Age-related bone loss and sarcopenia in men

Bone and muscle are required for mobility but they also have endocrine and metabolic functions. In ageing as well as in many chronic diseases, bone loss and muscle atrophy occur simultaneously, leading to concomitant osteoporosis and sarcopenia. This occurs in both genders but compared with postmenopausal women, men appear to be better protected against age-related bone and muscle decay. Sex steroids (both androgens like testosterone and oestrogens like estradiol) are mainly responsible for musculoskeletal sexual dimorphism. They stimulate peak bone and muscle mass accretion during puberty and midlife, and prevent subsequent loss in ageing men but not post-menopausal women. Still, recent studies have highlighted the importance of intrinsic ageing mechanisms such as cellular senescence and oxidative stress in both genders. Sarcopenia may predispose to dysmobility, frailty, falls and fractures, but whether so-called osteosarcopenia qualifies as a distinct entity remains debated. Although randomized clinical trials in male osteoporosis are smaller and therefore under-powered for some outcomes like hip fractures, the available evidence suggests that the clinical diagnostic and therapeutic approach to male osteoporosis is largely similar to that in postmenopausal women. There is a clear unmet medical need for effective and safe anabolic drugs to rebuild the ageing skeleton, muscle, and preferably both tissues simultaneously. The Wnt/sclerostin and myostatin/activin receptor signalling pathways appear particularly promising in this regard. In this narrative review, we aim to provide an overview of our current understanding of the pathophysiology and treatment of male osteoporosis and sarcopenia, and interactions between these two diseases.