OR 

Fermathron OR "gel-one" OR Healon OR Hyalgan OR Hyaluronan OR hyaluronate$ 

OR hyaluronic OR Hyaluronidate OR "hylan gf-20" OR Hyruan OR Hyvisc OR Luronit 

OR nuflexxa OR Orthovisc OR Ostenil OR Replasyn OR SLM-10 OR supartz OR 

Suplasyn OR Synject OR synvisc OR viscosupplement$ OR vitrax

12 Intervention -

Hyaluronates 

(controlled terms 

for therapy)

hyaluronic acid/tu OR hyaluronic acid/dt

13 Administration -

Injections

injections/ OR exp injections, intra-articular/ OR viscosupplementation/ OR 

intraarticular drug administration/ OR injection/ OR viscosupplement$.mp. OR 

inject$.mp. OR intraarticular OR intra-articular OR (intra ADJ articular) OR "IACI"

14 Administration -

Oral

exp administration oral/ OR oral drug administration/ OR oral OR buccal OR 

sublingual OR "p.o." OR "by mouth"

15 Administration –

Topical 

administration, topical/ OR administration, cutaneous/ OR topical treatment/ OR 

transdermal drug administration/ OR topical OR cutaneous OR transcutaneous OR 

topical$ OR dermal OR transcutaneous OR transdermal OR percutaneous OR skin OR 

massage OR embrocation OR gel OR ointment OR aerosol OR cream OR creme OR 

lotion OR mousse OR foam OR liniment OR spray OR rub OR balm OR salve OR 

emulsion OR oil OR patch OR plaster OR epicutaneous

16 Combine sets –

key question 4: 

acetaminophen 

compared to 

placebo

5 AND 6 AND 7

17 Combine sets –

key question 5: 

intra-articular 

corticosteroids 

compared to 

intra-articular 

hyaluronates

5 AND (8 AND 13) AND ((11 AND 13) OR 12)

18 Combine sets –

key question 6: 

intra-articular 

hyaluronates 

compared to 

sham injections

5 AND ((11 AND 13) OR 12) AND 7
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 67 of 126

Set # Concept Search Statement

19 Combine sets –

key question 7: 

joint injections 

compared to oral 

NSAIDS

5 AND 13 AND 9 

20 Combine setskey question 8: 

topical NSAIDS 

compared to oral 

NSAIDS

5 AND (10 OR (9 AND 15)) AND (9 AND 14)

21 Combine sets for 

key questions

16 OR 17 OR 18 OR 19 OR 20

22 Limit to humans limit 21 to humans

23 Limit to english 

language

limit 22 to english language

24 Exclude 

unwanted 

publication types

23 NOT (book/ OR edited book/ OR case report/ OR case reports/ OR comment/ OR 

conference abstract/ OR conference paper/ OR conference review/ OR editorial/ OR 

letter/ OR news/ OR note/ OR proceeding/ OR (book OR edited book OR case report 

OR case reports OR comment OR conference OR editorial OR letter OR news OR note 

OR proceeding).pt.)

25 Keep case series 23 AND (case series OR case control)

26 Combine sets 24 OR 25

27 Limit by 

publication date

Limit 26 to yr="2002-Current"

28 Eliminate overlap Remove duplicates from 27

Table A-7. Search Strategy for Non-pharmacologic Management Key Questions 9, 10, 11, and 12

Set # Concept Search Statement

1 Osteoarthritis of 

specific joints

osteoarthritis, knee/ OR osteoarthritis, hip/ OR hip osteoarthritis/ OR knee 

osteoarthritis/

2 Osteoarthritis osteoarthritis/ OR (arthrit$ OR osteoarthrit$ OR degenerative joint).ti.

3 Knee exp knee/ OR exp knee joint/ OR exp knee injuries/ OR exp knee injury/ OR (knee OR 

knees OR menisc$ OR patellofemor$ OR patell$ OR iliotibial OR ACL OR anterior 

cruciate ligament).ti.

4 Hip exp hip/ OR exp hip joint/ OR exp hip injuries/ OR exp hip fractures/ OR exp hip 

injury/ OR (hip OR hips).ti.

5 Combine sets 2 AND (3 OR 4)

6 1 OR 5

7 Land-based 

exercise

Controlled 

vocabulary

exp exercise/ OR exp exercise movement techniques/ OR exp exercise therapy/ OR 

fitness/ OR kinesiotherapy/ OR exp physical activity/ OR physical fitness/

8 Land-based 

exercise

Keywords

active stretching OR aerobic activity OR aerobic conditioning OR aerobics OR apos$ 

OR dance OR dancing OR endurance training OR exercise$ OR fitness OR 

kinesiotherapy OR land based OR motion therapy OR muscle strengthening OR 

physical activity OR physical conditioning OR plyometric training OR resistance 

training OR strength training OR tai chi OR walk$ OR weight lifting OR yoga

9 Aquatic exercise

Controlled 

vocabulary

aquatic exercise/ OR pools, swimming/ OR swimming/ OR swimming pool/
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 68 of 126

Set # Concept Search Statement

10 Aquatic exercise

Keywords

aquarobic$ OR (aquatic AND (exercise$ OR rehabilitation OR therapy OR training)) 

OR aquatics OR hydrotherapy OR pool based OR pool therapy OR swim$ OR (water 

AND (aerobics$ OR exercise$ OR therapy))

11 Manual physical 

therapy

Controlled 

vocabulary

manipulative medicine/ OR massage/ OR muscle training/ OR exp musculoskeletal 

manipulations/ OR orthopedic manipulation/ OR physical therapists/ OR physical 

therapy modalities/ OR physical therapy department, hospital/ OR physical therapy 

specialty/ OR physiotherapist/ OR exp physiotherapy/ OR stretching/

12 Manual physical 

therapy

Keywords

manipulation$ OR manipulative OR manual techniques OR manual therapy OR 

massage OR mobilisation OR mobilization OR muscle stretching OR physical therapy 

OR physiotherapies OR physiotherapy OR rehabilitation.ti. OR stretching

13 Walking aids or 

Devices

Controlled 

vocabulary

canes/ OR crutches/ OR orthopedic shoe/ OR exp orthosis/ OR orthotic devices/ OR 

orthotics/ OR walkers/ OR exp walking aid/

14 Walking aids or 

devices

Keywords

brace OR braces OR bracing OR cane OR canes OR crutch OR crutches OR footwear 

OR inshoe$ OR joint supports OR orthotic OR orthotics OR orthoses OR orthosis OR 

(orthopedic ADJ shoe$) OR taping OR splint OR splints OR walker$ OR (walking ADJ 

(aid OR aids OR device$ OR stick$)) OR wedge$

15 Land-based 

strengthening 

exercises 

vs. aquatic 

therapy

6 AND (7 OR 8) AND (9 OR 10)

16 Land-based 

strengthening 

exercises 

vs. manual 

physical therapy

6 AND (7 OR 8) AND (11 OR 12)

17 Aquatic therapy 

vs. manual 

physical therapy

6 AND (9 OR 10) AND (11 OR 12)

18 Walking aids or 

devices

6 AND (13 OR 14)

19 Combine sets 15 OR 16 OR 17 OR 18

20 Exclude 

unwanted 

publications

19 NOT (book/ OR edited book/ OR case report/ OR case reports/ OR comment/ OR 

conference abstract/ OR conference paper/ OR conference review/ OR editorial/ OR 

letter/ OR news/ OR note/ OR proceeding/ OR (book OR edited book OR case report 

OR case reports OR comment OR conference OR editorial OR letter OR news OR note 

OR proceeding).pt.)

21 Limit to humans limit 20 to humans

22 Limit to english 

language

limit 21 to english language

23 Limit by 

publication date

limit 22 to yr="2002-Current"
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 69 of 126

Set # Concept Search Statement

24 Limit to 

comparative 

studies and 

systematic 

reviews

23 AND (comparative study/ OR control groups/ OR controlled clinical trial/ OR 

controlled study/ OR cross-over studies/ OR double-blind method/ OR placebo/ OR 

placebos/ OR random allocation/ OR randomized controlled trial/ OR sham 

procedure/ OR single-blind method/ OR (compar* OR versus OR vs).ti. OR (blind$ OR 

(control ADJ group*) OR controlled study OR controlled trial OR crossover OR cross 

over OR latin square OR mask$ OR matched controls OR placebo$ OR pooled OR 

research synthesis OR sham OR ACTRN$ OR ISRTCN$ OR (NCT$ NOT NCT)).ti,ab. OR 

meta-analysis/ OR systematic review/ OR (evidence ADJ base$).ti. OR (meta-analysis

OR methodologic$ OR pooled OR search$ OR systematic literature review OR 

systematic review).ti,ab.)

25 Eliminate overlap Remove duplicates from 24

Table A-8. Search Strategy for Complementary and Alternative Medicine Questions 13 and 14

(chiropractic care and acupuncture)

Set # Concept Search Statement

1 Osteoarthritis of 

specific joints

osteoarthritis, knee/ OR osteoarthritis, hip/ OR hip osteoarthritis/ OR knee 

osteoarthritis/

2 Osteoarthritis osteoarthritis/ OR (arthrit$ OR osteoarthrit$ OR degenerative joint).ti.

3 Knee exp knee/ OR exp knee joint/ OR exp knee injuries/ OR exp knee injury/ OR (knee OR 

knees OR menisc$ OR patellofemor$ OR patell$ OR iliotibial OR ACL OR anterior 

cruciate ligament).ti.

4 Hip exp hip/ OR exp hip joint/ OR exp hip injuries/ OR exp hip fractures/ OR exp hip 

injury/ OR (hip OR hips).ti.

5 Combine sets 2 AND (3 OR 4)

6 1 OR 5

7 Chiropractic care

Controlled 

vocabulary

chiropractic/ OR chiropractic practice/ OR chiropractor/ OR manipulation, 

chiropractic/ OR manipulation, osteopathic/

8 Chiropractic care

Keywords

adjustment$ OR chiropractic$ OR chiropractor$ OR manipulation$ OR manipulative

9 Acupuncture

Controlled 

vocabulary

acupressure/ OR exp acupuncture/ OR exp acupuncture therapy/

10 Acupuncture

Keywords

((acupoint OR electroacupoint) ADJ stimulation) OR acupressure OR acupunctur$ OR 

acustimulation OR acu stimulation OR electroacupuncture OR electroacustimulation

11 Chiropractic care 6 AND (7 OR 8)

12 Acupuncture 6 AND (9 OR 10)

13 Combine sets 11 OR 12

14 Exclude 

unwanted 

publications

13 NOT (book/ OR edited book/ OR case report/ OR case reports/ OR comment/ OR 

conference abstract/ OR conference paper/ OR conference review/ OR editorial/ OR 

letter/ OR news/ OR note/ OR proceeding/ OR (book OR edited book OR case report 

OR case reports OR comment OR conference OR editorial OR letter OR news OR note 

OR proceeding).pt.)

15 Limit to humans limit 14 to humans

16 Limit to english 

language

limit 15 to english language

17 Limit by 

publication date

limit 16 to yr="2002-Current"
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 70 of 126

Set # Concept Search Statement

18 Limit to 

comparative 

studies and 

systematic 

reviews

17 AND (comparative study/ OR control groups/ OR controlled clinical trial/ OR 

controlled study/ OR cross-over studies/ OR double-blind method/ OR placebo/ OR 

placebos/ OR random allocation/ OR randomized controlled trial/ OR sham 

procedure/ OR single-blind method/ OR (compar* OR versus OR vs).ti. OR (blind$ OR 

(control ADJ group*) OR controlled study OR controlled trial OR crossover OR cross 

over OR latin square OR mask$ OR matched controls OR placebo$ OR pooled OR 

research synthesis OR sham OR ACTRN$ OR ISRTCN$ OR (NCT$ NOT NCT)).ti,ab. OR 

meta-analysis/ OR systematic review/ OR (evidence ADJ base$).ti. OR (meta-analysis

OR methodologic$ OR pooled OR search$ OR systematic literature review OR 

systematic review).ti,ab.)

19 Eliminate overlap Remove duplicates from 18

Table A-9. Search Strategy for Complementary and Alternative Medicine Key Question 15

(nutritional supplements)

Set # Concept Search Statement

1 Knee or Hip 

osteoarthritis

osteoarthritis, knee/ OR osteoarthritis, hip/ OR hip osteoarthritis/ OR knee 

osteoarthritis/ 

2 Osteoarthritis 

keywords

osteoarthritis/ OR arthrit$.ti. OR osteoarthrit$.ti. OR degenerative joint.ti.

3 Knee joint exp knee/ OR exp knee joint/ OR exp knee injuries/ OR exp knee injury/ OR knee.ti. 

OR knees.ti. OR menisc$.ti. OR patellofemor$.ti. OR patell$.ti. OR iliotibial.ti. OR 

ACL.ti. OR anterior cruciate ligament.ti.

4 Hip exp hip/ OR exp hip joint/ OR exp hip injuries/ OR exp hip fractures/ OR exp hip 

injury/ OR hip.ti. OR hips.ti.

5 Combine 

population sets

1 OR (2 AND (3 OR 4))

6 Nutritional 

supplements 

(controlled terms)

exp dietary supplements/ OR exp glucosamine/ OR exp chondroitin/ OR capsaicin/ 

OR plants, medicinal/ OR nutraceutical/ OR diet supplementation/ OR vitamin 

supplementation/ OR exp plant medicinal product/ OR exp glucosamine/ OR 

chondroitin/

7 Nutritional 

supplements 

(keywords)

((dietary OR nutritional OR herb$ OR plant$)AND (supplement$ OR remedy OR 

remedies OR medicinal)) OR nutraceutical$ OR glucosamine OR chondroitin OR 

capsaicin$ OR Capsaicine OR S-adenosylmethionine OR Methylsulfonylmethane OR 

Turmeric OR curcuma OR curcumin OR (Devils ADJ claw) OR Harpagophytum OR 

uncaria OR Eazmov OR Cyperus OR Tinospora OR Saussurea OR Picrorrhiza OR 

picrorhiza OR Ginger OR Zingiber OR nettle OR nettles OR Willow OR Gitadyl OR 

feverfew OR (tanacetum ADJ parthenium) OR milfoil OR Phytodolor OR Populus OR 

Fraxinus OR Solidago OR Reumalex OR Guaiacum OR (black ADJ cohosh) OR 

Cimicifuga OR Sarsaparilla OR Smilax OR Poplar OR (Rose ADJ hip$) OR alliums OR 

garlic OR omega-3 OR quercetin OR creatine

8 Combine sets – 5 AND (6 OR 7)

9 Limit to humans Limit 8 to humans

10 Limit to english 

language

limit 9 to english language

11 Exclude 

unwanted 

publication types

10 NOT (book/ OR edited book/ OR case report/ OR case reports/ OR comment/ OR 

conference abstract/ OR conference paper/ OR conference review/ OR editorial/ OR 

letter/ OR news/ OR note/ OR proceeding/ OR (book OR edited book OR case report 

OR case reports OR comment OR conference OR editorial OR letter OR news OR note 

OR proceeding).pt.)
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 71 of 126

Set # Concept Search Statement

12 Limit to 

controlled studies

11 AND (randomized controlled trial/ OR random allocation/ OR double-blind 

method/ OR single-blind method/ OR placebos/ OR cross-over studies/ OR crossover 

procedure/ OR cross over studies/ OR double blind procedure/ OR single blind 

procedure/ OR placebo/ OR latin square design/ OR crossover design/ OR doubleblind studies/ OR single-blind studies/ OR triple-blind studies/ OR random 

assignment/ OR exp controlled study/ OR exp clinical trial/ OR exp comparative 

study/ OR cohort analysis OR follow-up studies/ OR intermethod comparison/ OR 

parallel design/ OR control group/ OR prospective study/ OR retrospective study/ OR 

case control study/ OR major clinical study/ OR evaluation studies/ OR follow-up 

studies/ OR random$.hw. OR random$.ti. OR placebo$.mp. OR ((singl$ OR doubl$ 

OR tripl$ OR trebl$) and (dummy OR blind OR sham)).mp. OR latin square.mp. OR 

ISRCTN$.mp. OR ACTRN$.mp. OR (NCT$ not NCT).mp.)

13 Limit to 

guidelines

11 AND (st.fs. OR guideline.pt. OR consensus.pt. OR practice parameter OR position 

statement OR position paper OR policy statement OR standard$.ti. OR guideline$.ti. 

OR white paper OR clinical pathway OR practice guidelines/ OR exp practice 

guideline/ OR consensus development/)

14 Limit to 

systematic 

reviews

11 AND (systematic review/ OR meta-analysis/ OR meta-analysis/ OR pooled OR 

meta-analysis.pt. OR "systematic review" OR search$.ab.)

15 Combine sets 12 OR 13 OR 14

16 Limit by 

publication date

Limit 15 to yr="2002-Current"

17 Eliminate overlap Remove duplicates from 16

Table A-10. Search Strategy for Referral Key Question 16 (imaging findings) 

Set # Concept Search Statement

1 Osteoarthritis of 

specific joints

osteoarthritis, knee/ OR osteoarthritis, hip/ OR hip osteoarthritis/ OR knee 

osteoarthritis/

2 Osteoarthritis osteoarthritis/ OR (arthrit$ OR osteoarthrit$ OR degenerative joint).ti.

3 Knee exp knee/ OR exp knee joint/ OR exp knee injuries/ OR exp knee injury/ OR (knee OR 

knees OR menisc$ OR patellofemor$ OR patell$ OR iliotibial OR ACL OR anterior 

cruciate ligament).ti.

4 Hip exp hip/ OR exp hip joint/ OR exp hip injuries/ OR exp hip fractures/ OR exp hip 

injury/ OR (hip OR hips).ti.

5 Combine sets 2 AND (3 OR 4)

6 1 OR 5

7 Diagnostic 

imaging

Controlled 

vocabulary

exp *diagnostic imaging equipment/ OR exp *"imaging and display"/ OR exp 

*radiodiagnosis/ OR exp *echography/ OR exp *diagnostic imaging/ OR 

*tomography scanners, x-ray computed/

8 Diagnostic 

imaging

Keywords

(absorptiometry OR arthrography OR computed tomography OR CT OR DEXA OR 

dGEMRIC OR diffusion tensor OR image$ OR imaging OR magnetic resonance OR MR 

OR MRI OR neuroimaging OR NMR OR PET OR phonoarthrography OR positron 

emission tomography OR radiodiagnos$ OR radiograph$ OR scan OR scans OR 

scanning OR scintigraph$ OR sonograph$ OR SPECT OR spectroscopy OR Tc-99m OR 

technetium OR tomosynthesis OR ultrasonography OR ultrasound$ OR x-ray$ OR 

xray$).ti.

9 Combine sets 6 AND (7 OR 8)

10 Arthroplasty exp arthroplasty/ OR (arthroplast$ OR hemiarthroplast$ OR replace OR 

replacement$ OR resurfacing OR surgery OR surgical).ti.
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 72 of 126

Set # Concept Search Statement

11 Combine sets 9 AND 10

12 Referral 

Controlled terms

decision making/ OR decision trees/ OR exp disability/ OR disability evaluation/ OR 

exp disease severity/ OR patient care planning/ OR patient referral OR patient 

selection/ OR "referral and consultation"/ OR risk assessment/ OR risk factor/ OR risk 

factors/ OR severity of illness index/

13 Referral

Keywords

(consultation$ OR consult OR contraindicat$ OR criteria OR decision OR decide$ OR 

indication$ OR (patient ADJ2 characteristic$) OR (patient ADJ2 selection) OR predict$ 

OR "red flag" OR referral OR refer OR risk$ OR serious OR specialist OR surgeon OR 

urgent OR warning).ti.

14 Outcomes 

Controlled 

vocabulary

adverse effects.fs. OR comorbidity/ OR complication.fs. OR convalescence/ OR 

morbidity/ OR mortality/ OR mortality.fs. OR outcome assessment/ OR "outcome 

assessment (health care)"/ OR exp postoperative complication/ OR exp 

postoperative complications/ OR prognosis/ OR quality of life/ OR recovery of 

function/ OR reoperation/ OR survival rate/ OR treatment outcome/

15 Outcomes

Keywords

(appropriate$ OR comorbid$ OR complication$ OR morbidity OR mortality OR 

outcome$ OR prognos$ OR survival$ OR "quality of life" OR QOL).ti.

16 Combine sets 11 AND (12 OR 13) AND (14 OR 15)

17 Exclude 

unwanted 

publications

16 NOT (book/ OR edited book/ OR case report/ OR case reports/ OR comment/ OR 

conference abstract/ OR conference paper/ OR conference review/ OR editorial/ OR 

letter/ OR news/ OR note/ OR proceeding/ OR (book OR edited book OR case report 

OR case reports OR comment OR conference OR editorial OR letter OR news OR note 

OR proceeding).pt.)

18 Keep case series 16 AND (case series OR case control)

19 Combine 17 OR 18

20 Limit to humans limit 19 to humans

21 Limit to english 

language

limit 20 to english language

22 Limit by 

publication date

limit 21 to yr="2002 -Current"

23 Eliminate overlap Remove duplicates from 22

24 Retain relevant 

records

from 23 keep 1-4, 7-9, 14, 16, 21, 27

25 Examine 

combination of 

sets without 

limiting to those 

with outcomes

11 AND (12 OR 13 OR selection.ti.) 

26 Exclude 

previously 

identified results

25 NOT 16

27 Exclude 

unwanted 

publications

26 NOT (book/ OR edited book/ OR case report/ OR case reports/ OR comment/ OR 

conference abstract/ OR conference paper/ OR conference review/ OR editorial/ OR 

letter/ OR news/ OR note/ OR proceeding/ OR (book OR edited book OR case report 

OR case reports OR comment OR conference OR editorial OR letter OR news OR note 

OR proceeding).pt.)

28 Keep case series 26 AND (case series OR case control).mp.

29 Combine limit 27 to humans

30 Limit to humans limit 29 to english language

31 Limit to english 

language

limit 30 to yr="2002 –Current"
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 73 of 126

Set # Concept Search Statement

32 Limit by 

publication date

remove duplicates from 31

33 Retain relevant 

records

from 32 keep 7-8, 10, 12-14, 16, 18-24, 27

34 Combine sets 24 OR 33

35 Eliminate overlap remove duplicates from 34

Table A-11. Search Strategy for Referral Key Questions 17 and 18 (patient signs/symptoms and 

patient-centered risk factors) 

Set # Concept Search Statement

1 Knee or Hip 

osteoarthritis

osteoarthritis, knee/ OR osteoarthritis, hip/ OR hip osteoarthritis/ OR knee 

osteoarthritis/ 

2 Osteoarthritis 

keywords

osteoarthritis/ OR arthrit$.ti. OR osteoarthrit$.ti. OR degenerative joint.ti.

3 Knee joint exp knee/ OR exp knee joint/ OR exp knee injuries/ OR exp knee injury/ OR knee.ti. 

OR knees.ti. OR menisc$.ti. OR patellofemor$.ti. OR patell$.ti. OR iliotibial.ti. OR 

ACL.ti. OR anterior cruciate ligament.ti.

4 Hip exp hip/ OR exp hip joint/ OR exp hip injuries/ OR exp hip fractures/ OR exp hip 

injury/ OR hip.ti. OR hips.ti.

5 Combine 

population sets 

(osteoarthritis)

1 OR (2 AND (3 OR 4))

6 Arthroplasty exp arthroplasty/ OR arthroplast$.ti. OR replace.ti. OR replacement$.ti. OR 

surgery.ti. OR surgical.ti. OR resurfac$.ti.

7 Referral –

controlled terms

"referral and consultation"/ OR decision making/ OR patient selection/ OR "severity 

of illness index"/ OR risk factors/ OR disability evaluation/ OR risk assessment/ OR

decision trees/ OR patient referral/ OR patient care planning/ OR risk factor/ OR exp 

disability/ OR exp disease severity/

8 Referral -

keywords

(referral OR refer OR criteria OR indication$ OR contraindicat$ OR predict$ OR risk$ 

OR consultation$ OR consult OR decision OR decide$ OR (patient adj2 selection) OR 

(patient adj2 characteristic$) OR warning OR "red flag" OR urgent OR serious OR 

surgeon OR specialist).ti.

9 Outcomes -

controlled terms 

prognosis/ OR treatment outcome/ OR exp postoperative complications/ OR survival 

rate/ OR outcome assessment/ OR "Outcome Assessment (Health Care)"/ OR exp 

"quality of life"/ OR mortality.fs. OR reoperation/ OR adverse effects.fs. OR recovery 

of function/ OR comorbidity/ OR exp postoperative complication/ OR mortality/ OR 

morbidity/ OR complication.fs. OR convalescence/

10 Outcomes -

keywords

(appropriate$ OR prognos$ OR outcome$ OR morbidity OR mortality OR comorbid$ 

OR complication$ OR survival* OR "quality of life" OR QOL).ti.

11 Combine sets -

Referral

7 OR 8

12 Combine setsOutcomes9 OR 10

13 Combine sets key 

questions 17 and 

18 

5 AND 6 AND 11 AND 12

14 Limit to english 

language

limit 13 to english language

15 Limit to Human 

studies

limit 14 to humans
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 74 of 126

Set # Concept Search Statement

16 Exclude 

unwanted 

publication types

15 NOT (book/ OR edited book/ OR case report/ OR case reports/ OR comment/ OR 

conference abstract/ OR conference paper/ OR conference review/ OR editorial/ OR 

letter/ OR news/ OR note/ OR proceeding/ OR book OR edited book OR case report 

OR case reports OR comment OR conference OR editorial OR letter OR news OR 

note OR proceeding.pt. OR conference abstract.pt.)

17 Include case 

series

15 AND (case series OR case control)

18 Combine sets 16 OR 17 

19 Limit by 

publication date

Limit 18 to yr="2002-Current"

20 Eliminate overlap Remove duplicates from 20

Table A-12. Search Strategy for Referral Key Question 19 (trial of injection therapy) 

Set # Concept Search Statement

1 Osteoarthritis of 

specific joints

osteoarthritis, knee/ OR osteoarthritis, hip/ OR hip osteoarthritis/ OR knee 

osteoarthritis/

2 Osteoarthritis osteoarthritis/ OR (arthrit$ OR osteoarthrit$ OR degenerative joint).ti.

3 Knee exp knee/ OR exp knee joint/ OR exp knee injuries/ OR exp knee injury/ OR (knee OR 

knees OR menisc$ OR patellofemor$ OR patell$ OR iliotibial OR ACL OR anterior 

cruciate ligament).ti.

4 Hip exp hip/ OR exp hip joint/ OR exp hip injuries/ OR exp hip fractures/ OR exp hip injury/ 

OR (hip OR hips).ti.

5 Combine sets 2 AND (3 OR 4)

6 1 OR 5

7 Hyaluronates

Controlled terms 

for therapy

hyaluronic acid/ AND (ad OR dt OR tu).fs.

8 Hyaluronates viscosupplementation/ OR hyaluronic acid/ OR adant OR amvisc OR arthrease OR 

arthrum h OR artz OR biolon OR biohy OR durolane OR etamucine OR euflexxa OR 

fermathron OR "gel-one" OR healon OR hyalgan OR hyaluronan OR hyaluronate$ OR 

hyaluronic OR hyaluronidate OR "hylan gf-20" OR hyruan OR hyvisc OR luronit OR 

nuflexxa OR orthovisc OR ostenil OR replasyn OR SLM-10 OR supartz OR suplasyn OR 

synject OR synvisc OR viscosupplement$ OR vitrax 

9 Corticosteroids exp adrenal cortex hormones/ OR exp corticosteroid/ OR "adrenal cortex hormones" 

OR betamethasone OR corticoid$ OR corticosteroid$ OR cortisone$ OR 

dexamethasone OR glucocorticoid$ OR hydrocortisone OR hydroxycorticosteroid$ OR 

methylprednisolone OR prednisolone OR prednisone OR steroid$

10 Administration 

by injections 

Injection/ OR injections/ OR exp injections, intra-articular/ OR intraarticular drug 

administration/ OR viscosupplementation/ OR (inject$ OR intraarticular OR intraarticular OR (intra ADJ articular) OR "IACI" OR viscosupplement$).mp. 

11 Combine sets 7 OR ((8 OR 9) AND 10)

12 Combine sets 6 AND 11

13 Arthroplasty exp arthroplasty/ OR (arthroplast$ OR hemiarthroplast$ OR replace OR replacement$ 

OR resurfacing OR surgery OR surgical).ti,ab.

14 Effect / 

Influence / 

Relationship

Treatment failure/ OR alternative$ OR avoid$ OR cancel$ OR delay$ OR eligib$ OR 

repeated cycles OR repeated doses OR (repeat$ ADJ treatment$) OR postpone$ OR 

second course

15 Combine sets 12 AND 13 AND 14
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 75 of 126

Set # Concept Search Statement

16 Exclude 

unwanted 

publications

15 NOT (book/ OR edited book/ OR case report/ OR case reports/ OR comment/ OR 

conference abstract/ OR conference paper/ OR conference review/ OR editorial/ OR 

letter/ OR news/ OR note/ OR proceeding/ OR (book OR edited book OR case report 

OR case reports OR comment OR conference OR editorial OR letter OR news OR note 

OR proceeding).pt.)

17 Keep case series 15 AND (case series OR case control)

18 Combine 16 OR 17

19 Limit to humans limit 18 to humans

20 Limit to english 

language

limit 19 to english language

21 Limit by 

publication date

limit 20 to yr="2002 -Current"

22 Eliminate 

overlap

Remove duplicates from 21
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 76 of 126

Search Results

Extensive literature searches identified 6,872 citations potentially addressing the key questions of 

interest to this evidence review. Of those, 5,315 were excluded upon title review for clearly not 

meeting inclusion criteria (e.g., not pertinent to the topic, published prior to 2002). Overall, 1,557 

abstracts were reviewed with 735 of those being excluded for the following reasons: not a 

systematic review or clinical study, clearly did not address a Key Question of interest to this review, 

clearly did not report outcomes of interest to this review, or published prior to 2002 for clinical 

studies or 2008 for systematic reviews. A total of 822 full-length articles were reviewed. Of those, 

459 were excluded at a first pass review for not addressing a key question (mainly because the study 

did not address a comparison of interest), not reporting on outcomes of interest to the review, not 

being a full-length systematic review or clinical study, not including the required number of patients, 

or being a duplicate. A total of 363 full-length articles were thought to address one or more key 

questions and were further reviewed. Of these, 208 were ultimately excluded. Reasons for their 

exclusion are presented in Figure A-1 below.

Overall, 155 studies addressed one or more of the Key Questions and were considered as evidence in 

this review. Table A-13 indicates the number of studies that addressed each of the questions. 

Figure A-1. PRISMA Diagram of Literature Search Results
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 77 of 126

Table A-13. Evidence Base for Key Questions

Key Question # of Studies

Diagnostic Questions:

1. In adults with clinical symptoms and signs consistent with OA of the hips or knees, 

which imaging strategies, including plain radiograph, MRI, and CT contribute to 

improved clinical outcomes?

3

2. In adults with clinical symptoms and signs consistent with OA of the hips or knees, 

do laboratory tests contribute to improved clinical outcomes?

Searches did not identify any 

studies that met inclusion criteria

3. In adults with clinical symptoms and signs consistent with OA of the knees, does 

synovial fluid analysis contribute to improved clinical outcomes?

Searches did not identify any 

studies that met inclusion criteria

Intervention Questions:

4. In adults with OA of the hips or knees, what is the comparative effectiveness of 

acetaminophen to placebo with respect to pain, improved function, and harms?

4

5. In adults with OA of the hips or knees, what is the comparative effectiveness of 

intra-articular corticosteroids to intra-articular hyaluronates with respect to pain, 

improved function, and harms?

7

6. In adults with OA of the hips or knees, what is the comparative effectiveness of 

intra-articular hyaluronates to sham injections with respect to pain, improved 

function, and harms?

6

7. In adults with OA of the hips or knees, what is the comparative effectiveness of joint 

injections to oral NSAIDs (selective or non-selective) with respect to pain, improved 

function, and harms?

Searches did not identify any 

studies that met inclusion criteria

8. In adults with OA of the hips or knees, what is the comparative effectiveness of 

topical NSAIDs to oral NSAIDs (selective or non-selective) with respect to pain, 

improved function, and harms?

5

9. In adults with OA of the hips or knees, what is the comparative effectiveness of 

traditional land-based strengthening exercises to aquatic therapy with respect to 

pain, improved function, and harms?

6

10. In adults with OA of the hips or knees, what is the comparative effectiveness of 

traditional land-based strengthening exercises to manual physical therapy with 

respect to pain, improved function, and harms?

3

11. In adults with OA of the hips or knees, what is the comparative effectiveness of 

aquatic therapy to manual therapy with respect to pain, improved function, and 

harms?

Searches did not identify any 

studies that met inclusion criteria

12. What is the comparative effectiveness of walking aids or devices (e.g., cane 

ambulation to OA unloader braces for the knees) used to treat OA of the hips or 

knees with respect to pain, improved function, and harms?

4

13. In adults with OA of the hips or knees, what is the comparative effectiveness of 

chiropractic care to usual therapy with respect to pain, improved function, and 

harms?

1

14. In adults with OA of the hips or knees, what is the comparative effectiveness of 

acupuncture to usual therapy with respect to pain, improved function, and harms?

5

15. In adults with OA of the hips or knees, what is the comparative effectiveness of 

nutritional supplements (e.g., glucosamine) to usual therapy with respect to pain, 

improved function, and harms?

37

Referral Questions:

16. In patients with clinical symptoms and signs consistent with OA, what imaging 

findings indicate that referral for total/partial joint replacement surgery is the best 

option for achieving optimal clinical outcomes?

7

17. For adults with OA of the hips or knees, what patient symptoms or signs (e.g., level 

of pain and/or disability) indicate that referral for total/partial joint replacement 

surgery is the best option for achieving optimal clinical outcomes?

13

18. In adults with OA of the hips or knees, what patient-centered risk factors would 

preclude referral for surgery?

50

19. For adults with OA of the hips or knees, should a trial of injection therapy 

(corticosteroids or viscosupplementation) be attempted before referral for 

total/partial joint replacement surgery?

5
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 78 of 126

Assessing the Quality of the Evidence

The strength of the evidence supporting findings for the outcomes of interest under each key question 

was assessed using the categories listed in Table A-14. We considered the evidence for each outcome 

according to four core domains, as follows: study quality (internal validity), consistency, directness, and 

precision. Our methods for judging the quality of individual studies are described above. Consistency is 

the similarity in effect sizes or direction of an effect of different studies in an evidence base. An 

inconsistent evidence base is one in which the studies report conflicting results. Consistency cannot be 

assessed when a body of evidence has only a single study (consistency is unknown). Directness refers to 

whether there is a direct link between the intervention and the ultimate health outcome. An ultimate 

health outcome (e.g., improved pain) is typically more clinically meaningful than an indirect outcome, 

and a direct link between outcome and intervention is strongest in head-to-head comparisons. Precision 

is a measure of the degree of certainty around a single outcome’s effect size. In this report, we define a 

“precise” result as one in which the data were informative (e.g., the confidence interval [CI] around the 

effect size clearly indicated there was a difference between groups) and an “imprecise” result as one in 

which the data were not informative (e.g., the CI was sufficiently wide that an estimate is consistent with 

either benefit or no benefit in comparison to another intervention). 

Table A-14. Assessment of Evidence Base

Evidence 

Category

Definition Example of Assessment of Evidence

Study Quality 

(Internal Validity 

or Risk of Bias)

Study Quality takes into account the 

overall risk of bias rating of all the 

studies included in the evidence base.

Example: The overall risk of bias was fair. A couple of 

studies were rated as poor because they did not 

blind the patients or outcome assessors and did not 

report the method used to randomize patients.

Consistency of 

Results

Consistency of Results considers if the 

studies demonstrated similar positive 

or negative results (an inconsistent 

rating would indicate that the findings 

across studies were mixed).

Example: The majority of studies (20 out of 25) 

indicated a statistically positive effect of 

acetaminophen over placebo in reducing pain and 

improving function. In five studies, the results were 

not significant.

Directness of 

Evidence

Directness of Evidence considers the 

link between the interventions and 

patient outcomes (head-to-head 

comparisons provide the most direct 

evidence).

Example: The evidence linking the effects of 

acetaminophen to patient outcomes of pain and 

function was direct as it came primarily from headto-head comparisons of acetaminophen to placebo.

Precision of 

Results

Precision estimates the degree of 

certainty around an outcome’s effect 

size.

Example: The 95% confidence interval around the 

between-group difference in pain scores was wide 

enough to allow the possibility that the treatments 

were equivalent, treatment A is more effective than 

treatment B, or treatment B is more effective than 

treatment A.

Final Evidence Report 

The evidence review team at ECRI Institute synthesized the results of the systematic review and 

provided a detailed analysis of relevant information for each key question. Some of the key elements 

discussed in the report include the quality of the evidence base and the magnitude of effect of specific 

interventions. Furthermore, the synthesis report contained critical information on potential limitations 

of certain studies, allowing for a better understanding of the certainty of the evidence. The review 

team produced a comprehensive evidence review report and distributed it to the Champions and 

Work Group members approximately two weeks prior to the face-to-face meeting.
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 79 of 126

Face-to-Face Meeting

In consultation with the Contracting Officer Representative, the Champions, and the Work Group, the 

Lewin Team convened a three and a half day face-to-face meeting of the CPG Champions and Work 

Group members in May 2013. These experts were gathered in order to review the evidence, develop 

recommendations, and grade the recommendations in accordance with the U.S. Preventive Services 

Task Force (USPSTF) methods for assessing and grading the evidence. 

Developing Recommendations

During the face-to-face meeting, and under the direction of the Champions, the Work Group members 

were charged with interpreting the results of the evidence review, and asked to review initial 

recommendations and/or develop new recommendations. In order to accomplish this task, the 

experts were divided into four smaller subgroups, each of which was led by a Champion. In addition, 

Work Group members were responsible for assessing the overall strength of evidence for each 

recommendation, by determining the magnitude and certainty of net benefit.

Grading Recommendations

The graded recommendations are based on two main dimensions: 1) net benefit of an intervention 

and 2) certainty of evidence associated with that net benefit. 

Net benefit (or impact) refers to the benefit minus the harm of an intervention. As shown in Table 

A-15, the four categories of net benefit are: Substantial, Moderate, Small, and Zero/Negative. For 

example, a Substantial benefit could result from high benefit and minimal harm. These categories 

only reflect the order of magnitude of net benefit, they do not reflect how certain we are of that 

magnitude of net benefit. 

Table A-15. USPSTF Recommendations – Net Benefit [5,150]

Substantial

More than a small relative impact on a frequent condition with a substantial burden of suffering; 

or

A large impact on an infrequent condition with a significant impact on the individual patient 

level.

Moderate

A small relative impact on a frequent condition with a substantial burden of suffering; 

or

A moderate impact on an infrequent condition with a significant impact on the individual patient 

level.

Small

A negligible relative impact on a frequent condition with a substantial burden of suffering; 

or

A small impact on an infrequent condition with a significant impact on the individual patient 

level.

Zero or 

Negative

Negative impact on patients; 

or

No relative impact on either a frequent condition with a substantial burden of suffering, or an 

infrequent condition with a significant impact on the individual patient level.

Certainty refers to the level of certainty that is associated with a net benefit. The level of certainty is 

greater with stronger evidence (i.e., from a greater number of well-designed and well-conducted 

studies). As shown in Table A-16, the three levels of certainty are High, Medium, and Low. Higher 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 80 of 126

certainty suggests that the observed net benefit (regardless of its magnitude as described in Fig. 2) is 

correct. For any given magnitude of net benefit (whether it is Substantial or Zero), the certainty can 

range from High to Low. 

When considering what grade should accompany a recommendation, it may help to consider these 

two dimensions separately before arriving at a grade. That is, based on the health outcomes in the 

available evidence, “How big is the net benefit here?” Then, based on the strength of that available 

evidence, “How certain are we that this net benefit (no matter its size) is real?”

Table A-16. USPSTF Recommendations – Certainty [5]

Level of 

Certainty*

Description

High

The available evidence usually includes consistent results from well-designed, well-conducted 

studies in representative primary care populations. These studies assess the effects of the 

preventive service on health outcomes. This conclusion is therefore unlikely to be strongly affected 

by the results of future studies.

Moderate

The available evidence is sufficient to determine the effects of the preventive service on health 

outcomes, but confidence in the estimate is constrained by such factors as: The number, size, or 

quality of individual studies.

• Inconsistency of findings across individual studies.

• Limited generalizability of findings to routine primary care practice.

• Lack of coherence in the chain of evidence.

As more information becomes available, the magnitude or direction of the observed effect could 

change, and this change may be large enough to alter the conclusion.

Low

The available evidence is insufficient to assess effects on health outcomes. Evidence is insufficient 

because of: 

• The limited number or size of studies.

• Important flaws in study design or methods.

• Inconsistency of findings across individual studies.

• Gaps in the chain of evidence.

• Findings not generalizable to routine primary care practice.

• Lack of information on important health outcomes.

More information may allow estimation of effects on health outcomes.

*The USPSTF defines certainty as "likelihood that the USPSTF assessment of the net benefit of a preventive service is correct." 

The net benefit is defined as benefit minus harm of the preventive service as implemented in a general, primary care 

population. The USPSTF assigns a certainty level based on the nature of the overall evidence available to assess the net benefit 

of a preventive service.

The grade of recommendation is based on a framework that combines the two dimensions, as shown 

in Table A-17. As described above, the grade depends on both net benefit and certainty. For example, 

in the USPSTF grading scheme, a grade of A is assigned to a recommendation that is based on a High 

certainty of a Substantial net benefit. Three combinations of certainty and net benefit can yield a 

grade of B. Note that, in the USPSTF framework, any recommendation associated with Low certainty 

of net benefit results in a recommendation of I, regardless of the magnitude of net benefit. 

Given: 1) the level of certainty that a net benefit exists and 2) the magnitude of that net benefit, what 

grade of recommendation do we assign?
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Table A-17. USPSTF Recommendations – Grade [5]

Certainty of Net 

Benefit

Magnitude of Net Benefit

Substantial Moderate Small Zero/Negative

High A B C D

Moderate B B C D

Low Insufficient

Grade A indicates that the certainty of evidence is high that the magnitude of net benefits is 

substantial.

Grade B indicates that the certainty of evidence is moderate and that the magnitude of net benefits is 

either moderate or substantial, or that the certainty of evidence is high that the magnitude of net 

benefits is moderate.

Grade C indicates that the certainty of the evidence is either high or moderate and that the magnitude 

of net benefits is small.

Grade D indicates that the certainty of the evidence is high or moderate and that the magnitude of net 

benefits is either zero or negative.

Grade I indicates that the evidence is insufficient to determine the relationship between benefits and 

harms (i.e., net benefit). 

Figure A-2 is a framework that incorporates Expert Opinion. The dimensions of Net Benefit of an 

intervention and Certainty of evidence still correspond to the USPSTF framework, and grades of 

recommendation (A, B, C, D, I) are the same, except for the use of E in place of I in one sector of the 

framework. We made slight modifications in this framework to make the cross-walk from USPSTF 

more clear and better reflect the sense of our work group discussions. 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 82 of 126

Figure A-2. Framework with Expert Opinion

Final Evidence-Based Clinical Practice Guideline for the Management of OA

Following the face-to-face meeting in May, the OA CPG Champions and Work Group developed several 

drafts of the Guideline, submitting the final document to the VA/DoD Evidence-Based Practice 

Working Group in August 2014.
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 83 of 126

Appendix B: Evidence Table

No. Recommendation Sources of 

Evidence

Certainty of 

Net Benefit

Magnitude of 

Net Benefit

Strength of 

Recommendation

Diagnosis and Evaluation

1 Clinicians should conduct a history and physical examination for all patients, with an 

emphasis on the musculoskeletal examination.

[7]

[27]

Low Moderate EO

2 Clinicians may use plain radiography to confirm the clinical diagnosis of hip and knee 

osteoarthritis.

[26] Moderate Small C

3 Clinicians should not use magnetic resonance imaging (MRI) as an evaluative tool to 

diagnose, confirm, or manage the treatment of osteoarthritis.

[28]

[143]

[144]

Low Zero D

4 Clinicians should avoid routine use of laboratory examinations or synovial fluid 

analysis to diagnose osteoarthritis of the hip and/or knee.

[25] Low Substantial EO

Core Non-Surgical Treatment Principles

5 The decision to prescribe any intervention should be based on consideration of 

assessment findings, risk vs. benefit analysis, pain severity, functional status, patient 

preference, and resource utilization.

Expert 

consensus

Low Moderate EO

6 For patients with osteoarthritis of the hip and/or knee, clinicians should attempt the 

core non-surgical therapies prior to referral to surgery.

[154] Moderate Small C

7 For patients with osteoarthritis of the hip and/or knee, clinicians should refer for 

physical therapist services early on, as part of a comprehensive management plan.

[31]

[32]

[33]

[39]

[37]

[38]

[40]

[41]

[42]

Moderate Moderate B

8 Clinicians should refer overweight or obese patients (defined by a BMI > 25 kg/m2) 

with osteoarthritis of the knee to a weight management program to lose a minimum 

of five percent body weight and maintain this new level of weight.

[35]

[36]

Moderate Moderate C

9 Clinicians should refer overweight or obese patients (defined by a BMI > 25 kg/m2) 

with osteoarthritis of the hip to a weight management program to lose a minimum 

of five percent body weight and maintain this new level of weight.

Expert 

consensus

Low Substantial EO

Physical Therapy Approaches

10 For patients with osteoarthritis of the knee, the addition of manual physical therapy [31] Moderate Moderate B
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No. Recommendation Sources of 

Evidence

Certainty of 

Net Benefit

Magnitude of 

Net Benefit

Strength of 

Recommendation

as an adjunct to traditional physical therapy and supervised exercise can improve 

pain, function, and walking distance.

11 For patients with osteoarthritis of the hip, the addition of manual physical therapy 

as an adjunct to traditional physical therapy and supervised exercise can improve 

pain, function, and range of motion.

[32]

[33]

Moderate Moderate B

12 For adults with osteoarthritis of the knee who do not tolerate land-based 

therapeutic exercise, clinicians should consider adjunctive aquatic physical therapy.

[39]

[37]

[38]

[40]

[41]

[42]

Moderate Small C

13 For patients with osteoarthritis of the knee or hip, the prescription and training of 

ambulation or walking aids should be carried out by a physical therapist or the 

referring provider.

Expert 

Opinion

Low Substantial EO

Pharmacologic Therapies

14 In patients with no contraindications to pharmacologic therapy, clinicians should 

consider acetaminophen or oral non-steroidal anti-inflammatory drugs (NSAIDs) as 

first line treatment.

[64]

[67]

[69]

[68]

[70]

[71]

[72]

[74]

Moderate Moderate B

15 Clinicians should ensure that patients receive no more than four grams of 

acetaminophen daily from all sources of prescribed and non-prescribed medications.

[65]

[66]

High Substantial A

16 In patients requiring treatment with oral NSAIDs and who are at risk for serious 

upper gastrointestinal (GI) adverse events, clinicians should consider the addition 

of a proton-pump inhibitor (PPI) or misoprostol.

[84]

[85]

[86]

High Substantial A

17 Clinicians should consider the balance of benefit and potential harm in prescribing 

oral NSAIDs in patients at risk for or with known cardiovascular disease or renal 

injury/disease.

[87]

[88]

[83]

[95]

[96]

Moderate Substantial B

18 In patients with mild to moderate pain associated with osteoarthritis of the knee, 

topical capsaicin can be considered as first line or adjunctive therapy.

[105]

[102]

Moderate Small C
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No. Recommendation Sources of 

Evidence

Certainty of 

Net Benefit

Magnitude of 

Net Benefit

Strength of 

Recommendation

[103]

[104]

19 There is insufficient evidence to recommend for or against the use of topical 

capsaicin for the hip as first line or adjunctive therapy.

[104] Low Small I

20 For patients with persistent moderate or moderately severe osteoarthritis pain, 

clinicians may offer duloxetine or tramadol as an alternative or adjunct to oral 

NSAIDs.

[133]

[107]

[108]

[136]

[155]

[156]

[157]

[158]

[159]

[160]

[161]

[162]

[163]

[164]

[165]

[166]

[167]

[168]

[169]

[170]

[171]

[172]

High Moderate B

21 For patients with persistent severe osteoarthritis pain who have contraindications, 

inadequate response, or intolerable adverse effects with non-opioid therapies and 

tramadol, clinicians may consider prescribing non-tramadol opioids.

[173]

[174]

[175]

[166]

[111]

[176]

Moderate Small C

22 For patients with symptomatic osteoarthritis of the knee, clinicians may consider 

consider intra-articular corticosteroid injection.

[177]

[178]

[119-121]

Moderate Small C
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No. Recommendation Sources of 

Evidence

Certainty of 

Net Benefit

Magnitude of 

Net Benefit

Strength of 

Recommendation

23 There is insufficient evidence to recommend for or against the use of intra-articular 

hyaluronate/hylan injection in patients with osteoarthritis of the knee; however, it 

may be considered for patients who have not responded adequately to 

nonpharmacologic measures and who have an inadequate response, intolerable 

adverse events, or contraindications to other pharmacologic therapies.

[179,180]

[181]

[182]

Moderate None I

24 For patients with moderate to severe osteoarthritis of the hip, clinicians may 

consider imaging/ultrasound directed corticosteroid injection to reduce pain.

[117] Low Moderate C

25 Intra-articular injection of hyaluronate/hylan is not recommended for patients with 

osteoarthritis of the hip.

Expert 

consensus

Low Substantial EO

Complementary and Alternative Therapies

26 In patients with hip and/or knee osteoarthritis, there is insufficient evidence to 

recommend for or against the use of dietary supplements for relief of pain and 

improved function.

[183]

[184]

[185]

[186]

[187]

Low Small I

27 In patients with hip and/or knee osteoarthritis, clinicians should not prescribe 

chondroitin sulfate, glucosamine, and/or any combination of the two, to treat joint 

pain or improve function.

[126]

[127]

[133]

[128]

[129]

[130]

[131]

[132]

Moderate None D

28 In adults with hip and/or knee osteoarthritis, there is insufficient evidence to 

recommend for or against referral for short term trial needle acupuncture or 

chiropractice therapy for relief of pain and improved function.

[134]

[135]

[136]

[138]

[137]

Low Small I

Referrals for Surgical Consultation

29 For patients with osteoarthritis of the hip and/or knee, who experience joint 

symptoms (such as pain, stiffness, and reduced function) with substantial impact on 

their quality of life (individualized based upon patient assessment), and who have 

not benefited from the core non-surgical therapies, clinicians may offer referral for 

joint replacement surgery.

[142]

[140]

[188]

Moderate Moderate B
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No. Recommendation Sources of 

Evidence

Certainty of 

Net Benefit

Magnitude of 

Net Benefit

Strength of 

Recommendation

30 In patients with osteoarthritis of the hip and/or knee considered for surgical 

consultations, clinicians should obtain weight-bearing plain radiographs within 6 

months prior to the referral to surgical consultation.

[189]

[190]

[142]

[191]

[192]

Moderate Moderate B

31 In candidates for joint replacement of the hip and/or knee, joint injections should 

not be given into the involved joint if surgery is anticipated within three months.

Expert 

Consensus

Low Substantial EO
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Appendix C: Patient History and Physical Examination

Knee History

Patients with knee OA may present with either localized or diffuse knee pain that is activity related.

Occasionally, patients with hip OA present with knee pain. It is imperative to examine both the hip and 

knee in patients with either knee or hip pain. A patient with an abnormal hip examination may result 

in early detection of hip OA.

Patients with knee osteoarthritis may have a prior history of knee injury or surgery. Prior anterior 

cruciate ligament (ACL) injury and/or reconstruction as well as prior meniscectomy or patellar 

dislocation should increase suspicion of early knee OA.

Knee Physical Examination

Gait and Alignment: The most common pattern for knee OA is primarily medial compartment 

degeneration with progressive development of genu varum (bow legged). Less commonly patients 

may display genu valgum (knock knee) or primary lateral compartment degeneration. Patients with 

some form of mechanical malalignment are at higher risk to develop osteoarthritis. It is important for 

the health care provider to record overall knee alignment as well as gait patterns. Patients with knee 

OA may ambulate with an antalgic gait favoring the involved knee or walk with a stiff and semi-flexed 

involved knee.

Knee Effusion and Range of Motion: Patients with OA occasionally may have an effusion that can be 

detected on physical examination. Furthermore, stiffness and limitations in range of motion are often 

found in OA, especially, lack of terminal extension or flexion contracture.

Joint Line Tenderness and Crepitus: Although non-specific, patients with symptomatic osteoarthritis 

may have localized or more diffuse knee tenderness. Crepitus, especially involving the patellofemoral 

joint can be appreciated during passive knee range of motion testing.

Hip History

The pain related to the hip osteoarthritis occurs in different locations including the groin, thigh, 

buttocks, or knee. Although the classic complaint of patients with hip OA is groin pain, the patients will 

often localize their pain by placing their ipsilateral thumb in their groin with their hand and fingers 

cupping their greater trochanter and buttocks forming the “C sign.” The pain experienced by the 

patient can be stabbing, sharp, or dull. Similarly to osteoarthritis of the knee, the hip becomes 

increasingly stiff as the disease progresses. Ultimately the patient will experience a sense of grinding in 

the joint and can lose range of motion. At this point walking and performing routine activities of daily 

living can become difficult.

Hip Physical Examination

Gait and stance: Patients with a painful hip will often stand with a slightly flexed hip and knee to relax 

the hip joint capsule. Furthermore, while seated, they may feel more comfortable shifting their weight 

to the contralateral hemi pelvis and slouching to avoid excessive flexion or internal rotation of the 

involved hip.
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When ambulating, they may walk with an abductor lurch while standing on the involved hip. During 

the stance phase the patient will shift their center of mass over the involved hip. This serves to relax 

the hip abductors (gluteus medius and gluteus minimus) thereby decreasing the joint reactive forces 

about the hip.

Range of Motion: Hip OA often results in loss of motion as well as pain at the extremes of motion.

Flexion is best measured with the patient supine and the contralateral hip in full extension to stabilize 

the pelvis. Likewise, in order to assess for a flexion contracture (lack of full extension) the contralateral 

hip should be maximally flexed to see if the involved hip can extend to touch the exam table. Internal 

and external rotation can be easily measured with the hip and knee flexed to 90 degrees. Loss of 

internal rotation is frequently seen in hip osteoarthritis.

Special Tests: A passive straight leg raise can help to differentiate nerve root tension signs from true 

intra-capsular hip pathology. The Patrick or Faber test (flexion, abduction, external rotation) stresses the 

femeroacetabular as well as the sacroiliac joint. The passive log roll is the most specific test for hip 

pathology as only the femoral head is moving in relation to the acetabulum; however, it is not very 

sensitive. More sensitive special tests include the anterior “impingement test” where the hip is brought 

into maximal flexion, adduction and internal rotation. Additionally, a resisted straight leg raise or 

Stinchfield reproducing groin pain is sensitive at identifying intra-articular pathology. This maneuver 

works by generating more force than walking across the hip joint.

Appendix D: Pharmacologic Therapies

Tramadol

The adverse event profile of tramadol is the main reason for recommending that tramadol be 

considered after trials of non-opioids and before advancing to trials of more potent opioids. Although 

classified as an opioid, tramadol is considered safer than other opioids because it is associated with 

lower risks of respiratory depression and constipation, and is not a controlled substance. Tramadol 

abuse and addiction are less problematic than with conventional opioids. [193-198] Some patients 

may develop physical dependence with regular use and experience withdrawal symptoms typical of 

opioid withdrawal if tramadol therapy is stopped too quickly. Atypical withdrawal symptoms that may 

be related to the SNRI effects (e.g., hallucinations, paranoia, extreme anxiety, panic attacks, confusion 

and unusual sensory experiences such as numbness and tingling in the extremities) may also occur. 

[199,200] If tramadol is discontinued, the dose should be slowly tapered off to avoid withdrawal 

symptoms.

The main safety concern with tramadol is development of seizures. Tramadol should be avoided or 

used with caution in patients with a history or risk of seizures or those who are taking drugs that 

reduce the seizure threshold, such as antidepressants, anorectics, SSRIs, SNRIs, tricyclic 

antidepressants, tricyclic compounds (such as cyclobenzaprine, promethazine), other opioids, 

monoamine oxidase inhibitors (MAOIs), and neuroleptics. 

Careful attention should be given to recommended dosage adjustments and maximal dosage limits in 

at-risk populations (e.g., the elderly and patients with renal or hepatic impairment). This is of particular 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 90 of 126

importance in the typical elderly patient population with OA. Maximal recommended doses are 400 

mg per day for the IR formulation and 300 mg per day for the ER formulation in patients with normal 

renal function. The dosage of tramadol should be reduced in patients:

• With creatinine clearances of less than 30 ml/min (maximum 200 mg per day and extension of 

dosing intervals to 12 hours with the IR form of tramadol; avoid ER form); 

• In the presence of cirrhosis (usual dose is 50 mg every 12 hours of the IR form; avoid the ER 

form in Child-Pugh class C / severe hepatic impairment); and 

• older than 75 years (maximum 300 mg per day of tramadol IR). 

The incidences of adverse events are dose-related. [201] Tolerability with tramadol IR can be improved 

by using a low initial dose and slowly titrating doses over a period of 10 to 16 days. Incremental 

titration of the ER form of tramadol is also suggested. More studies are needed to determine whether 

the ER formulation can be titrated up faster than the IR product while maintaining tolerability. [202] 

Although differences in adverse events have been observed between IR and ER formulations in one OA 

study, [201] overall the ER formulations of tramadol, dosed once daily or twice daily, are similar in 

efficacy and safety to the IR formulations. [203,204] The main advantage of the ER formulation seems 

to be the convenience of less frequent dosing for the patient.

Tramadol as an Alternative Monotherapy

There is fair quality, consistent evidence that tramadol, mainly as an extended release (ER) 

formulation, in treatment courses of up to three months long are effective in improving pain, physical 

function, and sleep in patients with OA of the knee or hip; however, the effects are small. [155-163] 

Results of a meta-analysis of 11 clinical trials published up to 2005 (N = 1939) showed that pain 

improved by 12 percent and physical function improved by 8.5 percent. The NNT was six relative to 

placebo for at least moderate improvement on patient global assessment. [155] 

Although effect sizes for analgesia with tramadol ER have been small, patients have gained clinically 

meaningful improvements in physical function, [161] health status [161] and sleep disturbances. [162] 

One post hoc analysis of a 12-week clinical trial by the manufacturer showed that reductions in OA 

pain by only 15 percent to 29 percent (in contrast to cutoffs of 30 percent and 50 percent in mixed 

chronic pain conditions) were clinically meaningful. [161] Improvement in pain was not associated 

with improvement in OA related tiredness or fatigue. [161]

Higher doses improve the effect size slightly and doses of 300 mg per day or more of tramadol ER 

worsened the risk of adverse events and did not improve efficacy. [159,160] Whereas the 

recommended maximum dose of tramadol immediate-release (IR) is 400 mg per day, for ER 

formulations the maximum dose is 300 mg per day because the risk of seizures was shown to be 

increased at 400 mg per day. [164] 

Tramadol was also poorly tolerated when the dose was not titrated up slowly. The NNT for treatment 

discontinuations due to adverse events in fixed-dose studies was eight, which is close to the NNT for 

benefit, suggesting a narrow benefit–risk margin without slow upward dosage titration. Studies using 
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slow dosage titration reduced the risk of treatment discontinuations due to adverse events, with an 

NNT of 33. [155] 

Tramadol Compared with Alternative Therapies 

The relative efficacy of tramadol is uncertain because of the limited number of active-control trials.

Tramadol versus Acetaminophen

Tramadol IR 150 mg per day was shown to be better than acetaminophen 1500 mg per day in a small

(N = 20), seven-day randomized trial included in a meta-analysis. [155] The mean difference between 

treatments in pain reduction was 20 (95% CI 1.36–38.64) on a 0–100 mm visual analogue scale. [205] 

Tramadol versus NSAIDs

In comparative clinical trials, tramadol was similar to NSAIDs in improving pain, physical function, and 

sleep. Relative to diclofenac IR, tramadol IR had a similar risk of treatment discontinuations due to 

adverse events, although was more likely to cause minor adverse events, with an NNT for minor 

adverse events of six versus diclofenac. [155] Using titrated doses, tramadol ER (200–400 mg once 

daily) was shown to be similar to diclofenac ER (75–100 mg once daily) in pain, physical function and 

sleep, as well as incidences of adverse events and treatment discontinuations due to adverse events; 

however, improvements in efficacy measures were small (16 percent or less) for both treatments.

[165] 

Tramadol versus Duloxetine

In a meta-analysis that included indirect comparisons of duloxetine (three trials; N = 383) and tramadol 

(five trials; N = 1507), the two agents were shown to be similar in improving normalized Western 

Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total scores (reflecting pain, 

stiffness and function). [166] When adjustment was made for baseline pain scores in a Bayesian 

analysis, duloxetine was statistically better than tramadol, but the magnitude of difference was of 

questionable clinical relevance (4.92; 95% CI 1.51 to 8.34 on a 0–100 scale).

Tramadol versus Other Weak Opioids

In indirect comparisons from a meta-analysis, tramadol was associated with a larger decrease in OA 

pain intensity than dihydrocodeine or pentazocine, and a higher likelihood of global impression of at 

least moderate improvement than pentazocine (by 150 percent). [155] Tramadol was less likely to 

cause minor adverse events relative to pentazocine (NNT = four in favor of tramadol). Tramadol was 

similar to pentazocine in treatment discontinuations due to adverse events. 

A 12-week, open-label, non-inferiority, randomized trial (N = 134) showed that, in patients with 

moderate to severe OA of the hip or knee, twice daily tramadol ER (75, 100, 150, or 200 mg per day, 

maximum 400 mg per day) and once daily low-dose transdermal buprenorphine (5, 10 or 20 

mcg/hour) were similar in pain reduction. [167] Transdermal buprenorphine was non-inferior to twice

daily tramadol ER therapy. The incidences of adverse events were similar for both treatments but the 

risk of treatment discontinuations due to adverse events was higher on tramadol (29.2 percent versus 

14.5 percent). A once daily buprenorphine transdermal patch was preferred over a twice daily 

tramadol therapy by 70 percent of patients in each treatment group.
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Tramadol as Add-On Therapy

The addition of tramadol to acetaminophen therapy is often thought to enhance analgesia by 

complementary mechanisms of action. Whereas additional benefit was shown with IR 

tramadol/acetaminophen over the individual agents alone in acute, post-operative dental pain, [206] 

there is insufficient evidence to make conclusions for OA pain. Tramadol and 

tramadol/acetaminophen showed similar efficacy and safety in indirect comparisons, suggesting that 

there was little additional benefit from the addition of tramadol to acetaminophen in patients with OA 

pain. However, these observations were based on only two RCTs included in a meta-analysis. [155] 

There is more evidence available for the addition of tramadol or tramadol/acetaminophen to NSAIDs 

with some potential caveats to consider. The addition of tramadol IR for breakthrough OA pain during 

daily NSAID therapy was inconsistently beneficial in a short-term (13-day) trial. [168] The results of 

another trial suggested that NSAID responders may be more likely than NSAID non-responders to 

obtain additional relief from add-on tramadol therapy. [169] Tramadol/acetaminophen as add-on 

therapy to NSAIDs including COX-2 inhibitors was shown to improve pain to only a small extent, 

[155,170,171] although in one trial [172] the small reduction in pain was accompanied by significant 

improvement in physical function.

The addition of tramadol to duloxetine therapy has not been evaluated in OA clinical trials. 

Concomitant use of tramadol with duloxetine is not a contraindication; however, exercise caution and 

consider potential patient risk factors (e.g., increasing age or renal impairment) if using tramadol in 

combination with duloxetine. Concomitant use of tramadol and duloxetine may result in additive 

serotonergic effects and increase the risk for serotonin syndrome. Duloxetine co-therapy may increase 

tramadol plasma concentrations because it is a moderate CYP2D6 inhibitor and increase the risk for 

seizures.

Non-Tramadol Opioids

Non-tramadol Opioids as Alternative Monotherapy

A Cochrane meta-analysis of ten trials (N = 2268) involving oxycodone (four trials), codeine (three 

trials), oxymorphone (two trials), transdermal fentanyl and oral morphine (one trial each) showed 

small to moderate improvements relative to placebo in pain (for at least 50 percent improvement, 

NNT = 8; 95% CI 7 to 11) and physical function (NNT = 10; 95% CI 8 to 15). [173] These benefits were 

outweighed by large increases in the risk of treatment discontinuations due to adverse events relative

to placebo (NNT = 19; 95% CI 13 to 29). More potent opioids did not seem to be substantially better 

than less potent opioids. The authors concluded that non-tramadol opioids should not be used 

routinely even if OA pain is severe. The results reflect short-term treatment courses (median, four 

weeks) using morphine equivalent doses ranging from 13 to 160 mg per day (median, 51 mg per day).

An investigational formulation of hydromorphone ER showed inconsistent benefit in OA pain 

depending on the imputation method of data analysis. [174] 

In patients with OA with uncontrolled persistent pain who were receiving or could not tolerate 

standard therapy with NSAIDS, acetaminophen, or short-acting opioids, a 90-day course of treatment 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 93 of 126

with oxycodone ER (20 mg per day) was efficacious in improving pain, physical function and sleep. 

[175]

Non-tramadol Opioids Compared with Non-opioid Therapies

In meta-analytic indirect comparisons using Bayesian analyses, oxycodone was similar to duloxetine in 

WOMAC total score change from baseline. [166]

Tapentadol Compared with Non-tramadol Opioids 

In a ten-day major safety and efficacy clinical trial to support an acute pain indication, every four to six 

hour dosing regimens of tapentadol IR (50 or 75 mg) were shown to be non-inferior to oxycodone IR 

(10 mg every four to six hours) in 666 patients whose pain was not controlled by current therapy and 

who were surgical candidates for hip or knee replacement because of end-stage OA. [111] Compared 

with oxycodone, tapentadol therapy was associated with significantly lower incidences of nausea, 

vomiting and constipation.

Opioid Rotation to Tapentadol ER 

Patients already on opioids for OA pain may be considered for rotation to tapentadol ER. In a small, 

manufacturer-sponsored, 12-week open-label study which was terminated early because of slow 

enrollment and drug shortages, the rotation of World Health Organization (WHO) step III opioids to 

tapentadol ER led to improvements in efficacy and safety. [176] In patients who responded but were 

not tolerating WHO step III opioid therapy for severe OA knee pain, rotation to tapentadol ER reduced 

total WOMAC scores over a 12-week period, reflecting improvements in pain, stiffness and physical 

function, and in sleep disturbances. Although the intent was to maintain the same level of pain 

control, after the switch to tapentadol there were at least ten percent decreases in the percentages of 

patients experiencing nausea, constipation, dry mouth and fatigue. These four adverse events and 

dizziness were the main reasons for switching to tapentadol ER.

Non-tramadol Opioids as Add-on Therapy

No studies evaluating non-tramadol opioids as add-on therapy in OA were found. The evidence to 

support add-on therapy is inferred from monotherapy studies.

Corticosteroids versus Placebo

Intra-articular corticosteroids are commonly used to reduce pain in patients with OA of the knee and 

less commonly of the hip. Available evidence provides support for reducing pain in patients with OA of 

the knee but evidence is limited for hip OA. In the majority of studies, samples sizes were small and 

the severity of OA was stated to range from mild to severe. 

Knee

Three systematic reviews/meta-analyses were identified in which intra-articular steroids were 

compared to placebo in patients with OA of the knee. A fourth meta-analysis, examining the effect of 

various pharmacologic interventions (including intra-articular steroids) compared to placebo for knee 

OA was also included. In the review by Arroll, et al., [207] ten trials met the inclusion criteria and six of 

the trials provided data on improvement of OA symptoms. There was a statistically significant 

difference in favor of steroid injections versus placebo for improvement in OA symptoms (RR 1.66, 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 94 of 126

95% CI 1.37-2.01, NNT 1.3-3.5). Symptoms were improved up to two weeks after injection but one 

study, using a higher steroid dose (40 mg triamcinolone), reported a prolonged duration of reduced 

symptoms. [207] Godwin, et al., included five randomized trials involving 312 patients. From their 

review, patients receiving corticosteroid joint injections reported reduced pain at one week and 

through three to four weeks when compared to placebo. No differences were reported in pain scores 

between groups by week six in any of the included studies. Adverse events resulting from the steroid 

injection were not reported in any of the five included trials. [208] The third systematic review was 

conducted by the Cochrane Collaboration and included a comparison of intra-articular knee injection 

with corticosteroids versus placebo or hyaluronates/hylan. For the comparison to placebo, intraarticular injection with steroids improved pain (weighted mean difference [WMD] -21.91, 95% CI -

29.93 to -13.89) and patient global assessment (RR 1.44, 95% CI 1.13-1.82) at one week after injection 

(NNT 3-4). Pain was significantly reduced in the steroid group between two and three weeks post

injection (RR 1.81, 95% CI 1.09-3, RR 3.11, 95% CI 1.61-6.01, respectively). No differences were noted 

in pain between 4 and 24 weeks post injection. There were no statistical differences reported for 

improvement in function between groups. [177]

Hip

There was one review of the use of intra-articular corticosteroids in patients with OA of the hip as a 

therapeutic intervention. [209] In this review, the authors identified eight trials, in which only four 

were randomized, placebo-controlled trials and included a total of 268 patients. In each of the studies, 

joint injection was performed using fluoroscopic or ultrasound guidance. Benefit of the steroid 

injection was noted in reducing pain, stiffness and increasing function and/or range of motion. An 

improvement in symptoms was reported up to three months, but in one study was limited to 28 days. 

There were no serious adverse events that were reported in any of the trials. [209]

Another use of intra-articular steroid injection of the hip is to assist in the differential diagnosis to help 

distinguish pain arising from the hip (intra-articular), the spine or other extra-articular origin in those 

patients presenting with atypical lower extremity or hip pain. This diagnostic tool may be helpful in 

determining whether total hip replacement (THR) will resolve painful symptoms. In a retrospective 

assessment of 204 consecutive diagnostic hip injections, investigators found hip injection with a 

steroid and local anesthetic to have a sensitivity of 91.5 percent, specificity and positive predictive 

value of 100 percent and a negative predictive value of 84.6 percent for a favorable response to THR. 

[210]

Hyaluronate/Hylan (HA)

There were a large number of published studies investigating the effect of intra-articular HA injections 

versus placebo in patients with OA of the knee. Many of these studies have been deemed of lower 

quality as many are small and have flawed study methodology and data analysis. Furthermore in the 

process of conducting meta-analyses, negative results from unpublished trials have led to concerns of 

publication bias in this area. [179] With regard to intra-articular HA in patients with OA of the hip, 

limited published data are available. In these studies, pain improvement was measured using the VAS, 

WOMAC, and Osteoarthritis Research Society International (OARSI) 2004 criteria. Physical function 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 95 of 126

was assessed by the OARSI 2004 criteria, Patient Global Assessment (PGA), and WOMAC. Adverse 

events were classified as serious or non-serious events in five studies. 

Knee

There were eight published systematic reviews with meta-analyses examining the benefit of intraarticular HA/hylan to placebo in patients with OA of the knee; two of which were published in 2012. 

[179,180] Of the meta-analyses published prior to 2010 (n=six), four reported at least a modest benefit 

in comparison to placebo. [118,211-213] While the remaining two studies found minimal to no 

benefit, [214,215] Rutjes et al., reported an overall effect size of HA on pain improved compared to 

placebo as -0.37 (95% CI -0.46 to -0.28). [179] While this is a typically considered as a moderate effect 

size, it was deemed to be minimally clinically significant by the authors. Additionally, when reanalyzed 

to include only those data from larger studies, there was an even a smaller effect size (-0.16, 95% CI -

0.26 to -0.07), which was statistically different from placebo but did not reach the pre-specified 

minimal clinically important difference. Overall, the effect size for improved function was moderate (-

0.33, 95% CI -0.43 to -0.22). However, when only data from larger studies were analyzed, differences 

in physical function were no longer significant. In the meta-analysis by Colen et al., the authors noted a 

change in WMD of -10.20 (95% CI -15.97 to -4.42) in visual analogue scale from baseline to three 

months, after taking into account the placebo response observed with intra-articular saline. [180]

Treatment related adverse events were fairly consistent across all studies and intra-articular HAs were 

not associated with an increased risk of overall adverse events in comparison to placebo. In the metaanalysis by Rutjes et al., a higher rate of serious adverse events were reported in the group receiving 

hyaluronates but the authors acknowledge that the causal nature of those serious events is not 

known. [179]

Hip

Two published studies [216,217] met our inclusion criteria and included 186 patients. In the study by 

Richette et al., [216] intra-articular HA was administered using fluoroscopic guidance versus placebo. 

The authors did not observe any differences between groups in pain assessed by VAS, WOMAC sub 

scores for pain, stiffness or disability, differences in physician global assessment or any other outcome 

measured. Rates of adverse events were consistent in both studies and were not different between 

HA and placebo. [216,217]

There were two published systematic reviews of intra-articular injection of HA in patients with OA of 

hip. Both authors concluded that the available evidence is limited and of lower quality and therefore 

additional studies are recommended prior to make conclusive recommendations regarding its use in 

hip OA. [218,219]

The effect of hyaluronic acid intra-articular hip injections on the need for total hip replacement surgery 

was examined in two studies. One of the studies was a non-randomized comparative trial comparing 

three different HA formulations [181] and was of fair quality. The second study, Migliore et al., [182]

was a retrospective cohort study, and was of Fair quality. In the study, 82 percent of patients avoided 

total hip arthroplasty at 48 months following HA injections every six months. [182] Survival analysis of 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 96 of 126

the 2008 study indicated that 51 percent of patients had not undergone surgery at three years and 

adverse events (none serious) ranged from 10 to 30 percent. [181] Both studies showed reduction of 

pain and increase in function following the HA injections. However, no placebo or non-intervention 

comparative group was considered

Corticosteroids versus Hyaluronate/Hylan

Seven studies comparing corticosteroids to HA in patients with OA were identified. These studies 

compared corticosteroid to hyaluronate injections and include one systematic review and six 

randomized controlled trials (RCTs) involving a total of 1436 enrolled patients. The systematic review 

and four of the six RCTs evaluated patients with OA of both the knees and hips while the remaining 

RCTs enrolled only patients with OA of the hips. The mean patient age ranged from 39 to 83 years and 

all studies included more females than males. The type of intra-articular hyaluronates (HA) and 

corticosteroid used as well as the doses used varied across the studies. Pain improvement was 

measured using the Visual Analog Scale (VAS), WOMAC pain sub-scores, the Knee Society clinical 

rating, and the Lequesne score, the blinded clinical observer global assessment (COGA), the patient 

global assessment, and the total arthritis index. Physical function was assessed by the WOMAC 

physical function subscales and the Knee Society clinical rating. Five of the seven studies reported 

adverse events that were classified as serious.

Knee

The systematic review [178] included seven RCTs and 606 patients. Of note, five of the seven RCTs 

included in this review were deemed low quality trials and two were rated as high quality. Pain scores 

at week two favored corticosteroids, at week four there was equal efficacy and at weeks 8, 12 and 26, 

pain scores favored HA. Three RCTs, [119-121] not included in the systematic review, consisted of 181 

patients. In these three studies, no statistically significant difference between agents in pain scores at 

any follow up interval (which ranged from five weeks to six months) was observed. [119-121]

Outcomes related to physical function were reported in two studies. Caborn et al. found a statistically 

significant difference between groups at week 12 and week 26 favoring HA utilizing the WOMAC 

domain C score. [122] However, Skwara et al. did not find a significant between group differences at 

any follow up time point. [120] Overall, adverse events were fairly consistent across all studies and 

there was no significant difference in overall incidence of adverse events in the corticosteroid groups

versus the HA groups. 

Hip

Two RCTs [217,220] included 406 patients showed consistent outcomes related to pain as there was 

no significant difference in pain improvement scores at any follow up time point between patients 

who received intra-articular HA versus corticosteroid. Spitzer et al. reported improvement in physical 

function at four weeks that was statistically significant favoring the corticosteroid group; however, this 

difference disappeared by week 26. [220] In these two studies, comparable rates of adverse events 

were noted and included hip infection, pain flares and joint stiffness. [217,220]
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 97 of 126

Corticosteroid Injection prior to Hip or Knee Arthroplasty

Although infection is a known complication arising from both joint injection and arthroplasty, there are 

limited data showing an increased risk of deep joint infection in patients who have undergone intraarticular corticosteroid injection prior to joint arthroplasty (e.g., knee or hip). Patient factors that may 

increase the risk for deep joint infection following joint arthroplasty including prior open surgical 

procedure, immunosuppressive therapy, poor nutrition, hypokalemia, diabetes, obesity and history of 

smoking. [221] Joint injections with corticosteroids are used to reduce pain in an attempt to delay joint 

arthroplasty or in those patients that are not appropriate surgical candidates and are also used as a 

diagnostic aide to identify the origin of joint pain and discomfort (e.g., intrinsic hip pain versus extrinsic 

pain arising from the spine or referred pain from the hip to the knee). Therapeutic corticosteroid joint 

injections are more commonly used prior to knee replacement since accessing the hip joint poses an 

increased technical challenge without the use of fluoroscopy or ultrasound guidance. The available 

evidence pertaining to the risk of deep joint infection after joint arthroplasty is in the form of 

retrospective or case-control studies. A literature review by McMahon, et al., included data from 

twelve studies in which the rates of superficial and deep joint infections (n=2068) in cohorts of 

patients who did receive or did not receive a corticosteroid joint injection and who underwent hip or 

knee arthroplasty were analyzed. From their review, the authors concluded that steroid injection prior 

to joint replacement (either hip or knee) did not statistically increase the risk for superficial or deep

joint infection. [222]

Knee

One retrospective [223] and two retrospective, case-control studies [224,225] were identified in 

patients having total knee replacement (TKR) surgery. In the study by Papavasailliou, 231 patients 

having undergone TKR over a period of 2.5 years were reviewed and 144 evaluated after exclusion 

criteria were applied. In those patients having received a steroid joint injection (n=54) in an 11-month 

period before surgery, three deep infections were identified versus none in patients who did not 

receive a joint injection (n=90). Five other patients having received an injection prior to surgery 

underwent further examination for possible deep joint infection because of ongoing swelling or pain. It 

was not noted whether these patients were later diagnosed with a deep infection. The number of 

superficial infections did not differ between those who did and did not receive an injection prior to 

TKR. The authors concluded that the decision to administer an intra-articular steroid injection in a 

potential candidate for TKR requires careful consideration. [223] In the study by Joshy et al., 32 

patients with deep joint infection following TKR were compared with 32 control patients with no 

infection. There was no significant difference in numbers of patients who had steroid joint injections 

prior to TKR between groups (p=one). [225] In the second study by Desai et al., 440 patients had TKR 

replacements and only 90 patients had an intra-articular steroid injection prior to surgery. Half of 

those patients received the injection within one year before surgery. A group of 180 patients, who did 

not have a steroid injection, served as the control. Two cases of superficial infection were found in the 

injection and five in the control group (NS). No deep infections were noted in any of the case or 

control patients (p=one). [224]
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 98 of 126

Hip

There have been nine published retrospective and case-control trials conducted to determine if the 

risk of deep infection is increased in patients having received intra-articular steroid injection prior to 

total hip replacements (THR). One of the case-control studies found an increased risk of deep joint 

infection in patients having hip joint injections and is the study that is responsible for raising these 

concerns. In their study, 40 patients having received a steroid joint injection prior to THR was 

compared to 40 patients having THR without receiving an injection. Five joint revisions were 

necessary, four of which were done because of deep infection versus none in the non-injection group. 

Six other patients experienced ongoing problems with their new hip in the injection group versus one 

in the control group. The authors noted that deep infection required joint revision in 10 percent of the 

injection patients (4/40) versus none in the control group. Overall, hip joint revision rates in the 

injection patients was 12.5 percent versus 1.02 percent of 979 THR performed during the same study 

period. The authors conclude that due to the potential complications from steroid joint injection prior 

to THR, their use should be contraindicated in possible candidates for THR. [226] In another casecontrol study, 224 patients having primary THR within one year of intra-articular steroid injection were 

compared with 224 patients having THR without steroid injection. In the injection group, there were 

three deep infections and 11 superficial infections versus one deep infection and eight superficial 

infections in the non-injection group; neither of these differences was statistically significant. Two of 

the four patients that developed a deep infection had a chronic comorbid condition. Of note, the 

average time to injection and THR was 112 days. However, in the patients that developed deep 

infections, the average time between the steroid injection and THR was 44 days (standard deviation 23 

days). [227] Of the remaining seven retrospective/case-control studies, none of them found an 

increased risk for deep joint infection in patients receiving intra-articular steroid injections in the 

operative joint. Many of the authors cited potential reasons for an increased rate of deep infections in 

the Kaspar, et al. study including concern regarding administration of intra-articular hip injections 

outside of a controlled, low-infection environment, such as an operating room and adhering to strict 

aseptic techniques. [228-234]
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 99 of 126

Table D-1. List of Pharmacologic Agents and their Selected Characteristics

List of Pharmaceuticals for treatment of Osteoarthritis*+

Generic Name Brand Formulations Usual Starting Dose Max Single Dose Frequency Notes

COX-2 selective NSAIDs:a

Celecoxib CELEBREX C 100-200 mg 200 mg once or twice 

daily

Max 200 mg/day for OA

Partially selective NSAIDs:a

Etodolac generic only/XR C, T; C (XR) 200 mg 400 mg 2-4 times daily XR up to 1200/daily

Meloxicam MOBIC/generics T, Susp 7.5 mg 15 mg once daily Max dose is 15 mg daily

Nabumetone generic only T 1000 mg 2000 mg once daily May divide twice daily. Max 

dose is 2000 mg daily

Non-aspirin, nonselective NSAIDs:a

Diclofenac 

potassium/sodium

generics several 50 mg 75 mg 2-3 times daily Max total daily dose is 150 mg. 

May divide up to 3 times daily 

Diclofenac sodium VOLTAREN XR T 100 mg 100 mg once daily Max dose is 100 mg daily

Diflunisal generic only T 250 mg 750 mg twice daily Max dose is 1500 mg daily

Fenoprofen NALFON/generics C, T 300 mg 600 mg 3-4 times daily Higher renal risk. Total daily 

dose should not exceed 3,200 

mg

Flurbiprofen ANSAID/generics T 50-100 mg 100 mg twice daily Max daily dose is 300 mg

Ibuprofen generics several 400 mg 800 mg 3-4 times daily Max dose in chronic pain is 

2400 mg daily

Indomethacin INDOCIN/SR/generi

cs

C, Supp, Susp 25-50 mg (IR)

75 mg (SR)

50 mg

75 mg

2-3 times daily

1-2 times daily

May divide up to 4 times daily 

(IR). Max dose is 150 mg daily

Ketoprofen IR generic only C; OTC T 50 mg 75 mg 3 or 4 times daily Max dose is 300 mg daily

Ketoprofen ER generic only C 200 mg once daily

Meclofenamate 

sodium

generic only C 50 mg 100 mg 4 times daily May give 3 times daily. Max 

dose is 400 mg daily

Naproxen/-EC NAPROSYN/generic

s

T, susp 250 mg 500 mg twice daily Max dose in chronic pain is 

1000 mg daily

Naproxen Sodium ANAPROX/generics T 275 mg 550 mg twice daily Max dose in chronic pain is 

1100 mg daily

Oxaprozin DAYPRO/generics T 1200 mg 1800 mg once daily Max dose is 26 mg/kg up to 

1800 mg, whichever is lower
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 100 of 126

List of Pharmaceuticals for treatment of Osteoarthritis*+

Generic Name Brand Formulations Usual Starting Dose Max Single Dose Frequency Notes

Piroxicam FELDENE/generics C 10 mg 20 mg once daily Max dose is 20 mg daily. May 

divide twice daily

Sulindac CLINORIL/generics T 150 mg 200 mg twice daily Max dose is 400 mg daily

Tolmetin generic only T, C 400-600 mg 600 mg 3 times daily Max dose is 1800 mg daily

Aspirin and Salsalate:

Aspirin several T, Supp 1000 mg 1000 mg 3 times daily May increase to 4 times daily 

Max dose is 4000 mg daily

Salsalate several T 500 mg-750 mg 1000 mg 2-3 times daily May increase to 3 times daily 

Max dose is 3000 mg daily

Acetaminophen and Supplements

Acetaminophen several several 650 mg 1300 mg 3-4 times daily 

(Max dose 2-4 

grams daily, 

depending upon 

the patient) 

Max 3000-4000 mg/day

Consider lower total daily 

doses (e.g., 2-3 grams) in 

elderly patients or in those with 

heavy use of alcohol 

The total daily dose of 

acetaminophen from all 

sources (single and multiple 

ingredient products) must not 

exceed 4000 mg/day

Chondroitin several several 400 mg 3 times daily Large variation in delivered 

dose

Not recommended due to lack 

of evidence showing benefit

Glucosamine several several 500 mg 3 times daily Large variation in delivered 

dose

Not recommended due to lack 

of evidence showing benefit

Topical Therapies 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 101 of 126

List of Pharmaceuticals for treatment of Osteoarthritis*+

Generic Name Brand Formulations Usual Starting Dose Max Single Dose Frequency Notes

Capsaicin generics cream, gel, liquid, 

lotion

Varied 

concentrations: 

0.025%-0.075%

-- -- Apply 3-4 times 

daily

Patients may experience 

burning/tingling sensation in 

the first few days of use. 

Instruct patients to wash their 

hands with soap and water 

after application.

Diclofenac Pennsaid Soln 1.5 and 2% 40 drops 40 drops 4 times daily Local skin irritation

Diclofenac Flector Patch 1.3% 1 patch (180 mg) 1 patch (180mg) twice daily Not FDA approved for OA

Local skin irritation

Diclofenac Solaraze Gel 3% -- -- twice daily Local skin irritation

Other Therapies

Duloxetine Cymbalta/generics Delayed release C 30 mg for 1 week, 

increase to 60 mg 

conce daily

60 mg Once daily Max dose is 60 mg daily. Higher 

doses are not associated with 

improved outcomes but a 

higher rate of adverse events is 

reported

Avoid in end-stage renal 

disease or CrCl <30 ml/min or 

in patients with substantial 

alcohol intake

Refer to prescribing 

information for other details 

including contraindications, 

drug-drug interactions, 

warnings and precautions and 

adverse events.
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 102 of 126

List of Pharmaceuticals for treatment of Osteoarthritis*+

Generic Name Brand Formulations Usual Starting Dose Max Single Dose Frequency Notes

Tramadol (IR) generics T, several 25-50 mg 100 mg Every 4-6 hours

Max daily dose 

400 mg

For patients not requiring rapid 

onset of pain relief, initiate 

dosing at 25 mg 4 times daily, 

increasing by 25 mg every 3 

days until reaching 25 mg 4 

times daily, and so on.

When combined with certain 

drugs or in those patients with 

a history of seizure disorder, 

tramadol may increase the risk 

of seizures.

Hyaluronate/Hylan Injections: Treatment Course (Each injection is given at weekly intervals)

Hyaluronate/Hylan Frequency Volume Notes

Euflexxa 3 weekly; repeat approved 2.0 ml ---

Gel-One Single injection 3.0 ml Caution in those with avian allergy

Hyalgan 3 or 5 weekly 2.0 ml Caution in those with avian allergy

Orthovisc 3 to 4 weekly 2.0 ml ---

Supartz 3 or 5 weekly 2.5 ml Caution in those with avian allergy

Synvisc 3 weekly 2.0 ml Caution in those with avian allergy

Synvisc-One Single injection 6.0 ml Caution in those with avian allergy

*Refer to VA or DoD formularies for availability of agents or comparable agents. The list of available formulations may not be all-inclusive or may change with time 

as will generic availability. +For additional details on warnings and precautions, drug-drug interactions, etc., refer to the prescribing information for the individual 

agents of interest. 

a

All NSAIDs have the potential to increase the risk for cardiovascular (CV) events and therefore should be used at the lowest effective dose for the shortest possible 

duration. Naproxen has a neutral or lowest risk for adverse CV events. Use with caution or avoid use of NSAIDs in patients with renal impairment, history of 

gastrointestinal bleeding, uncontrolled hypertension, congestive heart failure, advanced liver diseases, known cardiovascular disease, patients receiving 

anticoagulants, etc. 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 103 of 126

Appendix E: Nutraceuticals and Dietary Supplements

Table E-1. Key Findings from Studies on Nutraceuticals/Dietary Supplements

Dietary Supplement Summary of Study 

Characteristics

Key Findings Additional Comments

Ayurvedic formulations 

(components: Shunthi 

and Guduchi)

One RCT rated as Good 

quality; 5 Ayurvedic 

formulations were 

compared to placebo 

and glucosamine sulfate; 

total n = 245

Chopra et al. 2011 [235]

No statistically 

significant 

improvements in pain 

or function for any 

group.

Paracetamol rescue 

medication was 

permitted; participants 

were allowed to 

continue established 

physical therapy 

routines.

Boiogito (Sinomenium 

Stem)

One RCT (unblinded) 

rated as fair compared 

Boiogito with loxoprofen 

vs. loxoprefen alone; n = 

50

Majima et al. 2012 [236]

Both groups 

experienced 

improvements in pain 

from baseline and 

physical function.

Collagen Derivatives 

(Indentured Collagen; 

Gelatin; Collagen 

Hydrolysate)

One systematic review 

of 8 trials included 6 

RCTs, 1 quasi-RCT, and 1 

crossover design study, 

total n = 1187. The 

review was rated as 

Good quality, but the 

studies included were 

low to moderate in 

quality.

VanVijven et al. 2012 

[237]

For both pain and 

function, Collagen 

(various forms) did 

not appear to be 

more effective than 

placebo, based on 

meta-analysis of 3 

trials.

Use of rescue 

medication was not 

clearly described. 

Harms were poorly 

reported.

Curcuma (domestica 

and longa)

Two RCT’s, both rated as 

Fair quality (lack of 

blinding); compared 

curcuma to placebo plus 

rescue medication or 

curcuma to ibuprofen.

Madhu et al. 2012 [238]

Kuptniratsaikul et al. 

2009 [239]

One trial found 

statistically significant 

improvements in pain 

and function for 

patients treated with 

curcuma vs placebo;

[238] the other did 

not.

Rescue medication 

used significantly less 

often in the curcuma 

group. [238]

Derris Scandens One RCT rated as Fair for 

lack of blinding; 

compared Derris 

Sandens to naproxen, 

n=107.

Kuptniratsaikul et al. 

2011 [240]

No statistically 

significant findings by 

treatment group in 

mean pain reduction 

or for function.

Harms for Derris 

Scandens was not 

significantly different 

from naproxen.

Duhuo Jisheng Wan One RCT rated as Good, 

n =200, compared 

No statistically 

significant difference 

No other medications 

were permitted.
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 104 of 126

Dietary Supplement Summary of Study 

Characteristics

Key Findings Additional Comments

Duhuo Jisheng Wan to 

diclofenac.

Teekachunhatean et al. 

2004 [241]

in measures of pain 

or function seen 

between groups.

Eggshell membrane One RCT rated as Good 

quality, n =60, compared 

eggshell membrane to 

placebo.

Ruff et al. 2009 [242]

Eggshell group 

showed a statistically 

significant but not 

clinically meaningful 

reduction in pain 

compared to placebo; 

there was no 

statistically significant 

improvement in 

function.

Acetaminophen as 

rescue medication. No 

difference in harms 

(self-reported).

Flavocoxid (“Limbrel” 

proprietary product)

One RCT with a quality 

rating of Good, n=223; 

compared product to 

naproxen.

Levy et al. 2010 [243]

There were no 

between group 

differences in pain or 

function.

Harms (self-report, 

clinical exam, lab) were 

statistically 

significantly different, 

with those on 

naproxen reporting 

more edema and 

dyspepsia, and more 

flatulence with Librel.

Ginger One Good quality 

systematic narrative 

review and one Good 

quality RCT. 

Leach et al. 2008 [243]

Zakeri et al. 2011 [244]

Within the Leach 

review, 3 trials 

compared ginger to 

placebo; one trial 

found a statistically 

significant 

improvement in pain 

in the ginger group. In 

the Leach review, 2 

trials compared 

ginger to ibuprofen; 

there was no 

statistically significant 

difference between 

groups. 

Improvements in 

function favored 

ibuprofen only.

Harms for ginger 

included bad taste, 

heartburn, dyspepsia, 

nausea, stool changes 

and skin allergy, but 

there was no 

statistically significant 

differences in harms 

between ginger and 

placebo. For ginger and 

ibuprofen, reported 

harms were similar and 

were not different 

between groups.

MESACA 

(Methylsulfonylmethane 

and Boswellia Acid 

Combination)

One RCT of Good quality 

compared MESACA to 

placebo (total n = 30).

Notarnicola et al. 2012 

Both groups 

experienced 

statistically significant 

improvements in pain 

Paracetamol, 

pyroxicam or 

diclofenac were 

permitted as rescue 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 105 of 126

Dietary Supplement Summary of Study 

Characteristics

Key Findings Additional Comments

[245] from baseline, but 

the between group 

difference favored 

placebo; however, 

the MESACA group 

used significantly less 

rescue medication 

than at baseline. 

There was no 

statistically significant 

difference in 

measures of function 

between groups.

meds. No side effects 

were reported (harms 

were self-report).

Phytalgic (proprietary 

blend of fish oil; vitamin 

E; uritica dioica)

One RCT rated as Good 

quality compared 

Phytalgic to placebo 

(total n = 81).

Jacquet et al. 2009 [246]

There was a 

statistically significant 

reduction in pain and 

improved function for 

the Phytalgic group 

compared to placebo.

Various harms 

reported with Phytalgic 

included eructations 

smelling of fish, pain 

outside OA, infection; 

not reported as to 

significant difference in 

harms between 

Phytalgic and placebo.

Pycnogenol One RCT rated as Good 

quality compared 

Pycnogenol to placebo 

(total n = 100).

Cisar et al. 2008 [247]

There was no 

statistically significant 

difference between 

Pycnogenol and 

placebo for pain or 

daily activities; 

patients on 

Pycnogenol were able 

to decrease their 

analgesic doses, but 

statistical significance 

was not reported. 

Total WOMAC score 

was improved 

significantly for the 

Pycnogenol group.

Patients were 

permitted to use any 

medications taken preenrollment or to 

change medications if 

desired.

Harms were self-report 

and by lab value; no 

changes in biochemical 

parameters, unclear if 

reported harms 

differed between 

groups but were 

generally few.

SKI 306X (Clematis 

Radix, Trichosanthes 

Root, Prunella Spike)

N – 249, OA of the knee, 

patients aged 35-75 

years; SK1306X with 

placebo, administered 

200 mg 3 x/d for 4 

weeks, vs 100 mg 

dicolfenac 100 mg/d 

plus placebo. 

Statistically significant 

difference vbetween 

groups in favor of 

diclofenac for 

function; no between 

group difference for 

pain.

Patients permitted to 

exercise and receive 

massage.
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 106 of 126

Dietary Supplement Summary of Study 

Characteristics

Key Findings Additional Comments

Jung et al. 2001 [248]

SAMe A systematic review was 

rated as Good, but 

included trials of low 

quality rating; trials 

compared SAMe to 

placebo. One recently 

published RCT was 

considered Good quality 

and compared SAMe to 

nabumetone.

Rutjes et al. 2009 [249] 

Kim et al. 2009 [250] 

Rutjes et al. 

performed a metaanalysis of 2 RCTs and 

found no between 

group difference in 

pain reduction or 

improved function.

In the RCT by Kim, 

there was no 

statistically significant 

difference for pain or 

function between 

groups.

Kim et al. reported 

adverse events for 

SAMe at 35.8% and for 

nabumetone at 31.3%, 

but did not report if 

there was a statistically 

significant difference.

Sierrasil One RCT with a Good 

quality rating compared 

high dose Sierrasil, low 

dose Sierrasil and 

placebo (total n = 107). 

Miller et al. 2003 [251] 

There was no 

statistically significant 

between group 

difference for pain 

scores; all groups 

improved from 

baseline for measures 

of function, but it was 

not stated if groups 

differed in the 

improvement.

Patients were allowed 

to take paracetamol, 

but no other rescue 

medications or 

supplements.

Harms were reported 

as self-report and 

laboratory values; 

authors state that 

changes in lab values 

were not indicative of 

adverse response to 

study medications.

Siriraj Wattama Recipe 

(proprietary blend of 15 

herbs)

One RCT of Fair quality 

with unblinded design 

compared the 

supplement to 

diclofenac (total n = 60). 

Pengkhum et al. 2012 

[252] 

No statistically 

significant between 

group difference for 

pain score or 

function.

Marginally higher 

levels of AST and 

eosinophils with 

supplement.

Adverse events for 

supplement (n=2) 

compared to 

diclofenac (n=3).

The literature review included intervention studies with at least 25 patients per treatment arm in a 

prospective, randomized or nonrandomized comparative trial with an independent, concurrent control 

group. Alternately, recent systematic reviews were included. These inclusion criteria limited the 

number of studies included; for many dietary supplements, only one study meeting these criteria was 

located.

There were six dietary supplements for which more than one study met the inclusion criteria and 

indicated some effect on pain and function for patients with hip and/or knee OA: glucosamine or

chondroitin sulfate or the combination (one meta-analysis, 20 RCTs); avocado-soybean 
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 107 of 126

unsaponifiables (one meta-analysis rated as good, included four RCTs); Boswellia Serrata (one good 

and one fair quality RCT); Methysufonylmehtane (MSM) (one good quality systematic review on two

RCTs); Rosa Canina (Rose hips) (one good quality systematic review on one RCT and two crossover 

trials).

Meta-analysis by Christensen et al. compared avocado-soybean unsaponifiables to placebo, and 

included four double-blind RCTs and a total of 664 patients (427 female) with a mean age of 64.1 

years. [183] Two of the RCTs included hip and knee OA; one was knee OA only; one was hip OA only. 

The product used in all trials was Piascledine, and all trials were manufacturer funded. In the study, 

participants self-reported the pain using the VAS pain scale. Use of rescue medications was not 

reported. The meta-analysis of the four RCTs found a statistically significant and clinically meaningful 

reduction in pain compared to placebo (effect size 0.39, 95% confidence interval 0.01-0.76, p =0.042) 

but heterogeneity was high. Two trials clearly favored the avocado-soybean preparation; two trials did 

not favor the supplement over placebo. A meta-regression analysis showed that patients with knee OA 

can expect a larger clinical effect than patients with hip OA. Meta-analysis for improved function found 

significantly greater improvement in the avocado-soybean group than in placebo (effect size 0.45, 95% 

CI 0.21-0.70; p =0.0003) but heterogeneity was high. The three trials including knee OA patients 

favored avocado-soybean treatment. Measurement of harms was not reported in the RCTs; no 

evidence of significant adverse events was found per the meta-analysis authors.

There were three RCTs evaluating the effectiveness of Boswellia Serrata for treatment of OA pain and 

improvements in function. A good quality RCT by Vishal et al. compared the Boswellia Serrata 

preparation Alfapin (n=30) to placebo (n=29). [184] The Alfapin group showed a statistically significant 

reduction in pain and statistically significant improvements in function. There were no major differences 

in harms between the Alfapin and placebo groups. Sengupta et al. compared two dose levels of fiveLoxin (a Botswellia Serrata preparation; 250 mg, n=23; 100 mg, n=24) to placebo (n=23) in a RCT of good 

quality. [186] Both five-Loxin groups showed statistically significant improvements in pain and function. 

There were no statistically significant differences in harms among the three groups. A fair quality RCT by 

Sontakke et al.showed a statistically significant reduction in pain compared to valecoxib; the author’s 

note that valecoxib had a faster onset of action by month one, but that there was no end of treatment 

data reported. At final follow up, the authors found a statistically significant improvement in daily 

activities score compared to valecoxib. The Sontakke study was rated as fair quality because of unblinded 

study design. [185]

A good quality systematic review by Brien et al. was conducted on Methylsulfonylmethane (MSM); it 

included two RCTs and included a total of 168 patients (101 female) and a mean age range from 50-

55.6 between the two studies. The study designs did not allow for meta-analysis, as one trial 

compared MSM to placebo and the other compared MSM to glucosamine. Both trials found MSM to

be superior for pain reduction (p=0.001) and one trial found statistically significant improvements in 

physical function compared to placebo. Harms included GI discomfort and diarrhea, but were not 

broken down by group. [187]
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 108 of 126

Appendix F: Participants List

MAJ D. Ethan Brooks, DSc, PA-C

Orthopedic Physician Assistant

General Leonard Wood Army Community 

Hospital

CDR Pierre A. Bruneau, MD, FAAOS

Commander, U.S. Navy Medical Corps

Division Head Adult Reconstructive Surgery

Department of Orthopedic Surgery

Naval Medical Center, San Diego, CA 

Assistant Professor of Surgery, Uniformed 

Services University of the Health Sciences

Bethesda, Maryland

Grant Cannon, MD, MACP, FACR (Co-Chair)

Associate Chief of Staff of Academic Affiliations

George E. Whalen VA Medical Center 

Salt Lake City, Utah 84148

Carla Cassidy, CRNP, MSN, M.Ed

Director

VA/DoD Evidence-Based CPG Program

Office of Quality, Safety and Value

Department of Veterans Affairs

Washington, DC

Maj Heidi L Clark MS, RD

Faculty, Graduate Program in Nutrition

Registered Dietician 

Army Medical Department Center and School

MAJ Angelique N Collamer, MD

Rheumatologist 

Langley Air Force Base Hospital

Ernest Degenhardt, COL USA (Ret.) MSN, RN, 

ANP, FNP

Chief, Office of Evidence Based Practice

Clinical Performance Directorate

US Army Medical Command

Ft. Sam Houston, TX

Corinne K.B. Devlin MSN, RN, FNP-BC

Family Nurse Practitioner

Chronic Disease Clinical Practice Guideline 

Coordinator US Army Medical Command Quality 

Management Division, Office of Evidence Based 

Practice

Ft. Sam Houston, TX

LTC Jess D. Edison, MD, FACP, FACR (Co-Chair)

Lieutenant Colonel, U.S. Army Medical Corps

Assistant Chief, Rheumatology Service

Associate Program Director, Rheumatology 

Fellowship

Walter Reed National Military Medical Center

Assistant Professor of Medicine

Uniformed Services University of the Health 

Sciences, Bethesda, Maryland

Wanda Friday RN, BSN, MSM, CCM

Nurse Case Manager

Medical Management Center

Blanchfield Army Community Hospital

Ft Campbell, KY 42223

Francine Goodman, PharmD, BCPS

National PBM Clinical Pharmacy Program 

Manager – Formulary Management

VHA Pharmacy Benefits Management Services

Hines, IL

LTC Anthony Johnson, MD, FAAOS (Co-Chair)

Department Chief of Orthopedics and 

Rehabilitation

San Antonio Military Medical Center

San Antonio, TX

Linda Kaiser, RN, DNP, GNP-BC, NP-C

Nurse Practitioner

St. Louis VA Medical Center 

Catherine Kelley, PharmD

National PBM Clinical Pharmacy Program 

Manager-Formulary Management

VHA Pharmacy Benefits Management Services

Hines, Illinois

Anita Manns, RN, MBA, NP-C, DNP

Primary Care Services 

Jiby Mathew, MSN, APRN, FNP-c

Nurse Practitioner, Rheumatology Division
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 109 of 126

Women's Health Clinic 

John D. Dingell VA Medical Center

Rheumatology Research Coordinator

Dallas VA Medical Center

William C. McMaster MD, FAAOS, FACS (CoChair)

Clinical Professor, Orthopedics, UCI

Chief, Orthopedics 

Long Beach VA Medical Center

David Parish, DC

Civilian Chiropractor

Dean of Clinics at National University of Health 

Sciences

Chicago, Illinois

M. Eric Rodgers, PhD, FNP, BC

Acting Director

VA/DoD Evidence-Based CPG Program

Office of Quality, Safety and Value

Department of Veterans Affairs

Washington, DC

MAJ Jeffrey D Rumfield, CCRN, MPH, PH.D(c)

CNOIC, 2 East Surgical Intermediate Care Units 

San Antonio Military Medical Center

James Sall, PhD, FNP-BC

Office of Evidence Based Practice 

USA MEDCOM 

Fort Sam Houston, TX

John Seiverd, PT, DPT, CCCE

Physical Therapy Residency Program Director

Center Coordinator of Clinical Education

James A Haley Veterans' Hospital, PM&RS Tampa, 

FL

Robert Selvester, MD

Family Practice

Naval Air Station Corpus Christi

Corpus Christi, TX Department of Physical Medicine and 

Rehabilitation

LCDR Carter H. Sigmon MD, MHA

Medical Director, Comprehensive, Complex and 

Combat Casualty Care (C5) (Prior)

Fellow, Department of Pain Medicine (Current)

Department of Anesthesiology

Naval Medical Center

San Diego, CA

René M. Sutton, BS, HCA Jennifer Wood Silva, LCSW, BCD

Educational Program Specialist Assistant Chief, Social Work Service

Evidence-Based Clinical Practice Guidelines Central Texas VA Healthcare System

Office of Quality, Safety and Value

Department of Veterans Affairs 

Washington, DC
Clinical Practice Guideline for the Non-Surgical Management of Osteoarthritis Page 110 of 126

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