Vitamin D activities and metabolic bone disease

Clin Chim Acta. 2013 Oct 21:425:148-52. doi: 10.1016/j.cca.2013.07.024. Epub 2013 Jul 30.


Vitamin D activity requires an adequate vitamin D status as indicated by the serum level of 25-hydroxyvitamin D and appropriate expression of genes coding for vitamin D receptor and 25-hydroxyvitamin D 1α-hydroxylase, the enzyme which converts 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. Vitamin D deficiency contributes to the aetiology of osteomalacia and osteoporosis. The key element of osteomalacia, or rickets in children, is a delay in mineralization. It can be resolved by normalisation of plasma calcium and phosphate homeostasis independently of vitamin D activity. The well characterised endocrine pathway of vitamin D metabolism generates plasma 1,25-dihydroxyvitamin D and these endocrine activities are solely responsible for vitamin D regulating plasma calcium and phosphate homeostasis and protection against osteomalacia. In contrast, a large body of clinical data indicate that an adequate serum 25-hydroxyvitamin D level improves bone mineral density protecting against osteoporosis and reducing fracture risk. Recent research demonstrates that the three major bone cell types have the capability to metabolise 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D to activate the vitamin D receptor and modulate gene expression. Dietary calcium intake interacts with vitamin D metabolism at both the renal and bone tissue levels to direct either a catabolic action on bone through the endocrine system when calcium intake is inadequate or an anabolic action through a bone autocrine or paracrine system when calcium intake is sufficient.

Keywords: 25-Hydroxyvitamin D 1α-hydroxylase (CYP27B1); Dietary calcium; Fracture; Osteomalacia; Osteoporosis; Vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism
  • Bone Density
  • Bone and Bones / metabolism*
  • Bone and Bones / pathology
  • Calcification, Physiologic
  • Calcium / metabolism
  • Child
  • Gene Expression Regulation
  • Humans
  • Osteomalacia / etiology
  • Osteomalacia / metabolism*
  • Osteomalacia / pathology
  • Osteoporosis / etiology
  • Osteoporosis / metabolism*
  • Osteoporosis / pathology
  • Phosphates / metabolism
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism
  • Vitamin D / analogs & derivatives*
  • Vitamin D / metabolism
  • Vitamin D Deficiency / complications
  • Vitamin D Deficiency / metabolism*
  • Vitamin D Deficiency / pathology


  • Phosphates
  • Receptors, Calcitriol
  • Vitamin D
  • 1,25-dihydroxyvitamin D
  • 25-hydroxyvitamin D
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Calcium