Calcium and Vitamin D

Anti-osteoporotic drugs and calcium/vitamin D supplementation

In patients receiving anti-osteoporotic drugs, calcium and vitamin D supplements should be prescribed as co-therapy.

It is important to stress that all studies which have investigated the efficacy of bisphosphonates, SERMs, calcitonin, teriparatide, strontium ranelate or denosumab were performed with patients adequately supplemented with calcium and vitamin D. No demonstration of the anti-fracture efficacy of these compounds has been obtained without concomitant supplementation in calcium and vitamin D.

For general information on calcium and vitamin D and their role in osteoporosis prevention, together with other lifestyle factors, please see Prevention

Some recent research on calcium and vitamin D

Healthy children

A quantitative systematic review of calcium supplementation in healthy children concluded that calcium supplementation provided only a small effect on bone mineral density at the total body and upper limb. This effect persisted after the end of supplementation only at the upper limb. When analysing separately female children, point estimates were greater at all sites showing significant increases at the femoral neck, total body at the end of supplementation and after withdrawal of supplementation (1)

Postmenopausal women and elderly subjects

In the Women’s Health Initiative Calcium Plus Vitamin D trial (2), a large cohort (more than 36,000) of postmenopausal women between the ages of 50 and 70 received 500 mg of calcium carbonate with 200 IU of vitamin D3, twice daily or a matching placebo on an average of 7 years. According to an intention-to-treat analysis, there were no significant effects of calcium with vitamin D supplementation on hip, total and site-specific fracture rates. However, when data were excluded at the time of women’s adherence to therapy fell below 80%, the risk of hip fracture was significantly reduced. This study leaves many questions unanswered. The subjects were not selected on the basis of low bone mineral density or risk factors for fragility fractures. A vast majority of women had an adequate baseline daily calcium intake from diet and supplements (mean calcium intake 1150 mg/day) and 40% had a daily vitamin D intake of at least 400 IU. The dose of vitamin D may not have been sufficient since previous trials have demonstrated that at least 700 IU of vitamin D are requested to demonstrate a benefit. More than half of all participants in both groups were currently receiving hormone replacement therapy. The observed rate of hip fractures in the placebo group was about half the predicted rate. It should also be noticed that bisphosphonates and calcitonin use was allowed during this trial. Thus, the study has not a sufficient power to detect a reduction in the rate of hip fractures and the population studied did not appear to be calcium and vitamin D deficient. Although this study showed an increased risk of kidney stones, the benefit of calcium and vitamin D supplementation for reducing the risk of hip fractures in at risk populations, in patients compliant to therapy, should be emphasised. An editorial associated to this publication suggested to recommend that women consume the recommended daily levels of calcium and vitamin D through diet, supplements or both (3).

Despite the overall null finding in this community based trial, the benefits of calcium and vitamin D supplementation for reducing non-vertebral fracture rates in at risk populations, such as men and women over 65 years and the institutionalised elderly, have been demonstrated in other trials (4,5).

Compliance issues

The WHI trial also highlighted the need for ensuring patient compliance with supplementation. Similar conclusions were recently published in a five-year, double-blind, placebo-controlled study. It has been demonstrated that supplementation with calcium carbonate tablets supplying 1200 mg/day was shown ineffective in preventing clinical fractures in ambulatory elderly women (mean age 75 years), owing to poor long-term compliance, although it was effective (-34%) in those patients who were compliant (who took 80% or more of their tablets) (6).

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