The importance of BMPs and TGF-βs for endochondral bone repair - A longitudinal study in hip arthroplasty patients.

Introduction: Osseointegration of hip implants, although a decade-long process, shows striking similarities with the four major phases of endochondral bone repair. In the current study we investigated the spatiotemporal involvement of bone morphogenic proteins (BMPs) and transforming growth factor betas (TGF-βs) throughout the process of bone repair leading to successfully osseointegrated hip implants. Materials and methods: Twenty-four patients that had undergone primary total hip arthroplasty (THA) due to one-sided osteoarthritis (OA) were investigated during a period of 18 years (Y) with repeated measurements of plasma biomarkers as well as clinical and radiological variables. All implants were clinically and radiographically well anchored throughout the follow-up. Eighty-one healthy donors divided in three gender- and age-matched groups and twenty OA patients awaiting THA, served as controls. Plasma was analyzed for BMP-1, -2, -3, -4, -6, -7 -9 and TGF-β1, -β2, -β3 by use of a high-sensitivity and wide dynamic range electrochemiluminescence technique allowing for detection of minor changes. Results: Spatiotemporal changes during the follow-up are presented in the context of the four phases of endochondral bone repair shown in earlier studies and transposed to the current study based on similarities in biomarker responses. Phase 1: Conclusion: This study shows that the involvement of BMPs and TGF-βs in endochondral bone repair is a process of stepwise recruitment of individual biomarkers characterized by distinct, yet overlaping, spatiotemporal patterns that extend from the early phase of pre-chondrocyte recruitment until the late phase of coupled bone remodeling.