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Functions of vitamin D in bone

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Abstract

Vitamin D, synthesized in the skin or absorbed from the diet, undergoes multi-step enzymatic conversion to its active form, 1,25-dihydroxy vitamin D [1,25(OH)2D], followed by interaction with the vitamin D receptor (VDR), to modulate target gene expression. Loss-of function mutations in the genes encoding the enzymes regulating these processes, or in the VDR, result in human diseases, which have demonstrated the paramount role of 1,25(OH)2D in mineral and skeletal homeostasis. Mouse genetics has been used to create disease phenocopies which have produced considerable insight into the mechanisms of 1,25(OH)2D regulation of mineral and skeletal metabolism. Hypophosphatemia resulting from 1,25(OH)2D deficiency or resistance can inhibit apoptosis in hypertrophic chondrocytes leading to abnormal development of the cartilaginous growth plate in rickets. Decreased 1,25(OH)2D may also cause decreased vascular invasion associated with reduced chondroclast and osteoclast activity and thereby contribute to growth plate abnormalities. Reduced 1,25(OH)2D-mediated intestinal and renal calcium transport can reduce calcium availability, increase parathyroid hormone secretion and phosphaturia, and impair mineral availability for normal matrix mineralization, resulting in reduced growth plate mineralization and osteomalacia. 1,25(OH)2D may exert an anabolic effect in bone, apparently via the VDR in mature osteoblasts, by increasing osteoblast activity and reducing osteoclast activity. High ambient levels of exogenous 1,25(OH)2D, or of elevated endogenous 1,25(OH)2D in the presence of reduced calcium balance, can enhance bone resorption, and apparently prevent mineral deposition in bone. These actions demonstrate the critical role of vitamin D in regulating skeletal homeostasis both indirectly and directly via the 1,25(OH)2D/VDR system.

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Acknowledgements

Funding was provided by Canadian Institutes of Health Research (Grant no. PJT-152963).

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  1. Department of Medicine, McGill University, Montreal, QC, Canada

    D. Goltzman

  2. Department of Physiology, McGill University, Montreal, QC, Canada

    D. Goltzman

  3. Department of Medicine, McGill University Health Centre, Montreal, QC, Canada

    D. Goltzman

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Goltzman, D. Functions of vitamin D in bone. Histochem Cell Biol 149, 305–312 (2018). https://doi.org/10.1007/s00418-018-1648-y

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