

February 2020 

Prepared for:

Department of Veterans Affairs

Veterans Health Administration

Health Services Research & Development Service

Washington, DC 20420 

Prepared by:

Evidence Synthesis Program (ESP) Center

Minneapolis VA Medical Center

Minneapolis, MN 

Timothy J. Wilt, MD, MPH, Director 

Orthobiologics in Foot and Ankle 

Arthrodesis Sites: A Systematic Review 



Authors: 

Principal Investigator: 

Nancy Greer, PhD 

Co-Investigators: 

Patrick Yoon, MD 

Timothy J. Wilt, MD, MPH

Research Associate: 

Brittany Majeski, BA

Evidence Synthesis Program
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

i

PREFACE

The VA Evidence Synthesis Program (ESP) was established in 2007 to provide timely and accurate 

syntheses of targeted healthcare topics of importance to clinicians, managers, and policymakers as they 

work to improve the health and healthcare of Veterans. These reports help: 

• Develop clinical policies informed by evidence;

• Implement effective services to improve patient outcomes and to support VA clinical practice 

guidelines and performance measures; and 

• Set the direction for future research to address gaps in clinical knowledge.

The program is comprised of four ESP Centers across the US and a Coordinating Center located in 

Portland, Oregon. Center Directors are VA clinicians and recognized leaders in the field of evidence 

synthesis with close ties to the AHRQ Evidence-based Practice Center Program and Cochrane 

Collaboration. The Coordinating Center was created to manage program operations, ensure 

methodological consistency and quality of products, and interface with stakeholders. To ensure 

responsiveness to the needs of decision-makers, the program is governed by a Steering Committee 

comprised of health system leadership and researchers. The program solicits nominations for review 

topics several times a year via the program website. 

Comments on this evidence report are welcome and can be sent to Nicole Floyd, Deputy Director, ESP 

Coordinating Center at Nicole.Floyd@va.gov.

Recommended citation: Example: Greer N, Yoon P, Majeski B, Wilt TJ. Orthobiologics in Foot and

Ankle Arthrodesis Sites: A Systematic Review. Washington, DC: Evidence Synthesis Program, Health 

Services Research and Development Service, Office of Research and Development, Department of 

Veterans Affairs. VA ESP Project #09-009; 2020. Available at: 

https://www.hsrd.research.va.gov/publications/esp/reports.cfm. 

This report is based on research conducted by the Evidence Synthesis Program (ESP) Center located at the

Minneapolis VA Medical Center, Minneapolis, MN, funded by the Department of Veterans Affairs, Veterans Health 

Administration, Health Services Research and Development. The findings and conclusions in this document are 

those of the author(s) who are responsible for its contents; the findings and conclusions do not necessarily represent 

the views of the Department of Veterans Affairs or the United States government. Therefore, no statement in this 

article should be construed as an official position of the Department of Veterans Affairs. No investigators have any 

affiliations or financial involvement (eg, employment, consultancies, honoraria, stock ownership or options, expert 

testimony, grants or patents received or pending, or royalties) that conflict with material presented in the report.
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

ii

ACKNOWLEDGMENTS 

This topic was developed in response to a nomination by Jeffrey Whitaker, DPM, for the purpose of 

determining the clinical and cost-effectiveness of orthobiologics for foot and ankle arthrodesis surgery 

compared to no orthobiologics. The scope was further developed with input from the topic nominators 

(ie, Operational Partners), the ESP Coordinating Center, the review team, and the technical expert panel 

(TEP).

In designing the study questions and methodology at the outset of this report, the ESP consulted several 

technical and content experts. Broad expertise and perspectives were sought. Divergent and conflicting 

opinions are common and perceived as healthy scientific discourse that results in a thoughtful, relevant 

systematic review. Therefore, in the end, study questions, design, methodologic approaches, and/or 

conclusions do not necessarily represent the views of individual technical and content experts. 

The authors gratefully acknowledge the following individuals for their contributions to this project: 

Operational Partners

Operational partners are system-level stakeholders who have requested the report to inform decisionmaking. They recommend Technical Expert Panel (TEP) participants; assure VA relevance; help 

develop and approve final project scope and timeframe for completion; provide feedback on draft report; 

and provide consultation on strategies for dissemination of the report to field and relevant groups. 

Jeffrey Whitaker, DPM

Chair, Podiatric Surgery Surgical Advisory Board 

National Surgery Office

Technical Expert Panel (TEP)

To ensure robust, scientifically relevant work, the TEP guides topic refinement; provides input on key 

questions and eligibility criteria, advising on substantive issues or possibly overlooked areas of research; 

assures VA relevance; and provides feedback on work in progress. TEP members are listed below: 

Samuel B. Adams, Jr, MD 

Orthopedic Surgery

Duke University School of Medicine 

Rodney Stuck, DPM 

Section Chief, Podiatry – Surgical Service

Hines VA Medical Center

Peer Reviewers

The Coordinating Center sought input from external peer reviewers to review the draft report and 

provide feedback on the objectives, scope, methods used, perception of bias, and omitted evidence. Peer 

reviewers must disclose any relevant financial or non-financial conflicts of interest. Because of their 

unique clinical or content expertise, individuals with potential conflicts may be retained. The 

Coordinating Center and the ESP Center work to balance, manage, or mitigate any potential 

nonfinancial conflicts of interest identified.
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

iii

TABLE OF CONTENTS 

Preface ............................................................................................................................................. i

Acknowledgments ......................................................................................................................... ii

Executive Summary ...................................................................................................................... 1

Introduction ................................................................................................................................. 1

Methods....................................................................................................................................... 2

Results ......................................................................................................................................... 3

Discussion ................................................................................................................................... 4

Abbreviations Table .................................................................................................................... 6

Evidence Report ............................................................................................................................ 7

Introduction ................................................................................................................................... 7

Methods ........................................................................................................................................ 10

Topic Development ................................................................................................................... 10

Search Strategy ......................................................................................................................... 10

Study Selection ......................................................................................................................... 10

Data Abstraction ....................................................................................................................... 11

Quality Assessment ................................................................................................................... 11

Data Synthesis ........................................................................................................................... 11

Rating the Body of Evidence .................................................................................................... 11

Peer Review .............................................................................................................................. 11

Results .......................................................................................................................................... 12

Literature Flow .......................................................................................................................... 12

Key Question 1: What are the effectiveness and harms of adding orthobiologics compared to 

no orthobiologics when performing primary foot/ankle arthrodesis surgery? .......................... 13

Key Question 1a: Do effectiveness and harms vary by patient age, gender, smoking status, 

obesity, diabetes, bone quality, arthrodesis site, or use of medications that may impede healing 

(eg, immunosuppressives)? ....................................................................................................... 13

Summary of Findings ............................................................................................................ 13

Overview of Studies .............................................................................................................. 13

Quality of Evidence for Key Question 1 ............................................................................... 21

Key Question 2: What is the cost and/or cost-effectiveness (as reported in the literature) of 

adding orthobiologics compared to no orthobiologics when performing primary foot/ankle 

arthrodesis surgery? .................................................................................................................. 22

Summary of Findings ............................................................................................................ 22

Summary and Discussion ........................................................................................................... 23

Key Findings ............................................................................................................................. 23
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

iv

Discussion ................................................................................................................................. 24

Limitations ................................................................................................................................ 26

Applicability of Findings to the VA Population ....................................................................... 26

Research Gaps/Future Research ............................................................................................... 27

Conclusions ............................................................................................................................... 27

References .................................................................................................................................... 28 

TABLES

Table 1. Orthobiologics and Number of Studies ...................................................................... 14

Table 2. Orthobiologics and Outcomes Reported ..................................................................... 15

Table 3. Orthobiologics – Summary of Outcomes ................................................................... 16

FIGURES

Figure 1. Analytic Framework .................................................................................................... 9

Figure 2: Literature Flow Chart ................................................................................................ 12

Appendix A. Search Strategies .................................................................................................. 31

Appendix B. Criteria Used in Quality Assessment .................................................................. 32

Appendix C. Peer Reviewer Comments and Author Responses ............................................ 33

Appendix D. Evidence Tables .................................................................................................... 35

Table 1. Study Characteristics .................................................................................................. 35

Table 2. Quality Criteria ........................................................................................................... 45

Table 3. Patient-centered Outcomes, Part 1 .............................................................................. 51

Table 4. Patient-centered Outcomes, Part 2 .............................................................................. 52

Table 5. Intermediate and Cost Outcomes ................................................................................ 55

Table 6. Harms – Post-operative Complications ...................................................................... 62

Table 7. Harms – Donor Site Morbidity ................................................................................... 63
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

1 

EXECUTIVE SUMMARY

INTRODUCTION

Arthrodesis of the ankle, hindfoot, and midfoot joints is an operative treatment for patients with 

severe pain or disability caused by arthritis, degenerative joint disease, trauma, congenital 

deformity, Charcot neuropathy, and other conditions. However, reported rates of nonunion 

following foot and ankle arthrodesis range from 0 to 36% with an average of 10 to 11%. 

Nonunion following arthrodesis surgery is associated with poor function, disability, and the 

potential need for revision surgery. A number of factors have been reported to be associated with 

nonunion including patient factors, local factors at the site of surgery, and surgical factors. 

Orthobiologics are biologically derived materials that may be used, in the context of arthrodesis, 

to promote bone formation and union at the arthrodesis site. Autograft, harvested from the iliac 

crest, tibia, calcaneus, or other sites, is considered the “gold standard” orthobiologic given that it 

possesses all 3 of the critical properties for bone healing: osteoconduction, osteoinduction, and 

osteogenesis. 

Autograft has the advantages of minimizing risk of an immunologic response or infection that 

might occur with a donor product and is available at no cost (other than costs associated with 

harvesting the graft). However, the quantity of graft material is limited and there are potential 

complications, including the need for a separate incision site if a distant harvest site is chosen, 

longer operating time, nerve or vascular damage at the harvest site, and stress risers resulting in 

increased risk of bone fracture. 

Other orthobiologic products have been considered for use in arthrodesis. Of interest for this 

review are non-structural products including osteoinductive products (eg, platelet-derived growth 

factor [PDGF], demineralized bone matrix [DBM], bone morphogenetic proteins [BMP], 

platelet-rich plasma [PRP]) and osteogenic products (eg, bone marrow aspirate [BMA]). 

Concerns with manufactured products include variability in manufacturing and differences 

across products in the same class due to proprietary preparation methods. 

The purpose of our review was to examine the evidence from studies comparing use of an 

orthobiologic to no orthobiologic in primary foot (forefoot and proximally) and ankle arthrodesis 

procedures. Our focus was on non-structural autogenous orthobiologics. 

We addressed the following key questions: 

1) What are the effectiveness and harms of adding orthobiologics compared to no orthobiologics 

when performing primary foot/ankle arthrodesis surgery? 

1a) Do effectiveness and harms vary by patient age, gender, smoking status, obesity, 

diabetes, bone quality, arthrodesis site, or use of medications that may impede healing (eg, 

immunosuppressives)? 
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

2 

2) What is the cost and/or cost-effectiveness (as reported in the literature) of adding 

orthobiologics compared to no orthobiologics when performing primary foot/ankle arthrodesis 

surgery? 

METHODS 

Data Sources and Searches 

We searched Ovid MEDLINE, Embase, and the Cochrane Library from 1995 to July 2019 using 

Medical Subject Headings (MeSH) and title/abstract words for orthobiologics. We also searched

clinicaltrials.gov for recently completed or ongoing studies and reference lists of relevant 

systematic and narrative reviews and included studies for articles missed by our literature search. 

Study Selection

Citations were entered into Distiller SR (Evidence Partners). Titles and abstracts were reviewed 

independently by 2 reviewers with a citation moving to full-text review if either reviewer 

considered the citation eligible. At full-text review, agreement of 2 reviewers was needed for 

study inclusion or exclusion. Disputes were resolved by discussion with input from a third 

reviewer, if needed. 

We included randomized or controlled clinical trials, case series with concurrent controls, or preto post-intervention studies (eg. interrupted time series) that provided a comparison of the use of 

an orthobiologic of interest (see below) to no orthobiologic. 

Population: Adults undergoing primary foot/ankle arthrodesis surgery (forefoot to ankle). 

Intervention: Non-structural autogenous orthobiologics (autogenous bone graft, bone marrow 

aspirate, plasma products); synthetic products. 

Comparator: No orthobiologic. Although we label this as a comparator, the studies included in 

our review were not designed as comparative studies. Most were retrospective reviews of 

medical records and study groups consisted of those who received an orthobiologic and those 

who did not, most often at the surgeon’s discretion. 

Outcomes

Patient-centered Outcomes: Wound healing, need for reoperation/reintervention, pain, clinically 

meaningful differences in functional outcome or quality of life scale scores (eg, American 

Orthopedic Foot and Ankle Society [AOFAS], Mazur). 

Intermediate Outcomes: Radiographic fusion, mean time to union. 

Costs, Cost Effectiveness, Resource Utilization: Patient costs, facility costs.

Harms: Post-operative complications (eg, scar pain, wound dehiscence, wound complications, 

neuritis, infection, amputation, malalignment, lateral impingement, mortality, venous 

thromboembolism); donor site morbidity (eg, hematoma formation, infection, chronic pain, 

neurological deficits, iatrogenic fractures).
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

3 

We excluded studies not enrolling a population of interest (eg, Charcot foot, children); not 

evaluating an orthobiologic of interest; not involving a surgery of interest (eg, revision 

arthrodesis); involving a comparator other than no orthobiologic; using historical controls; or not 

reporting outcomes of interest. We also excluded case reports, animal or laboratory studies, 

papers describing a surgical approach but not reporting outcomes, and non-English publications. 

Data Abstraction and Quality Assessment

We abstracted study characteristics (inclusion/exclusion criteria, orthobiologic used, patient 

demographics), patient-centered outcomes, intermediate outcomes, costs, and harms (see above). 

Studies were organized by orthobiologic used. 

We used elements from the Joanna Briggs Institute Critical Appraisal Checklist for QuasiExperimental Studies and Critical Appraisal Checklist for Case Series to assess the quality of the 

studies (Appendix B). We describe the quality characteristics of the included studies.

Data Synthesis

Due to differences in orthobiologics used, methods of outcome assessment, and heterogeneity of 

the included populations (eg, reasons for arthrodesis, arthrodesis site, rationale for receiving or 

not receiving an orthobiologic), we narratively summarized the findings. 

Rating the Body of Evidence

We did not formally rate the overall body of evidence. We describe limitations of the available 

evidence. 

RESULTS

Results of Literature Search

Our literature search yielded 1,651 citations. Removing duplicates resulted in 1,564 abstracts for 

review. Of those, 282 were identified for full-text review along with 2 articles identified from 

hand-searching. We excluded 263 articles and included 21. 

Summary of Results for Key Question 1 

Accurately assessing effectiveness of orthobiologics is not possible due to poor methodological 

quality of studies. Most reports were small retrospective chart review studies with little 

controlling for patient factors (eg, health status, medications, severity of presentation) likely to 

affect intervention indication or effectiveness. No studies were designed specifically to assess the 

effect of orthobiologics versus no orthobiologics on outcomes following foot and ankle 

arthrodesis. Orthobiologics were typically used at a surgeon’s discretion for patients judged to be 

at higher risk for non-union (eg, large bone defects, malalignment, or patient health-related 

factors). Few studies reported significant differences in outcomes between patients receiving 

orthobiologics and those not receiving orthobiologics, though most studies were small and 

statistically significant results could not be ruled out. Evidence was insufficient to assess whether 

effectiveness of orthobiologics varied by patient age, gender, smoking status, obesity, diabetes, 

bone quality, arthrodesis site, or use of medications that may impede healing due to limited 

reporting. 
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

4 

Summary of Results for Key Question 2

We found insufficient evidence to assess costs or cost-effectiveness of orthobiologics. Two 

studies reported operation time, finding longer times for procedures involving graft harvest but 

no difference in operation time when non-graft orthobiologic products were used. 

DISCUSSION

Key Findings 

Accurately assessing effectiveness of orthobiologics is not possible due to poor methodological 

quality of studies. Most reports were small retrospective chart review studies with little 

controlling for patient factors (eg, health status, medications, severity of presentation) likely to 

affect intervention indication or effectiveness. 

1. No studies were designed specifically to assess the effect of orthobiologics versus no 

orthobiologics on outcomes following foot and ankle arthrodesis. All studies evaluating 

orthobiologic effectiveness as a primary study objective were retrospective. 

2. Orthobiologics were typically used at a surgeon’s discretion for patients judged to be at 

higher risk for non-union (eg, large bone defects, malalignment, or patient health-related factors). 

3. The greatest amount of information is on bone grafts. There is extremely limited 

information on other orthobiologics for foot and ankle arthrodesis. 

4. All studies reported either radiographic or CT fusion, or time to fusion, and nearly half 

reported a measure of function or quality of life. Other outcomes of interest were infrequently 

reported, including donor site morbidity. 

5. Few studies reported significant differences in outcomes between patients receiving 

orthobiologics and those not receiving orthobiologics, though most studies were small and 

statistically significant results could not be ruled out. 

6. Evidence was insufficient to assess whether effectiveness of orthobiologics varied by 

patient age, gender, smoking status, obesity, diabetes, bone quality, arthrodesis site, or use of 

medications that may impede healing due to limited reporting. Several studies addressed risk 

factors for healing but did not report results for orthobiologic and no orthobiologic subgroups. 

7. Evidence was insufficient to assess costs or cost-effectiveness of orthobiologics. Two 

studies reported operation time, finding longer times for procedures involving graft harvest but 

no difference in operation time when non-graft orthobiologic products were used. 

8. Although randomized trials are the gold standard for effectiveness research, a randomized 

trial would be difficult due to variability in patient health and bone structure factors. 

9. Data registries, including VA-NSQIP in combination with other VA databases, might 

provide useful information by evaluating outcomes after carefully controlling for patient factors 

likely to influence intervention indication and outcomes. It may be possible to also merge this 

information with VA cost data to more accurately assess the cost, cost-effectiveness, and budget 

impact of orthobiologics. 
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

5 

10. Some orthobiologics may be effective in, and are FDA approved for, spinal fusions or 

open tibial fractures. It is not known if these findings are applicable to foot and ankle arthrodesis. 

11. Given the current evidence, we suggest consideration of utilization review and approval 

prior to use to focus orthobiologic use and a potential second surgical procedure on patients 

and/or arthrodesis sites of greatest risk of nonunion. Providers and policymakers should be aware 

of the cost and possible morbidity associated with widespread use of orthobiologics, given the 

insufficient to low-strength evidence of benefit – in particular, mostly radiographic rather than 

clinical outcomes.

Limitations

In addition to limitations related to study design and sample size listed above, there are several 

other limitations of the available evidence.

1) The majority of studies assessed union rates using radiographs alone. In a previous case series, 

poor agreement was reported when radiographs and CT scans were used to determine the 

percentage of fusion following hindfoot arthrodesis involving the subtalar joint or a combination 

of the subtalar, talonavicular, and calcaneocuboid joints. Assessments based on standard 

radiographs generally overestimated the degree of joint fusion in comparison to assessments 

based on the CT scans. 

2) Few studies reported patient-centered outcomes such as pain, function, quality of life, or need 

for reoperation. 

3) No studies reported costs. For autograft, costs will vary depending on the harvest site. A 

second surgical procedure, possibly involving a second surgeon, will likely increase operating 

room time and related costs. For manufactured products, costs vary, with higher costs for 

products containing living cells (eg, allograft with stem cells) and lower cost for bone products 

such as DBM. Cost also varies depending on the volume of product needed. 

Applicability of Findings to the VA Population

None of the included studies was conducted specifically with a VA population. Eleven of the 21 

studies were from the US. Overall the mean age of patients included in the studies was 50 years 

with 55% male. 

Clinicians and patients should be aware that orthobiologic products are not specifically approved 

for use in foot and ankle arthrodesis. Thus, the clinical effectiveness, harms, and costs for foot 

and ankle arthrodesis are not well known and use of these products for these indications is 

considered “off label”. We suggest consideration of utilization review and approval prior to use. 

This would focus orthobiologic use and a potential second surgical procedure on patients and/or 

arthrodesis sites of greatest risk for nonunion. Providers and policymakers should be aware of 

the cost and possible morbidity associated with widespread use of orthobiologics, given the 

insufficient to low-strength evidence of benefit – in particular, mostly radiographic rather than 

clinical outcomes. 
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

6 

Research Gaps/Future Research

Existing studies for the comparison of an orthobiologic to no orthobiologic are largely 

retrospective chart reviews. Few of the identified risk factors for nonunion (eg, smoking status, 

diabetes) were captured in the chart reviews. Selection bias, with surgeons electing to use an 

orthobiologic for more complex cases (eg, bone defects, high risk for nonunion), is also a 

concern. There is limited evidence on specific indications for orthobiologic use during 

arthrodesis.

Future research should include standardized methods for processing and preparation of 

orthobiologics to allow for comparisons between studies. Outcome assessment should be 

standardized including protocols for capturing radiographic or CT images and measures of what 

constitutes fusion. Patient-centered outcomes should be captured and studies should include 

longer term monitoring to capture adverse events. 

Conclusions

The available evidence is of poor quality due to study designs with high potential for selection 

bias; small sample sizes; inadequate reporting of patient and surgical risk factors for nonunion; 

and variations in populations studied, orthobiologics and surgical techniques used, and outcome 

assessment. As a result, there is very little evidence to inform surgeons regarding which patients 

might benefit most from orthobiologics or which orthobiologic to use. The absence of evidence 

that use of orthobiologics is superior to no orthobiologics suggests that a careful assessment of 

individual patient risk for nonunion is critical prior to orthobiologic use. 

ABBREVIATIONS TABLE

Abbreviation Definition

BMA/BMAC Bone marrow aspirate/bone marrow aspirate concentrate

BMP Bone morphogenic protein

CT Computed tomography

DBM Demineralized bone matrix

FDA Food and Drug Administration

PDGF Platelet-derived growth factor

PRP Platelet-rich plasma

RCT Randomized controlled trial

SC Stem cells

VA Veterans Affairs
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

7 

EVIDENCE REPORT

INTRODUCTION

Arthrodesis of the ankle, hindfoot, and midfoot joints is an operative treatment for patients with 

severe pain or disability caused by arthritis, degenerative joint disease, trauma, congenital 

deformity, Charcot neuropathy, and other conditions.1,2 However, reported rates of nonunion 

following foot and ankle arthrodesis range from 0 to 36% with an average of 10 to 11%.3-6 The 

observed variability is likely due, in part, to varying definitions of nonunion including how 

nonunion is evaluated (ie, radiographs, computed tomography (CT) scans, or clinically) and the 

degree of bone bridging required to classify an outcome as union versus nonunion.3,4,6

Nonunion following arthrodesis surgery is associated with poor function, disability, and the 

potential need for revision surgery.4,7-9 A number of factors have been reported to be associated 

with nonunion including patient factors (eg, smoking, diabetes, alcohol consumption, low bone 

mineral density, age, obesity, rheumatoid arthritis, immunocompromised status, employment 

status, and certain medications), local factors (eg, infection, vascularity, bone defects or 

instability at the fusion site soft tissue injury, and revision arthrodesis procedure), and surgical

factors (eg, use of sufficient graft material and high-volume vs low-volume surgeons).4,7-10

Orthobiologics are biologically derived materials that may be used, in the context of arthrodesis, 

to promote bone formation and union at the arthrodesis site.6,11 Autograft, harvested from the 

iliac crest, tibia, calcaneus, or other sites, is considered the “gold standard” orthobiologic given 

that it possesses all 3 of the critical properties for bone healing: osteoconduction (providing a 

matrix or scaffold), osteoinduction (providing proteins and other factors to stimulate stem cells to 

differentiate into cells that can form bone), and osteogenesis (bone formation).2,10,11 Successful 

osteoconduction, osteoinduction, and osteogenesis results in osteointegration – the incorporation 

of the bone graft with the existing bone.12,13 

Autograft has the advantages of minimizing risk of an immunologic response or infection that 

might occur with a donor product and is available at no cost (other than costs associated with 

harvesting the graft). However, the quantity of graft material is limited and there are potential 

complications including the need for a separate incision site if a distant harvest site is chosen, 

longer operating time, nerve or vascular damage at the harvest site, and stress risers resulting in 

increased risk of bone fracture.2,5,10,11 To date, there has not been a randomized trial comparing 

autograft to no graft.2

As a result of the potential complications associated with harvesting autograft, other 

orthobiologic products have been considered for use in arthrodesis. Of interest for this review are 

non-structural products including osteoinductive products (eg, platelet-derived growth factor 

[PDGF], demineralized bone matrix [DBM], bone morphogenetic proteins [BMP], platelet-rich 

plasma [PRP]) and osteogenic products (eg, bone marrow aspirate [BMA]).5 Concerns with 

manufactured products include variability in manufacturing and differences across products in 

the same class due to proprietary preparation methods.6,10

Recombinant human PDGF (rhPDGF-BB), combined with beta-Tricalcium Phosphate (β-TCP) - 

an osteoconductive material, is a Food and Drug Administration (FDA) approved, bioengineered 
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

8

product for hindfoot and ankle fusions in the US.5,11,14 Although there are concerns about the 

increased risk of cancer based on studies of a topical form of rhPDGF-BB used for chronic 

wounds (becaplermin gel), recent studies comparing rhPDGF-BB/β-TCP to autograft for 

hindfoot or ankle arthrodesis found fewer or similar rates of serious treatment-emergent adverse 

events in the rhPDGF-BB/β-TCP group.15,16

DBM is an allograft product developed from bone harvested from cadavers. Through processing,

some of the osteoinductive capacity of bone is lost.5,6 DBM is used in filling bone defects, often 

in combination with another material.

BMPs are growth factors that influence the differentiation and proliferation of stem cells to boneforming cells.5,6,11,14 Recombinant human BMPs (rhBMP-2, rhBMP-7) are FDA-approved for 

use during spinal fusions, open tibial fractures, and long-bone nonunions and have been used offlabel for arthrodesis. A major complication of BMP use is heterotopic bone formation, and use of 

BMPs is not recommended for the cervical spine.

PRP is derived from autologous blood. The end-product contains a highly concentrated volume 

of platelets that, when activated, release growth factors that promote healing and regeneration of 

soft tissues and bone.

5,14 There are many variables involved in the manufacturing process so it is 

difficult to make comparisons across studies.

6,14 PRP is not regulated by the FDA.

BMA or BMA concentrate (BMAC) contains stem cells and growth factors.5,11,17 Harvesting of 

BMA is less invasive than graft harvesting. Typical harvest sites are the iliac crest, long bones, 

or calcaneus.5 BMAC may be combined with an osteoconductive material.11 The use of BMAC, 

to date, has largely been in fracture healing.17

The purpose of our review was to examine the evidence from studies comparing use of an 

orthbiologic to no orthobiologic in primary foot (forefoot and proximally) and ankle arthrodesis 

procedures. Our focus was on non-structural autogenous orthobiologics. 

We addressed the following key questions:

1) What are the effectiveness and harms of adding orthobiologics compared to no orthobiologics 

when performing primary foot/ankle arthrodesis surgery?

1a) Do effectiveness and harms vary by patient age, gender, smoking status, obesity, 

diabetes, bone quality, arthrodesis site, or use of medications that may impede healing (eg, 

immunosuppressives)?

2) What is the cost and/or cost-effectiveness (as reported in the literature) of adding 

orthobiologics compared to no orthobiologics when performing primary foot/ankle arthrodesis 

surgery?

The analytic framework (Figure 1) depicts the population, intervention, and outcomes of interest.
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

9 

Figure 1. Analytic Framework 

Adult patients 

undergoing 

primary foot/ankle 

arthrodesis 

surgery

Intermediate 

Outcomes

-Radiographic fusion

-Mean time to union

Patient-centered Outcomes

-Wound healing 

-Reoperation/reintervention

-Pain

-Functional outcomes or quality 

of life scale scores (clinically 

meaningful differences)

Costs, Cost Effectiveness, 

Resource Utilization (KQ2)

Harms

-Post-operative 

complications

-Donor site morbidity

Addition of 

orthobiologics

KQ1

KQ1a

KQ1

Patient Factors:

age, gender, 

smoking status, 

obesity, diabetes, 

bone quality, 

arthrodesis site, 

medications 
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

10

METHODS

TOPIC DEVELOPMENT

This topic was nominated by Jeffrey Whitaker, DPM, Chair of the Podiatric Surgery Surgical 

Advisory Board. The intended usage of the report was to inform best-practice guidelines for 

podiatric surgery in VHA. With input from Dr. Whitaker and Technical Expert Panel (TEP) 

members, we developed the key questions and scope for the review.

SEARCH STRATEGY

We searched Ovid MEDLINE, Embase, and the Cochrane Library from 1995 to July 2019. The 

MEDLINE search strategy (Appendix A) included Medical Subject Headings (MeSH) and 

title/abstract words for orthobiologics (eg, autografts, bone substitutes, platelet-derived growth 

factor, platelet-rich plasma), foot and ankle site (eg, foot joints, ankle joint) and arthrodesis. 

Searches of Embase and the Cochrane Library were conducted using similar search strategies. 

We also searched clinicaltrials.gov for recently completed or ongoing studies and reference lists 

of relevant systematic and narrative reviews and included studies for articles missed by our 

literature search. 

STUDY SELECTION

Citations were entered into Distiller SR (Evidence Partners). Titles and abstracts were reviewed 

independently by 2 reviewers with a citation moving to full-text review if either reviewer 

considered the citation eligible. At full-text review, agreement of 2 reviewers was needed for 

study inclusion or exclusion. Disputes were resolved by discussion with input from a third 

reviewer, if needed.

We included randomized or controlled clinical trials, case series with concurrent controls, or preto post-intervention studies (eg. interrupted time series) that provided a comparison of the use of 

an orthobiologic of interest (see below) to no orthobiologic.

Population 

Adults undergoing primary foot/ankle arthrodesis surgery (forefoot to ankle).

Intervention

Non-structural autogenous orthobiologics (autogenous bone graft, bone marrow aspirate, plasma 

products); synthetic products.

Comparator

No orthobiologic. Although we label this as a comparator, the studies included in our review 

were not designed as comparative studies. Most were retrospective reviews of medical records 

and study groups consisted of those who received an orthobiologic and those who did not, most 

often at the surgeon’s discretion.
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

11

Outcomes

Patient-centered Outcomes: Wound healing, need for reoperation/reintervention, pain, clinically 

meaningful differences in functional outcome or quality of life scale scores (eg, American 

Orthopedic Foot and Ankle Society [AOFAS], Mazur).

Intermediate Outcomes: Radiographic fusion, mean time to union.

Costs, Cost Effectiveness, Resource Utilization: Patient costs, facility costs.

Harms: Post-operative complications (eg, scar pain, wound dehiscence, wound complications, 

neuritis, infection, amputation, malalignment, lateral impingement, mortality, venous 

thromboembolism); donor site morbidity (eg, hematoma formation, infection, chronic pain, 

neurological deficits, iatrogenic fractures).

We excluded studies not enrolling a population of interest (eg, Charcot foot, children); not 

evaluating an orthobiologic of interest; not involving a surgery of interest (eg, revision 

arthrodesis); involving a comparator other than no orthobiologic; using historical controls; or not 

reporting outcomes of interest. We also excluded case reports, animal or laboratory studies, 

papers describing a surgical approach but not reporting outcomes, and non-English publications. 

DATA ABSTRACTION

We abstracted study characteristics (inclusion/exclusion criteria, orthobiologic used, patient 

demographics), patient-centered outcomes, intermediate outcomes, costs, and harms (see above). 

Studies were organized by orthobiologic used. 

QUALITY ASSESSMENT

We used elements from the Joanna Briggs Institute Critical Appraisal Checklist for QuasiExperimental Studies18 and Critical Appraisal Checklist for Case Series19 to assess the quality of 

the studies (Appendix B). We describe the quality characteristics of the included studies.

DATA SYNTHESIS

Due to differences in orthobiologics used, methods of outcome assessment, and heterogeneity of 

the included populations (eg, reasons for arthrodesis, arthrodesis site, rationale for receiving or 

not receiving an orthobiologic), we narratively summarized the findings. 

RATING THE BODY OF EVIDENCE

We did not formally rate the overall body of evidence. We describe limitations of the available 

evidence. 

PEER REVIEW

A draft version of this report was reviewed by content experts as well as clinical leadership. 

Reviewer comments and our responses are presented in Appendix C and the report was modified 

as needed.
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

12 

RESULTS 

LITERATURE FLOW

Figure 2 depicts the results of our abstract and full-text article review process. Our search of 

multiple databases yielded 1,651 citations. Removing duplicates resulted in 1,564 abstracts for 

review. Of those, 282 were identified for full-text review along with 2 articles identified from 

hand-searching. We excluded 263 articles, many of which involved a surgical procedure that was 

not of interest for our review or that did not have a no-graft comparator group, and included 21. 

Figure 2: Literature Flow Chart 

Records identified through 

database searching

N = 1651

Records after duplicates removed

N = 1564

Abstracts screened

N = 1564

Abstracts excluded

N = 1282

Full-text articles 

assessed for eligibility

N = 284

Full-text articles excluded

N = 263

• Ineligible population (eg, Charcot, 

children): 16

• Ineligible orthobiologic: 18

• Ineligible surgery (eg, revision, 

surgical site, arthroscopic): 49

• Ineligible comparator (eg, other 

orthobiologic): 53

• No concurrent comparator: 54

• No outcomes of interest: 16

• Not publication type of interest (eg, 

laboratory study, surgical procedures): 

52

• Full text not available: 5

Studies included

N = 21

Articles 

identified by 

hand-searching

N = 2

MEDLINE

N = 884

Cochrane

N = 42

Embase

N = 725
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

13

KEY QUESTION 1: What are the effectiveness and harms of adding 

orthobiologics compared to no orthobiologics when performing 

primary foot/ankle arthrodesis surgery?

KEY QUESTION 1A: Do effectiveness and harms vary by patient age, 

gender, smoking status, obesity, diabetes, bone quality, arthrodesis 

site, or use of medications that may impede healing (eg, 

immunosuppressives)?

Summary of Findings

Accurately assessing the effectiveness of orthobiologics is not possible due to poor 

methodological quality of studies. Most reports were small retrospective chart review studies 

with little controlling for patient factors (eg, health status, medications, severity of presentation)

likely to affect intervention indication or effectiveness. No studies were designed specifically to 

assess the effect of orthobiologics versus no orthobiologics on outcomes following foot and 

ankle arthrodesis. Orthobiologics were typically used at a surgeon’s discretion for patients 

judged to be at higher risk for non-union (eg, large bone defects, malalignment, or patient healthrelated factors). Few studies reported significant differences in outcomes between patients 

receiving orthobiologics and those not receiving orthobiologics, though most studies were small 

and statistically significant results could not be ruled out. Evidence was insufficient to assess 

whether effectiveness of orthobiologics varied by patient age, gender, smoking status, obesity, 

diabetes, bone quality, arthrodesis site, or use of medications that may impede healing due to 

limited reporting. 

Overview of Studies

We identified 21 studies that reported a comparison of an orthobiologic to no orthobiologic in 

foot and ankle arthrodesis.

20,21,22-26,27,28,29,30,31,32-36,37,38,39,40 Orthobiologics included autologous 

bone graft or slurry and recombinant human bone morphogenetic protein (rhBMP-2), 

demineralized bone matrix (DBM), or platelet products alone or in combination with autologous 

graft (Table 1). The number of subjects ranged from 9 to 133, mean age was 50 years (range 28-

62 years), 55% were male (range 13-80%), and follow-up periods ranged from 3 to 78 months 

(mean 32 months). Three studies reported that patients were followed until union.21,22,34 There 

were 11 studies from the US, 5 from Asia, 3 from Europe, and 1 from Canada. One study did not 

report where the procedures were performed.

20 Additional study information including 

inclusion/exclusion criteria, description of the orthobiologics, and patient demographics is 

presented in Appendix D, Table 1.

Included studies were predominantly retrospective chart reviews; 4 provided a retrospective 

analysis of prospectively enrolled cases.20,31,33,36 Seven studies, 5 using autologous bone graft or 

slurry,21,25,27,38,40 1 using rhBMP-2,28 and 1 using DBM,

23 reported that an objective of the study 

was to evaluate the use of an orthobiologic.
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

14 

Table 1. Orthobiologics and Number of Studies

Orthobiologic Number of 

Studies

Sample Size

Total (range) Age (mean) % Male (mean)

Autologous bone graft vs no graft 10 469 (9-133) 48 53

Remote autologous graft vs local graft 2 32 (15-17) 53 56

Local bone slurry vs no slurry 1 54 52 65

rhBMP-2 + graft vs rhBMP-2 only 2 117 (48-69) 52 56

DBM + graft vs no graft 1 88 57 20

Platelet products + femoral head 

allograft vs femoral head allograft 1 14 43 71

rhBMP-2 vs no orthobiologic 1 82 57 NR

DBM, Platelets, or BMP alone or in 

combination (some with bone graft) vs 

no orthobiologic

3 113 (16-57) 51 68 (2 studies 

reporting)

BMP=bone morphogenetic protein; DBM=demineralized bone matrix; NR=not reported

Table 2 provides an overview of the outcomes reported. All studies reported either fusion or time 

to fusion. Although we identified fusion as an intermediate outcome that would likely affect 

patient-centered outcomes such as pain, function, quality of life, and need for reoperation, there 

is consensus that fusion is an appropriate indicator of intervention effectiveness. A measure of 

functional ability or quality of life was reported in 10 of the 21 studies. Other outcomes of 

interest were rarely reported including need for reoperation (or amputation), wound 

complications or infections, and donor site morbidity. 

Outcomes reported for each study are presented in Table 3. The studies are grouped by the 

orthobiologic/non-orthobiologic used. A check mark indicates that the outcome was reported by 

that study. An arrow indicates the direction of the effect with a neutral arrow (↔) signifying no 

difference between the orthobiologic and non-orthobiologic groups. Outcomes data for each 

study are reported in Appendix D, Tables 3-7. 
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

15 

Table 2. Orthobiologics and Outcomes Reported

Orthobiologic (Number of 

Studies)

Wound HealingNeed for Reoperation PainFunction or QoL

Fusion

Time to FusionCosts (patient or facility)Wound Complications/InfectionDonor Site Morbidity

Bone Graft vs no Graft (10) 1 2 2 8 9 5 2 1

Remote Graft vs Local (2) 1 1 1 2 1 1

Bone Slurry vs No Slurry (1) 1 1

rhBMP-2 + Graft vs rhBMP2 (2) 1 2 

DBM + Graft vs No Graft (1) 1

PRP vs No PRP (1) 1

rhBMP-2 (1) 1 1

Mixed Products (3) 1 2 1 3 3 1 1

TOTALS 3 3 5 10 19 11 2 4 1

Other outcomes extracted: Mortality (no studies reporting), Amputation (2 studies reporting); Minimal Clinically 

Important Differences for Function or Quality of Life (no studies reporting)

BMP=bone morphogenetic protein; DBM=demineralized bone matrix; PRP=platelet-rich plasma; QoL=quality of 

life

Fusion/Time to Fusion

Fifteen of 19 studies reporting rate of fusion found no difference in fusion rates between the 

orthobiologic and non-orthobiologic groups. Studies used different methods of assessing fusion 

(eg, x-ray, CT, clinical) and had different criteria for defining fusion (Appendix D, Table 5). 

Three studies reported higher fusion in the orthobiologic group, including 1 that compared 

autologous bone graft with or without DBM to no graft (93% vs 72%),23 and 1 that compared 

rhBMP-2 to no rhBMP-2 (92% vs 82%).28 The third study reported a higher percentage of 

bridging with local bone slurry vs no slurry (94% vs 76%).38 One study reported significantly 

fewer fusions (ie, more nonunion) in a group treated with rhBMP-2 plus autograft compared to 

rhBMP-2 only (79% vs 100%).34
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

16 

Table 3. Orthobiologics – Summary of Outcomes

Author, Year,

Study Design, 

Sample Size

Site(s)

Orthobiologic(s) 

Non-Orthobiologic 

Wound Healing

Need for 

Reoperation/

Reintervention

Pain

Function/QoL 

(MCID)

Function/QoL 

Scale Scores

Radiographic 

Fusion 

Time to Fusion

Costs (

Patient/

Facility)

Wound 

Complications/

InfectionMortality

Amputation

Donor Site 

Morbidity

Bone Graft vs No Graft (k=10)

Abd-Ella, 201720

Prospective Case 

Series

N=12

Ankle/

subtalar

Autogenous bone graft 

(n=9)

No graft (n=3)



↔

a 

 

↔

a 

 

↔

Anderson, 201321

Retrospective 

Chart Review

N=114

First 

metatarsophalangeal 

joint

Autograft (local; reduced 

to cancellous bone 

chips) (n=62) 

End-to-end arthrodesis 

(n=52)

 

↔



↔



↔ 

Cao, 201724

Retrospective 

Chart Review

N=30

Talonavicular Autoallergic iliac bone 

graft (n=5)

No bone graft (n=11)

 

↔



↔ 

Chahal, 200625

Retrospective 

Chart Review

N=88

Isolated 

subtalar 

Local or iliac crest bone 

graft (n=46)

No graft (n=20)

 

↔ 

Chen, 199626

Retrospective 

Chart Review

N=38 (40 ankles)

Tibiotalar Tibial condyle graft (n=8 

ankles) or sliding graft 

(n=7 ankles) 

No graft (n=25)

 

↔



↔ ↔



↔

Easley, 200027

Retrospective 

Chart Review

N=174 (184 feet)

Isolated 

subtalar 

Cancellous autograft 

(n=94 feet)

No graft (n=39 feet)

 

↔



↔



↔ 
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

17 

Author, Year,

Study Design, 

Sample Size

Site(s)

Orthobiologic(s) 

Non-Orthobiologic 

Wound Healing

Need for 

Reoperation/

Reintervention

Pain

Function/QoL 

(MCID)

Function/QoL 

Scale Scores

Radiographic 

Fusion 

Time to Fusion

Costs (

Patient/

Facility)

Wound 

Complications/

InfectionMortality

Amputation

Donor Site 

Morbidity

Holm, 201530

Retrospective 

Chart Review

N=17

Subtalar Autogenous bone (n=3) 

No orthobiologic (n=6)



↔



↔



↔



↔

Lechler, 201231

Prospective Case 

Series

N=30

Talonavicular Autologous spongious 

bone graft from iliac 

crest (n=6)

No orthobiologic (n=24)



↔



↔



↔

Yavuz, 201439

Retrospective 

Chart Review

N=20 (21 feet) 

total

Subtalar Cancellous autograft 

(iliac crest) (n=8)

No graft (n=9)



↔



↔



↔

Yildirim, 201540

Retrospective 

Chart Review

N=31 (33 feet) 

total

Subtalar Autograft (iliac crest) 

(n=16 feet)

No graft (n=14 feet)



↔



↔

b 

↓

Remote Graft vs Local Graft (k=2)

Patil, 201132

Retrospective 

Chart Review

N=26 

Subtalar Autologous iliac crest 

bone graft (n=4)

Local bone graft (n=13)



↔



↔

Sun, 201936

Prospective Case 

Series N=15

Subtalar Bone graft from iliac 

crest to supplement 

local graft (n=4)

Local bone (n=11)



↔



↔



↔



↔

c 

↑
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

18 

Author, Year,

Study Design, 

Sample Size

Site(s)

Orthobiologic(s) 

Non-Orthobiologic 

Wound Healing

Need for 

Reoperation/

Reintervention

Pain

Function/QoL 

(MCID)

Function/QoL 

Scale Scores

Radiographic 

Fusion 

Time to Fusion

Costs (

Patient/

Facility)

Wound 

Complications/

InfectionMortality

Amputation

Donor Site 

Morbidity

Local Slurry vs No Slurry (k=1)

Wheeler, 200938

Retrospective 

Chart Review

N=54

CPT code 

27870 

(Arthrodesis 

Procedures 

on Leg & 

Ankle Joint)

Local bone slurry (n=32)

No slurry (n=22) 

↔

d 

↑

rhBMP-2 + Graft vs rhBMP-2 only (k=2)

Bibbo, 200922

Retrospective 

Chart Review

N=69 (112 fusion 

sites)

Ankle and 

hindfoot 

rhBMP-2 (INFUSE®) 

and autogenous iliac 

crest bone graft (n=17 

fusions)

rhBMP-2 only (n=85 

fusions)



↔

Rearick, 201434

Retrospective 

Chart Review

N=48 (51 cases, 

83 sites) total

Foot or 

ankle 

rhBMP-2 + autograft (14 

sites) (local=11, iliac 

crest=2, calcaneus=1)

rhBMP-2 only (60 sites)

e 

↓



↔

DBM + Graft vs No Graft (k=1)

Buda, 201823

Retrospective 

Chart Review

N=88 (189 joints)

TarsometatarsalAutologous bone graft 

(n=37)

Autologous bone graft + 

DBM (n=33)

No graft (n=18)

d 

↑
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

19 

Author, Year,

Study Design, 

Sample Size

Site(s)

Orthobiologic(s) 

Non-Orthobiologic 

Wound Healing

Need for 

Reoperation/

Reintervention

Pain

Function/QoL 

(MCID)

Function/QoL 

Scale Scores

Radiographic 

Fusion 

Time to Fusion

Costs (

Patient/

Facility)

Wound 

Complications/

InfectionMortality

Amputation

Donor Site 

Morbidity

Platelet Products (k=1)

Grunander, 

201229

Retrospective 

Chart Review

N=14 (16 feet)

Calcaneocuboid Femoral head allograft 

and PRP (n=7 feet)

Femoral head allograft 

alone (n=9 feet)



↔

rhBMP-2 (k=1)

Fourman, 201428

Retrospective 

cohort

N=82

Ankle rhBMP-2 (n=42)

No rhBMP-2 (n=40)

d 

↑



↔



↔

Other/Mixed Products (k=3)

Plaass, 200933

Prospective Case 

Series

N=29

Tibiotalar DBM (n=8) Platelet 

concentrate (n=1)

Both (n=2)

No orthobiologic (n=5)

a a a 

↔



↔

Rungprai, 201635

Retrospective 

Chart Review

N=57 (60 feet) 

Subtalar Cancellous autograft 

(n=12)

DBM + allograft (n=12)

BMP + allograft (n=12)

Platelet concentrator + 

allograft (n=7)

No orthobiologic (n=6)



↔



↔
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

20 

Author, Year,

Study Design, 

Sample Size

Site(s)

Orthobiologic(s) 

Non-Orthobiologic 

Wound Healing

Need for 

Reoperation/

Reintervention

Pain

Function/QoL 

(MCID)

Function/QoL 

Scale Scores

Radiographic 

Fusion 

Time to Fusion

Costs (

Patient/

Facility)

Wound 

Complications/

InfectionMortality

Amputation

Donor Site 

Morbidity

Weinraub, 201037

Retrospective 

Chart Review

N=45

Combined 

subtalar and 

talonavicula

r 

PRP (n=7)

PRP/DBM (n=6)

DBM (n=5)

BMP (n=1)

DBM/SC (n=1)

PGC (n=1)

PRP/SC (n=1)

No orthobiologic (n=18)

a 

↔



↔

f 

↔



↔

BMP=bone morphogenetic protein; DBM=demineralized bone matrix; MSC=mesenchymal stem cells; PGC=platelet gel concentrate; PRP=platelet-rich plasma, rhBMP2=recombinant human bone morphogenetic protein-2; SC=stem cell a Small n or few events – not able to interpret findings

b Significantly shorter time to fusion with orthobiologic 

c Significantly longer operating time for iliac crest graft group

d Significantly greater fusion rate with orthobiologic e Significantly more nonunions in rhBMP-2 + autograft group; all had history of nonunion f No difference in surgery duration; no graft harvesting procedures
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

21 

Including data from all orthobiologic products and arthrodesis sites, fusion rates ranged from 

71% to 100% in the orthobiologic group (mean 93%) and from 0% to 100% (mean 85%) in the 

no-orthobiologic group. Removing one study with a 0% fusion rate in the no-orthobiologic group 

of 3 individuals,20 the range was 44% to 100% (mean 90%) in the no-orthobiologic group. 

All but 2 of the 15 studies reporting no difference between study groups reported fusion rates of 

85% or higher for both groups. One exception was 1 study of iliac crest or local bone graft 

versus no graft for 66 isolated subtalar fusions related to primary or secondary osteoarthritis.25

Smoking status was not reported for the orthbiologic/non-orthobiologic groups, but overall 43% 

had smoked at least 1 week before and after surgery. Diabetes was reported in 10% of the 

population. Fusion rates were 84% in the orthobiologic group and 65% in the non-orthobiologic 

group. The other exception was a study of PRP with femoral head allograft versus femoral head 

allograft alone for 14 patients undergoing calcaneocuboid distraction arthrodesis.29 Fusion rates 

were 71% in the PRP group and 44% in the allograft group. 

Time to fusion was reported in 11 studies. Three reported that time to fusion did not differ 

between the orthobiologic and non-orthobiologic groups but did not report actual times.31,36,39

For the 8 studies reporting time to fusion, the mean was 12.2 weeks in both the orthobiologic and 

non-orthobiologic groups.21,22,27,33-35,37,40 Only 1 study reported a significant difference in mean 

time to fusion – 14.4 weeks for 19 patients receiving iliac crest autograft versus 17.5 weeks for 

14 patients receiving no graft for subtalar arthrodesis.40

Patient-centered Outcomes

The most frequently reported patient-centered outcome was a measure of functional status or 

quality of life (Appendix D, Table 4). None of the 10 studies reporting this outcome found a 

difference between the orthobiologic and non-orthobiologic groups.20,21,24,26,27,30,31,33,36,40 Seven 

studies reported American Orthopedic Foot and Ankle Society (AOFAS) scores, a measure of 

function, pain, and alignment.24,27,30,31,33,36,40 Three studies assessed patient satisfaction,

20,21,24

willingness to have the procedure again,

21 and ability to walk a long distance 6 months postsurgery.24 One study used a clinical outcomes rating system.26

Other patient-centered outcomes of interest including wound healing, need for reoperation or 

reintervention, and pain were infrequently reported. Where reported, no differences were 

observed between the orthobiologic and non-orthobiologic groups (Appendix D, Tables 3 and 4) 

Harms

Few studies reported harms. Only one study reported donor site morbidity, finding no instances 

among 12 patients undergoing ankle or subtalar arthrodesis with and without autograft.20 Two 

studies reported amputation with each identifying 1 case in the non-orthobiologic group and no 

cases in the orthobiologic group, either autograft26 or rhBMP-2.28 Three studies reported 

infection with few cases and no significant differences between orthobiologic and nonorthobiologic groups.26,28,39

Quality of Evidence for Key Question 1 

We did not formally rate risk of bias or quality of evidence. We evaluated each included study 

based on critical appraisal criteria for quasi-experimental studies and case series (Appendix B, 
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

22 

Appendix D, Table 2). Several characteristics of the studies suggest likely selection and 

detection bias. 

Criteria for inclusion in the study were clearly defined in 16 of 21 studies (76%); however, only 

48% (10 studies) reported complete inclusion (ie, including consecutive cases or all cases within

a specified time period). Although 7 studies reported that a primary objective of the study was to 

evaluate the use of an orthobiologic, in 16 studies (76%), patients were treated with an 

orthobiologic at the surgeon's discretion – most often due to large bone defects, poor bone 

alignment, or patient risk factors for nonunion – and the evaluation of orthobiologic use was a 

retrospective analysis based on whether the product was used during the surgery. The remaining 

5 studies did not report a reason why some patients received an orthobiologic and others did not. 

Only 4 studies (19%) reported that radiographs were reviewed by individuals unaware of 

whether or not patients received an orthobiologic. Five studies (24%) stated that reviews were

not blinded while reporting of blinding/no blinding was unclear in 12 studies (57%). Five studies 

(24%) used CT scans to confirm fusion observed on radiographs. 

KEY QUESTION 2: What is the cost and/or cost-effectiveness (as 

reported in the literature) of adding orthobiologics compared to no

orthobiologics when performing primary foot/ankle arthrodesis

surgery?

Summary of Findings

We found insufficient evidence to assess costs or cost-effectiveness of orthobiologics. Two 

studies reported operation time, finding longer times for procedures involving graft harvest but 

no difference in operation time when non-graft orthobiologic products were used. 

Operation Time

Only 2 of our included studies reported a cost-related outcome. 

One study, conducted in the US, included 40 patients who underwent combined subtalar joint 

and talonavicular joint arthrodesis.37 The group treated with orthobiologics received non-graft 

products including platelet-rich plasma, demineralized bone matrix, stem cells, and bone 

morphogenetic protein alone or in combination. The mean duration of surgery ranged from 82 to 

98 minutes for surgeries involving an orthobiologic product compared to 83 minutes for 

surgeries with no orthobiologic product. 

A study from China of 15 minimally invasive subtalar arthrodesis procedures performed with 

local graft or local graft supplemented by graft harvested from the iliac crest reported mean

operation times.36 The mean operation time for procedures involving iliac crest harvest was 

longer than the operation time for procedures using only local graft (83.8 minutes vs 50.9 

minutes, P<.01). 
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

23 

SUMMARY AND DISCUSSION 

KEY FINDINGS

Accurately assessing effectiveness of orthobiologics is not possible due to poor methodological 

quality of studies. Most reports were small retrospective chart review studies with little 

controlling for patient factors (eg, health status, medications, severity of presentation) likely to 

affect intervention indication or effectiveness. 

1. No studies were designed specifically to assess the effect of orthobiologics versus no

orthobiologics on outcomes following foot and ankle arthrodesis. All studies evaluating

orthobiologic effectiveness as a primary study objective were retrospective.

2. Orthobiologics were typically used at a surgeon’s discretion for patients judged to be at

higher risk for non-union (eg, large bone defects, malalignment, or patient health-related factors).

3. The greatest amount of information is on bone grafts. There is extremely limited

information on other orthobiologics for foot and ankle arthrodesis.

4. All studies reported either radiographic or CT fusion, or time to fusion, and nearly half

reported a measure of function or quality of life. Other outcomes of interest were infrequently

reported, including donor site morbidity.

5. Few studies reported significant differences in outcomes between patients receiving

orthobiologics and those not receiving orthobiologics, though most studies were small and

statistically significant results could not be ruled out.

6. Evidence was insufficient to assess whether effectiveness of orthobiologics varied by

patient age, gender, smoking status, obesity, diabetes, bone quality, arthrodesis site, or use of

medications that may impede healing due to limited reporting. Several studies addressed risk

factors for healing but did not report results for orthobiologic and no orthobiologic subgroups.

7. Evidence was insufficient to assess costs or cost-effectiveness of orthobiologics. Two

studies reported operation time, finding longer times for procedures involving graft harvest but

no difference in operation time when non-graft orthobiologic products were used.

8. Although randomized trials are the gold standard for effectiveness research, a randomized

trial would be difficult due to variability in patient health and bone structure factors.

9. Data registries, including VA-NSQIP in combination with other VA databases, might

provide useful information by evaluating outcomes after carefully controlling for patient factors

likely to influence intervention indication and outcomes. It may be possible to also merge this

information with VA cost data to more accurately assess the cost, cost-effectiveness, and budget

impact of orthobiologics.

10. Some orthobiologics may be effective in, and are FDA-approved for, spinal fusions or

open tibial fractures. It is not known if these findings are applicable to foot and ankle arthrodesis.
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

24 

11. Given the current evidence, we suggest consideration of utilization review and approval

prior to use. This would focus orthobiologic use and a potential second surgical procedure on

patients and/or arthrodesis sites of greatest risk of nonunion. Providers and policymakers should

be aware of the cost and possible morbidity associated with widespread use of orthobiologics

given the insufficient to low-strength evidence of benefit – in particular, mostly radiographic

rather than clinical outcomes.

DISCUSSION

No orthobiologic can replace good surgical technique and good academic decision-making.10

Surgeons can optimize success by taking into consideration the risk factors for nonunion when 

selecting patients for orthobiologics, emphasizing the importance of compliance with postsurgery protocols, and using sound surgical principles such as careful preparation of opposing 

bone surfaces, compression across the arthrodesis site, and external fixation where needed.

6,13

As new orthobiologics are introduced (likely at higher costs), surgeons need to critically analyze

any product information and research results including risks, benefits, cost, surgical complexity 

(including the possibility of an additional surgical procedure for bone graft harvesting that may

involve donor site morbidity), and volume of material available.

6,11,13 There is a need for more 

rigorous outcome data to compare fusion rates of each product as well as one product versus 

another and different products within the same class (different due to proprietary manufacturing 

processes).6

A survey of North American and Canadian orthopedic foot and ankle surgeons was designed to 

determine clinical and radiographic factors associated with the decision to use supplemental bone 

graft.

1 The survey was completed by 48 of 66 (73% response rate) surgeons (representing

academic and private practice) who received the survey. It is important to note that the surgeons 

were all involved in a large clinical trial of an autograft substitute. The most frequently reported 

clinical factors were nonunion (ie, regarding use of graft in a revision surgery), nonunion of an 

adjacent joint, smoking history, use of medications known to interfere with bone healing, and 

vitamin D deficiency. Frequently reported radiologic factors included nonunion, avascular 

necrosis, evidence of potential incongruous apposition, radiographic evidence of bone loss,

osteoporosis, or post-trauma with subchondral collapse. There was variation in the sample with 

regard to the weighting of the clinical and radiographic factors when deciding whether to use 

bone graft although all surgeons reported that they considered both types of information to some 

degree. 

Two recent systematic reviews noted that few studies reported on use of autograft versus no 

autograft.2,41 Müller et al included studies comparing cortical or cancellous autologous bone 

grafts with any structural or non-structural substitute.41 Both prospective and retrospective 

controlled trials were included provided a minimum of 20 patients were enrolled. The review 

included 10 studies; quality was low. The authors concluded that “structural allografts appear to 

be at least non-inferior to autologous grafts” for union in hindfoot arthrodesis but called for

RCTs with larger sample sizes. Only one of the studies from the Müller et al review, a study that

also included a non-graft group,27 was included in our review. 

Lareau et al included 159 papers reporting union and nonunion rates associated with the use of 

autograft, allograft, or no bone graft in arthrodesis, osteotomies, and treatment of nonunions. 
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

25 

They excluded studies that supplemented bone graft insertion with a bone graft substitute or 

other orthobiologic, studies in children younger than 10 years of age, non-English language 

articles, case reports with fewer than 4 patients, and use of xenograft or any vascularized bone 

graft.2 Of relevance to our review, the authors presented data from 2213 patients in 70 studies 

who received cancellous autograft and from 1208 patients in 50 studies who did not receive a 

bone graft. Relative to no graft, the odds ratio for union with cancellous autograft was 1.39 

(95%CI 0.92, 2.1; P=.11). The probability of union was 93.7% with cancellous autograft and 

91.4% for no graft. When the analysis was limited to studies with both cancellous autograft and 

no graft groups, the union rates were 95.1% and 91.9% for cancellous autograft and no graft, 

respectively. The odds ratio was 1.79 (95%CI 0.91, 3.3; P=.09). The authors did not provide 

results by type of surgical procedure. They also attempted to evaluate the potential impact of 

patient risk factors and fusions sites on union rates but found that primary studies did not report 

data in a way that would allow that analysis.

Randomized Controlled Trials

We found no RCTs comparing use of an orthobiologic to no orthobiologic. We did identify 2 

RCTs, both non-inferiority studies, in patients undergoing hindfoot or ankle arthrodesis. In the 

first study, patients (n=434) requiring non-structural supplemental bone graft (<9 cc) as part of

the arthrodesis procedure were randomized to receive either recombinant human platelet-derived 

growth factor-BB (rhPDGF-BB) homodimer combined with beta-tricalcium phosphate (β-TCP)

or autograft.16 The autografts were harvested from separate surgical sites. CT-confirmed fusion 

rates at 24 weeks post-surgery, the primary effectiveness outcome, were similar for the 2 groups. 

The groups were also comparable on other clinical outcomes including function and quality of 

life. There was less pain and fewer adverse events in the rhPDGF-BB/β-TCP group. The second 

study evaluated an injectable form of rhPDGF-BB/β-TCP.

15 In this study, 75 patients were 

randomized in a 5:1 ratio to rhPDGF-BB/β-TCP or autograft. An additional 142 patients who 

received autografts in the earlier RCT16 were included as historical controls. The primary 

outcome (CT-confirmed fusion at 24 weeks) was similar for the 2 groups. Mean time to fusion 

was shorter in the rhPDGF-BB/β-TCP group. Non-inferiority was also demonstrated for pain,

function, quality of life, and safety measures.

Donor Site Morbidity

A commonly cited concern with bone graft harvesting is donor site morbidity including 

infection, prolonged wound drainage, sensory loss, and pain.13 Only one of our included studies 

reported a measure of donor site morbidity. Several case series, without a no-orthobiologic 

comparator, have assessed morbidity associated with graft harvest. In a retrospective study from 

the US, DeOrio and Farber included data from 180 patients with an iliac crest bone graft harvest 

procedure for foot and ankle surgery.

42 From the medical records, there were no major 

complications and 17 (9.5%) with minor complications – 12 with hematoma or seroma, 3 with 

lateral femoral cutaneous nerve irritation, 1 partial wound dehiscence, and 1 superficial wound 

infection. No extra hospital days were required, and no deep infections were reported. At a mean 

follow-up of 6 years (range 1 to 13), 134 of 169 (79%) of patients were able to be contacted. Of 

the 134 contacted, 120 (90%) reported no pain at the graft site. Among the 120 patients, 57% 

reported greater postoperative pain at the foot or ankle surgical site than at the harvest site; 27% 

reported greater postoperative pain at the harvest site than at the foot or ankle surgical site; and 

16% reported that the postoperative pain was equal at the 2 sites. 
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

26 

A retrospective study from the United Kingdom focused on proximal tibia grafts for 148 foot and 

ankle arthrodesis procedures in 131 patients.43 The mean time from surgery was 28 months 

(range 3 to 69 months). On a scale of 1 (no pain) to 5 (severe pain), the mean pain level postsurgery was 1.25. At follow-up, the mean was 1.04. No patient reported moderate or severe pain 

at any time. Four reported mild pain and 29 reported very mild pain initially with none reporting 

mild pain and 6 reporting very mild pain at follow-up. Post-operative paresthesia was reported in 

8 patients (5.4%) with 4 resolved at follow-up. The single case of early superficial wound 

infection also resolved. There were no reported cases of hematoma or fracture. 

Patients in the autograft group from the RCT comparing rhPDGF-BB/β-TCP to autograft16 were 

assessed for harvest site pain during study follow-up.44 The harvest site was selected by the study 

surgeons with 13% iliac crest, 51% proximal tibia, 18% distal tibia, and 15% calcaneus. Pain 

was assessed on a 100-point visual analog scale (VAS) with scores of 20 or higher indicating 

clinically significant pain. Post-surgery, the mean pain score was 32.9 with 49 patients (35.8%) 

reporting clinically significant pain at the harvest site. At 52 weeks, the mean score was 6.1 with 

11 patients (8.5%) reporting clinically significant pain. The percentage of patients reporting 

clinically significant pain at 52 weeks was 0% for the iliac crest site, 13% for the distal tibia, 6% 

for the proximal tibia, and 20% for the calcaneus. 

LIMITATIONS

In addition to limitations related to study design and sample size listed above, there are several 

other limitations of the available evidence.

1) The majority of studies assessed union rates using radiographs alone. In a previous case series,

poor agreement was reported when radiographs and CT scans were used to determine the

percentage of fusion following hindfoot arthrodesis involving the subtalar or a combination of the 

subtalar, talonavicular, and calcaneocuboid joints.3 Assessments based on standard radiographs 

generally overestimated the degree of joint fusion in comparison to assessments based on the CT 

scans.

2) Few studies reported patient-centered outcomes such as pain, function, quality of life, or need

for reoperation.

3) No studies reported costs. For autograft, costs will vary depending on the harvest site. A

second surgical procedure, possibly involving a second surgeon, will likely increase operating

room time and related costs. For manufactured products, costs vary, with higher costs for

products containing living cells (eg, allograft with stem cells) and lower cost for bone products

such as DBM. Cost also varies depending on the volume of product needed.

APPLICABILITY OF FINDINGS TO THE VA POPULATION

None of the included studies was conducted specifically with a VA population. Eleven of the 21 

studies were from the US. Overall the mean age of patients included in the studies was 50 years 

with 55% male. 

Based on the current state of evidence, we suggest consideration of utilization review and 

approval prior to use. This would focus orthobiologic use and a potential second surgical 

procedure on patients and/or arthrodesis sites of greatest risk for nonunion. Providers and policy 

makers should be aware of the cost and possible morbidity associated with widespread use of 
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

27 

orthobiologics given the insufficient to low-strength evidence of benefit – in particular, mostly 

radiographic rather than clinical outcomes. Furthermore, clinicians and patients should be aware 

that orthobiologic products are not specifically approved for use in foot and ankle arthrodesis. 

Thus, the clinical effectiveness, harms, and costs for foot and ankle arthrodesis are not well

known and use of these products for these indications is considered “off label”. 

RESEARCH GAPS/FUTURE RESEARCH

Existing studies for the comparison of an orthobiologic to no orthobiologic are largely 

retrospective chart reviews. Few of the identified risk factors for nonunion (eg, smoking status, 

diabetes) were captured in the chart reviews. Selection bias, with surgeons electing to use an 

orthobiologic for more complex cases (eg, bone defects, high risk for nonunion), is also a 

concern.1,5 There is limited evidence on specific indications for orthobiologic use during 

arthrodesis. Additionally, there is little information on cost of the products and cost/morbidity 

including donor site morbidity if autografts are used.

Future research should include standardized methods for processing and preparation of 

orthobiologics to allow for comparisons between studies. Outcome assessment should be 

standardized including protocols for capturing radiographic or CT images and measures of what 

constitutes fusion. Patient-centered outcomes should be captured and studies should include 

longer-term monitoring to capture adverse events.11

CONCLUSIONS

The available evidence is of poor quality due to study designs with high potential for selection 

bias; small sample sizes; inadequate reporting of patient and surgical risk factors for nonunion; 

and variations in populations studied, orthobiologics and surgical techniques used, and outcome 

assessment. As a result, there is very little evidence to inform surgeons regarding which patients 

might benefit most from orthobiologics or which orthobiologic to use. The absence of evidence 

that use of orthobiologics is superior to no orthobiologics suggests that a careful assessment of 

individual patient risk for nonunion is critical prior to orthobiologic use and that patients and 

clinicians should be informed that use of orthobiologics for foot and ankle arthrodesis is 

considered “off-label”. 
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

28

REFERENCES

1. Baumhauer JF, Pinzur MS, Daniels TR, et al. Survey on the need for bone graft in foot 

and ankle fusion surgery. Foot Ankle Int. 2013;34(12):1629-1633.

2. Lareau CR, Deren ME, Fantry A, Donahue RM, DiGiovanni CW. Does autogenous bone 

graft work? A logistic regression analysis of data from 159 papers in the foot and ankle 

literature. Foot Ankle Surg. 2015;21(3):150-159.

3. Coughlin MJ, Grimes JS, Traughber PD, Jones CP. Comparison of radiographs and CT 

scans in the prospective evaluation of the fusion of hindfoot arthrodesis. Foot Ankle Int. 

2006;27(10):780-787.

4. Krause F, Younger AS, Baumhauer JF, et al. Clinical outcomes of nonunions of hindfoot 

and ankle fusions. J Bone Joint Surg Am. 2016;98(23):2006-2016.

5. Yeoh JC, Taylor BA. Osseous healing in foot and ankle surgery with autograft, allograft, 

and other orthobiologics. Orthop Clin North Am. 2017;48(3):359-369.

6. Wallace GF. Current Orthobiologics for elective arthrodesis and nonunions of the foot 

and ankle. Clin Podiatr Med Surg. 2017;34(3):399-408.

7. DiGiovanni CW, Lin SS, Daniels TR, et al. The importance of sufficient graft material in 

achieving foot or ankle fusion. J Bone Joint Surg Am. 2016;98(15):1260-1267.

8. Thevendran G, Shah K, Pinney SJ, Younger AS. Perceived risk factors for nonunion 

following foot and ankle arthrodesis. J Orthop Surg. 2017;25(1):2309499017692703.

9. Thevendran G, Younger A, Pinney S. Current concepts review: risk factors for nonunions 

in foot and ankle arthrodeses. Foot Ankle Int. 2012;33(11):1031-1040.

10. DiDomenico LA, Thomas ZM. Osteobiologics in foot and ankle surgery. Clin Podiatr 

Med Surg. 2015;32(1):1-19.

11. West TA, Williams ML. Orthobiologics. Clin Podiatr Med Surg. 2019;36(4):609-626.

12. American Academy of Orthopaedic Surgeons. Helping Fractures Heal (Orthobiologics). 

OrthoInfo Web site. https://orthoinfo.aaos.org/en/treatment/helping-fractures-healorthobiologics/. Published 2010. Accessed 17 November 2019.

13. Fitzgibbons TC, Hawks MA, McMullen ST, Inda DJ. Bone grafting in surgery about the 

foot and ankle: indications and techniques. J Am Acad Orthop Surg. 2011;19(2):112-120.

14. Lin SS, Montemurro NJ, Krell ES. Orthobiologics in Foot and Ankle Surgery. J Am Acad 

Orthop Surg. 2016;24(2):113-122.

15. Daniels TR, Younger AS, Penner MJ, et al. Prospective randomized controlled trial of 

hindfoot and ankle fusions treated with rhPDGF-BB in combination with a beta-TCPcollagen matrix. Foot Ankle Int. 2015;36(7):739-748.

16. DiGiovanni CW, Lin SS, Baumhauer JF, et al. Recombinant human platelet-derived 

growth factor-BB and beta-tricalcium phosphate (rhPDGF-BB/beta-TCP): an alternative 

to autogenous bone graft. J Bone Joint Surg Am. 2013;95(13):1184-1192.
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

29

17. Harford JS, Dekker TJ, Adams SB. Bone marrow aspirate concentrate for bone healing in 

foot and anklesurgery. Foot Ankle Clin. 2016;21(4):839-845.

18. Tufanaru C MZ, Aromataris E, Campbell J, Hopp L. Chapter 3: Systematic reviews of 

effectiveness. In: Aromataris E MZ, ed. Joanna Briggs Institute Reviewer's Manual: The 

Joanna Briggs Institute, 2017. Available from https://reviewersmanual.joannabriggs.org/ 

(Accessed October 2, 2019)

19. Moola S MZ, Tufanaru C, Aromataris E, Sears K, Sfetcu R, et al. Chapter 7: Systematic 

reviews of etiology and risk. In: Aromataris E MZ, ed. Joanna Briggs Institute 

Reviewer's Manual: The Joanna Briggs Institute; 2017. Available from 

https://reviewersmanual.joannabriggs.org/ (Accessed October 2, 2019)

20. Abd-Ella MM, Galhoum A, Abdelrahman AF, Walther M. Management of nonunited 

talar fractures with avascular necrosis by resection of necrotic bone, bone grafting, and 

fusion with an intramedullary nail. Foot Ankle Int. 2017;38(8):879-884.

21. Anderson J, Jeppesen N, Hansen M, Brady C, Gough A, Fowler Z. First 

metatarsophalangeal joint arthrodesis: comparison of mesenchymal stem cell allograft 

versus autogenous bone graft fusion rates. Surgical Science. 2013;4:263-267.

22. Bibbo C, Patel DV, Haskell MD. Recombinant bone morphogenetic protein-2 (rhBMP-2) 

in high-risk ankle and hindfoot fusions. Foot Ankle Int. 2009;30(7):597-603.

23. Buda M, Hagemeijer NC, Kink S, Johnson AH, Guss D, DiGiovanni CW. Effect of 

fixation type and bone graft on tarsometatarsal fusion. Foot Ankle Int. 2018;39(12):1394-

1402.

24. Cao HH, Lu WZ, Tang KL. Isolated talonavicular arthrodesis and talonavicularcuneiform arthrodesis for the Muller-Weiss disease. J Orthop Surg Res. 2017;12(1):83.

25. Chahal J, Stephen DJ, Bulmer B, Daniels T, Kreder HJ. Factors associated with outcome 

after subtalar arthrodesis. J Orthop Trauma. 2006;20(8):555-561.

26. Chen YJ, Huang TJ, Shih HN, Hsu KY, Hsu RW. Ankle arthrodesis with cross screw 

fixation. Good results in 36/40 cases followed 3-7 years. Acta Orthop Scand. 

1996;67(5):473-478.

27. Easley ME, Trnka HJ, Schon LC, Myerson MS. Isolated subtalar arthrodesis. J Bone 

Joint Surg Am. 2000;82(5):613-624.

28. Fourman MS, Borst EW, Bogner E, Rozbruch SR, Fragomen AT. Recombinant human 

BMP-2 increases the incidence and rate of healing in complex ankle arthrodesis. Clin 

Orthop Relat Res. 2014;472(2):732-739.

29. Grunander TR, Thordarson DB. Results of calcaneocuboid distraction arthrodesis. Foot 

Ankle Surg. 2012;18(1):15-18.

30. Holm JL, Laxson SE, Schuberth JM. Primary subtalar joint arthrodesis for comminuted 

fractures of the calcaneus. J Foot Ankle Surg. 2015;54(1):61-65.
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

30

31. Lechler P, Graf S, Kock FX, Schaumberger J, Grifka J, Handel M. Arthrodisis of the 

talonavicular joint using angle-stable mini-plates: a prospective study. Int Ortho. 

2012;36:2491-2494.

32. Patil S, Auyeung J, Gower A. Outcome of subtalar fusion using bovine cancellous bone 

graft: a retrospective case series. J Foot Ankle Surg. 2011;50(4):388-390.

33. Plaass C, Knupp M, Barg A, Hintermann B. Anterior double plating for rigid fixation of 

isolated tibiotalar arthrodesis. Foot Ankle Int. 2009;30(7):631-639.

34. Rearick T, Charlton TP, Thordarson D. Effectiveness and complications associated with 

recombinant human bone morphogenetic protein-2 augmentation of foot and ankle 

fusions and fracture nonunions. Foot Ankle Int. 2014;35(8):783-788.

35. Rungprai C, Phisitkul P, Femino JE, Martin KD, Saltzman CL, Amendola A. Outcomes 

and complications after open versus posterior arthroscopic subtalar arthrodesis in 121 

patients. J Bone Joint Surg Am. 2016;98(8):636-646.

36. Sun L, Kong Z, Xu M. Minimally invasive subtalar arthrodesis for traumatic subtalar 

arthritis. J Int Med Res. 2019;47(12):6129-6138.

37. Weinraub GM, Schuberth JM, Lee M, et al. Isolated medial incisional approach to 

subtalar and talonavicular arthrodesis. J Foot Ankle Surg. 2010;49(4):326-330.

38. Wheeler J, Sangeorzan A, Crass SM, Sangeorzan BJ, Benirschke SK, Hansen ST. 

Locally generated bone slurry accelerated ankle arthrodesis. Foot Ankle Int. 

2009;30(7):686-689.

39. Yavuz U, Sokucu S, Demir B, Ozer D, Ozcan C, Kabukcuoglu YS. Isolated subtalar 

fusion for neglected painful intra-articular calcaneal fractures. Acta Orthop Traumatol 

Turc. 2014;48(5):541-545.

40. Yildirim T, Sofu H, Camurcu Y, Ozcan C, Oner A, Sahin V. Isolated subtalar arthrodesis. 

Acta Orthop Belg. 2015;81(1):155-160.

41. Muller MA, Frank A, Briel M, et al. Substitutes of structural and non-structural 

autologous bone grafts in hindfoot arthrodeses and osteotomies: a systematic review. 

BMC Musculoskelet Disord. 2013;14:59.

42. DeOrio JK, Farber DC. Morbidity associated with anterior iliac crest bone grafting in 

foot and ankle surgery. Foot Ankle Int. 2006;25(2):147-151.

43. Whitehouse MR, Lankester BJ, Winson IG, Hepple S. Bone graft harvest from the 

proximal tibia in foot and ankle arthrodesis surgery. Foot Ankle Int. 2006;27(11):913-

916.

44. Baumhauer J, Pinzur MS, Donahue R, Beasley W, DiGiovanni C. Site selection and pain 

outcome after autologous bone graft harvest. Foot Ankle Int. 2014;35(2):104-107.
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

31

APPENDIX A. SEARCH STRATEGIES

MEDLINE search strategy

exp Transplantation, Autologous/ or exp Autografts/ or exp Bone Transplantation/ 

exp Bone Marrow Transplantation/ or exp Bone Substitutes/ 

exp Platelet-Derived Growth Factor/ or exp Platelet-Rich Plasma/ 

(orthobiologic* or (autologous and graft*) or (autogenous and graft*) or (autogenic and graft*) or 

autograft* or (iliac and graft*) or (tibia* and graft*) or (calcan* and graft*) or (fibul* and graft*) or "bone 

graft*").ti,ab. 

("bone marrow aspirate*" or (bone adj2 transplantation) or "plasma product*" or "platelet-derived" or 

"platelet derived" or "platelet-rich" or "platelet rich" or "mesenchymal stem cell*" or "bone morphogen* 

protein*" or PRP or PDGF or MSC or rhPDGF-BB or BMP-2 or rhBMP-2 or BMP-7 or "tricalcium 

phosphate").ti,ab. 

1 or 2 or 3 or 4 or 5 

exp Foot Joints/ 

exp Foot Bones/ 

exp Ankle Joint/ 

(foot or ankle or naviculocuneiform or Lisfranc or Chopart or midfoot or mid-foot or hindfoot or hind-foot or 

calcaneous or calcaneal or talus or talar or subtalar or tarsal or tibiotalar or tibiotalocalcaneal or 

calcaneocuboid or talonavicular or mid-tarsal or midtarsal or tarsometatarsal or 

metatarsophalangeal).ti,ab. 

exp Arthrodesis/ or (arthrodes* or fusion* or union* or fixation*).mp. 

7 or 8 or 9 or 10 

11 and 12 

6 and 13 

limit 14 to "all child (0 to 18 years)" 

limit 15 to "all adult (19 plus years)"

14 not 15 

16 or 17 

limit 18 to (english language and humans and yr="1995 -Current") 
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

32 

APPENDIX B. CRITERIA USED IN QUALITY ASSESSMENT

We completed a critical appraisal included studies (retrospective chart reviews or prospective 

case series) based on a modification of the Joanna Briggs Institute 1) Critical Appraisal Checklist 

for Quasi-Experimental Studies18 and 2) Critical Appraisal Checklist for Case Series.

19 Each 

item below was rated Yes/No/Unclear/Not Applicable. 

Item Rating

1. Is there evidence of ethical approval for the study?

2. Were there clear criteria for inclusion?

3. Was there complete inclusion of participants?

4. Was there clear reporting of the demographics of the study participants?

5. Were the study groups formed in a way that minimizes bias? 

6. Did the participants included in any comparison receive similar treatment/care 

other than the intervention of interest?

7. Was follow-up complete with no differential follow-up between groups? 

8. Was outcome assessment blinded?

9. Were outcomes measured in valid and reliable ways?
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

33 

APPENDIX C. PEER REVIEWER COMMENTS AND AUTHOR RESPONSES

Question Text Comment Author Response

Are the objectives, 

scope, and methods 

for this review clearly 

described?

Yes Thank you

Yes

Yes

Yes

Is there any 

indication of bias in 

our synthesis of the 

evidence?

No Thank you

No

No

No

Are there any 

published or 

unpublished studies 

that we may have 

overlooked?

No Thank you

No

No

No

Additional 

suggestions or 

comments can be 

provided below. If 

applicable, please 

indicate the page 

and line numbers 

from the draft report.

Page 26--lines 22-28. Please note that cost data for biologics can be very 

difficult for surgeons to obtain from the vendors so it cannot be used in 

consideration of biologic use.

Page 8--lines 29/30. Is the major complication of joint stiffness related to its 

use in long bone fracture treatment adjacent to joints, causing the 

stiffness?

Page 8--line 41--typo? "than", not then 

Page 27--line 57 might read better as--"initial post surgical pain at the foot 

or ankle" for each example. I had to reread to understand this well. 

General questions/comments:

1. Was Vitamin D a consideration in the reviewed manuscripts? It is often a

consideration for revision surgery, but not always looked at prior to the first

arthrodesis attempt.

2. I appreciate the commentary on "selection bias". This is impossible to

avoid in all the case series reports that are available for this review.

3. I also appreciate the commentary regarding off-label use for certain

products. Off label use is a necessary issue with many of these products.

4. The recommendation for pre-authorization for the biologics appears to

Page 26: We agree that cost data can be 

difficult for surgeons to obtain and may vary 

between facilities and over time. 

Furthermore, the cost of the product is only 

one component of the overall cost of care, 

which includes the possibility for a second 

surgery or more complex surgical procedure 

versus improved health outcomes which 

may both lower future costs as well as 

improve health outcomes. However, given 

the limited evidence on effectiveness and 

the fact that these products are not 

specifically approved for this indication, 

clinicians and health systems should be 

aware that use of these products increases 

surgical cost and complexity. Health care 

systems, including the VA, should be more 

transparent regarding the cost of these 

products, negotiate lower cost options, and 
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

34 

be appropriate. The cost of biologics must be more transparent to aid in 

decision making by the surgeon.

encourage clinician awareness and patient 

communication of these issues. 

Page 8: We modified this statement. Joint 

stiffness and pain was related to heterotopic 

bone formation.

Page 8, Line 41: Thank you – changed to 

“than”

Page 27: Thank you for the suggestion – we 

revised this sentence. 

1. None of the included studies reported on

Vitamin D.

2,3,4: Thank you. We have added some 

additional information regarding the 

importance of cost assessment, negotiation, 

and awareness for patients, clinicians, and 

health care systems. 

The use of orthobiologics in foot and ankle surgery is replete of data and 

controversial. I commend the authors for addressing the lack of knowledge 

around this topic by performing this exhaustive analysis of controlled 

studies on the use of orthobiologics. The results of this study are not 

surprising. Trying to make sense of the ever-expanding orthobiologics 

world is difficult. The results also indicate the heterogeneous nature of 

patients presenting for foot and ankle fusions and the hap-hazard nature of 

implementation of orthobiologics by clinicians. The report also highlights 

the low incidence of reported (and possibly the actual) harms when using 

orthobiologics. Finally, the report emphasizes the need for more rigorous 

studies evaluating the use of orthobiologics.

Thank you.

p. 1 line 45 beginning with "Our focus......." some studies used allografts 

(bone) which would not be included in this sentence. Should be.

As requested in the topic nomination, our 

scope was limited to autogenous 

orthobiologics. 
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

35 

APPENDIX D. EVIDENCE TABLES 

Table 1. Study Characteristics

Author, year 

Country 

Funding 

Study Design

Inclusion/Exclusion Criteria

Arthrodesis Site

Orthobiologic(s) (n)

Non-Orthobiologic(s) (n)

Follow-up 

Demographics A Priori Comparison?

Abd-Ella, 201720

Country unclear

Funding: No 

funding

Prospective case 

series

Inclusion: Nonunion of talar neck or

body fracture associated with 

extensive avascular necrosis of the 

talar dome

Exclusion: Infection; septic AVN

Indications for arthrodesis: NR

Orthobiologic(s): Mix of bulk strut graft 

and cancellous graft harvested from 

posterior iliac crest (n=9)

Non-Orthobiologic(s): “No need for 

graft” (n=3)

Number of sites: NR

Number of surgeons: NR

Follow-up: 23 months (range 12-60)

N=12 patients 

Age (years, mean): 27.7

Gender (% male): 67% 

Race/ethnicity: NR

Smoking status: 33% smokers

Obesity (%): NR

BMI: NR

Diabetes (%): 0% 

Bone mineral density: NR

Medications related to healing: 

NR

A priori plan to compare 

orthobiologics to no 

orthobiologics: No 

Anderson, 201321

USA

Funding: Not 

Reported 

Retrospective 

chart review

Inclusion: Primary first MPJ 

arthrodesis

Exclusion: Revision first MPJ fusion 

secondary to malunion or previous 

non-union, previously infected joint, 

history of Charcot neuroarthropathy, 

or history of first MPJ dislocation with 

sesamoidal fracture 

Indications for arthrodesis: End-stage 

deformity correction

Orthobiologic(s): Autograft (local; 

reduce to cancellous bone chips); 

cases with soft bone, bone voids, or 

bone cysts at fusion site (n=62 

patients)

Non-Orthobiologic(s): End-to-end 

arthrodesis; no graft interposition used 

or necessary (n=52 patients)

NOTE: additional 51 patients received 

allograft (not included in outcomes)

Number of surgical facilities: NR

Number of surgeons:1

Follow-up: weekly (for first 2 weeks) 

then biweekly until clinical union

N=165 patients (including 51 

receiving allograft)

Age (years, mean): 62

Gender (% male): 44%

Race/ethnicity: NR

Smoking status:19%

Obesity (%): 3%

BMI: NR

Diabetes (%): 7%

Bone mineral density: NR 

Medications related to healing: 

NR

A priori plan to compare 

orthobiologics to no 

orthobiologics: Yes

NOTE: Use of any graft 

was surgeon’s judgment. 

Patients in the end-to-end 

arthrodesis groups all had 

sufficient bone quality.

The 2 graft groups had 

different and less than 

desirable bone quality.

Bibbo, 200922

USA

Inclusion: High-risk, elective ankle 

and hindfoot fusions treated with 

rhBMP-2 augmentation

Orthobiologic(s): rhBMP-2 (INFUSE®) 

and autogenous iliac crest bone graft 

(n=17 fusions)

N=69 patients (112 fusion sites)

(includes allograft group)

Age (years, mean): 52 

A priori plan to compare 

orthobiologics to no 

orthobiologics: No 
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

36 

Author, year 

Country 

Funding 

Study Design

Inclusion/Exclusion Criteria

Arthrodesis Site

Orthobiologic(s) (n)

Non-Orthobiologic(s) (n)

Follow-up 

Demographics A Priori Comparison?

Funding: None

Retrospective 

chart review

“High-risk” inclusion criteria:

Smoking, diabetes, high energy 

injury, multiple surgeries, history of 

delayed/ non-union, alcohol abuse, 

immunosuppression, chronic 

infections, suboptimal inflow, collagen 

disorders, multiple medical 

comorbidities

Exclusion: Active infection, peripheral 

vascular disease that might preclude 

healing, or any inability to participate 

in usual follow-up

Indications for arthrodesis: NR

Non-Orthobiologic(s): rhBMP-2 only 

(n=85 fusions)

Additional 10 fusions received rhBMP2 and allograft (excluded from 

analysis)

Number of surgical facilities: NR

Number of surgeons: NR

Follow-up: every 2-4 weeks 

Gender (% male): 53%

Race/ethnicity: NR

Smoking status: 64% 

Obesity (%): NR

BMI: NR

Diabetes (%): 19%

Bone mineral density: NR

Medications related to healing: 

NR

Bone grafting performed 

only to fill osseous defects 

and correct malalignment. 

Buda, 201823

USA

Funding: None

Retrospective 

chart review

Inclusion: Adults, single or multilevel 

TMT arthrodesis (CPT codes 28730 

and 28735)

Exclusion: Age <18, post-op follow-up 

<12 months, prior midfoot surgery, 

arthrodesis in context of acute foot 

trauma, concomitant foot procedure 

other than bone graft harvest

Indications for arthrodesis: End-stage 

TMT arthritis 

Intervention: TMT arthrodesis with 

autologous bone graft harvested from 

iliac crest or calcaneus (n=70 feet, 

53% graft only, 47% graft + DBM)

Control: TMT arthrodesis without 

autologous bone graft (n=18)

Number of sites: 3

Number of surgeons: 9

Follow-up: mean of 77.5 months 

(range 12-179)

N=88 feet (189 joints)

Age (years, mean): 57

Gender (% male): 20% 

Race/ethnicity: 91% white race

Smoking status: Current 12.5%

Obesity (%): 56% 

BMI: NR

Diabetes (%): 9% 

Bone mineral density: NR 

(Osteoporosis: 12.5%)

Medications related to healing: 

NR

A priori plan to compare 

orthobiologics to no 

orthobiologics: Yes

Cao, 201724

China

Funding: 

Foundation

Retrospective 

chart review

Inclusion: Isolated TN arthrodesis 

(n=16 patients) for

stage III and IV Müller-Weiss disease

Exclusion: Multiple site arthritis or 

infection, obvious deformity in 

hindfoot 

Orthobiologic(s): Autoallergic iliac 

bone graft (n=5 patients with stage IV 

Müller-Weiss disease)

Non-Orthobiologic(s): No bone graft 

(n=11 patients with stage III MüllerWeiss disease)

Number of surgical facilities: 1

N=16 patients

Age (years, mean): 50.3

Gender (% male): 12.5%

Race/ethnicity: NR

Smoking status: NR

Obesity (%): NR

BMI: NR

Diabetes (%): NR

Bone mineral density: NR

A priori plan to compare 

orthobiologics to no 

orthobiologics: No

Only stage IV MüllerWeiss cases received

graft. No-graft group was

stage III Müller-Weiss 

cases only.
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

37 

Author, year 

Country 

Funding 

Study Design

Inclusion/Exclusion Criteria

Arthrodesis Site

Orthobiologic(s) (n)

Non-Orthobiologic(s) (n)

Follow-up 

Demographics A Priori Comparison?

Indications for arthrodesis: MüllerWeiss disease (stages III and IV)

NOTE: Additional 14 patients 

underwent TNC arthrodesis with 

tricortical autogenous graft (not 

reported here).

Number of surgeons: 2

Follow-up: 39.8 months (11-66) (TN 

group)

Medications related to healing: 

NR

Chahal, 200625

Canada

Funding: None

Retrospective 

chart review

Inclusion: Isolated subtalar fusion 

(ISSA, n=67 patients or SBBDA, 

n=21 patients); hindfoot pain 

attributable to subtalar joint, 

preoperative diagnosis of primary or 

secondary osteoarthritis of subtalar 

joint

Exclusion: Rheumatoid arthritis or 

previous triple fusion

Indications for arthrodesis: Primary 

osteoarthritis: 19.3% Secondary 

osteoarthritis: 80.7%

NOTE: SBBDA patients not included 

in outcomes analyses. 

Orthobiologic(s): ISSA group only -

local or iliac crest bone graft (n=46 

with data, n=1 missing data)

Non-Orthobiologic(s): ISSA group only

- no graft (n=20)

Number of surgical facilities: 2

Number of surgeons: 2

Follow-up: 

Radiographic outcome: 2 and 6 

weeks; 3, 6, 12, and 24 months; every 

year after as required

Functional outcome: Mean=35.5 

months (10-83 months)

N=88 patients (includes 21 

SBBDA patients)

Age (years, mean): 46 

Gender (% male): 61.4%

Race/ethnicity: NR

Smoking status: 43.7% smoked 

at least 1 week before and after 

surgery

Obesity (%): NR

BMI: NR

Diabetes (%): 10.2%

Bone mineral density: NR

Medications related to healing: 

NR

A priori plan to compare 

orthobiologics to no 

orthobiologics: Yes 

Bone graft group: Local 

graft used if a lateral wall 

ostectomy was performed. 

Iliac crest bone graft used 

at surgeon’s discretion. 

Chen, 199626

Taiwan

Funding: Not 

Reported

Retrospective 

Chart Review

Inclusion: Internal compression 

tibiotalar arthrodesis

Exclusion: NR

Indications for arthrodesis: 

posttraumatic arthritis (45%), 

rheumatoid arthrosis (18%), paralytic 

ankle (10%), post-septic arthrosis 

(10%), nonunion after previous 

tibiotalar arthrodesis (10%), 

osteonecrosis of the talus (8%)

Orthobiologic(s): Tibial condyle graft 

(n=8 ankles) or sliding graft (n=7 

ankles) (cases with severe bone loss 

or poor bone quality) 

Non-Orthobiologic(s): No graft 

(patients with good apposition and 

rigid fixation) (n=25 ankles)

Number of surgical facilities: NR

Number of surgeons: 1

Follow-up: Mean=4 years (3-7 years)

N=38 patients (40 ankles)

Age (years, mean): 49 

Gender (% male): 63% 

Race/ethnicity: NR

Smoking status: NR 

Obesity (%): NR

BMI: NR

Diabetes (%): NR

Bone mineral density: NR

Medications related to healing: 

NR

A priori plan to compare 

orthobiologics to no 

orthobiologics: No
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

38 

Author, year 

Country 

Funding 

Study Design

Inclusion/Exclusion Criteria

Arthrodesis Site

Orthobiologic(s) (n)

Non-Orthobiologic(s) (n)

Follow-up 

Demographics A Priori Comparison?

Easley, 200027

USA

No Funding

Retrospective 

chart review

Inclusion: Failed nonoperative 

treatment; isolated subtalar 

arthrodesis (ISSA, n=150 feet or

bone-block distraction arthrodesis, 

n=34 feet)

Exclusion: NR

Indications for arthrodesis: 

posttraumatic arthritis (73%), failure 

of previous subtalar arthrodesis 

(15%), primary subtalar arthritis (7%), 

residual congenital deformity (4%)

NOTE: Bone-block distraction 

arthrodeses not included in outcome 

analyses. 

Orthobiologic(s): Cancellous autograft 

(n=94 feet)

Non-Orthobiologic(s): No bone graft 

(n=39 feet)

NOTE: 17 feet underwent ISSA with 

cancellous allograft (excluded from 

analysis)

Number of surgical facilities: NR

Number of surgeons: NR

Follow-up: Mean=51 months (24-130 

months) 

N=174 patients (184 feet)

(includes 17 receiving 

cancellous allograft)

Age (years, mean): 43 

Gender (% male): 66%

Race/ethnicity: NR

Smoking status: 46% (smoked 

at time of arthrodesis)

Obesity (%): NR

BMI: NR

Diabetes (%): NR

Bone mineral density: NR

Medications related to healing: 

NR

A priori plan to compare 

orthobiologics to no 

orthobiologics: Yes

*Purpose was to identify 

factors influencing union 

rate

Radiographic and clinical 

outcomes for N=139 

patients (148 feet)

Fourman, 201428

USA

Funding: None

Retrospective 

chart review

Inclusion: Ankle arthrodesis with the 

Ilizarov technique

Exclusion: Not deemed complex, had 

internal fixation for the ankle 

arthrodesis, inadequate follow-up 

(failure to appear for 3- and 6-month 

follow-up visits)

Indications for arthrodesis: Complex 

patients (comorbidities precluding a 

successful arthrodesis using 

traditional internal fixation including 

systemic or local compromise, 

infection about or in ankle, 

simultaneous limb lengthening if <70 

years with limb length discrepancy 

>2.5 cm, deformity of the ankle 

contraindicating internal fixation, 

osteopenia or poor skin quality)

Orthobiologic(s): rhBMP-2 (n=42 

patients)

Non-Orthobiologic(s): No rhBMP-2 

(n=40 patients)

Number of surgical facilities: 1

Number of surgeons: 1 

Follow-up: Mean of 43 months from 

date of frame removal (range 16-84

months) 

N=82 patients 

Age (years, mean): 57 

Gender (% male): NR

Race/ethnicity: NR

Smoking status: 7%

Obesity (%): 16% (BMI>30)

BMI: 29.6

Diabetes (%): 11.5% 

Bone mineral density: NR

Medications related to healing: 

NR

A priori plan to compare 

orthobiologics to no 

orthobiologics: Yes
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

39 

Author, year 

Country 

Funding 

Study Design

Inclusion/Exclusion Criteria

Arthrodesis Site

Orthobiologic(s) (n)

Non-Orthobiologic(s) (n)

Follow-up 

Demographics A Priori Comparison?

Grunander, 

201229

USA

Funding: None

Retrospective 

chart review

Inclusion: Calcaneocuboid distraction 

arthrodesis with femoral head 

allograft 

Exclusion: Patient who received

autogenous bone graft 

Indications for arthrodesis: Adult 

acquired flatfoot deformity 

Orthobiologic(s): Femoral head 

allograft with platelet rich plasma (n=7 

feet)

Non-Orthobiologic(s): Femoral head 

allograft alone (n=9 feet) 

Number of surgical facilities: NR

Number of surgeons: 1

Follow-up: Mean=23 months (8-39

months)

N=14 patients (16 feet)

Age (years, mean): 43 

Gender (% male): 71% 

Smoking status: 0%

Obesity (%): NR

BMI: NR

Diabetes (%): 0%

Bone mineral density: NR

Medications related to healing: 

NR

A priori plan to compare 

orthobiologics to no 

orthobiologics: No

PRP was used when it 

became available at study 

hospital (later cases in 

series)

Holm, 201530

USA

Funding: NR

Retrospective 

chart review

Inclusion: Comminuted intra-articular 

calcaneal fractures classified as 

Sanders type IV; treated with primary 

STJ arthrodesis 1998-2012; follow-up 

for ≥1 year

Exclusion: Open fractures, 

concomitant fractures in other lower 

extremity or spinal locations, 

unavailability of complete 

radiographic file

Indications for arthrodesis: Fracture 

related to MVA 44%; fall from height 

56%

Orthobiologic(s): Autogenous bone 

from tibia (n=3)

Non-Orthobiologic(s): No bone graft 

(n=6)

NOTE: Additional 8 patients received 

cancellous allograft chips (not 

reported)

Number of sites: 2

Number of surgeons: 2

Follow-up: mean 30 months (range 12-

61 months)

N=9 patients

Age (years, mean): 53.8

Gender (% male): 33% 

Race/ethnicity: NR

Smoking status: NR

Obesity (%): NR

BMI: NR

Diabetes (%): NR

Bone mineral density: NR

Medications related to healing: 

NR

A priori plan to compare 

orthobiologics to no 

orthobiologics: No

Lechler, 201231

Germany

Funding: Not 

reported

Prospective case 

series

Inclusion: Destruction of talonavicular 

joint; treated by talonavicular 

arthrodesis

Exclusion: NR

Indications for arthrodesis: 

Primary osteoarthritis: 53%

Post-traumatic destruction: 13%

Rheumatoid arthritis: 13% Psoriatic 

arthritis: 7%

Orthobiologic(s): Autologous 

spongious bone graft (iliac crest) (n=6)

Non-Orthobiologic(s): No reported use 

of any orthobiologic (n=24)

Number of sites: 1

Number of surgeons: NR

Follow-up: 15.8 months (range 6-24 

months)

N=30 patients (30 feet)

Age (years, mean): 58.8 

Gender (% male): 40% 

Race/ethnicity: NR

Smoking status: NR

Obesity (%): NR

BMI: NR

Diabetes (%): NR

Bone mineral density: NR

A priori plan to compare 

orthobiologics to no 

orthobiologics: No
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

40 

Author, year 

Country 

Funding 

Study Design

Inclusion/Exclusion Criteria

Arthrodesis Site

Orthobiologic(s) (n)

Non-Orthobiologic(s) (n)

Follow-up 

Demographics A Priori Comparison?

Peripheral neurological impairment: 

10%

Revision: 3%

Medications related to healing: 

NR

Patil, 201132

United Kingdom

Funding: Not

reported

Retrospective 

chart review

Inclusion: Primary subtalar fusion or 

triple arthrodesis using either local 

bone graft or autologous cancellous 

bone graft from iliac crest

Exclusion: Revision subtalar fusion 

for malunion or nonunion

Indications for arthrodesis: 

Primary osteoarthritis: 59%

Post-traumatic arthritis: 35%

Rheumatoid arthritis: 6%

NOTE: Additional group of patients 

(n=9) received bovine cancellous 

bone (not reported) 

Orthobiologic(s): Autologous iliac crest 

bone graft (n=4)

Non-Orthobiologic(s): Local bone from 

excised surfaces (n=13)

Number of sites: NR

Number of surgeons: 1

Follow-up: 12 months

N=17 patients 

Age (years, mean): 56

Gender (% male): 59% 

Race/ethnicity: NR

Smoking status: 6% (1 smoker)

Obesity (%): NR

BMI: NR 

Diabetes (%): NR

Bone mineral density: NR

Medications related to healing: 

NR

A priori plan to compare 

orthobiologics to no 

orthobiologics: No 

(purpose was to compare 

bovine cancellous bone 

grafting to no bovine 

grafting)

Plaass, 200933

Switzerland

Funding: Not 

reported

Prospective case 

series

Inclusion: Isolated tibiotalar 

arthrodesis with anterior double 

plating (2006-2007)

Exclusion: NR

Indications for arthrodesis: Main 

diagnoses were primary arthritis, 

post-traumatic osteoarthritis, and 

failed ankle replacement; 4 had nonunited arthrodesis of the ankle and 9 

had failed total ankle replacement 

Orthobiologic(s): Demineralized bone 

matrix (DBX®) and/or Platelet 

concentrate (Symphony II®) 

DBX® (n=7)

Symphony II® (n=1)

Both (n=3)

Non-Orthobiologic(s): No orthobiologic 

(n=5)

Additional 13 received allograft with or 

without other orthobiologic (not 

reported here)

Number of sites: NR

Number of surgeons: NR

Follow-up: 12 months

N=16 patients 

Age (years, mean): 54

DBX®: 56

Symphony II®: 39

Both: 40

No Orthobiologic: 64

Gender (% male): 62.5%

DBX®:

: 57%

Symphony II®: 100%

Both: 67%

No Orthobiologic: 60%

Race/ethnicity: NR

Smoking status: 38% tobacco 

use

Obesity (%): NR

BMI: NR

Diabetes (%): 38%

A priori plan to compare 

orthobiologics to no 

orthobiologics: No
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

41 

Author, year 

Country 

Funding 

Study Design

Inclusion/Exclusion Criteria

Arthrodesis Site

Orthobiologic(s) (n)

Non-Orthobiologic(s) (n)

Follow-up 

Demographics A Priori Comparison?

Bone mineral density: NR 

(radiographic signs of reduced 

bone quality noted in 38%) 

Medications related to healing: 

NR

Rearick, 201434

USA

Funding: None

Retrospective 

chart review

Inclusion: Received rhBMP-2 during 

treatment for foot or ankle fracture, 

fusion, or osteotomy (2010-2012); 

minimum 12 months follow-up

(Fusions included 10 midfoot, 10 

tibiotalar, 8 tibiotalo-calcaneal, 7 

subtalar, 4 triple, 1 each 

calcaneocuboid, talonavicular, & 

pantalar)

Exclusion: Skeletally immature, 

pregnant, active infection, active 

malignancy (2 patients subsequently 

excluded from analysis due to loss to 

follow-up or ineligible procedure) 

Indications for arthrodesis: NR

Orthobiologic(s): rhBMP-2 plus 

autograft (n=14 sites; 11 local graft, 2 

iliac crest graft, 1 calcaneus graft); 

used if larger bony defects were 

present

Non-Orthobiologic(s): rhBMP-2 with no 

supplemental graft (n=60 sites)

Number of sites: NR

Number of surgeons: 3 

Follow-up: Until bony union 

(mean=111 days in those with 

successful union)

N=48 patients (83 sites)*

Age (years, mean): 52 

Gender (% male): 63% 

Race/ethnicity: NR

Smoking status: 25% tobacco 

use

Obesity (%): NR

BMI: NR

Diabetes (%): 17% 

Bone mineral density: NR

Medications related to healing: 

NR

*Includes patients receiving 

allograft (9 sites)

A priori plan to compare 

orthobiologics to no 

orthobiologics: No

Rungprai, 201635

USA

Funding: None

Retrospective 

chart review

Inclusion: Open subtalar arthrodesis 

(2001-2003) 

Exclusion: Other arthrodesis sites or 

triple arthrodesis, revision subtalar 

arthrodesis, required structural bone 

grafts

Indications for arthrodesis: 

Primary arthritis: 25%

Posttraumatic arthritis: 49%

Other: 26%

Orthobiologic(s): Cancellous autograft 

(n=12 feet); DBM with cancellous 

allograft (n=12 feet); BMP with 

cancellous allograft (n=12 feet); 

platelet concentrator with cancellous 

allograft (n=7 feet)

 

Non-Orthobiologic(s): no bone graft 

(n=6 feet)

Other patients received structural 

autograft (n=2 feet), structural allograft 

(n=4 feet), or cancellous allograft (n=5 

feet)

N=57 patients (60 feet)

Age (years, mean): 47 

Gender (% male): 70% 

Race/ethnicity: NR

Smoking status: 12%

Obesity (%): NR

BMI: 33.9 (range 18.4-56.8)

Diabetes (%): 7% 

Bone mineral density: NR

Medications related to healing: 

NR

A priori plan to compare 

orthobiologics to no 

orthobiologics: No
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

42 

Author, year 

Country 

Funding 

Study Design

Inclusion/Exclusion Criteria

Arthrodesis Site

Orthobiologic(s) (n)

Non-Orthobiologic(s) (n)

Follow-up 

Demographics A Priori Comparison?

NOTE: Review also identified cases 

with arthroscopic subtalar arthrodesis 

– not reported here. 

Number of sites: 1

Number of surgeons: 4

Follow-up: 25.8 months (range 6-126

months)

Sun, 201936

China

Funding: None

Prospective case 

series

Inclusion: Traumatic subtalar arthritis; 

underwent minimally invasive 

subtalar arthrodesis (2011-2014); 

type I, II, or III calcaneal fracture 

(Zwipp classification); no severe 

deformity after early surgical 

treatment; STJ pain affecting normal 

daily life; normal or mildly deformed 

calcaneal morphology, uneven STJ 

surface, subchondral sclerosis of 

articular surface, and hypertrophy of 

joint edge (radiograph or CT)

Exclusion: Type V calcaneal 

malunion; >1 joint fusion; treatment 

with drugs that might impact fracture 

healing and functional scores;

peripheral bone fusion and joint 

trauma that affects functional score

Indications for arthrodesis: Traumatic 

subtalar arthritis (100%)

Orthobiologic(s): Bone from iliac crest 

to supplement local graft (n=4)

 

Non-Orthobiologic(s): Local graft only 

(n=11)

Number of sites: 1

Number of surgeons: 1

Follow-up: 21 months (range 12-34)

N=15 patients

Age (years, mean): 49 (range 

36-56)

Gender (% male): 53%

Race/ethnicity: NR

Smoking status: NR

Obesity (%): NR

BMI: NR

Diabetes (%): NR

Bone mineral density: NR

Medications related to healing: 

excluded patients treated with 

drugs that might impact healing

A priori plan to compare 

orthobiologics to no 

orthobiologics: No

Weinraub, 201037

USA

Funding: Not 

reported

Retrospective 

chart review

Inclusion: Combined STJ and TNJ 

arthrodesis (2006-2009) using single 

medial incision approach

Exclusion: None reported

Indications for arthrodesis: 

Posterior tibial tendon dysfunction: 

58% 

Tarsal coalition: 13%

Orthobiologic(s): PRP (n=7 patients); 

DBM (n=5); PRP/DBM (n=6); BMP 

(n=1); PGC (n=1); PRP/SC (n=1); 

DBM/SC (n=1)

Non-Orthobiologic(s): No orthobiologic 

(n=18 patients)

Additional 5 patients received 

bioactive glass (not reported here)

N=40 patients 

Age (years, mean): 

PRP: 45.6

DBM: 63.4

PRP/DBM: 56.8

Other: 60

No orthobiologic: 51.2

Gender (% male): NR

Race/ethnicity: NR

Smoking status: NR

A priori plan to compare 

orthobiologics to no 

orthobiologics: No

Orthobiologics used at 

surgeon’s discretion to fill 

any defects in the fusion 

site or as an adjunct in 

patients with biologic 

healing deficits. 
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

43 

Author, year 

Country 

Funding 

Study Design

Inclusion/Exclusion Criteria

Arthrodesis Site

Orthobiologic(s) (n)

Non-Orthobiologic(s) (n)

Follow-up 

Demographics A Priori Comparison?

Degenerative joint disease: 15% 

Rheumatoid arthritis: 5%

Other: 10%

Number of sites: 5 practices

Number of surgeons: 5

Follow-up: NR

Obesity (%): NR

BMI: NR

Diabetes (%): NR

Bone mineral density: NR

Medications related to healing: 

NR

Wheeler, 200938

USA

Funding: None

Retrospective 

chart review

Inclusion: Treated by CPT code 

27870 (Arthrodesis Procedures on 

Leg and Ankle Joint)

Exclusion: Missing radiographs at 6 

or 12 weeks

Indications for arthrodesis: posttraumatic arthritis (50%), prior failed 

ankle fusions (13%), limb 

misalignment (22%), degenerative 

arthritis (13%), septic arthritis (4%)

Orthobiologic(s): Bone slurry (burr to 

scuff subchondral bone and correct 

misalignment of surfaces when 

uneven; small particles left in the joint 

and mixed with blood from bleeding 

bone surfaces) (n=32 patients). NOTE: 

includes 2 patients who received 

structural graft

Non-Orthobiologic(s): No burr to 

produce bone slurry (n=22 patients)

NOTE: includes 2 patients who 

received structural graft

Number of surgical facilities: NR

Number of surgeons: 3

Follow-up: 6 and 12 weeks

N=54 patients 

Age (years, mean): 52.4 

Gender (% male): 64.8%

Race/ethnicity: NR

Smoking status: NR

Obesity (%): NR

BMI: NR

Diabetes (%): NR

Bone mineral density: NR

Medications related to healing: 

NR

A priori plan to compare 

orthobiologics to no 

orthobiologics: Yes

Yavuz, 201439

Turkey

Funding: Not 

Reported

Retrospective 

chart review

Inclusion: Symptomatic subtalar 

arthrosis after conservative treatment 

for intra-articular calcaneal fracture

Exclusion: NR

Indications for arthrodesis: 

Talocalcaneal arthrosis 

Orthobiologic(s): Iliac crest-derived 

cancellous autograft (n=8 patients) or 

cancellous allografts (n=3 patients)

 

Non-Orthobiologic(s): No bone graft 

(n=9 patients)

Number of surgical facilities: NR

Number of surgeons: NR

Follow-up: Mean=43 months (range 

21-83 months)

N=20 patients (21 feet)

Age (years, mean): 44 

Gender (% male): 80% 

Race/ethnicity: NR

Smoking status: NR

Obesity (%): NR

BMI: NR

Diabetes (%): NR

Bone mineral density: NR

Medications related to healing: 

NR

A priori plan to compare 

orthobiologics to no 

orthobiologics: No

Bone graft used in 

absence of appropriate 

surface contact; Allograft 

was used in the cases 

where patients refused to 

sign the informed consent 

form for autograft 

application.
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

44 

Author, year 

Country 

Funding 

Study Design

Inclusion/Exclusion Criteria

Arthrodesis Site

Orthobiologic(s) (n)

Non-Orthobiologic(s) (n)

Follow-up 

Demographics A Priori Comparison?

Yildirim, 201540

Turkey

Funding: None

Retrospective 

chart review

Inclusion: Isolated subtalar 

arthrodesis

Exclusion: Degenerative changes of 

the ankle or other intertarsal joints, 

previous arthrodesis (any foot joint), 

osteotomy to correct coronal plane 

hindfoot deformity during same 

surgery

Indications for arthrodesis: 

Degenerative subtalar arthritis 

secondary to calcaneal fracture 

(55%), nontraumatic arthritis due to 

hindfoot valgus deformity (18%), 

talocalcaneal coalition (15%), 

subtalar instability as a sequela of 

neurovascular conditions (6%), and 

flatfoot secondary to tibialis posterior 

tendon dysfunction (6%)

Orthobiologic(s): Grafting of joint 

space following removal of chondral 

surfaces with iliac crest autograft 

(n=16 feet) or cancellous allograft (n=3 

feet)

Non-Orthobiologic(s): No grafting 

(n=14 feet)

Number of surgical facilities: NR

Number of surgeons: NR

Follow-up: Mean=36.8 months (range 

24-74 months

N=31 patients (33 feet)

Age (years, mean): 44 

Gender (% male): 61%

Race/ethnicity: NR

Smoking status: NR

Obesity (%): NR

BMI: NR

Diabetes (%): NR

Bone mineral density: NR

Medications related to healing: 

NR

A priori plan to compare 

orthobiologics to no 

orthobiologics: Yes

AVN=avascular necrosis; BMI=body mass index; BMP=bone morphogenic protein; CPT=Current Procedural Terminology; CT=computed tomography; DMB=demineralized 

bone matrix; ISSA=In situ subtalar arthrodesis; MPJ=metatarsophalangeal joint; MVA=motor vehicle accident; NR=not reported; PGC=platelet gel concentrate; PRP=platelet-rich

plasma; rhBMP-2=recombinant human BMP-2; SBBDA=subtalar bone block distraction arthrodesis; SC=stem cell; STJ=subtalar joint; TMT=tarsometatarsal; TNJ=talonavicular 

joint; TNC=talonavicular-cuneiform
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

45 

Table 2. Quality Criteria 

Is there 

evidence 

of ethical 

approval 

for the 

study?

Were there 

clear criteria 

for 

inclusion?

Was there 

complete 

inclusion of 

participants?

Was there 

clear reporting 

of the 

demographics 

of the study 

participants?

Were the study 

groups formed in a 

way that minimizes 

bias?

Did the 

participants 

included in any 

comparison 

receive similar 

treatment/care 

other than the 

intervention of 

interest?

Was follow-up 

complete with 

no differential 

follow-up 

between 

groups?

Was outcome 

assessment 

blinded?

Were outcomes 

measured in valid 

and reliable 

ways?

Abd=Ella 201720

NR No Unclear Yes No – used to fill gap Yes Yes Unclear Yes – CT to 

confirm

Anderson, 201321

No Yes Yes – 

consecutive Yes 

No—surgeon 

discretion and graft 

for less desirable 

bone quality 

Yes Unclear—not 

reported

Unclear—

radiographs 

assessed in 

“time blinded 

fashion” by 3 

independent 

podiatric 

surgeons

No—studycreated office 

visit survey; CT 

not used

Bibbo, 200922

Yes Yes Unclear Yes

No—graft used to fill 

defects and correct 

misalignment 

Yes Yes Unclear

Yes—CT used to 

confirm 

radiographs

Buda 201823

Yes Yes Yes Yes

Unclear – no 

reported rationale 

for use of graft

Unclear – no 

information about 

treatment/followup protocol

Yes – required 

to have 12 

month follow-up 

for inclusion

No

No – not all nonunions confirmed 

with CT scans
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

46 

Is there 

evidence 

of ethical 

approval 

for the 

study?

Were there 

clear criteria 

for 

inclusion?

Was there 

complete 

inclusion of 

participants?

Was there 

clear reporting 

of the 

demographics 

of the study 

participants?

Were the study 

groups formed in a 

way that minimizes 

bias?

Did the 

participants 

included in any 

comparison 

receive similar 

treatment/care 

other than the 

intervention of 

interest?

Was follow-up 

complete with 

no differential 

follow-up 

between 

groups?

Was outcome 

assessment 

blinded?

Were outcomes 

measured in valid 

and reliable 

ways?

Cao, 201724

Yes No No No No—more severe 

cases got graft Yes Yes Unclear No—radio-graphs 

only 

Chahal, 200625

Yes Yes Yes Yes No—surgeon 

discretion 

No—ostectomy 

performed in 

local graft cases

No—graft group 

has missing 

data for 1 case

Yes—radiologic 

outcome 

independently 

assessed by 

radiologists

No—not all nonunions confirmed 

with CT scans

Chen, 199626

No No Unclear No

No—graft used in 

severe bone loss or 

poor bone quality

No – weight 

bearing delayed 

for graft patients

No—2 patients 

lost to follow up Unclear

Unclear—

radiographic 

methods not 

reported

Easley, 200027

Yes No Yes - 

consecutive Yes 

Unclear – reason for 

use of autograft not 

reported

No—surgical 

procedure not 

standardized; 

different post-op 

if iliac crest graft 

harvested

No—18% 

patients lost to 

follow up and 

80% completed 

both clinical and 

radiographic 

outcomes 

Yes—3 

investigators not 

involved in 

procedures 

conducted 

review

No—AOFAS 

preop scores 

assigned 

retrospectively for 

some patients; 

study created 

questionnaire 
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

47 

Is there 

evidence 

of ethical 

approval 

for the 

study?

Were there 

clear criteria 

for 

inclusion?

Was there 

complete 

inclusion of 

participants?

Was there 

clear reporting 

of the 

demographics 

of the study 

participants?

Were the study 

groups formed in a 

way that minimizes 

bias?

Did the 

participants 

included in any 

comparison 

receive similar 

treatment/care 

other than the 

intervention of 

interest?

Was follow-up 

complete with 

no differential 

follow-up 

between 

groups?

Was outcome 

assessment 

blinded?

Were outcomes 

measured in valid 

and reliable 

ways?

Fourman, 201428

Yes Yes Yes-“all” Yes

No—use of rhBMP2 came as change 

in practice 

No-- some 

patients with 

larger defects got 

allograft

No—47%

("large 

proportion”) did 

not receive CT 

Unclear—

surgeon at time 

of study not 

blinded; 

retrospective 

validation by 

blinded 

radiologist 

Yes, CT exams 

used to assess 

bone bridging

Grunander, 201229

Yes Yes Unclear Yes

No—PRP used only 

in later cases (ie, 

when it became 

available)

Yes Yes Unclear

Yes—CT used to 

evaluate cases of 

questionable 

union 

Holm, 201

530

Yes Yes Yes (“the” 17 

cases) Yes No – used to fill void Yes Yes

No – surgeons 

reviewed their 

own cases

No – no CT 

confirmation

Lechler, 201231

Yes Yes Yes - 

consecutive No No – surgeon 

discretion Yes Yes Unclear – not reported No – CT not used
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

48 

Is there 

evidence 

of ethical 

approval 

for the 

study?

Were there 

clear criteria 

for 

inclusion?

Was there 

complete 

inclusion of 

participants?

Was there 

clear reporting 

of the 

demographics 

of the study 

participants?

Were the study 

groups formed in a 

way that minimizes 

bias?

Did the 

participants 

included in any 

comparison 

receive similar 

treatment/care 

other than the 

intervention of 

interest?

Was follow-up 

complete with 

no differential 

follow-up 

between 

groups?

Was outcome 

assessment 

blinded?

Were outcomes 

measured in valid 

and reliable 

ways?

Patil, 201132

NR Yes Unclear Yes Unclear – not 

reported Yes

Yes – but 2/17 

did not return 

questionnaire

Unclear No – no CT 

confirmation

Plaass, 200933

Yes Yes Yes - 

consecutive Yes

No – DBM or 

platelets in high risk 

cases

No – weight 

bearing delayed 

for orthobiologic 

patients

Yes Yes - 

radiographs

Yes – CT to 

confirm union if 

unclear on x-ray

Rearick, 201434

Yes Yes Unclear Yes

No – surgeon 

discretion and graft 

for larger bony 

defects 

No – some use 

of bone 

stimulators

Yes

No – treating 

surgeon 

determined 

union

No – CT not 

routinely used

Rungprai, 201635

Yes Yes Yes Yes No – graft used to fill 

defects as needed Unclear Yes for union data

No – blinded to 

2nd rater but not 

to procedure

Unclear – some 

CT; nonunion on 

basis of clinical 

judgement
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

49 

Is there 

evidence 

of ethical 

approval 

for the 

study?

Were there 

clear criteria 

for 

inclusion?

Was there 

complete 

inclusion of 

participants?

Was there 

clear reporting 

of the 

demographics 

of the study 

participants?

Were the study 

groups formed in a 

way that minimizes 

bias?

Did the 

participants 

included in any 

comparison 

receive similar 

treatment/care 

other than the 

intervention of 

interest?

Was follow-up 

complete with 

no differential 

follow-up 

between 

groups?

Was outcome 

assessment 

blinded?

Were outcomes 

measured in valid 

and reliable 

ways?

Sun, 201936

Yes Yes Unclear No

No – iliac crest bone 

graft used if quantity 

of local bone was 

inadequate

Yes Yes Unclear

Unclear how 

many were 

confirmed with 

CT

Weinraub, 201037

No Yes Yes No

No –surgeon 

discretion to fill 

defects or if healing 

deficits

Yes Yes

No – surgeon 

determined 

union

No – clinical 

judgement, no 

valid quality of life 

measure

Wheeler, 200938

Yes Yes Unclear No

Unclear – no 

reported rationale 

for additional 

procedure

Yes

Yes – required 

to have 6 or 12 

week 

radiographs for 

inclusion

Yes – reviewers 

of radiographs 

were blinded

No – no CT 

confirmation or 

standard 

positioning for 

lateral 

radiographs

Yavuz, 201439

No No Unclear No

No-allograft used in 

cases when patients 

did not consent to 

autograft. Grafting 

performed in cases 

with absence of 

appropriate contact 

Yes Yes Unclear

Unclear—

radiographs used 

to confirm union

(no CT)
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

50 

Is there 

evidence 

of ethical 

approval 

for the 

study?

Were there 

clear criteria 

for 

inclusion?

Was there 

complete 

inclusion of 

participants?

Was there 

clear reporting 

of the 

demographics 

of the study 

participants?

Were the study 

groups formed in a 

way that minimizes 

bias?

Did the 

participants 

included in any 

comparison 

receive similar 

treatment/care 

other than the 

intervention of 

interest?

Was follow-up 

complete with 

no differential 

follow-up 

between 

groups?

Was outcome 

assessment 

blinded?

Were outcomes 

measured in valid 

and reliable 

ways?

Yildirim, 201540

No Yes Unclear No Unclear Yes Yes Unclear

Unclear—X-rays 

used to confirm 

union. No CTs

AOFAS=American Orthopaedic Foot and Ankle Society; CT=computed tomography; rhBMP-2=recombinant human BMP-2 
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

51 

Table 3. Patient-centered Outcomes, Part 1

Author Year

Study Design

Follow-up 

Wound Healing

(describe measure)

Need for Reoperation/Reintervention

% (n/N)

Pain

(describe measure)

Orthobiologic(s) NonOrthobiologic(s) Orthobiologic(s) NonOrthobiologic(s) Orthobiologic(s) Non-Orthobiologic(s) 

Abd-Ella, 201720

Prospective case 

series

Follow-up: 23 

months (range 12-

60)

No wound healing problems were 

encountered

0% (0/0) 100% (3/3) NR NR

Holm, 201530

Retrospective chart 

review

Follow-up: mean 30 

months (range 12-

61)

NR NR 0% (0/3) 0% (0/6) VAS 0-9 (pain at most 

recent visit)

Mean (SD)

2.0 (1.0)

(n=3)

VAS 0-9 (pain at most 

recent visit)

Mean (SD)

1.7 (1.4)

(n=6)

Lechler, 201231

Prospective case 

series

Follow-up: 15.8 

months (range 6-24)

NR NR NR NR VAS score (subjective pain) not significantly 

influenced by autologous bone grafting (P=.52)

Patil, 201132

Retrospective chart 

review

Follow-up: 12 

months

NR NR NR NR None reported pain on weightbearing

Plaass, 200933

Prospective case 

series

Follow-up: 12 

months

Delayed wound 

healing

DBM: 14% (1/7)

Platelet 0% (0/1)

Both 0% (0/2)

Delayed wound 

healing

0% (0/5)

NR NR AOFAS pain (range 0-40)

DBM Only

(n=7)

Pre: 12.9 (12.5)

Post: 27.1 (7.6) 

Platelet Only (n=1)

Pre: 0.0

Post: 20.0

DBM+Platelet (n=3)

Pre: 20.0 (0.0)

Post: 26.7 (5.8)

AOFAS pain

(range 0-40)

No Orthobiologic 

(n=5)

Pre: 8.0 (11.0)

Post: 34.0 (5.5)
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

52 

Author Year

Study Design

Follow-up 

Wound Healing

(describe measure)

Need for Reoperation/Reintervention

% (n/N)

Pain

(describe measure)

Orthobiologic(s) NonOrthobiologic(s) Orthobiologic(s) NonOrthobiologic(s) Orthobiologic(s) Non-Orthobiologic(s) 

Sun, 201936

Prospective case 

series

Follow-up: 21 

months

All posterolateral incisions healed 

smoothly in an average of 10-12 days

NR NR NR NR

Weinraub, 201037

Retrospective Chart 

Review

Follow-up: NR

NR NR NR NR CCJ pain (y/n)

PRP/DBM 

17% (1/6)

CCJ pain (y/n)

6% (1/18)

Wheeler, 200938

Retrospective chart 

review Follow-up: 6 

and 12 weeks

NR NR 0% (0/32)

At 6 months

4.5% (1/22)

At 6 months

NR NR

AOFAS=American Orthopaedic Foot and Ankle Society (Ankle-Hindfoot Score for Pain: 40 point scale where 40=no pain); CCJ=calcaneocuboid joint; DBM=demineralized bone 

matrix; NR=not reported; PRP=platelet-rich plasma; SD=standard deviation; VAS=visual analog scale

Table 4. Patient-centered Outcomes, Part 2

Author Year 

Study Design

Follow-up 

Functional Outcome

Clinically Meaningful Differences

(describe measure)

Quality of Life

Clinically Meaningful Differences

(describe measure)

Function or Quality of Life Scale Scores 

(mean, SD)

(describe measure)

Orthobiologic(s) NonOrthobiologic(s) Orthobiologic(s) NonOrthobiologic(s) Orthobiologic(s) Non-Orthobiologic(s) 

Abd-Ella, 201720

Prospective case 

series

Follow-up: 23 months 

(range 12-60)

NR NR NR NR Subjective patient satisfaction graded good or 

excellent in all cases

(4 options: excellent, good, fair, poor)

Anderson, 201321

Retrospective chart 

review

Follow-up: weekly (for 

first 2 weeks) then 

biweekly until clinical 

union

NR NR NR NR Patient satisfaction 

(willing to have 

procedure again)

98% (60/62)

P=NS

Patient satisfaction 

(willing to have 

procedure again)

96% (50/52)
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

53 

Author Year 

Study Design

Follow-up 

Functional Outcome

Clinically Meaningful Differences

(describe measure)

Quality of Life

Clinically Meaningful Differences

(describe measure)

Function or Quality of Life Scale Scores 

(mean, SD)

(describe measure)

Orthobiologic(s) NonOrthobiologic(s) Orthobiologic(s) NonOrthobiologic(s) Orthobiologic(s) Non-Orthobiologic(s) 

Cao, 201724

Retrospective chart 

review

Follow-up: 39.8 

months

NR NR NR NR AOFAS Score

Preop: 36.8 (3.0)

Postop: 89.0 (2.1), 

P=.51 (calculated) 

Reported that all 

patients were satisfied 

with clinical results and 

able to walk “long 

distances” 6 months 

after surgery

AOFAS Score

Preop: 38.6 (7.7)

Postop: 87.6 (4.2)

Chen, 199626

Retrospective Chart 

Review

Follow-up: 4 years 

(mean)

NR NR NR NR Morgan et al (1985)a

clinical outcomes 

ratings:

Excellent: 7% (1/15 feet)

Good: 73% (11/15 feet)

Fair: 13% (2/15 feet)

Poor: 7% (1/15 feet)

Morgan et al (1985) a

clinical outcomes 

ratings:

Excellent: 44% (11/25 

feet)

Good: 52% (13/25 feet)

Fair: 0% (0/25 feet)

Poor: 4% (1/25 

feet)

Easley, 200027

Retrospective chart 

review

Follow-up: 51 months 

(mean)

NR NR NR NR Modified AOFAS Score 

(n=94 feet):

Preop: NR

Postop: 73 (25-94)

P=NS

Scale: Maximum=94

Modified AOFAS Score 

(n=39 feet):

Preop: NR

Postop: 70 (30-94)

Holm, 201530

Retrospective chart 

review

Follow-up: mean 30 

months (range 12-61)

NR NR NR NR AOFAS Ankle-Hindfoot 

Score

Mean (SD)

81.3 (3.5)

(n=3)

AOFAS Ankle-Hindfoot 

Score

Mean (SD)

74.5 (11.6)

(n=6)

Lechler, 201231

Prospective case 

series

Follow-up: 15.8 

months (range 6-24)

NR NR NR NR Improvement in mean AOFAS not significantly 

influenced by autologous bone grafting (P=.62)
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

54 

Author Year 

Study Design

Follow-up 

Functional Outcome

Clinically Meaningful Differences

(describe measure)

Quality of Life

Clinically Meaningful Differences

(describe measure)

Function or Quality of Life Scale Scores 

(mean, SD)

(describe measure)

Orthobiologic(s) NonOrthobiologic(s) Orthobiologic(s) NonOrthobiologic(s) Orthobiologic(s) Non-Orthobiologic(s) 

Plaass, 200933

Prospective case 

series

Follow-up: 12 months

NR NR NR NR AOFAS Total

(range 0-92)

DBM only (n=7)

Pre: 44.0 (12.6)

Post: 66.1 (15.0)

Platelet Only (n=1)

Pre: 28

Post: 54

DBM+Platelet (n=3)

Pre: 59.0 (5.3)

Post: 62.3 (9.8)

AOFAS Total

(range 0-92)

Pre: 33.0 (15.7)

Post: 70.8 (12.1)

Sun, 201936

Prospective case 

series

Follow-up: 21 months

NR NR NR NR AOFAS Outcome

50% (2/4) “good” 

50% (2/4) “excellent”

AOFAS Outcome

45% (5/11) “good”

55% (6/11) “excellent”

Yildirim, 201540

Retrospective chart 

review Follow-up: 36.8 

months

NR NR NR NR AOFAS

No significant difference in mean scores between 

graft and no-graft groups

AOFAS=American Orthopedic Foot and Ankle Society (Ankle-Hindfoot score for function, pain, & alignment: maximum of 92-94 points (full function, no pain) depending on site 

of fusion); DBM=demineralized bone matrix; NR=not reported; SD=standard deviation

aMorgan et al (1985) clinical outcomes ratings: Excellent (solid fusion, no pain, no limp, no job restriction, esthetic appearance); Good (solid fusion, mild pain, mild occasional 

limp, same job with some restrictions, acceptable appearance); Fair (solid fusion, moderate pain, constant limp, job change, poor appearance); Poor (failure of fusion or severe 

pain)
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

55 

Table 5. Intermediate and Cost Outcomes

Author Year

Study Design

Follow-up 

Radiographic Fusion

% (n/N) Mean Time to Fusion (weeks) Patient Costs(describe measure)

Facility Costs

(describe measure

Orthobiologic(s)Non-Orthobiologic(s)Orthobiologic(s)Non-Orthobiologic(s)Orthobiologic(s)Non-Orthobiologic(s)Orthobiologic(s)Non-Orthobiologic(s)

Abd-Ella, 201720

Prospective case 

series

Follow-up: 23 

months (range 

12-60)

Solid osseous 

union

89% (8/9)* 

(2 smokers, 6 

non-smokers)

(9th patient, a 

smoker, had 

painless fibrous 

union) *Bridging 

trabeculae 

included 50% or 

more of the joint 

surface on CT 

scan

Solid osseous 

union

0% (0/3)

(1 smoker, 2 

non-smokers)

NR NR NR NR NR NR

Anderson, 201321

Retrospective 

chart review

Follow-up: weekly 

(for first 2 weeks) 

then biweekly 

until clinical union

Total radiographic 

Non-Unions:

7% (4/62 

patients), P=NS

% of 

Radiographic 

Fusion:

94.1%

Total 

radiographic 

Non-Unions:

4% (2/52 

patients)

% of 

Radiographic 

Fusion:

96.0%

Time to Clinical 

Union (weeks)

Mean (SD)

6.52 (1.46)

P=NS

Time to 

Radiographic 

Union: Mean

(SD)

6.69 (1.70)

P=NS

Time to Clinical 

Union (weeks)

Mean (SD)

6.46 (1.31) 

Time to 

Radiographic 

Union:

Mean (SD)

6.76 (1.31)

NR NR NR NR

Bibbo, 200922

Retrospective 

chart review

Follow-up: every 

2-4 weeks

NR NR Ankle joint 

fusions (n=8): 

Mean 13.3

weeks

P=.267

Subtalar joint 

fusions (n=8): 

Mean 13.2 

weeks

P=.116

Ankle joint 

fusions (n=24): 

Mean 9.1

weeks

Subtalar joint 

fusions (n=27): 

Mean 10.4

weeks

NR NR NR NR
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

56 

Author Year

Study Design

Follow-up 

Radiographic Fusion

% (n/N) Mean Time to Fusion (weeks) Patient Costs(describe measure)

Facility Costs

(describe measure

Orthobiologic(s)Non-Orthobiologic(s)Orthobiologic(s)Non-Orthobiologic(s)Orthobiologic(s)Non-Orthobiologic(s)Orthobiologic(s)Non-Orthobiologic(s)

Calcaneocuboid joint 

fusions (n=1):

Mean 12 weeks

P NR

*Union: minimum of 50% 

bony bridging 

across arthrodesis site, or 

multiple spot 

welding areas 

equaling 50% of 

fusion site

Calcaneocuboid joint 

fusions (n=14): 

Mean 11

weeks 

Buda, 201823

Retrospective 

chart review

Follow-up: 77.5 

months

Non-union*

7% (5/70)

OR 0.22 (95%CI 

0.1, 0.6; P=.005)

*presence of

radiolucent line 

through TMT 

joint, sealing off 

of medullary 

cavity with 

sclerosis at edge 

of TMT join, and 

bony resorption 

or regional 

osteoporosis 

above and below 

TMT joint

Non-union

28% (5/18)

NR NR NR NR NR NR

Cao, 201724

Retrospective 

chart review

Follow-up: 39.8 

months

All feet fused solidly (at 3 or 6 

months post-surgery) per 

radiographs.

NR NR NR NR NR NR
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

57 

Author Year

Study Design

Follow-up 

Radiographic Fusion

% (n/N) Mean Time to Fusion (weeks) Patient Costs(describe measure)

Facility Costs

(describe measure

Orthobiologic(s)Non-Orthobiologic(s)Orthobiologic(s)Non-Orthobiologic(s)Orthobiologic(s)Non-Orthobiologic(s)Orthobiologic(s)Non-Orthobiologic(s)

Chahal, 200625

Retrospective 

chart review

Follow-up: 35.5 

months (mean)

Union*

84.8% (39/46), 

P<.107

OR for non-union: 

0.32 (95%CI 

0.12, 1.29) (adj 

for age, sex)

*Complete 

bridging callus or 

trabeculation 

across subtalar 

joint with no pain 

when stress 

applied to joint

(from lateral view 

of foot, 2 oblique 

radiographs of 

hindfoot, and 

axial view of 

hindfoot)

Union

65.0% (13/20)

NR NR NR NR NR NR

Chen, 199626

Retrospective 

Chart Review

Follow-up: 4 

years (mean)

Nonunion: 0% 

(0/15 feet)

Delayed union: 

7% (1/15 feet)

Nonunion: 4% 

(1/25 feet)

Delayed union:

0% (0/25 feet)

Mean

15 weeks (12-

20)

NR NR NR NR NR

Easley, 200027

Retrospective 

chart review

Follow-up: 51 

months (mean)

Union*

85% (80/94)

P=NS

*Clinical or 

radiographic 

evidence of nonunion. Clinical 

union based on 

pain when stress 

applied. 

Radiographic 

Union

87% (34/39)

Weeks

Mean (range)

11 (8-20)

P=NS

Weeks

Mean (range)

11 (8-24)

NR NR NR NR
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

58 

Author Year

Study Design

Follow-up 

Radiographic Fusion

% (n/N) Mean Time to Fusion (weeks) Patient Costs(describe measure)

Facility Costs

(describe measure

Orthobiologic(s)Non-Orthobiologic(s)Orthobiologic(s)Non-Orthobiologic(s)Orthobiologic(s)Non-Orthobiologic(s)Orthobiologic(s)Non-Orthobiologic(s)

union based on

lateral radiograph and 2 

Broden 

radiographs

Fourman, 201428

Retrospective 

chart review

Follow-up: 43 

months

Initial Union (3 

months):

92% (39/42)

P<.001

OR 11.76 (95%CI 

3.12, 44.41)

Final Union (at 

time of frame 

removal – mean 

124 days)):

92% (40/42)

P=.08

Bridging bone 

(CT at 3 months)

Mean (SD)

48% (4.18)

P=.04

Initial Union (3 

months):

53% (21/40)

Final Union (at 

time of frame 

removal – mean 

161 days)):

82% (33/40)

Bridging bone 

(CT at 3 

months)

Mean (SD)

32% (5.90)

NR NR NR NR NR NR

Grunander, 

201229

Retrospective 

chart review

Follow-up: 23 

months (mean)

Non-union*: 29% 

(2/7 patients)

P=.36 

(calculated)

*Evaluated on 

radiographs (AP, 

lateral, and 

oblique). CT scan 

used occasionally 

and union defined 

as > 50% bone 

union

Non-union: 56% 

(5/9 patients)

NR NR NR NR NR NR
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

59 

Author Year

Study Design

Follow-up 

Radiographic Fusion

% (n/N) Mean Time to Fusion (weeks) Patient Costs(describe measure)

Facility Costs

(describe measure

Orthobiologic(s)Non-Orthobiologic(s)Orthobiologic(s)Non-Orthobiologic(s)Orthobiologic(s)Non-Orthobiologic(s)Orthobiologic(s)Non-Orthobiologic(s)

Holm, 201530

Retrospective 

chart review

Follow-up: mean 

30 months (range 

12-61)

“Osseous union was achieved in all 

patients”

(osseous union not defined)

NR NR NR NR NR NR

Lechler, 201231

Prospective case 

series

Follow-up: 15.8 

months (range 6-

24)

NR NR Time to osseous union not 

significantly influenced by 

autologous bone grafting (P=.38)

NR NR NR NR

Patil, 201132

Retrospective 

chart review

Follow-up: 12 

months

Union

100% (4/4)

Plain radiographs

Union

100% (13/13)

Plain 

radiographs

NR NR NR NR NR NR

Plaass, 200933

Prospective case 

series

Follow-up: 12 

months

100% in all 

groups (16/16)

*Presence of 

bridging 

trabeculae at the 

level of the 

arthrodesis on 

standard x-ray; 

CT used if doubt 

about union

100% (5/5) DBM Only (n=7)

Weeks

12.7 (6.1)

Platelet Only 

(n=1)

Weeks

8.0

DBM+Platelet 

(n=3)

Weeks

13.0 (7.8)

No 

Orthobiologic 

(n=5)

Weeks

12.0 (7.8)

NR NR NR NR

Rearick, 201434

Retrospective 

chart review

Follow-up: until 

union

Non-union

21% (3/14 sites)

2 tibiotalar 

fusions, 1 midfoot 

fusion 

Nonunion

0% (0/60 sites)

Tibiotalar: 

16.9 weeks

Subtalar: 

14.3 weeks 

Talonavicular: 

16.3 weeks

Midfoot: 

N/A

All P=NS

Tibiotalar:

17.0 weeks

Subtalar: 

16.9 weeks

Talonavicular: 

16.7 weeks

Midfoot: 

13.0 weeks

NR NR NR NR
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

60 

Author Year

Study Design

Follow-up 

Radiographic Fusion

% (n/N) Mean Time to Fusion (weeks) Patient Costs(describe measure)

Facility Costs

(describe measure

Orthobiologic(s)Non-Orthobiologic(s)Orthobiologic(s)Non-Orthobiologic(s)Orthobiologic(s)Non-Orthobiologic(s)Orthobiologic(s)Non-Orthobiologic(s)

Rungprai, 201635

Retrospective 

Chart Review

Follow-up: 25.8 

months

Union*

Cancellous 

autograft: 83% 

(10/12)

DBM+cancel-lous 

autograft: 92% 

(11/12)

BMP+cancel-lous 

autograft: 83% 

(10/12)

Platelet 

concentrator + 

cancellous 

autograft: 86% 

(6/7)

All P=NS

Union*

100% (6/6)

*Appearance of 

osseous 

trabeculae 

across the 

subtalar 

arthrodesis site 

on a lateral 

weight-bearing 

radiograph

Time (weeks)

Cancellous 

autograft: 16.7 

(11.0)

DBM+cancellous autograft: 

16.2 (9.4)

BMP+cancellous autograft: 

14.3 (2.7)

Platelet 

concentrator + 

cancellous 

autograft: 16.0 

(4.0)

All P=NS

Time (weeks)

14.6 (0.9)

NR NR NR NR

Sun, 201936

Prospective case 

series

Follow-up: 21 

months

Bone fusion confirmed (radiographs 

or CT scans) in all patients

Fusion within 3-5 months (range 

2-4 months)

NR NR Operation timea

Mean (SD)

83.8 (4.8) 

minutes (range 

40-85)

P<.01

Operation 

timea

Mean (SD)

50.9 (7.0) 

minutes (range 

40-60)

Weinraub, 201037

Retrospective 

Chart Review

Follow-up: NR

No non-unions observed Time (weeks)

Mean (SD)

PRP (n=7 

patients):

7.9 (1.2)

DBM (n=5): 

7.4 (0.9)

PRP/DBM 

(n=6):

8.5 (1.2)

BMP (n=1): 20

PGC (n=1): 8

PRP/SC (n=1): 

8 

Time (weeks)

Mean (SD)

8.4 (1.7)

NR NR Duration of 

surgery

(minutes)

Mean (SD)

PRP (n=7 

patients): 84.6 

(13.3)

DBM (n=5): 

82.6 (12.4)

PRP/DBM 

(n=6): 81.7 

(15.7)

BMP (n=1): 

164

PGC (n=1): 98

Duration of 

surgery 

(minutes) 

Mean (SD)

82.9 (11.8)
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

61 

Author Year

Study Design

Follow-up 

Radiographic Fusion

% (n/N) Mean Time to Fusion (weeks) Patient Costs(describe measure)

Facility Costs

(describe measure

Orthobiologic(s)Non-Orthobiologic(s)Orthobiologic(s)Non-Orthobiologic(s)Orthobiologic(s)Non-Orthobiologic(s)Orthobiologic(s)Non-Orthobiologic(s)

DBM/SC (n=1):

10

PRP/SC (n=1): 

93

DBM/SC (n=1): 

91

Wheeler, 200938

Retrospective 

chart review

Follow-up: 6 and 

12 weeks

Bridging bone 

(mean % of 

healing)

AP view

6 weeks: 94.1%, 

P=.0099

12 weeks: 98.1%, 

P=.026

Lateral view*

6 weeks:

89.7%, P=.2

12 weeks: 91.3%, 

P=.14

*Substantial 

challenges noted 

in interpretation of 

lateral

radiographs

Bridging bone 

(mean % of 

healing)

AP view

6 weeks: 76.4%

12 weeks: 

85.7%

Lateral view*

6 weeks:

80.9%

12 weeks: 

82.9%

*Substantial 

challenges 

noted in 

interpretation of

lateral 

radiographs

NR NR NR NR NR NR

Yavuz, 201439

Retrospective 

chart review

Follow-up: 43 

months (mean)

Non-union: 0% 

(0/11 patients)

Non-union:

11% (1/9 

patients)

No significant difference in time 

required for unification between 

patients that did and did not 

receive bone grafting, P=.544

NR NR NR NR

Yildirim, 201540

Retrospective 

chart review

Follow-up: 36.8 

months

Non-union

5.3% (1/19 feet)

Non-union

7.1% (1/14 feet)

14.4 (1.7)

weeks

n=19

P<.05

17.5 (2.8)

weeks

n=14

NR NR NR NR

AP=anteroposterior; BMP=bone morphogenic protein; CI=confidence interval; CT=computed tomography; DMB=demineralized bone matrix; N/A=not applicable; NR=not 

reported; NS=not statistically significant; OR=odds ratio; PGC=platelet gel concentrate; PRP=platelet-rich plasma; rhBMP-2=recombinant human BMP-2; SC=stem cell; 

SD=standard deviation; TMT=tarsometatarsal a

Time from cutting skin to stitching wound
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

62 

Table 6. Harms – Post-operative Complications

Author Year

Study Design

Follow-up 

Wound Complications 

(describe); % (n/N)

Mortality

% (n/N)

Amputation 

% (n/N)

Infection/Other (describe)

% (n/N)

Orthobiologic(s)

NonOrthobiologic(s)

Orthobiologic(s)

NonOrthobiologic(s)

Orthobiologic(s)

NonOrthobiologic(s)

Orthobio-logic(s) Non-Orthobio-logic(s)

Abd-Ella, 201720

Prospective case 

series

Follow-up: 23 months 

(range 12-60)

NR NR NR NR NR NR NR NR

Chen, 199626

Retrospective Chart 

Review

Follow-up: 4 years 

(mean)

NR NR NR NR 0% (0/15 

feet)

4% (1/25

feet)

Infection

13% (2/15 feet)

Subtalar varus:

7% (1/15 feet)

Reflex sympathetic 

dystrophy: 7% (1/15 

feet)

Infection

0% (0/25 feet)

Subtalar varus: 0% 

(0/25 feet)

Reflex sympathetic 

dystrophy: 0% (0/25 

feet)

Fourman, 201428

Retrospective chart 

review Follow-up: 43 

months

No compartment syndrome 

or wound breakdown in 

either group

NR NR 2.4% (1/42) 

(for infection)

0% (0/40) Infection, pin site

14.3% (6/42)

P=NS

Infection, pin site

12.5% (5/40)

Weinraub, 201037

Retrospective Chart 

Review

Follow-up: NR

No reported 

wound 

complications

6% (1/18)

Incision 

dehiscence

NR NR NR NR PRP/DBM: 17% (1/6) 

Lateral column pain

17% (1/6) Elevated first 

ray

BMP: 100% (1/1) Poor 

exposure (abandoned 

procedure)

6% (1/18) Painful 

fixation

6% (1/18)

Talar fracture

Yavuz, 201439

Retrospective chart 

review

Follow-up: 43 months 

(mean)

NR NR NR NR NR NR Infection

12.5% (1/8 patients who 

received autograft)

33% (1/3 patients who 

received allograft)

Infection

0% (0/9 patients)

BMP=bone morphogenic protein; DBM=demineralized bone matrix; NR=not reported; NS=not statistically significant; PRP=platelet-rich plasma
Orthobiologics for Foot and Ankle Arthrodesis Evidence Synthesis Program

63 

Table 7. Harms – Donor Site Morbidity

Author Year 

Study Design

Follow-up 

Hematoma Formation 

% (n/N)

Donor Site Infection

% (n/N)

Chronic Pain 

% (n/N)

Other (describe)

% (n/N)

Orthobiologic(s)NonOrthobiologic(s)Orthobiologic(s)Non-Orthobiologic(s)Orthobiologic(s)Non-Orthobiologic(s)Orthobiologic(s)Non-Orthobiologic(s) 

Abd-Ella, 201720

Prospective case 

series

Follow-up: 23 months 

(range 12-60)

NR NR NR NR NR NR No donor site morbidity was 

encountered

NR=not reported