Frontiers in Endocrinology · Nov 9, 2026
The Role and Mechanisms of β-Hydroxybutyrate in Musculoskeletal Diseases
By Yangting Zhao, Wang He, Jia Zhen et al.
With advancing age, The musculoskeletal system undergoes a series of progressive degenerative changes accompanied by functional impairment, which ultimately lead to age-related musculoskeletal disorders, including sarcopenia, osteoporosis (OP), and osteoarthritis (OA). These disorders pose a substantial threat to the health and well-being of the elderly. Sarcopenia is a prevalent degenerative skeletal muscle disorder among the elderly, characterized by a progressive loss of skeletal muscle mass and deterioration of muscle function. OP is characterized by reduced bone mass and impaired bone microarchitecture as its primary pathological changes, leading to increased bone fragility and elevated fracture risk. OA, a chronic degenerative disorder, affects the entire synovial joint, resulting in joint pain and decreased mobility. The prevalence of these conditions has been increasing annually, severely impacting the quality of life for the aged and increasing the risk of falls, fractures, disability, and even death. Therefore, in-depth investigation into the pathogenesis and preventive strategies of these muscle-bone disorders is critical for effectively addressing the health problems associated with an aging society. However, the precise pathogenesis of musculoskeletal disorders remains incompletely elucidated, and there is a lack of effective clinical therapeutic strategies, thus warranting further investigation. β-Hydroxybutyrate (β-HB) is generated via fatty acid oxidation and acts as a critical energy source for peripheral tissues, including the brain, heart, and skeletal muscle. It not only acts as an alternative energy source for extrahepatic tissues to maintain metabolic homeostasis but also participates in the regulation of cellular functions and adaptive responses. Multiple studies indicate that β-HB possesses numerous vital physiological functions for muscle, bone, and joint health. It plays a pivotal role in skeletal and muscular metabolic disorders by modulating gene expression, activating cell-surface receptors, modifying histones, participating in oxidative stress responses, and regulating lipolysis.