Department of Veterans Affairs

Department of Defense

VA/DoD Clinical Practice Guideline

for 

NON-SURGICAL MANAGEMENT OF 

HIP AND KNEE OSTEOARTHRITIS

Guideline Summary

Prepared by:

The Osteoarthritis

Working Group

With support from:

The Office of Quality Safety and Value, VA, Washington, DC

and

Quality Performance Assurance Directorate, United States Army MEDCOM

Full guideline available at:

http://www.healthquality.va.gov or https://www.qmo.amedd.army.mil

QUALIFYING STATEMENTS

The Department of Veterans Affairs (VA) and The Department of Defense (DoD) 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.

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

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

making use of these guidelines is responsible for evaluating the appropriateness of applying them in the setting of any 

particular clinical situation. 

Version 1.0 – 2014
2 | Guideline Summary – 2014

DISCLAIMER

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

Developed by a panel of multidisciplinary experts (all practicing clinicians), 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.

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.

GUIDELINE WORKING GROUP

VA DoD

Grant W. Cannon, MD, MACP, FACR LTC Jess D. Edison, MD, FACP, FACR

William C. McMaster, MD, FAAOS, FACS 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 Office of Evidence Based Practice

Carla Cassidy, MSN, ANP

M. Eric Rodgers, PhD, FNP, BC

Rene Sutton, BS, HCA

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

James Sall, PhD, FNP-BC

Lewin Group ECRI Institute

Cliff Goodman, PhD 

Erin Gardner, BS 

Hillary Kleiner, MPH 

Sneha Rangarao, MPH 

Mariam Siddiqui, BS 

Paul Wallace, MD

James Reston, PhD, 

Stacey Uhl, MS
The Non-Surgical Management Of Hip & Knee Osteoarthritis | INTRODUCTION | 3

INTRODUCTION

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. Research suggests that military service-related overuse 

and injuries may be a contributing factor for the increased risk of developing OA. Severe OA of the hip and knee causes 

debilitating pain and is a common cause of mobility impairment in elderly patients.

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 for surgical 

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

The goal of this CPG 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.

TABLE OF CONTENTS

INTRODUCTION............................................................................................................................................................... 3

ALGORITHM...................................................................................................................................................................... 5

RECOMMENDATIONS....................................................................................................................................................... 6

PHARMACOLOGIC AGENTS............................................................................................................................................. 8
4 | Guideline Summary – 2014

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.

Strength of Recommendation Rating [SR]

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.

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 Non-Surgical Management Of Hip & Knee Osteoarthritis | ALGORITHMS | 5

Algorithm Management of Hip & Knee Osteoarthritis

2

3

6

4

5

7

9

8

12

10 11

1

Yes

Yes

No

No

No

Conduct a history and physical examination

(Avoid the routine use of laboratory examinations, 

synovial fluid analyses, or MRI)

Confirm the presence of OA and assess 

severity of pain/functional limitations

Has the patient’s pain or 

functional limitation improved to their 

satisfaction?

Is patient at risk for or 

with known cardiovascular 

disease or renal injury/

disease?

Is patient at risk for serious 

upper gastrointestinal 

events?

Consider the addition of a 

proton-pump inhibitor (PPI) 

or misoprostol to oral NSAIDs

Consider topical capsaicin, as 

an alternative or adjunct

Avoid NSAIDs, 

consider acetaminophen over 

oral NSAIDs?

Has the patient’s pain or 

functional limitation improved to 

their satisfaction?

Recommend core non-surgical therapies. 

Considering risk vs. benefit assessment, patient 

preferences, and resources utilization

(see Box A)

Adult person presents with hip or 

knee pain, suggestive of OA

Consider duloxetine or tramadol as an alternative or adjunct 

therapy to oral NSAIDs

Consider other pain medications with careful assessment of 

risks and benefits.

In patient with OA of the knee, consider intra-articular 

corticosteroid injection

Recommend traditional 

manual, land-based, and 

aquatic physical therapy, as 

mono or adjunctive therapies

Consider acetaminophen 

or oral NSAIDs as an 

adjunct to physical therapy 

approaches

(see Box B)

Obtain weight-bearing plain radiographs within 

6 months prior to referral for surgical consultation

Refer for surgical consultation

Recommend long-term management of OA 

through core non-surgical therapies and 

reassess annually or as needed

There is insufficient evidence 

to recommend the use of 

capsaicin for the hip

There is insufficient evidence to recommend for or against the use of intraarticular hyaluronate/hyalin injection in patients with OA of the knee. Evidence 

does not support use of these agents for OA of the hip

Box A: Core Non-surgical Therapies

1. Physical therapy approaches

2. Pharmacologic therapies

Box B: Pharmacotherapy Considerations

• Acetaminophen: 

- Ensure patient received no more than 4 grams per day from 

all sources, prescribed or non-prescribed.

- Lower maximum doses (2 to 3 grams daily)may be preferred 

in patients of advanced age or those with heavy alcohol use

• Opioid toxicity/dependence

Does the patient have mild 

to moderate pain associated with OA of the knee?
6 | Guideline Summary – 2014

Recommendations Management of Hip & Knee Osteoarthritis

A. 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]

B. 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]

C. 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]
The Non-Surgical Management Of Hip & Knee Osteoarthritis | Recommendations | 7

D. 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 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]

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 nontramadol 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]

E. 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 ]

F. 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]
8 | Guideline Summary – 2014

Pharmacologic Agents for Osteoarthritis

Table 1: Pharmacologic Agents for the Treatment of Osteoarthritis*+

Generic 

Name Brand Formulation

Dose [mg] Frequency

[daily]

Max Daily 

Dose

[mg]

Notes Usual 

Starting

Max 

Single 

COX-2 Selective NSAIDs:a

Celecoxib CELEBREX C 100-200 200 once or twice 200 mg for OA

 Partially selective NSAIDs:a

Etodolac generic only/XR C, T, C(XR) 200 400 2-4 times XR up to 1200

Meloxicam MOBIC/generics T, Susp 7.5 15 once 15 mg

Nabumetone generic only T 1000 2000 once 2000 mg May divide twice

Non-aspirin, nonselective NSAIDs:a

Diclofenac 

potassium/ 

sodium

generics several 50 75 2-3 times 150 mg May divide up to 

3 times

Diclofenac 

sodium VOLTAREN XR T 100 100 once 100 mg

Diflunisal generic only T 250 750 twice 1500 mg

Fenoprofen NAFLON/generics C, T 300 600 3-4 times 3,200 mg Higher renal risk.

Flurbiprofen ANSAID/generics T 50-100 100 twice 300 mg

Ibuprofen generics several 400 800 3-4 times 2400 mg for 

chronic pain

Indomethacin Indocin/SR/ 

generics C, Supp, Susp 25-50 {IR]

75 [SR]

50

75

2-3 times

1-2 times 150 mg May divide up to 4 times (IR)

Ketoprofen IR generic only C; OTC T 50 75 3-4 times 300 mg

Ketoprofen ER generic only C 200 once

Meclofenamate 

sodium generic only C 50 100 4 times 400 mg May give 3 times daily

Naproxen/-EC NAPROSYN/

generics T, susp 250 500 twice 1000 mg in chronic pain

Naproxen 

Sodium

ANAPROX/

generics T 275 550 twice 1100 mg in chronic pain

Oxaprozin DAYPRO/

generics T 1200 1800 once

26 mg/kg 

up to 1800 mg

whichever is lower

Piroxicam FELDENE/generics C 10 20 once 20 mg May divide twice

Sulindac CLINORIL/generics T 150 200 twice 400 mg

Tolmetin generic only T, C 400-600 600 3 times 1800 mg

* 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.

T= Tablet; C=Capsule; Supp=Suppository; Susp= Suspension; ER=Extend release; 
The Non-Surgical Management Of Hip & Knee Osteoarthritis | Pharmacologic Agents| 9

Generic 

Name Brand Formulation

Dose [mg] Frequency 

[daily]

Max Daily 

Dose

[mg]

Usual Notes

Starting

Max 

Single 

Aspirin and Salsalate

Aspirin several T, Supp 1000 1000 3 times 4000 May increase to 4 times daily

Salsalate several T 500-750 1000 2-3 times 3000 May increase to 3 times daily

Acetaminophen

Acetaminophen several several 650 1300 3-4 times

3000-4000

Include 

acetaminophen 

from all 

sources (single 

and multiple 

ingredient 

products)

Consider lower total 

daily dose (e.g., 2-3 

grams) in elderly patients or in those with 

heavy use of alcohol

Supplements

Chondroitin several several 400 - 3 times

Large variation in 

delivered dose

Not recommended 

due to lack of evidence 

Glucosamine several several 500 - 3 times showing benefit

Topical Therapies

Capsaicin generics

cream, gel, liquid, 

lotion

Varied 

concentrations: 

0.025%-0.075%

- - 3-4 times

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 Local skin irritation

Flector Patch 1.3% 180

1 patch

180

1 patch twice 

Not FDA 

approved for OA

Local skin irritation

Solaraze Gel 3% - - twice Local skin irritation

Other Therapies

Duloxetine Cymbalta/

generics Delayed release C

30 for 1 

week, 

increase 

to 60 once 

daily

60 once 

60 

Higher doses are 

not associated 

with improved 

outcomes but 

a higher rate of 

adverse events

Avoid in end-stage renal 

disease or CrCl <30 ml/

min or in patients with 

substantial alcohol 

intake +

Tramadol (IR) generics T, several

25-50 100

every 4-6 

hours 

400

When combined with 

certain drugs or in those 

patients with a his- tory of seizure disorder, 

tramadol may increase 

the risk of seizures 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. 

T= Tablet; C=Capsule; Supp=Suppository; Susp= Suspension; ER=Extend release; 
10 | Guideline Summary – 2014

Table 2. Hyaluronate/Hylan Injections: Treatment Course (Each injection is given at weekly intervals)

Hyaluronate/Hylan Frequency Volume Notes

Euflexxa Once weekly for total of 3; 

repeat approved 2.0 ml ---

Gel-One Single injection 3.0 ml Caution in those with avian allergy

Hyalgan Once weekly for total of 3 to 5 2.0 ml Caution in those with avian allergy

Orthovisc Once weekly for total of 3 to 4 2.0 ml ---

Supartz Once weekly for total of 3 to 5 2.5 ml Caution in those with avian allergy

Synvisc Once weekly for total of 3 2.0 ml Caution in those with avian allergy

Synvisc-One Single injection 6.0 ml Caution in those with avian allergy
The Non-Surgical Management Of Hip & Knee Osteoarthritis | Pharmacologic Agents| 11

Table 3: Key Findings from Studies on Nutraceuticals/Dietary Supplements (Glucosamine and Chondroitin)

Dietary 

Supplement

Summary of Study Characteristics Key Findings

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

No statistically significant improvements in pain or function for any group.

Boiogito (Sinomenium 

Stem)

One RCT (unblinded) rated as fair compared Boiogito with 

loxoprofen vs. loxoprefen alone; n = 50 

Majima et al. 2012

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 quasiRCT, 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

For both pain and function, Collagen (various forms) did not appear to be 

more effective than placebo, based on meta-analysis of 3 trials.

Curcuma (domestica and 

longa)

Two RCTs, both rated as Fair quality (lack of blinding); 

compared curcuma to placebo plus rescue medication or 

curcuma to ibuprofen. 

Madhu et al. 2012 Kuptniratsaikul et al. 2009

One trial found statistically significant improvements in pain and function 

for patients treated with curcuma vs placebo; the other did not.

Derris Scandens One RCT rated as Fair for lack of blinding; compared Derris 

Sandens to naproxen, n=107.

Kuptniratsaikul et al. 2011

No statistically significant findings by treatment group in mean pain reduction or for function.

Duhuo Jisheng Wan One RCT rated as Good, n =200, compared Duhuo Jisheng 

Wan to diclofenac. 

Teekachunhatean et al. 2004

No statistically significant difference 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

Eggshell group showed a statistically significant but not clinically meaningful reduction in pain compared to placebo; there was no statistically 

significant improvement in function.

Flavocoxid (“Limbrel” 

proprietary product)

One RCT with a quality rating of Good, n=223; compared 

product to naproxen.

Levy et al. 2010

There were no between group differences in pain or function.

Ginger One Good quality systematic narrative review and one Good 

quality RCT.

Leach et al. 2008

Zakeri et al. 2011

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.

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 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.

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

There was a statistically significant reduction in pain and improved function 

for the Phytalgic group compared to placebo.

Pycnogenol One RCT rated as Good quality compared Pycnogenol to 

placebo (total n = 100).

Cisar et al. 2008

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.

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.

Jung et al. 2001

Statistically significant difference between groups in favor of diclofenac for 

function; no between group difference for pain.

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 Kim et al. 2009

Rutjes et al. performed a meta-analysis 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.

Sierrasil One RCT with a Good quality rating compared high dose 

Sierrasil, low dose Sierrasil and placebo (total n = 107). 

Miller et al. 2003

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.

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

No statistically significant between group difference for pain score or func- tion.
12 | Guideline Summary – 2014

NOTES

http://www.healthquality.va.gov

https://www.qmo.amedd.army.mil