Implications for Clinical Practice
In the WHI study, more women taking calcium and vitamin D developed kidney stones compared with women in the placebo group (449 versus 381, respectively; HR, 1.17; 95% CI, 1.02–1.34). An increase in kidney stones in study subjects taking calcium was not reported in the other studies, but significantly more constipation and gastrointestinal adverse effects were reported in subjects treated with calcium.[18,19,21] Porthouse et al. did not report on adverse effects.
When applying the results of these five trials to clinical practice, there are several issues to consider. The first is that adherence rates were low (55–60%) in all of the studies. When nonadherent participants were excluded from analysis, significant reductions in fracture rates were seen in three of the five studies.[17–19] Poor adherence may be one key reason fracture reduction did not reach statistical significance in the intention-to-treat analyses.
In two of the studies, the statistical power to detect the primary outcome of decreased fractures was lower than planned due to lower-than-predicted observed fracture rates.[17,20] A number of factors could have contributed to this, including evaluation of women at low risk for osteoporotic fracture in the WHI study and high calcium intake at baseline. Also, if supplementation was allowed in the control group, or if the dietary calcium intake was high, the participants randomized to placebo may have been, in effect, taking the same amount of calcium as those in the intervention group. This would reduce the possibility of detecting a difference in fracture rates between the two groups.
In four of the five studies, subjects enrolled in the treatment group were given calcium carbonate, a substance that requires an acidic environment for absorption and may not be an optimal source of calcium for the elderly.[17,19–21] Porthouse et al. did not specify whether the calcium carbonate used in their study was taken with meals, an important determinant of calcium absorption. In other studies, participants were instructed to take calcium supplementation with meals;[17,19,21] if they were also consuming calcium from dietary sources, they were probably absorbing only about 500 mg of elemental calcium per meal, and any additional calcium intake likely conferred no benefit.[27,32] Also, in three of the studies, vitamin D was not included in the treatment arm or was used in amounts insufficient for optimal calcium absorption.[18,19] Vitamin D is known to increase calcium absorption, and combined use of both substances has been shown to reduce the risk of fractures.
Most medications to prevent or treat other diseases are available by prescription only. Because calcium supplements can be obtained without a prescription, they may not be perceived as medication by many in the general public, and their use may be considered optional. Our patients should be informed that they must take calcium and vitamin D supplements consistently and as recommended if they are to attain any potential benefit in decreased fracture risk.
There is minimal risk associated with the use of calcium supplements. Although its impact on fracture risk is uncertain, calcium supplementation appears to confer some preventive benefits in women who are adherent to therapy. The cost and resulting morbidity and mortality of an osteoporotic fracture are great. In light of these factors, it is suggested that postmenopausal women who are unable to achieve the recommended daily amount of calcium through diet alone continue to use calcium supplementation. Pharmacists can play a key role educating women on the importance of good adherence in achieving the benefits of calcium supplementation.
Am J Health Syst Pharm. 2011;68(4):309-318. © 2011 American Society of Health-System Pharmacists, Inc.
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Cite this: Calcium Supplementation in Postmenopausal Women to Reduce the Risk of Osteoporotic Fractures - Medscape - Feb 15, 2011.