Calcium for ADT Bone Loss May Worsen PCa: An Interview with Gary G. Schwartz, PhD, MPH


Considering that bone loss is a known side effect of androgen-deprivation therapy (ADT) for men with prostate cancer (PCa), it might seem logical that calcium and vitamin D supplementation would help manage this consequence.

Not necessarily, explains PCa epidemiologist Gary G. Schwartz, PhD, MPH, of Wake Forest Baptist Medical Center in Winston-Salem, N.C. He and co-investigator Mridul Datta uncovered data that demonstrate such supplementation can increase the risk of cardiovascular disease and, ironically, aggressive PCa (The Oncologist 2012;17[9]:1171–1179;).

What made you start suspecting that calcium and vitamin D supplementation might actually do more harm than good in men suffering ADT-related bone loss?

Dr. Schwartz: Many urologists have presumed that, with respect to PCa, dietary calcium is beneficial, or is at least benign. Conversely, many epidemiologic studies have implicated dietary calcium with an increased risk of PCa. Recent prospective studies also report an increased risk of fatal PCa for men with higher levels of calcium in blood (Cancer Epidemiol Biomarkers Prev 2012;21:1768-1773). Although the mechanisms underlying the association between calcium and PCa are incompletely understood, many cancer epidemiologists regard dietary calcium as a probable prostate carcinogen.

Do you think urologists should stop prescribing such supplementation until more studies are done?

Dr. Schwartz: That's a tough question. My guess is that, like many treatment decisions in PCa, the decision whether or not to take calcium supplements may need to be individualized based on clinical judgment and patients' wishes.

So calcium supplements, rather than vitamin D supplementation or a combination of the two, are the main problem?

Dr. Schwartz: I do think that calcium is the culprit, since vitamin D seems to have a beneficial effect on prostate cells. However, in practice, vitamin D and calcium are often taken together.

The vitamin D is probably protective—there is a wealth of papers on that one (Ann Epidemiol 2009;19:96-102).

If you don't believe that stopping supplementation is the right strategy at this time, how do you think urologists should proceed at this point in terms of prescribing such supplementation for these patients?

Dr. Schwartz: Common sense suggests caution regarding calcium supplements in patients with a history of significant cardiovascular disease.

What sort of reaction has your finding evoked in the urology community? As you pointed out in your report, many professional and lay groups advocate calcium and/or vitamin D supplementation for men undergoing ADT.

Dr. Schwartz: The first reaction of many urologists and oncologists was surprise. However, in my experience, the urologic community is a very pragmatic one. Thus, after the initial reaction, the response quickly became, “What do we do now?”

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.

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.

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