SLR - June 2014 - Kyle R. Moore
Reference: DiGiovanni C, Lin S, Baumhauer J, Daniels T, Younger A, Glazebrook M, Anderson J, Anderson R, Evangelista P, Lynch S, North American Orthopedic Foot and Ankle Study Group. Recombinant Human Platelet-Derived Growth Factor-BB and Beta-Tricalcium Phosphate: An Alternative to Autogenous Bone Graft. J Bone Joint Surg Am, 2013.95:1184-92.
Scientific Literature Review
Reviewed By: Kyle R. Moore, DPM
Residency Program: Western Pennsylvania Hospital
Podiatric Relevance: Hindfoot and ankle fusions are frequently performed by foot and ankle specialists worldwide. Arthrodesis has become a mainstay procedure to treat severe joint degeneration, instability, and pedal deformity in patients amendable to surgical intervention. Furthermore, it is commonly deemed necessary to utilize bone graft products for augmentation of a fusion site. The potential complications of harvesting autogenous graft have been well documented in the surgical literature over the past decade. As such, the search for the ideal substitute for autograft has been an ongoing topic of discussion for researchers and practitioners alike. Recently, bioengineered products such as bone morphogenic proteins (BMPs) and purified recombinant human platelet-derived growth factor (rh-PDGF) have shown potential promise in providing near equal rates of successful union when compared to the oft cited gold standard, autograft. This therapeutic level -1, prospective, randomized controlled, non-inferiority trial assesses the efficacy of a combination rh-PDFG/Beta-TCP graft compared to autogenous bone graft in ankle and hindfoot fusions.
Methods: In this study, an initial cohort of four hundred thirty four (434) patients requiring hindfoot or ankle arthrodesis was randomized into two groups receiving either rh-PDGH/Beta-TCF or autogenous bone graft for fusion site augmentation. Thirty-seven of these patients were ultimately removed from the study for failing to meet eligibility criteria. Of this remaining cohort to be evaluated, 260 patients received rh-PDGF-BB/Beta-TCP and 137 received autogenous bone graft during their arthrodesis procedure. Primary end points assessed included evaluation of fusion by means of computed tomography (CT) scan at multi-week intervals postoperatively. Furthermore, secondary end points evaluated included functional and clinical scoring systems such as the American Orthopedic Foot & Ankle Society (AOFAS) hindfoot and ankle outcome score, visual analogue scale (VAS), and Short Form -12 (SF-12).
Results: Upon evaluation of the primary end point, 61.2 percent (159) in the rh-PDGF group compared with 62 percent of autograft patients (85) were found to have undergone successful fusion by CT evaluation at 26 weeks. Furthermore, 86.2 percent of patients in the rh-PDGF group were deemed to be clinically fused at 52 weeks compared to 87.6 percent of patients in the autograft group. No statistically significant differences existed between the groups regarding analysis of the primary end point. Furthermore, nearly all functional outcome and quality-of-life data (15 of 16 secondary end-point criteria) were comparable at 52 weeks post-surgery between the two groups. There were no device related adverse events reported in the rh-PDGF/beta-TCF group.
Conclusions: Platelet derived growth factors are well known to be powerful mitogenic, chemotactic, and pro-angiogenic stimulatory products that do not alter the target cell phenotype like bone morphogenic proteins. Preparing purified PDGF-BB via recombinant DNA technology allows delivery of a highly concentrated dose in a reproducible, controlled manner. By mobilizing mesenchymal stems cells and stabilizing new vasculature, many supporters feel this particular subset of stimulatory factors are ideally suited to address the challenges of lower limb arthrodesis. When employed along with an osteoconductive agent such as beta-tricalcium phosphate, the authors of this study feel that rhPDGF-BB is equally effective as autograft in performing hindfoot and ankle arthrodesis.