You also noted that no study has tested whether calcium and/or vitamin D supplementation results in higher bone mineral density (BMD) than no supplementation for men undergoing ADT. What do you think such a study would reveal?

Dr. Schwartz: I imagine that BMD loss would be greater among men who are not supplemented. My belief is based on the results of the meta-analysis reported by the U.S. Preventive Services Task Force (Ann Intern Med 2011;155:827-838;). That analysis showed that combined vitamin D (300–1100 IU/day) and calcium supplementation (500–1200 mg/day) can modestly reduce fracture risk.

In two recent studies (J Bone Min Res 2012;27:187-194 and Cancer Epidemiol Biomarkers Prev; 2012; published online ahead of print; doi:10.1158/1055-9965.EPI-12-0922-T), you noted a possible link between high intestinal absorption of calcium and PCa risk. How does this influence your interpretation of your latest findings, if at all?

Dr. Schwartz: Our findings that men who, genetically, are good calcium absorbers have an increased risk of PCa increases my belief in the validity of studies showing that dietary calcium increases the risk of PCa. This is because it provides a plausible mechanism whereby dietary calcium could affect PCa cells. However, those findings have had little direct influence on my interpretation of the present results.

There are two steps in interpreting the results we summarized on the effect of calcium supplements on BMD. First, is there a benefit? And second, does the benefit outweigh the risks? Because there was no obvious benefit, the appreciation of the risks becomes more salient.

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Does dietary intake of calcium and/or vitamin D pose the same dangers as supplementation for men on ADT?  

Dr. Schwartz: Most epidemiologic studies show that the risks for aggressive PCa increases with both dietary calcium and calcium supplements. The data for cardiovascular disease are less clear.

Do you believe that there is probably some threshold at which calcium and/or vitamin D supplementation can help restore BMD effectively enough to balance the other risks?

Dr. Schwartz: That is the key question for a future trial. The goal of maintaining BMD at older ages typically involves accumulating enough skeletal mass in youth so that age-related skeletal losses can be withstood in later life. The problem resembles saving money for retirement.  Unfortunately, it is nearly impossible to save effectively for retirement if saving begins at retirement age. Thus, by analogy, it is possible that calcium and/or vitamin D supplements alone may be unable to safely restore BMD in older men undergoing accelerated bone loss caused by ADT.