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Summary

Calcium supplement use has been common in North America since calcium balance studies in the 1970s suggested that balance was directly related to the intake of this element [1]. Subsequent more rigorous analyses of balance studies [2] and randomized controlled trials of calcium supplements on bone density [3] and fractures [4,5] have not supported calcium supplement use. Recently, Bailey et al. have used data from an observational study of women entering the menopause and compared fracture rates and changes in bone mineral density (BMD) over a 10-year period between users and non-users of calcium supplements [6]. Supplement use had no impact on fracture incidence (relative risk 1.16, P=0.5) nor on bone loss in those who were perimenopausal at study entry. In women who were premenopausal at study entry, there was no difference in the unadjusted bone loss but, after adjustment, spine BMD loss was 0.36%/year and 0.47%/year in supplement users and non-users, respectively, and hip BMD loss was 0.35%/year and 0.44%/year in the two groups (P≤0.002).

Commentary

This observational study accords with the meta-analyses of clinical trials of calcium supplements, in finding that they do not affect fractures in community-dwelling older women. Accordingly, the United States Preventive Services Taskforce recommends against calcium or vitamin D supplementation in non-institutionalized postmenopausal women [7]. While there is a statistically significant difference in rates of bone loss in the premenopausal sub-group, the small magnitude of this difference casts doubt on its biological significance, the fracture data confirming that such a slight difference does not impact on fracture risk. As it is an observational study, residual confounding is likely. While women receiving hormone treatment at the time of recruitment were excluded from the analysis, there is no mention of removing those who started hormones subsequently. Calcium supplement use is more common in hormone users, so this could be a confounder accounting for the effect found in those who were premenopausal at baseline. Clinical trials show that the initiation of calcium supplements is accompanied by a slowing of bone resorption, followed by a ~1% benefit to BMD, which does not cumulate over time [3]. Thus, there is no long-term effect on rates of bone loss. This is consistent with long-term studies of bone balance in postmenopausal women, which demonstrate a zero effect of dietary calcium intake on rates of bone loss over 5-6 years [8,9]. Thus, the advent of precise BMD measurement techniques and the performance of large clinical trials addressing effects on fracture have demonstrated that the early studies of calcium balance do not reflect the true impact of calcium on bone health and that these studies should no longer guide our clinical practice. In contrast to the lack of effect of calcium supplements on bone clinical endpoints, there is strong evidence for adverse effects on gastrointestinal symptoms and incidence of renal calculi, with proof of adverse cardiovascular outcomes as well [8]. In contrast to the negative findings with calcium, there is consistent evidence body weight impacts on fracture risk, so nutritional advice for bone health should not focus on calcium, but on taking a balanced diet to maintain a healthy body mass index between 20 and 30.

Ian Reid
Department of Medicine, University of Auckland, Auckland, New Zealand

References

  1. Heaney RP, Recker RR, Saville PD. Menopausal changes in calcium balance performance. J Lab Clin Med 1978;92:953-63.
    https://www.ncbi.nlm.nih.gov/pubmed/739173
  2. Hunt CD, Johnson LK. Calcium requirements: new estimations for men and women by cross-sectional statistical analyses of calcium balance data from metabolic studies. Am J Clin Nutr 2007;86(4):1054-63.
    https://www.ncbi.nlm.nih.gov/pubmed/17921384
  3. Tai V, Leung W, Grey A, Reid IR, Bolland MJ.Calcium intake and bone mineral density: systematic review and meta-analysis. BMJ 2015;351:h4183.
    https://www.ncbi.nlm.nih.gov/pubmed/26420598
  4. Bolland MJ, Leung W, Tai V, Bastin S, Gamble GD, Grey A, Reid IR. Calcium intake and risk of fracture: systematic review. BMJ 2015;351:h4580.
    https://www.ncbi.nlm.nih.gov/pubmed/26420387
  5. Zhao JG, Zeng XT, Wang J, Liu L. Association between calcium or vitamin d supplementation and fracture incidence in community-dwelling older adults: A systematic review and meta-analysis. JAMA 2017;318(24):2466-82.
    https://www.ncbi.nlm.nih.gov/pubmed/29279934
  6. Bailey RL, Zou P, Wallace TC, McCabe GP, Craig BA, Jun S, Cauley JA, Weaver CM. Calcium Supplement Use Is Associated With Less Bone Mineral Density Loss, But Does Not Lessen the Risk of Bone Fracture Across the Menopause Transition: Data From the Study of Women’s Health Across the Nation. JBMR Plus 2020;4(1):e10246.
    https://www.ncbi.nlm.nih.gov/pubmed/31956850
  7. Moyer VA, U. S. Preventive Services Task Force. Vitamin D and Calcium Supplementation to Prevent Fractures in Adults: US Preventive Services Task Force Recommendation Statement. Ann Intern Med 2013;158(9):691-96.
    https://www.ncbi.nlm.nih.gov/pubmed/24490274
  8. Reid IR, Bristow SM, Bolland MJ. Calcium supplements: benefits and risks. J Intern Med 2015;278(4):354-68.
    https://www.ncbi.nlm.nih.gov/pubmed/26174589
  9. Bristow SM, Horne AM, Gamble GD, Mihov B, Stewart A, Reid IR. Dietary Calcium Intake and Bone Loss Over 6 Years in Osteopenic Postmenopausal Women. J Clin Endocrinol Metab 2019;104(8):3576-84.
    https://www.ncbi.nlm.nih.gov/pubmed/30896743
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