COCHRANE FOR CLINICIANS: PUTTING EVIDENCE INTO PRACTICE
Calcium Supplementation in Postmenopausal Women
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Am Fam Physician. 2004 Jun 15;69(12):2822-2323.
This clinical content conforms to AAFP criteria for evidence-based continuing medical education (EB CME). EB CME is clinical content presented with practice recommendations supported by evidence that has been systematically reviewed by an AAFP-approved source. The practice recommendations in this activity are available online at http://www.cochrane.org/cochrane/revabstr/ab004526.htm.
A 53-year-old woman who is one year postmenopausal comes in for a routine examination. She asks about taking supplemental calcium to prevent osteoporosis.
Should we recommend calcium supplementation for postmenopausal women?
Calcium supplementation has a beneficial effect on bone density and may reduce vertebral fractures. It has no clear effect on nonvertebral fractures, although the number of patients studied may be too small to predict this outcome.
Although calcium is one of the simplest and least expensive strategies for preventing osteoporotic fractures, calcium supplementation is not without controversy. The U.S. Food and Drug Administration has permitted a bone health claim for calcium-rich foods, and a National Institutes of Health consensus statement notes that high calcium intake reduces the risk of osteoporosis.
To assess the effects of calcium supplementation on bone density and fractures in postmenopausal women.
The authors1 searched Cochrane Controlled Register, MEDLINE, and EMBASE up to 2001 and examined citations of relevant articles and proceedings of international meetings.
Trials that randomized post-menopausal women to calcium supplementation or usual dietary calcium intake; followed patients for at least one year; and reported bone mineral density of the total body, vertebral spine, hip, or forearm or recorded the number of fractures were considered for inclusion in the study.
Data Collection and Analysis
Three independent reviewers assessed the methodologic quality and extracted data from each trial. For each bone-density site (i.e., lumbar spine, total body, combined hip, and combined forearm), the authors calculated the weighted mean difference (WMD) in bone density between treatment and control groups using the percentage change from baseline. The authors constructed regression models in which the independent variables were year and dosage, and the dependent variable was the effect size. This regression was used to determine the years across which pooling was appropriate. Heterogeneity was asssessed. The authors calculated a risk ratio for each fracture analysis.
Fifteen trials including 1,806 participants were included. Calcium was more effective than placebo in reducing rates of bone loss after two or more years of treatment. The pooled difference in percentage change from baseline was 2.05 percent for total body bone density (95 percent confidence interval [CI], 0.24 to 3.86), 1.66 percent for the lumbar spine at two years (95 percent CI, 0.92 to 2.39), 1.60 percent for the hip (95 percent CI, 0.78 to 2.41), and 1.91 percent for the distal radius (95 percent CI, 0.33 to 3.50). The relative risk (RR) for vertebral fractures was 0.79 (95 percent CI, 0.54 to 1.09), the RR for nonvertebral fractures was 0.86 (95 percent CI, 0.43 to 1.72).
Calcium supplementation alone has a small positive effect on bone density. The data show a trend toward reduction in vertebral fractures, but it is unclear if calcium reduces the incidence of nonvertebral fractures.
These summaries have been derived from Cochrane reviews published in the Cochrane Database of Systematic Reviews in the Cochrane Library. Their content has, as far as possible, been checked with the authors of the originalreviews, but the summaries should not be regarded as an official product of the Cochrane Collaboration; minorediting changes have been made to the text (http://www.cochrane.org)
This was a well-conducted systematic review of calcium supplementation to increase bone density and reduce fracture risk in postmenopausal women. Although not statistically significant, there was a trend toward reduced vertebral fracture risk in postmenopausal women who take calcium. These data were consistent across trials. It is likely that the data did not reach statistical significance because of the small number of women enrolled in the studies (fewer than 600 total) and varying duration of follow-up (one to four years).
Results for secondary prevention of fractures also did not reach statistical significance. Results for bone mineral density, an intermediate outcome, showed less bone loss in women taking calcium than in those who received placebo. The decrease in bone loss was not statistically significant in women without osteoporosis, but it was statistically significant in women with osteoporosis.
Despite the limited data, calcium supplementation in postmenopausal women makes sense. The Institute for Clinical Systems Improvement guideline on diagnosis and treatment of osteoporosis2 recommends 1,200 mg of calcium per day for healthy women over age 50 and 1,500 mg per day for women who have osteoporosis, use glucocorticoids, or are pregnant, nursing, or older than 65. Other options for bone loss prevention include vitamin D, estrogen, bisphosphonates, and raloxifene. Bisphosphonates have the strongest evidence for prevention of fracture in women with osteoporosis.2 The 2000 National Institutes of Health consensus conference3 also recommends calcium supplementation in women who do not achieve recommended intake in their diet.
Based on the best available evidence, calcium supplementation seems like a worthwhile approach to bone health in postmenopausal women. Although no definitive conclusions about dosage or formulation can be drawn from this meta-analysis, calcium carbonate at 1,000 mg per day was the most common dosage and is a reasonable choice.
Cheryl A. Flynn, M.D., M.S., is assistant professor of family medicine at State University of New York Upstate Medical University, Syracuse. She has a special interest in evidence-based medicine.
Address correspondence to Cheryl A. Flynn, M.D., M.S., SUNY Upstate Medical University, 475 Irving Ave., Suite 200, Syracuse, NY 13210 (e-mail: email@example.com). Reprints are not available from the author.
1. Shea B, Wells G, Cranney A, Zytaruk N, Robinson V, Griffith L, et al. Calcium supplementation on bone loss in postmenopausal women. Cochrane Database Syst Rev. 2004:CD004526.
2. Institute for Clinical Systems Improvement. Diagnosis and treatment of osteoporosis. Accessed February 2004 at: http://www.icsi.org/knowledge/detail.asp?catID=29&itemID=547.
3. Osteoporosis prevention, diagnosis, and therapy. NIH Consens Statement. 2000;17:1–45.
The Cochrane Abstract is a summary of a review from the Cochrane Library. It is accompanied by an interpretation that will help clinicians put evidence into practice. Cheryl A. Flynn, M.D., M.S., presents a clinical scenario and question based on the Cochrane Abstract, along with the evidence-based answer and a full critique of the abstract.
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