ArticlesUse 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
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
References (54)
- et al.
Epidemiology and outcomes of osteoporotic fractures
Lancet
(2002) - et al.
Calcium-vitamin D3 supplementation is cost-effective in hip fractures prevention
Maturitas
(2003) - et al.
Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement
Lancet
(1999) - et al.
Cumulative meta-analysis of clinical trials builds evidence for examplary medical care
J Clin Epidemiol
(1995) The ‘file drawer problem’ and tolerance for null result
Psychol Bull
(1979)- et al.
Randomized controlled trial of calcium in healthy older women
Am J Med
(2006) - et al.
Spinal bone loss in postmenopausal women supplemented with calcium and trace minerals
J Nutr
(1994) - et al.
Effects on bone mineral density of calcium and vitamin D supplementation in elderly women with vitamin D deficiency
Joint Bone Spine
(2003) US Department of Health and Human Services: bone health and osteoporosis: a report of the Surgeon-General
(2004)- et al.
Healthcare use among US women aged 45 and older: total cost and costs for selected postmenopausal health risks
J Womens Health Gend Based Med
(1999)
Vitamin D3 and calcium to prevent hip fractures in the elderly women
N Engl J Med
Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older
N Engl J Med
Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial
Lancet
Calcium plus vitamin D supplementation and the risk of fractures
N Engl J Med
Effects of calcium supplementation on clinical fracture and bone structure: results of a 5-year, double-blind, placebo-controlled trial in elderly women
Arch Intern Med
Meta-analysis of calcium supplementation for the prevention of postmenopausal osteoporosis
Endocr Rev
Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials
JAMA
Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis
Cochrane Database Syst Rev
Need for additional calcium to reduce the risk of hip fracture with vitamin D supplementation: evidence from a comparative meta-analysis of randomized controlled trials
J Clin Ednocrinol Metab
Cochrane handbook for systematic reviews of interventions 4.2.6
Interaction revisited: the difference between two estimates
BMJ
United States Department of Agriculture: dietary reference intakes: elements
Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials
JAMA
How to select the doses of vitamin D in the management of osteoporosis
Osteoporos Int
Bias in meta-analysis detected by a simple, graphical test
BMJ
A fail-safe N for effect size in meta-analysis
J Educ Stat
Vitamin D and calcium supplementation prevents osteoporotic fractures in elderly community dwelling residents: a pragmatic population-based 3-year intervention study
J Bone Miner Res
Cited by (1081)
Vitamin D: 100 years of discoveries, yet controversy continues
2023, The Lancet Diabetes and EndocrinologyDo Titanium Dioxide Particles Stimulate Macrophages to Release Proinflammatory Cytokines and Increase the Risk for Peri-implantitis?
2023, Journal of Oral and Maxillofacial Surgery