We thank Drs. Dang and colleagues for their interest and commentary on our paper entitled, “Calcium plus Vitamin D Supplementation and Health Outcomes Five Years After Active Intervention Ended: The Women's Health Initiative,” which was published in the Journal of Women's Health 2013;22(11):915–926. We agree that the sensitivity analyses of the hip fracture data showed that among adherent women—those who had taken ≥80% of their study pills—calcium plus vitamin D was associated with a 23% statistically significant reduction in hip fracture compared with women adherent with placebo pills. This suggests, as Drs. Dang et al. suggest, that if “you take it, it works.” However, interpretation of sensitivity analyses is difficult. The intent to treat principle states that all participants randomized should be accounted for in the primary analyses.
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This requirement is also part of the Food and Drug Administration guidelines.
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Final interpretation of the paper needs to be based on this intent to treat principle. A fundamental of all randomized clinical trials is that omitting participants can bias the results of the study. “Adherent” women are very different from non-adherent women, and women adherent with intervention can even be different from women adherent with placebo. The balanced distribution at randomization can be sacrificed in subgroup analyses or complier-only analyses. However, we agree that the promising results among adherent participants are supportive of bone health benefits from calcium plus vitamin D supplementation. Moreover, calcium plus vitamin D supplementation was associated with hip bone mineral density benefits even in intention-to-treat analyses, as reported in the original publication.
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Additionally, we observed a significantly lower risk of vertebral fractures over the entire follow-up period, and vertebral fractures are the most common osteoporotic fracture.
