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.