Long-term effects of bone morphogenetic protein- based treatments in humans

Bone morphogenetic proteins (BMPs) are low-molecular-weight proteins of the transforming growth factor-beta (TGF-β) superfamily. In recent years, these growth and differentiation factors have been extensively researched for their multifunctional properties ranging from embryonic development to postnatal homeostasis. The defining ability of BMPs is the role they play in skeletal development and maintenance, especially the powerful osteoinductive activity for which these proteins are currently sought after. There are over 20 BMPs that have been discovered, with BMP-2 and BMP-7 currently being the only proteins of the group that are approved by the US Food and Drug Administration for clinical use as an autograft substitute for lumbar spinal interbody fusion procedures and for open tibial fractures with intramedullary nail fixation. BMP-2 has also been approved for use in dental bone grafting indications. However, a significant amount of off-label usage of these proteins has been reported, which has led to an industry approaching a billion dollars annually. In this review, we examine the long-term effects of BMPs as evidenced from in vitro, preclinical, and clinical studies.