Abstract
Randomized trials have indicated that calcium or vitamin D supplements—or both—may slow bone loss in postmenopausal women, but whether the risk of bone fracture is reduced remains uncertain. This study randomly assigned 36,282 postmenopausal women 50 to 79 years of age, who were enrolled in the Women’s Health Initiative clinical trial, to receive either 1000 mg calcium in carbonate form plus 400 IU vitamin D3 daily or placebo and followed them for an average of 7 years. Women on active treatment had levels of 25-hydroxyvitamin D 28% higher than those in placebo recipients.Bone mineral density (BMD) at the hip remained higher than in women assigned to receive placebo. The mean group difference at the ninth annual visit was 1.06%. Annualized rates of fracture per 10,000 person-years in the supplement and placebo groups were 14 and 16, respectively, for hip fracture; 44 and 44 for lower arm/wrist fractures; 14 and 15 for clinical vertebral fractures; and 164 and 170 for all fractures combined. Women assigned to supplements had a 12% lower risk of hip fracture than placebo recipients, but this was not a statistically significant effect. There were no significant group differences in rates of major diseases, including cardiovascular disease and cancer. The hazard ratio for kidney stones in women receiving supplements was 1.17 (95% confidence interval, 1.02–1.34). This finding was not related to a high baseline calcium intake. Gastrointestinal symptoms occurred in approximately 9% to 10% of both groups.In generally healthy postmenopausal women, daily supplements of calcium and vitamin D were associated with modest improvement in bone density at the hip, but did not substantially lower the risk of hip fracture in this large-scale study. Compared with placebo, supplementation did appear to increase the risk of kidney stones.