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Vitamin D physiology.

P Lips1

  • 1Department of Endocrinology, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, Netherlands. p.lips@vumc.nl

Progress in Biophysics and Molecular Biology
|March 28, 2006
PubMed
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Vitamin D is crucial for calcium absorption and bone health, with deficiency linked to rickets, osteomalacia, and osteoporosis. Supplementation improves bone density and may reduce fractures in the elderly.

Area of Science:

  • Endocrinology
  • Bone Biology
  • Nutritional Science

Background:

  • Vitamin D3 is synthesized in the skin or obtained from diet, undergoing hydroxylation to its active form, 1,25-dihydroxyvitamin D (1,25(OH)2D).
  • The active metabolite binds to the vitamin D receptor, influencing gene expression for proteins like calcium-binding protein, essential for gut calcium absorption.
  • Vitamin D deficiency risk factors include premature birth, obesity, malabsorption, and advanced age, with immigrants and the elderly being at-risk groups.

Purpose of the Study:

  • To elucidate the multifaceted roles of vitamin D metabolites and the vitamin D receptor in calcium homeostasis, bone metabolism, and cellular functions.
  • To investigate the impact of vitamin D deficiency and supplementation on bone health markers and fracture incidence.
  • To explore the potential involvement of vitamin D in the pathogenesis of autoimmune diseases and cancer.

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Main Methods:

  • Review of existing literature on vitamin D metabolism, its effects on gene expression, and its clinical implications.
  • Analysis of studies investigating the relationship between serum 25(OH)D levels, parathyroid hormone (PTH), and bone mineral density.
  • Examination of data from genetic defect studies and knockout mouse models to understand the essentiality of 1,25(OH)2D and its receptor.

Main Results:

  • Severe vitamin D deficiency leads to rickets and osteomalacia, while less severe deficiency increases PTH, causing bone resorption, osteoporosis, and fractures.
  • A threshold of approximately 75 nmol/l for serum 25(OH)D is identified, below which serum PTH levels begin to rise.
  • Vitamin D supplementation in deficient elderly individuals suppressed PTH, increased bone mineral density, and potentially reduced fracture risk.
  • Both 1,25(OH)2D and its receptor are essential for calcium absorption, bone growth, and osteoblast/osteoclast activity; bone mineralization is primarily dependent on calcium concentration.
  • Rapid, non-genomic effects of 1,25(OH)2D via a membrane receptor influence pancreas, vascular smooth muscle, and monocytes.
  • Serum 25(OH)D levels correlate with physical performance, and 1,25(OH)2D exhibits antiproliferative and anti-inflammatory effects.
  • Extrarenal synthesis of 1,25(OH)2D plays a role in paracrine regulation, suggesting vitamin D's involvement in autoimmune diseases and cancer pathogenesis.

Conclusions:

  • The active metabolite 1,25(OH)2D exerts pleiotropic effects through genomic and rapid non-genomic pathways.
  • Adequate 1,25(OH)2D formation and an intact vitamin D receptor are critical for intestinal calcium absorption.
  • Bone mineralization is predominantly influenced by ambient calcium concentrations.
  • Vitamin D metabolites may play a role in preventing autoimmune diseases and cancer.