Osteosarcopenia: cross-talking between muscle and bone

Evolving Treatment Strategies for Osteoporosis: Signaling a change in the conversationSponsor: MSDObjective : Based on the advance of knowledge in biology and medicine, a shift toward a new holistic paradigm and integrative perspective, after decades of reductionist research, will help to understand the complex issue of musculoskeletal health. The present lecture will address the current understanding of the bone-muscle system to define new levers to simultaneously prevent/treat sarcopenia and osteoporosis and to provide effective recommendations.Material and methods : Literature review.Results : Loss of bone and muscle with advancing age represents a huge threat to dependency in the elderly. Both tissues share many similarities and are essential for locomotion and individual autonomy. This is why, in the past decades, the idea of a bone-muscle unit has emerged. Indeed, simultaneous bone and muscle dysfunction has been reported in various situations such as ageing, immobilization, or secondary to diseases (obesity, diabetes, paralysis...). On the opposite many regulation factors, including nutrition, vitamin D, hormones (GH/IGF1 axis, sex steroids) are beneficial. Mechanical loading is also a key mechanism linking both tissues with a central promoting role of physical activity. Moreover, at the cellular and molecular levels, bone cells and myoblasts share common targets and signaling pathways and the close anatomical location of both cell types suggests a possibility of paracrine communication. The skeletal muscle secretome accounts various molecules that affect bone, including insulin-like growth factor-1 (IGF-1), IGF2, basic fibroblast growth factor (FGF-2), interleukin-6 (IL-6), IL7, IL-15, myostatin, follistatin, osteoglycin (OGN), FAM5C, Tmem119, leukemia inhibitory factor (LIF), irisin and osteoactivin. Besides, few osteokines have been identified as well. Prostaglandin E2 (PGE2), and Wnt3a, which are secreted by osteocytes, osteocalcin (OCN) and IGF-1, which are produced by osteoblasts and sclerostin which is secreted by both cell types, might impact skeletal muscle cells. Connexin 43 has also been shown to impair skeletal muscle development.Conclusion : The understanding of the musculoskeletal system will enable to identify concomitant therapies, or how each condition may benefit from treatment of the othe