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Dr B Tang, University of Sydney, Penrith, New South Wales, Australia;
in patients ⩾50 years of age, does calcium supplementation, with or without vitamin D, prevent osteoporotic fractures?
Medline, EMBASE/Excerpta Medica, Current Contents, CINAHL, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (all to January 2007); clinical trials repositories; resource web sites; conference abstracts; review articles; and bibliographies of primary studies.
Study selection and assessment:
published or unpublished randomised controlled trials (RCTs) in any language that compared the effects of calcium, with or without vitamin D, with placebo on fractures or bone mineral density (BMD) in patients ⩾50 years of age. Exclusion criteria were use of dietary calcium as an intervention, use of calcium as part of a nutritional supplementation regimen or combined with other treatment, secondary osteoporosis, and use of vitamin D without calcium. 29 studies met the selection criteria (n = 63 897, mean age 68 y, 92% women, median baseline risk of fracture 16%). Mean duration of treatment was 3.5 years. Dosage thresholds were set at 1200 mg/day for calcium and 800 IU/day for vitamin D. Quality assessment of individual studies was based on a 4-item checklist (reporting of randomisation method, allocation concealment, blinding of outcome assessment, and completeness of follow-up).
fracture of any site, including hip, vertebra, and wrist; only the first fracture in a given patient was counted as an event. Secondary outcome was percentage of change in BMD.
Meta–analysis showed that calcium, with or without vitamin D, reduced risk of fractures more than placebo (table) and reduced bone loss in the hip (difference in mean BMD 0.54%, 95% CI 0.35 to 0.73; 24 trials, n = 44 990) and spine (difference in mean BMD 1.19%, CI 0.76 to 1.61; 24 trials, n = 3913).
Calcium supplementation, with or without vitamin D, prevents osteoporotic fractures and reduces bone loss at the hip and spine.
Abstract and commentary also appear in ACP Journal Club
Tang BM, Eslick GD, Nowson C, et al 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. Lancet 2007;370:657–66.
Clinical impact ratings: GP/FP/Primary care 6/7; IM/Ambulatory care 6/7; Rheumatology 6/7; Surgery/Orthopaedics 6/7; Geriatrics 5/7
The meta-analysis by Tang et al shows that, compared with placebo, calcium supplements of ⩾1200 mg/d can reduce fracture risk by up to 12% in men and women ⩾50 years of age. Subgroup analyses showed that only those compliant with calcium had reduced fracture risk. This finding may explain why recent trials, using intention-to-treat analyses, failed to find an association between calcium and risk reduction.1 For clinicians, this finding highlights the importance of promoting lifelong adherence to calcium for bone health.
These results are not generalisable to persons obtaining calcium from dietary sources. Such persons could have even greater fracture reductions because of the micronutrients in dietary sources of calcium. Furthermore, some evidence2 shows that long-term adherence to calcium supplementation is better if changes are made to diet rather than by taking pills.
An important issue not addressed in this meta-analysis is the role of vitamin D in fracture prevention; Tang et al found that adding vitamin D to calcium did not enhance treatment effect. This conclusion may seem surprising because there is a close relation between calcium and vitamin D in maintaining bone homeostasis, and with increasing age, calcium and vitamin D deficiency often coexist. Further, vitamin D deficiency is independently associated with decreased muscle strength and some3 but not all summary data4 demonstrate that vitamin D, without calcium, can reduce falls. Thus, the physiological rationale for using calcium and vitamin D for fracture prevention is persuasive. The lack of vitamin D effect in the meta-analysis by Tang et al could be explained by the low doses of vitamin D in the included studies. Indeed, subgroup analyses found a greater treatment effect with increasing doses of vitamin D.
Until further studies are available, it seems reasonable for clinicians to prescribe vitamin D, in doses ⩾800 IU, in addition to calcium.
Source of funding: Australian Government.