On a Quest to Dethrone the Long-Reigning King

Abstract

Autograft is still regarded as the gold standard in bone-grafting, despite its well-appreciated limitations. The iliac crest has been the primary source of autologous bone, but other sites, such as the tibial metaphyses and the calcaneus, have also been commonly used. The techniques of autograft harvesting have recently evolved to include reamer-irrigator-aspirator (RIA) harvesting. RIA-harvested autograft can be used as stand-alone graft material or, for enhanced structural integrity, in combination with firmly packed cancellous graft. Both cancellous and RIA-harvested grafts have the distinction of being osteogenic, osteoinductive, and osteoconductive, all in their physiologic ratio. However, a need for additional surgical exposure, limited availability, and potential risks associated with graft harvesting have prompted a search for suitable autograft alternatives. The advent of recombinant human bone morphogenetic proteins (rhBMPs) generated optimism that the pursuit for an optimal alternative to autogenous bone graft had, at last, successfully ended. Bone morphogenetic proteins (BMPs) proved to be an extremely potent autograft substitute as evidenced by numerous preclinical and clinical studies. Although cleared by the U.S. Food and Drug Administration (FDA) for the highly selected orthopaedic indications, BMPs (rhBMP-2, rhBMP-7) have been extensively used off-label by many clinicians. However, the prevalent and serious adverse events associated with the on and off-label use of rhBMPs call for a revisiting of its clinical safety and efficacy1. The quest for an optimal bone graft alternative is, again, back on track. Recombinant human platelet-derived growth factor BB (rhPDGF-BB) has been introduced as another potent biologic graft substitute to stimulate cell proliferation, recruitment, and revascularization. Platelet-derived growth factor (PDGF) natively occurs as a dimeric polypeptide with A, B, C, or D chains, and …