Branched-chain amino acids in bone health: From molecular mechanisms to therapeutic potential

Branched-chain amino acids (BCAAs)-leucine, isoleucine, and valine-are essential amino acids involved in protein synthesis, cellular metabolism, and key signaling pathways such as mTOR and AMPK. Recent studies suggested that BCAAs play a significant role in bone metabolism by regulating osteoblast and osteoclast activity, thereby influencing bone remodeling and homeostasis. This review systematically examined the molecular mechanisms by which BCAAs affect bone metabolism, focusing on their roles in cell differentiation, energy sensing, oxidative stress, and immune regulation. Evidence from in vitro experiments, animal models, and clinical studies indicated that BCAAs may promote bone formation and inhibit bone resorption, suggesting potential applications in osteoporosis prevention and musculoskeletal rehabilitation. However, current findings are partially inconsistent, and the underlying mechanisms remain incompletely understood. Moreover, clinical evidence is still limited. Further research is needed to elucidate the metabolic context and specificity of BCAA actions, providing a foundation for precision nutrition strategies in bone health management.