Relationship between bone mineral density changes and risk of fractures among patients receiving calcium with or without vitamin D supplementation: a meta-regression

Osteoporos Int. 2011 Mar;22(3):893-901. doi: 10.1007/s00198-010-1469-x.


Surrogate measures of fracture risk, such as effects on bone mineral density, may be of great interest to assess the efficacy of available osteoporosis treatments.Our results suggest that bone mineral density (BMD)changes cannot be used as a surrogate of anti-fracture efficacy, among patients receiving calcium, with or without vitamin D.

Introduction: The purpose of this study is to examine the association between changes in bone mineral density with reduction in the risk of fractures in patients receiving calcium with or without vitamin D.

Methods: We selected all randomized placebo-controlled clinical trials of calcium with or without vitamin D supplementation. To be included in this analysis, the studies were required to report both BMD (hip/proximal femur and/or lumbar spine) and the incidence of fractures. Meta-regression analyses were used to examine the associations of changes in BMD with reduction in risk of fracture over the duration of each study. The change in BMD was the difference between changes (from baseline) observed in the active treatment group and placebo group.

Results: A total of 15 randomized trials (n=47,365) were identified, most of whom (77%) came from the Women's Health Initiative trial. Results show that larger increases in BMD at the lumbar spine were not associated with greater reduction in fracture risk. Concerning hip BMD changes,we found a statistically significant relationship between hip BMD changes and reduction in risk. However, results were not quite significant after excluding the both largest studies, in which BMD changes were measured in very small subset of patients. These points may have largely biased our results.

Conclusions: In conclusion, there was no evidence of a relationship between BMD changes and reduction in risk of fractures among patients receiving calcium with or without vitamin D supplementation. Calcium and/or Vitamin D may reduce fracture rates through a mechanism independent of bone density.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bone Density / drug effects
  • Bone Density / physiology*
  • Bone Density Conservation Agents / administration & dosage*
  • Calcium, Dietary / administration & dosage*
  • Female
  • Fractures, Bone / epidemiology*
  • Hip / physiology
  • Humans
  • Lumbar Vertebrae / physiology
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Regression Analysis
  • Risk Factors
  • Vitamin D / administration & dosage
  • Vitamin D / analogs & derivatives*


  • Bone Density Conservation Agents
  • Calcium, Dietary
  • Vitamin D
  • 25-hydroxyvitamin D