AJM Theme Issue: GI and Nutrition
Clinical research study
Randomized Controlled Trial of Calcium in Healthy Older Women

https://doi.org/10.1016/j.amjmed.2006.02.038Get rights and content

Abstract

Purpose

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.

Section snippets

Methods

This is a randomized controlled trial in healthy postmenopausal women that is designed to assess the effects of calcium on bone density and fracture incidence over a period of 5 years. The methods have been described.13 Briefly, subjects were aged more than 55 years, not receiving therapy for osteoporosis or taking calcium supplements, and free of major ongoing disease. Serum creatinine was less than 2.3 mg/dL (0.2 mmol/L), and serum 25-hydroxyvitamin D was greater than 10 μg/L (25 nmol/L).

Subject Disposition and Adherence

Subject disposition is shown in Figure 1. Of the women entering the study, noncompletion was attributable to death in 63, illness in 103, and personal reasons in 50. Among those still taking trial medication at 5 years, tablet compliance was approximately 85% in both treatment groups in each 6-month period. When subjects who discontinued trial medication are included, compliance over the entire study was 58% in the placebo group and 55% in the calcium group (P = .13).

Bone Mineral Density

In the intention-to-treat

Discussion

This study confirms the beneficial effects of calcium supplementation on bone density in healthy older women. It shows that these benefits are present throughout the skeleton, that they are independent of age, and that they are present in individuals with both high and low dietary calcium intakes. These results provide confirmation of similar findings in a number of smaller studies, but the size of the present trial allows these conclusions to be reached with much greater certainty. In

Acknowledgments

The authors are grateful to Professors Tim Cundy and Andrew Grey for their comments on the article, to Dr. James Davidson for undertaking the bone turnover marker analyses, and to Mission Pharmacal, San Antonio, Tex, for supplying the calcium citrate tablets and placebo.

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