Osteosarcopenia Revisited: From Mechanisms to Management

Sarcopenia and osteoporosis are characterized by insufficient mass and function of skeletal muscle and bone, and often co-occur in older persons, a condition called osteosarcopenia. Loss of bone and skeletal muscle mass and function is driven by multiple risk factors that activate the hallmarks of aging. Recent genome-wide association studies in humans and animal models suggest pivotal roles for mitochondria, the nucleus, and nutrient anabolism, which are closely associated with the hallmarks of aging, as well as for osteokines and myokines, in the development of osteosarcopenia. Osteosarcopenia is associated with a higher risk of adverse outcomes, such as falls, fractures, depression, and frailty, and consequently with mortality. Diagnosis of osteosarcopenia involves various imaging techniques to assess bone mineral density and skeletal muscle mass, as well as assessments of physical performance or muscle function. Moreover, a comprehensive evaluation of medical history, medications, and laboratory data is important for identifying potential contributing factors and assessing risk. To manage and treat osteosarcopenia, a multimodal approach, such as exercise therapy, nutritional supplementation, and pharmacotherapies, is required. Future prospects include technological innovations such as artificial intelligence and the identification of novel biomarkers based on multi-omics analyses, which will help enhance early detection of this condition. Emerging drugs that positively regulate bone and muscle mass are under development and are expected to contribute to individually optimized care for osteosarcopenia.