Vitamin D, muscle and bone: Integrating effects in development, aging and injury

• Vitamin D exerts integrated effects in musculoskeletal development, aging and injury.
• Vitamin D regulates bone and muscle-derived hormones, thereby potentially facilitating cross-talk.
• Effects of vitamin D in muscle and bone are predominantly indirect via calcium and phosphate levels.
• Vitamin D also exerts direct effects in muscle and bone by the local activity of the vitamin D receptor.
• Vitamin D signaling presents a potential therapeutic target in the approach to musculoskeletal disease.

Beyond the established effects of muscle loading on bone, a complex network of hormones and growth factors integrates these adjacent tissues. One such hormone, vitamin D, exerts broad-ranging effects in muscle and bone calcium handling, differentiation and development. Vitamin D also modulates muscle and bone-derived hormones, potentially facilitating cross-talk between these tissues. In the clinical setting, vitamin D deficiency or mutations of the vitamin D receptor result in generalized atrophy of muscle and bone, suggesting coordinated effects of vitamin D at these sites. In this review, we discuss emerging evidence that vitamin D exerts specific effects throughout the life of the musculoskeletal system – in development, aging and injury. From this holistic viewpoint, we offer new insights into an old debate: whether vitamin D's effects in the musculoskeletal system are direct via local VDR signals or indirect via its systemic effects in calcium and phosphate homeostasis.