Current Insights On An Innovative Alternative To Autogenous Bone Graft
Arthrodesis is a commonly performed procedure for numerous arthropathies and deformities of the foot and ankle. Non-union remains a frequent complication of foot and ankle arthrodesis with non-union rates reported in the literature ranging from 0 to 47 percent.1-5 Numerous risk factors can affect non-union rate including location, fixation, smoking, diabetes and infection.5
Surgeons have frequently used autogenous bone graft to promote bone fusion, especially in high-risk patient populations.6-10 Autogenous cancellous iliac crest bone graft is considered to be the gold standard for foot and ankle surgery.10
However, there are several downsides to the use of autogenous bone graft. Bone graft harvesting increases operative time and procedure cost. Complications of bone graft harvesting include blood loss, chronic donor site pain, fracture, seroma, scar tissue formation, infection, heterotopic ossification, hernia, peritoneal perforations, arterial injury and nerve injury.8,10-15 Additionally, the quality of autogenous bone graft can vary and host factors including age and health status can affect this.16 Given the limitations of autograft, many surgeons have sought alternatives to promote bone healing and reduce non-union rates.
Recombinant human platelet-derived growth factor (rhPDGF) is an alternative to autogenous bone graft. Platelet-derived growth factor-BB (PDGF-BB) is the most active isoform in bone and other connective tissues.19 This growth factor is an osteostimulatory and angiogenic protein with mitogenic and chemotactic effects on mesenchymal cells that play key roles in the early phase of bone healing.17,18 The PDGF-BB additionally helps to stabilize newly forming blood vessels.20,21
Given the poor vascularity at many foot and ankle arthrodesis sites, the angiogenic potential of rhPDGF-BB can significantly aid in bone healing.22,23 Due to the preparation of PDGF with recombinant DNA under highly controlled conditions, there is no variability in the quality or quantity of rhPDGF-BB, yielding a more predictable outcome in comparison to autogenous bone graft. To further enhance bone healing, one may combine rhPDGF-BB with beta-tricalcium phosphate (β-TCP) and an osteoconductive scaffold.22,24
In 2013, DiGiovanni and colleagues examined the combined use of recombinant human PDGF-BB and beta-tricalcium phosphate (rhPDGF-BB/β-TCP) as an alternative to autogenous bone autograft.19 In this randomized, controlled, multicenter study, the authors compared the safety and efficacy of rhPDGF-BB/β-TCP to autograft in 434 patients undergoing hindfoot and ankle arthrodesis. At six months, 61.2 percent of patients in the rhPDGF-BB/β-TCP group and 62 percent of patients in the autograft graft group achieved fusion as determined by computed tomography. Clinically, 86.2 percent of patients in the rhPDGF-BB/β-TCP group and 87.6 percent of patients in the autograft group were healed at 52 weeks. Patients in the rhPDGF-BB/β-TCP group had less pain and an improved safety profile in comparison to the autograft group.
Currently manufactured by Wright Medical as Augment Bone Graft, rhPDGF-BB/β-TCP offers an alternative to autograft for hindfoot and ankle arthrodesis. The level 1 evidence led to subsequent FDA approval of Augment Bone Graft in September 2015.19 Further analysis is needed to assess the economic value of this new technology but given the increased resource utilization with autograft, including increased operating room time, staff and personnel cost; potential increased length of hospital stay; and the cost of managing donor site complications, rhPDGF-BB/β-TCP may very well prove to be a cost-effective modality.
References
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19. 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.
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24. Digiovanni CW, Baumhauer J, Lin SS, et al. Prospective, randomized, multi-center feasibility trial of rhPDGF-BB versus autologous bone graft in a foot and ankle fusion model. Foot Ankle Int. 2011;32(4):344-354.
