Effect of low-dose calcium supplements on bone loss in perimenopausal and postmenopausal Asian women: a randomized controlled trial

J Bone Miner Res. 2012 Nov;27(11):2264-70. doi: 10.1002/jbmr.1676.


Current standard-dose calcium supplements (eg, 1000 mg/d) may increase the risk for cardiovascular events. Effectiveness of lower-dose supplements in preventing bone loss should thus be considered. This study aimed to assess whether calcium supplements of 500 or 250 mg/d effectively prevent bone loss in perimenopausal and postmenopausal Japanese women. We recruited 450 Japanese women between 50 and 75 years of age. They were randomly assigned to receive 500 mg of calcium (as calcium carbonate), 250 mg of calcium, or placebo daily. Medical examinations conducted three times over a 2-year follow-up period assessed bone mineral density (BMD) of the lumbar spine and femoral neck. One-factor repeated measures ANOVA was used for statistical tests. Subgroup analyses were also conducted. Average total daily calcium intake at baseline for the 418 subjects who underwent follow-up examinations was 493 mg/d. Intention-to-treat analysis showed less dramatic decreases in spinal BMD for the 500-mg/d calcium supplement group compared to the placebo group (1.2% difference over 2 years, p = 0.027). Per-protocol analysis (≥80% compliance) revealed that spinal BMD for the 500-mg/d and 250-mg/d calcium supplement groups decreased less than the placebo group (1.6%, p = 0.010 and 1.0%, p = 0.078, respectively), and that femoral neck BMD for the 500-mg/d calcium supplement group decreased less relative to the placebo group (1.0%, p = 0.077). A low-dose calcium supplement of 500 mg/d can effectively slow lumbar spine bone loss in perimenopausal and postmenopausal women with habitually low calcium intake, but its effect on the femoral neck is less certain. Calcium supplementation dosage should thus be reassessed. (Clinical Trials Registry number: UMIN000001176).

Publication types

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

MeSH terms

  • Aged
  • Asian Continental Ancestry Group*
  • Biomarkers / blood
  • Bone Density / drug effects
  • Bone Resorption / blood
  • Bone Resorption / drug therapy*
  • Bone Resorption / physiopathology
  • Calcium / blood
  • Calcium, Dietary / administration & dosage
  • Calcium, Dietary / pharmacology*
  • Calcium, Dietary / therapeutic use*
  • Dietary Supplements*
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Humans
  • Intention to Treat Analysis
  • Middle Aged
  • Perimenopause / blood
  • Perimenopause / drug effects*
  • Placebos
  • Postmenopause / blood
  • Postmenopause / drug effects*
  • Treatment Outcome


  • Biomarkers
  • Calcium, Dietary
  • Placebos
  • Calcium