The report is a product of the VA/HSR Evidence Synthesis Program.

Orthobiologics in Foot and Ankle Arthrodesis Sites: A Systematic Review

Arthrodesis (joint fusion) 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, and other conditions. However, reported rates of non-union following foot and ankle arthrodesis range from 0 to 36%, with an average of 10 to 11%. Non-union following arthrodesis surgery is associated with poor function, disability, and the potential need for revision surgery. Several factors have been reported to be associated with non-union including patient factors, local factors at the site of surgery, and surgical factors. Made from substances naturally found in the body, orthobiologics – in the context of arthrodesis – are used to promote bone formation and union at the arthrodesis site.

This systematic review examined the evidence from studies comparing the use of an orthobiologic to no orthobiologic in primary foot (forefoot and proximally) and ankle arthrodesis procedures. Investigators with VA’s Evidence Synthesis Program (ESP) Center in Minneapolis, MN searched Ovid MEDLINE, Embase, and the Cochrane Library from 1995 to July 2019. Investigators 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 their literature search. The search yielded 1,651 citations, with 282 identified for full-text review along with 2 articles identified from hand-searching; of these, 21 were included for this analysis.

Summary of Findings

Accurately assessing the effectiveness of orthobiologics is not possible due to the poor methodological quality of studies. Most reports were small retrospective chart review studies with little controlling for patient factors (i.e., health status, medications, and severity of presentation) likely to affect intervention indication or effectiveness. In addition, the available evidence is of poor quality due to variations in populations studied, orthobiologics and surgical techniques used, as well as 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.

Implications

The absence of evidence that the use of orthobiologics is superior to no orthobiologics suggests that a careful assessment of individual patient risk for non-union is critical prior to orthobiologic use. Clinicians and patients should be aware that orthobiologic products are not specifically approved for use in foot and ankle arthrodesis; thus, the use of these products for these indications is “off label.” Providers and policymakers also should be aware of the cost and possible morbidity associated with the widespread use of orthobiologics, given the insufficient to low-strength evidence of benefit.

Research Gaps/Future Research

Existing studies for the comparison of an orthobiologic to no orthobiologic are largely retrospective chart reviews, and few of the identified risk factors for non-union (i.e., smoking status, diabetes) were captured in the chart reviews. Selection bias, with surgeons electing to use an orthobiologic for more complex cases (e.g., bone defects, high risk for non-union), also is a concern.

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.

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.

To view the full report, go to vaww.hsrd.research.va.gov/publications/esp/orthobiologics.cfm (Intranet only, copy and paste the URL into your browser if you have intranet access.)

ESP is currently soliciting review topics from the broader VA community. Nominations will be accepted electronically using the online Topic Submission Form. If your topic is selected for a synthesis, you will be contacted by an ESP Center to refine the questions and determine a timeline for the report.

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This report is a product of VA/HSR&D's Evidence Synthesis Program (ESP), which was established to provide timely and accurate synthesis of targeted healthcare topics of particular importance to VA managers and policymakers –; and to disseminate these reports throughout VA.

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