Pathogenesis of Sarcopenia-Osteoporosis

Osteosarcopenia(OS) is the coexistence of sarcopenia(SP) and osteoporosis(OP). SP is a decrease in the number and strength of muscle fibers, causing impaired skeletal muscle function, and OP manifests itself as bone loss, decreased density, and degradation of bone microarchitecture. Mechanical loading is an important factor in maintaining the skeletal muscle-skeletal units in the interaction between skeletal muscle and bone. Increased muscle mass promotes bone growth and development and improves bone density and strength. As we age, skeletal muscle mass progressively decreases, leading to reduced skeletal loading which triggers wasting atrophy of the skeleton. Hormonal imbalance, chronic inflammation, oxidative stress, imbalance between protein degradation and synthesis, decreased physical activity and malnutrition are all closely associated with the development of OS. Interleukin(IL)-6 and tumor necrosis factor α(TNF-α)are important regulators of bone metabolism, and their elevated levels are negatively correlated with bone mineral density. IL-6 and TNF-α also inhibit protein synthesis in muscle by interfering with PI3K/Akt signaling pathways. NOD-like receptor protein 3(NLRP3) causes up-regulation of the NF-κB(nuclear factor-kappa B) pathway by activating damage-related molecules, and NLRP3 recruits pro-Caspase-1 to promote the release of IL-1β and IL-18, leading to increased chronic inflammation and inducing OS. The interdependence between skeletal muscle and bone and the interaction of multiple biological factors combine to contribute to the development of OS. As global aging increases, the incidence of OS will continue to rise, and in-depth investigation of its mechanisms is urgently needed to provide a theoretical basis for OS prevention and treatment.