Metabolic Rewiring and Post-Translational Modifications: Unlocking the Mechanisms of Bone Turnover in Osteoporosis

Osteoporosis is a metabolic disease characterized by low bone density resulting from abnormal bone metabolism, caused by impaired osteogenesis and/or excessive bone resorption. The coordinated differentiation of osteoblasts (originating from mesenchymal stem cells) and osteoclasts (derived from hematopoietic progenitor cells) is necessary for maintaining normal bone remodeling and homeostasis. Metabolites have been confirmed to regulate cellular behavior through post-translational modifications (PTMs), including acetylation, lactylation, and succinylation. During osteoblast and osteoclast differentiation, progenitor cells undergo metabolic rewiring to meet the energy demands of these biological processes. Consequently, local metabolite profiles and intermediate metabolic products dynamically change during bone remodeling, influencing cell differentiation via PTMs. Given the regulatory role of PTMs in bone metabolism, this review systematically examines PTMs involved in osteoblast and osteoclast differentiation and explores potential avenues for addressing osteoporosis.