Lactate and lactylation in osteoporosis: pathogenesis, regulation, and future perspectives.

Osteoporosis is a metabolic bone disease characterized by bone microstructural degeneration and increased fracture risk, primarily driven by an imbalance in bone homeostasis. Recent studies have revealed that lactate metabolic remodeling and its derived lactylation modifications play a pivotal role in the dynamic balance between bone formation and resorption by regulating the metabolic-epigenetic network within the bone microenvironment. This review systematically examines the role of lactate metabolic pathways in the energy reprogramming of osteoblasts, analyzes the molecular mechanisms of lactylation in osteogenesis-osteoclastogenesis coupling, and discusses the challenges and future directions of novel therapeutic strategies targeting the lactate metabolism axis. By elucidating the critical role of lactate metabolism in the pathogenesis of osteoporosis, this review aims to enhance comprehensive understanding and facilitate the development of effective therapeutic interventions.