Randomized controlled trial of calcium in healthy older women.
OBJECTIVE
Calcium has been shown to have positive effects on bone mineral density in postmenopausal women. However, these effects are small, it is unknown whether they are sustained with long-term use, they have not been shown with intention-to-treat analyses, and the evidence for fracture prevention with calcium monotherapy is inconsistent.


METHODS
A randomized controlled trial of calcium (1 g/day as the citrate) in 1471 healthy postmenopausal women (aged 74+/-4 years) was performed to assess the effects on bone density and fracture incidence over 5 years.


RESULTS
Follow-up was complete in 90% of subjects, and average medication compliance was 55% to 58%. Calcium had a significant beneficial effect on bone density (intention-to-treat analysis), with between-groups differences at 5 years of 1.8% (spine), 1.6% (total hip), and 1.2% (total body). Effects were greater in a per-protocol analysis (5-year differences of 2.3%, 2.8%, and 1.8%, respectively). A total of 425 fractures occurred in 281 women. Hazard ratios, based on time to first fracture, were 0.90 (95% confidence interval [CI], 0.71-1.16) for any symptomatic fracture, 0.72 (95% CI, 0.44-1.18) for vertebral, 3.55 (95% CI, 1.31-9.63) for hip, and 0.65 (95% CI, 0.41-1.04) for forearm fracture. Per-protocol analysis found respective hazard ratios of 0.86 (95% CI, 0.64-1.17), 0.62 (95% CI, 0.33-1.16), 3.24 (95% CI, 0.65-16.1), and 0.45 (95% CI, 0.24-0.87). Height loss was reduced by calcium in the per-protocol population (P=.03). Serum alkaline phosphatase and procollagen type-I N-terminal propeptide were lower in the calcium group at 5 years, but constipation was more common.


CONCLUSIONS
Calcium results in a sustained reduction in bone loss and turnover, but its effect on fracture remains uncertain. Poor long-term compliance limits its effectiveness.
Reid
Ian R
IR
Department of Medicine, University of Auckland, Auckland, New Zealand. i.reid@auckland.ac.nz
Mason
Barbara
B
Horne
Anne
A
Ames
Ruth
R
Reid
Helen E
HE
Bava
Usha
U
Bolland
Mark J
MJ
Gamble
Gregory D
GD
D000368:Aged; D015415:Biomarkers; D015519:Bone Density / Q000187:drug effects*; D019355:Calcium Citrate / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D050723:Fractures, Bone / Q000517:prevention & control*; D006801:Humans; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy / Q000517:prevention & control*; D017698:Postmenopause; D013997:Time Factors
D015415:Biomarkers; D019355:Calcium Citrate