The latest findings from a Cochrane review on the benefit of supplementing premenopausal women with calcium and vitamin D.

Background

Osteoporosis (OP) is characterised by porous and weaker bones.¹ It is estimated that, globally, OP affects about 21% of women and 6% of men over the age of 50.² In terms of actual numbers, this translates to 500 million men and women who have the condition.² OP is a serious public health concern, as it contributes to increased risk of fractures, increased number of years lived with disability by musculoskeletal disorders, low quality of life, significant morbidity and mortality.^3,4

Preventing OP relies on ensuring adequate dietary intake and supplementation of both calcium and vitamin D.⁴ The most common calcium supplements include calcium citrate and calcium carbonate. Vitamin D products include ergocalciferol (vitamin D 2) and cholecalciferol (vitamin D 3).⁴ Several clinical trials have been conducted to determine the efficacy of calcium and vitamin D supplementation in several groups, including children and postmenopausal women, with varying evidence.^5,6 However, no reviews had been done to investigate their effectiveness for healthy premenopausal women. This summary will present data from a Cochrane review addressing this gap.

Characteristics of the studies

The studies included in the review were randomised controlled trials examining healthy premenopausal women, with or without calcium or vitamin D deficiency. Studies with women who have coexisting conditions such as OP, chronic conditions, cardiovascular disorders or autoimmune diseases were excluded. Trials comparing calcium, vitamin D, or calcium plus vitamin D with placebo, were included. There were no language restrictions.

Quality of the studies

The quality of the evidence for most of the studies was rated as low to moderate due to imprecision, inconsistency and attrition.

Conclusion

The current evidence does not support the supplementation of calcium or combined calcium and vitamin D in healthy premenopausal women. It is unlikely that further research will change the conclusion. Implication for practice and research Given the current evidence, it is probably more important to design future studies to investigate premenopausal women with chronic conditions, rather than healthy women, to determine the benefit of supplementation with calcium and vitamin D.

Results

• The following databases were searched: MEDLINE Ovid (1946 to 12 April 2022); Embase Ovid (1947 to 12 April 2022); Cochrane Central Register of Controlled Trials (April 2022) including Ovid and Database of Reviews of Effects (DARE). Additionally, the following registers were searched: ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (www. who.int/clinical-trials-registry-platform).
• The main outcome measures included: total hip bone mineral density (BMD), lumbar spine BMD, quality of life (QoL), new symptomatic vertebral fractures confirmed by imaging, new symptomatic non‐vertebral fractures confirmed by imaging, withdrawals due to adverse events (all adverse events attributed directly to supplementation or placebo group) and serious adverse events (i.e. hospitalisations, or those resulting in disability or death). Other outcome measures included all other reported adverse events and withdrawals for any reason.
• The review included a total of seven studies with 941 participants, of whom 138 were randomised to calcium supplementation, 110 to vitamin D supplementation, 271 to vitamin D plus calcium supplementation, and 422 to placebo. Participant mean ages ranged between 18.1 and 42.1 years.
• Four studies compared calcium versus placebo (138 participants in the calcium group and 123 in the placebo group) with mean ages from 18.0 to 47.3 years. Calcium supplementation had no effect on total hip or lumbar spine BMD after 12 months in three studies and after 6 months in one study (total hip BMD: mean difference (MD) −0.04 g/cm 2 , 95% confidence interval (CI) −0.11 to 0.03; I 2 = 71%; 3 studies, 174 participants; based on low‐ certainty evidence; lumbar spine BMD: MD 0 g/cm 2 , 95% CI −0.06 to 0.06; I 2 = 71%; 4 studies, 202 participants, based on low‐certainty evidence).
• When calcium was compared with placebo; calcium supplementation did not reduce or increase the withdrawals in the studies (risk ratio (RR) 0.78, 95% CI 0.52–1.16; I 2 = 0%; 4 studies, 261 participants, based on moderate‐certainty evidence).
• Two studies compared vitamin D versus placebo (110 participants in the vitamin D group and 79 in the placebo group), with mean ages from 18.0 to 32.7 years. There were no differences in lumbar BMD between groups. Vitamin D alone supplementation did not reduce or increase withdrawals for any reason between groups (RR 0.74, 95% CI 0.46–1.19, based on moderate‐ certainty evidence).
• Two studies compared calcium plus vitamin D versus placebo (271 participants in the calcium plus vitamin D group and 270 in the placebo group; 220 participants with a mean age ranging 18.0 to 36 years. The studies found no difference between groups in percent of change on total hip BMD (−0.03, 95% CI −0.06 to 0, based on moderate‐certainty evidence), and lumbar spine BMD (MD 0.01, 95% CI −0.01 to 0.03 based on moderate‐ certainty evidence). Calcium plus vitamin D supplementation did not reduce or increase withdrawals for any reason (RR 0.82, 95% CI 0.29 to 2.35; I 2 = 72%; 2 studies, 541 participants based on low‐certainty evidence).

References 

1. Méndez-Sánchez L, Clark P, Winzenberg TM, et al. Calcium and vitamin D for increasing bone mineral density in premenopausal women. Cochrane Database of Systematic Reviews 2023, Issue 1. 
2. Kanis JA, McCloskey EV, Johansson H, et al. A reference standard for the description of osteoporosis. Bone 2008;42(3):467–75.
3. Borgström F, Lekander I, Ivergård M, et al. The international costs and utilities related to osteoporotic fractures study (ICUROS) – quality of life during the first 4 months after fracture. Osteoporosis International 2013;24(3):811–23.
4. Papaioannou A, Morin S, Cheung A, et al. 2010 Clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. Canadian Medical Association Journal 2010;182(17):1829–30.
5. Winzenberg TM, Powell S, Shaw KA, et al. Vitamin D supplementation for improving bone mineral density in children. Cochrane Database of Systematic Reviews 2010, Issue 10. 
6. Rizzoli R, Boonen S, Brandi ML, et al. Vitamin D supplementation in elderly or postmenopausal women: a 2013 update of the 2008 recommendations from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Current Medical Research and Opinions 2013;29(4):305–13.

ASSOCIATE PROFESSOR HANAN KHALIL BPharm, MPharm, PhD, AACPA is the Lead of Health Services Administration at Latrobe University. She is also Editor in Chief of Current Opinion in Epidemiology and Public Health.