Calcium With or Without Vitamin D May Help Prevent Osteoporosis

August 28, 2007 — Calcium, or calcium in combination with vitamin D, may prevent osteoporosis in people aged 50 years and older, according to the results of a systematic review and meta-analysis in the August 25 issue of The Lancet.
"Calcium alone, or in combination with vitamin D, has been suggested as an inexpensive treatment to prevent osteoporotic bone loss and fractures, costing as little as €0.41 per day in one European study," write Benjamin M.P. Tang, MD, from the University of Western Sydney in New South Wales, Australia, and colleagues. "However, there has been substantial uncertainty about its efficacy in lowering the fracture rate.... We did a meta-analysis to include all the randomised trials in which calcium, or calcium in combination with vitamin D, was used to prevent fracture and osteoporotic bone loss."
Using electronic databases, as well as a hand-search of reference lists, review articles, and conference abstracts, the study authors identified 29 randomized trials enrolling a total of 63,897 subjects. Average duration of treatment with calcium, or calcium in combination with vitamin D, was 3.5 years.
Eligibility criteria were randomized design and recruitment of people aged 50 years or older. Primary endpoints were all types of fractures and the percentage change of bone mineral density (BMD) from baseline. A random-effect model allowed pooling of data.
There were 17 trials that reported fracture as an outcome, enrolling a total of 52,625 subjects. In these trials, treatment with calcium, or calcium in combination with vitamin D, was associated with a 12% risk reduction in fractures of all types (risk ratio [RR], 0.88; 95% confidence interval [CI], 0.83 - 0.95; P = .0004).
There were 23 trials, enrolling a total of 41,419 subjects, that reported BMD as an outcome. In these trials, treatment was associated with a decrease in the rate of bone loss of 0.54% (95% CI, 0.35 - 0.73; P < .0001) at the hip and 1.19% (95% CI, 0.76 - 1.61%; P < .0001) at the spine.
In trials with high rates of compliance, the reduction in the risk for fractures was significantly greater (24%; P < .0001). Calcium doses of 1200 mg or more were associated with a greater treatment effect than were doses of less than 1200 mg (0.80 vs 0.94; P = .006), and vitamin D doses of 800 IU or more were associated with a greater treatment effect than were doses of less than 800 IU (0.84 vs 0.87; P = .03).
Subjects who were elderly, lived in institutions, had a low body weight and low calcium intake or were at a high baseline risk had a greater reduction in fracture risk than did others. The treatment effect was consistent regardless of sex, fracture sites, or history of previous fractures.
"Evidence supports the use of calcium, or calcium in combination with vitamin D supplementation, in the preventive treatment of osteoporosis in people aged 50 years or older," the study authors write. "For best therapeutic effect, we recommend minimum doses of 1200 mg of calcium, and 800 IU of vitamin D (for combined calcium plus vitamin D supplementation)."
Limitations of the study include the scarcity of data for vitamin D doses of more than 800 IU, probable underestimation of the treatment efficacy because of poor compliance in some trials, exclusion of trials that studied calcium as part of a dietary intake or nutritional supplementation regimen, exclusion of observational studies, absence of men-only trials, and inability to determine the interaction of physical exercise on the treatment effect.
The Australian Government supported this study. The study authors have disclosed no relevant financial relationships.
In an accompanying editorial, Jean-Yves Reginster, MD, PhD, from the Bone and Cartilage Metabolism Unit, CHU Centre Ville in Liege, Belgium, notes that this study does not fully address the cost-conscious use of calcium or calcium with vitamin D supplementation.
"Tang and colleagues' contribution is important because it paves the way for future research aiming at the best clinical, pharmacological, and economic use of calcium and vitamin D in patients at increased risk of osteoporotic fractures," Dr. Reginster writes. "Various treatment options have been advocated, including systematic supplementation at the onset of menopause and restriction of calcium with or without vitamin D to patients receiving other anti-osteoporotic drugs. Tang suggests that the number needed to treat (NTT) (63 patients over 3.5 years) with calcium or calcium and vitamin D to prevent one osteoporotic fracture compares favourably with similar calculations from the cardiovascular field."
Dr. Reginster has disclosed various financial relationships with Servier, Novartis, Negma, Lilly, Wyeth, Amgen, GlaxoSmithKline, Roche, Merckle, Nycomed, NPS, Theramex, Merck Sharp and Dohme, Rottapharm, IBSA, Genevrier, Teijin, Teva, Ebewee Pharma, Zodiac, Analis, Theramex, Nycomed, and Novo-Nordisk.
Lancet. 2007;370:632-633, 657-666.