Local delivery of rhBMP-2 affects systemic metabolic response during healing of critically-sized segmental defects in...

Understanding the biological mechanisms behind fracture nonunions and their treatments remains incomplete. Since these mechanisms are linked to phenotypic expression, studying the longitudinal metabolic profile of bone regeneration has emerged as a potential way to better understand healing progress and treatment effectiveness. In this study, we tracked the serum metabolome of rats with critically-sized femoral defects treated with either a control, a minimum effective dose, or a supraphysiologic dose of rhBMP-2 over time. We observed distinct changes in the metabolome across control, impaired healing, and rhBMP-2-treated animals. Early in the process, we saw increased levels of metabolites that support angiogenesis in the rhBMP-2 groups. Supraphysiologic doses of rhBMP-2 significantly affected metabolite expression, especially in pathways related to angiogenesis, fatty acid metabolism, and ATP production. These longitudinal trends and individual metabolite changes provide a deeper understanding of rhBMP-2's mechanisms, improve our knowledge of its biological effects-guiding appropriate dosing-and offer a metabolic profile that may indicate healing impairment.