Short-term effects on bone turnover markers of a single high dose of oral vitamin D₃

J Clin Endocrinol Metab. 2012 Apr;97(4):E622-6. doi: 10.1210/jc.2011-2448. Epub 2012 Feb 1.

Abstract

Context: Vitamin D deficiency is often treated or prevented by high intermittent doses of vitamin D to achieve a better treatment adherence, but treatment outcomes were contradictory, and even a transient increase in fracture and fall risk was reported.

Objective: The objective of the study was to investigate the short-term effects on bone turnover markers of a single bolus of vitamin D₃.

Design, setting, patients, and intervention: Twelve elderly subjects (eight women, four men; mean age 76 ± 3 yr) were given a single oral bolus of 600,000 IU vitamin D₃. Blood samples were taken at baseline and 1, 3, 7, 14, 30, 60, and 90 d after vitamin D₃ administration. Twenty-four subjects served as controls.

Main outcome measures: Changes in serum levels of 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D, PTH, C-terminal-telopeptides of type I collagen, cross-linked N-telopeptide of type I collagen (sNTX), osteocalcin, and bone-specific alkaline phosphatase.

Results: No relevant changes in 25OHD and bone turnover markers were observed in the controls. In treated subjects, serum 25OHD attained a peak increment to 67.1 ± 17.1 ng/ml (P < 0.001) at d 3. Subsequently it slowly decreased to 35.2 ± 5.8 ng/ml (P <0.01 vs. a baseline value of 21.7 ± 5.6 ng/ml). Mean serum PTH concentration decreased by 25-50% and serum 1,25-dihydroxyvitamin D rose by 25-50%. Serum CTX and sNTX rose significantly at d 1 (P < 0.01), they attained a peak increment greater than 50% at d 3, and they subsequently decreased almost back to baseline values at d 90. Serum osteocalcin slightly rose within the first 3 d and then declined by d 60. No changes were observed in serum bone-specific alkaline phosphatase.

Conclusions: Our results indicate that the use of large doses of vitamin D may be associated with acute increases in C-terminal-telopeptides of type I collagen and sNTX, which may explain the negative clinical results obtained by using intermittent high doses of vitamin D to treat or prevent vitamin D deficiency.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Biomarkers / blood
  • Biotransformation
  • Bone Density Conservation Agents / administration & dosage
  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / therapeutic use*
  • Bone and Bones / drug effects*
  • Bone and Bones / metabolism
  • Calcifediol / blood
  • Calcitriol / blood
  • Cholecalciferol / administration & dosage*
  • Cholecalciferol / adverse effects
  • Cholecalciferol / pharmacokinetics
  • Cholecalciferol / therapeutic use
  • Collagen Type I / blood
  • Female
  • Humans
  • Male
  • Osteocalcin / blood
  • Osteoporosis / blood*
  • Osteoporosis / complications
  • Osteoporosis / drug therapy*
  • Parathyroid Hormone / blood
  • Peptides / blood
  • Phosphopeptides / blood
  • Procollagen / blood
  • Vitamin D Deficiency / blood*
  • Vitamin D Deficiency / complications
  • Vitamin D Deficiency / drug therapy*

Substances

  • Biomarkers
  • Bone Density Conservation Agents
  • Collagen Type I
  • N-propeptide type I collagen
  • PTH protein, human
  • Parathyroid Hormone
  • Peptides
  • Phosphopeptides
  • Procollagen
  • collagen type I trimeric cross-linked peptide
  • Osteocalcin
  • Cholecalciferol
  • Calcitriol
  • Calcifediol