Elsevier

The Lancet

Volume 370, Issue 9588, 25–31 August 2007, Pages 657-666
The Lancet

Articles
Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis

https://doi.org/10.1016/S0140-6736(07)61342-7Get rights and content

Summary

Background

Whether calcium supplementation can reduce osteoporotic fractures is uncertain. 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.

Methods

We identified 29 randomised trials (n=63 897) using electronic databases, supplemented by a hand-search of reference lists, review articles, and conference abstracts. All randomised trials that recruited people aged 50 years or older were eligible. The main outcomes were fractures of all types and percentage change of bone-mineral density from baseline. Data were pooled by use of a random-effect model.

Findings

In trials that reported fracture as an outcome (17 trials, n=52 625), treatment 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). In trials that reported bone-mineral density as an outcome (23 trials, n=41 419), the treatment 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) in the spine. The fracture risk reduction was significantly greater (24%) in trials in which the compliance rate was high (p<0·0001). The treatment effect was better with calcium doses of 1200 mg or more than with doses less than 1200 mg (0·80 vs 0·94; p=0·006), and with vitamin D doses of 800 IU or more than with doses less than 800 IU (0·84 vs 0·87; p=0·03).

Interpretation

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. 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).

Introduction

The social and economic burden of osteoporotic fractures is increasing worldwide, as the population ages. In the USA, osteoporosis affects more than 10 million individuals,1 and the yearly expenditure on osteoporotic fractures has exceeded that on breast cancer.2 The prevention of fractures has therefore become a major public-health priority. However, preventive drugs can be as expensive as the treatment of fractures themselves, albeit far less painful to the patients.3 Furthermore, as the demographic trend of ageing shifts to Asia, Africa, and Latin America, much of the rising cost of prevention of fractures will be disproportionately borne by some of the poorest health-care systems in the world. As a result, the development of an affordable preventive therapy will have a great effect on health, and its economic management, worldwide.

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.4 However, there has been substantial uncertainty about its efficacy in lowering the fracture rate. Data from earlier clinical trials showed that it reduced the fracture rate,5, 6 but this finding was not confirmed in subsequent multicentre trials.7, 8, 9 Moreover, results from meta-analyses have been inconsistent.10, 11, 12, 13 All meta-analyses have included a different subset of the available trials, but none has offered a comprehensive review of all the relevant evidence. Consequently, the role of calcium supplementation in the preventive treatment of osteoporotic fractures has remained uncertain.

We aimed to do a systemic review to quantitatively assess all the published randomised controlled trials that assessed the effect of calcium, or calcium in combination with vitamin D supplementation, on osteoporotic fractures and bone-mineral density, in adults aged 50 years and older.

Section snippets

Search strategy and selection criteria

The study was done with a prospectively developed protocol, which prespecified the research objective, search strategy, study eligibility criteria, and the methods of data extraction and statistical analysis. All subgroup variables were defined before analysis. The reporting of the study's findings was in accordance with the Quality of Reporting of Meta-analyses (QUOROM) conference statement.14

We searched, without language restrictions, for all publications on calcium and vitamin D between

Results

Of the 7867 references screened, 29 studies were included in the final analysis (figure 1).5, 6, 7, 8, 9, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46 17 trials reported fractures as an outcome, 5, 6, 7, 8, 9, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34 and 24 reported bone-mineral density.5, 6, 8, 9, 25, 26, 27, 28, 30, 31, 32, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46 Some trials reported both outcomes (table 1). One study7 had a

Discussion

Our meta-analysis has shown that calcium supplementation, alone or in combination with vitamin D, is effective in the preventive treatment of osteoporotic fracture. Over an average treatment duration of 3·5 years, the risk of fracture was reduced and was accompanied by a reduction of bone loss at the hip and spine. The fracture risk reduction was greater in individuals who were elderly, lived in institutions, had a low bodyweight, had a low calcium intake, or were at a high baseline risk than

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