Calcium Supplements Reduce Fractures in Older People

SYDNEY, Australia, Aug. 24 -- Calcium supplementation, alone or with vitamin D, reduced osteoporotic fractures in individuals 50 or older by 12%, researchers here reported.

However, poor compliance was a major obstacle to obtaining the full benefit of supplementation, Benjamin M.P. Tang, M.D., of the University of Sydney, and colleagues, reported in the Aug. 25 issue of The Lancet

Calcium supplementation has been suggested as an inexpensive treatment to prevent osteoporotic bone loss and fractures but even in meta-analyses, there has been substantial uncertainty about supplementation's efficacy in lowering the fracture rate, the researchers said.

Their findings were based on a meta-analysis of 17 randomized trials that included 52,625 people, mainly women, age 50 or older, over an average treatment period of 3.5 years. The trials were conducted from Jan. 1966 to Jan. 2007.

Calcium supplementation, with or without vitamin D was associated with a 12% risk reduction in fractures of all types (risk ratio 0.88, 95% CI 0.83-0.95; P=0.0004).

The difference in relative risk between calcium-only supplementation and calcium with vitamin D was very small (0.87 versus 0.90) and was not significant (P=0.63).

However, the writer of a comment in the same issue said for practical purposes, the vitamin D finding would probably not be a major contribution to patient management.

The reduction in fractures was higher in trials with a high compliance rate (P<0.0001), the researchers reported. Of the eight trials, including 4,508 individuals, with a compliance rate of 80% or more, the treatment was associated with a 24% reduction in fractures of all types (P<0.0001).

In a separate analysis of 23 trials (41,419 individuals) that reported bone-mineral density as an outcome, the calcium supplementation was associated with a reduced rate of bone loss of 0.54% (0.35-0.73; P<0.0001) at the hip and 1.19% (0.76-1.61%; P<0.0001) at the spine. A positive treatment effect on bone-mineral density was evident in most studies, the investigators said.

When analyzed separately, the treatment effect was better with calcium doses of 1,200 mg or more than with lower doses -- 20% versus 6% (0.80 versus 0.94; P=0.006) -- and with vitamin D doses of 800 IU or more than with lower doses, 16% versus 13% (0.84 versus 0.87; P=0.03).

Treatment benefits were also greater for individuals who were older than 70, lived in an institution, had a lower bodyweight, had a low calcium intake, or were at higher baseline risk.

It is possible, the authors said, that those in institutions may have benefited more from assistance by nurses overseeing compliance with the dosing regimens.

The treatment benefit was consistent irrespective of gender, fracture sites, history of previous fracture, or the use of vitamin D. However, the investigators emphasized, poor compliance was a major obstacle to obtaining the full benefit of calcium supplementation.

Although the addition of vitamin D did not offer an additional benefit, significant differences were observed for different vitamin D doses, Dr. Tang said. This discrepancy could be caused by a statistical artifact, he said, but added that the analysis was limited by the scarcity of data for vitamin D doses higher than 800 IU.

For calcium-only supplementation, the researchers recommended a minimum daily dose of 1,200 mg. It is possible, they said, that vitamin D might be beneficial at higher doses, but in the absence of such data, the minimum dose for vitamin D, if used, should be 800 IU.

In addition to the lack of data on vitamin D, study limitations included the exclusion of trials that included dietary calcium as part of the regimen, and the lack of men-only trials. As a result, the findings of gender on treatment efficacy were inferred indirectly by comparison of women-only to mixed-sex trials.

This study, the researchers wrote, has implications for both clinicians and policymakers. A needed-to-treat estimate showed that 63 patients would have to be treated over 3.5 years to prevent one fracture, a result comparable to other preventive treatments such as statins.

According to the dose recommendations made in this study, Dr. Tang wrote, many formulations of calcium or calcium with vitamin D supplements contain insufficient quantities of the active ingredients. In view of the large number of such tablets sold worldwide, adequate dosage is an important issue to address if the best possible public-health benefits are to be realized.

Also, he said, because the therapeutic benefit generally increased with age, the cost-effectiveness of selecting people 70 or older needs to be addressed in future studies.

In an accompanying comment, Jean-Yves Reginster, of the Bone and Cartilage Metabolism Unit in Liege, Belgium, wrote that despite the finding of benefit with calcium alone, this isolated statement, even though supported by a strong method, would probably not be a major contribution to an evidence-based management of patients with osteoporosis.

The minimum doses of calcium and vitamin D recommended by Dr. Tang and colleagues are consistent with previous reports that found that doses of 400 IU per day of vitamin D are not sufficient for fracture prevention, he said.

The contribution by Dr. Tang and his colleagues 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 said.

The study was supported by a grant from the Australian Government.

Dr. Reginster has received consulting fees from Servier, Novartis, Negma, Lilly, Wyeth, Amgen, GlaxoSmithKline, Roche, Merckle, Nycomed, NPS, and Theramex; lecture fees from Merck Sharp and Dohme, Lilly, Rottapharm, IBSA, Genevrier, Novartis, Servier, Roche, GlaxoSmithKline, Teijin, Teva, Ebewee Pharma, Zodiac, Analis, Theramex, Nycomed, and Novo-Nordisk; and grant support from Bristol Myers Squibb, Merck Sharp & Dohme, Rottapharm, Teva, Lilly, Novartis, Roche, GlaxoSmithKline, Amgen, and Servier.