Emerging therapeutic concepts for muscle and bone preservation/building

• Therapies to reduce fractures provide a range of mechanisms for improving bone strength.
• Improvements in cortical bone structure can be achieved with some treatments.
• Translation of these effects into fracture reduction remains to be established.

Loss of muscle or bone mass occurs with ageing, immobility and in association with a variety of systemic diseases. The interaction of these two processes is most evident in the major contribution of falls to the risk of fractures in the elderly population. Exercise and nutrition are key common physiological variables that allow for preservation or formation of greater muscle or bone mass. However, although several pharmacological approaches have the potential to benefit both muscle and bone health, for example vitamin D, selective androgen receptor modulators and ghrelin mimetics, clinical trials with appropriate primary outcomes are lacking. Conventional approaches to address muscle loss are being extended to include stem cell biology and conserved molecular mechanisms of atrophy/hypertrophy. Pharmacological interventions to reduce fracture risk are exploring new mechanisms of action, in particular the uncoupling of bone resorption and formation. Emerging key issues for clinical trial design include adequate phenotyping of patients (personalised medicine), optimisation of the physiological background (multimodal approach) and the use of meaningful and robust outcomes relevant to daily clinical practice. At present, effective treatments that combine beneficial effects on both muscle and bone are lacking, although this is an important target for the future. This review therefore considers current and developing strategies to improve muscle function and bone strength in separate sections.