A meta-analysis of multiple randomized trials does not support the use of either calcium or vitamin D supplements or their combination to reduce fracture risk of any kind in healthy older adults, Chinese investigators reaffirm.
“The increased social and economic burdens for osteoporosis-related fractures worldwide make the prevention of such injuries a major public health goal,” Jia-Guo Zhao, MD, Tianjin Hospital, China and colleagues write. “[But] results of this meta-analysis showed that calcium, calcium plus vitamin D, and vitamin D supplementation alone were not significantly associated with a lower incidence of hip, nonvertebral, vertebral, or total fractures in community-dwelling older adults,” they observe.
“[And] these results were generally consistent regardless of the calcium or vitamin D dose, sex, fracture history, dietary calcium intake, and baseline serum 25-hydroxyvitamin D concentrations,” the authors conclude.
The study was published online December 26, 2017 in the Journal of the American Medical Association.
The meta-analysis included 33 randomized clinical trials involving 51,145 participants over age 50 years. “Fourteen trials compared calcium supplements with placebo or no treatment,” researchers write. They noted a 53% relative risk (RR) reduction in hip fracture with calcium supplementation (RR, 1.53; 95% CI, 0.97 – 2.42), but this was not significant, at an absolute risk difference (ARD) of 0.01 compared with placebo or no treatment.
Similarly, the relative risk reduction with calcium supplementation and nonvertebral fractures was 0.95 (95% CI, 0.82 – 1.11), at an ARD of -0.01. This was again not significant compared with either placebo or no treatment. Nor was any significant association seen between vertebral fracture risk, at a relative risk reduction of 0.83 (95% CI, 0.66 – 1.05) and an ARD of -0.01, or in total fractures, at a relative risk reduction of 0.88 (95% CI, 0.75 – 1.03) and an ARD of -0.02, compared with placebo or no treatment, investigators add.
“Seventeen trials compared vitamin D supplementation with a placebo or no treatment,” researchers continue. There was again a slight 21% reduction in the relative risk of hip fracture with vitamin D supplementation compared with placebo or no treatment (RR, 1.21; 95% CI, 0.99 – 1.47), at an ARD of 0.00.
However, the difference between the supplemented group and those who took no supplements was again not significant, as researchers point out. Nor was a significant reduction seen in nonvertebral fractures and vitamin D supplementation (RR, 1.10; 95% CI, 1.00 – 1.21), at an ARD of 0.01. The same held true for both vertebral and total fractures compared with placebo or no treatment, with a relative risk for vertebral fractures of 0.97 (95% CI 0.54 – 1.77) and 1.01 for total fractures (95% CI, 0.87 – 1.17), at an ARD of 0.00 for both fracture endpoints.
Looking at the combination of calcium and vitamin D supplementation, investigators identified 13 trials where the combination was compared with placebo or no treatment. The main trial included in this subanalysis was the Women’s Health Initiative, in which over 36,000 women received calcium plus vitamin D, with or without hormone therapy, or placebo.
Here again, researchers found no clinically relevant association between the use of vitamin D plus calcium supplementation and any of the fracture endpoints. For hip fracture, the relative risk was 1.09 between the supplemented and unsupplemented groups (95% CI, 0.85 – 1.39), at an ARD of 0.00. For vertebral fracture, the relative risk reduction was 0.63 (95% CI, 0.29 – 1.40), at an ARD of -0.00, while for total fractures, the relative risk reduction was 0.90 (95% CI 0.78 – 1.04), at an ARD of -0.01, compared with no supplementation.
“Sensitivity analyses that excluded low-quality trials and studies that exclusively enrolled patients with particular medical conditions did not alter these results,” investigators note.
The authors caution it is possible that patients living in residential care facilities may still benefit from calcium or vitamin D supplementation, as residents are more at risk for osteoporosis because of multiple lifestyle factors. Thus, “the benefits of calcium and vitamin D supplementation may differ between people living in the community and people living in residential institutions.”
However, among men and women healthy enough to still live in the community, the “findings do not support the routine use of these supplements,” the authors stress.
The authors have reported no relevant financial relationships.
JAMA. 2017;318:2466-2482. Abstract
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