Calcium, vitamin D supplements failed to prevent BMD loss

Azeez Farooki, MD, FACE

This review tells us what we already know: that calcium plus D is not enough to prevent bone loss in men with prostate cancer receiving ADT.  Numerous studies in women and men (not receiving ADT) with osteoporosis show that calcium plus D modestly reduces bone turnover and prevents bone loss versus no therapy.  Although as the authors point out, a study of calcium and D vs. placebo in the ADT population has not been done, it follows that similar benefits as seen in the general population should exist in men receiving ADT.

What does prevent bone loss in the setting of ADT are antiresorptive drugs like bisphosphonates and denosumab — it is important for calcium intake to be adequate and vitamin D levels to be replete in order to prevent hypocalcemia and/or secondary hyperparathyroidism and assure adequate response to these therapies. The epidemiologic data concerning calcium intake and cancer risk/outcome as well as recent data on a possible increase in cardiovascular risk with calcium supplement use is noteworthy yet definitive conclusions are difficult to draw.

Donald L. Trump, MD, FACP

The paper by Datta and Schwartz draws attention to an important issue — loss of bone in men on androgen deprivation therapy. These authors reviewed the available clinical trials literature examining whether supplemental calcium and vitamin D (cholecalciferol) reduces bone loss. Perhaps the most important phrase in the paper was, “We found no trials that addressed the role of calcium and/or vitamin D supplements versus no supplements.” The authors reviewed the available data, which consisted primarily of small, uncontrolled trials or the evaluation of ”control” arms of randomized trials that used calcium supplementation  (500 mg to 1,040 mg calcium per day) and vitamin D (presumably cholecalciferol, 200 IU to 500 IU per day). Bone density loss was frequent in the studies examined; in 37 of 39 measurements made across 12 studies of about 2,500 men, bone mineral density (BMD) decreased from –0.1% to –5%. Only two sites studied in two studies detected no changes. The inescapable conclusion is that BMD loss is frequent in men on ADT, and the doses of calcium with or without cholecalciferol studied do not prevent a decline in BMD. As the authors point out, this would be one thing if calcium and cholecalciferol were “free” with respect to side effects and risk, but there are data that associate higher calcium intake with increased coronary artery calcification, as well as more aggressive prostate cancer. So calcium may not be free. There are very few data indicating any morbidity of cholecalciferol at the doses described. Other points to consider include the stage of disease for which ADT is used. Is BMD loss more important in men with non-metastatic disease than those with established metastases? The endpoint measured is another important aspect. While loss of bone density is associated with fracture risk, 2% loss of BMD is not intrinsically harmful or risky, as far as we know. The most important endpoint is fracture risk, and it is fracture risk that is reduced in institutionalized, ambulatory elderly women with calcium (1,200 mg) and cholecalciferol (800 IU) supplements, as well as community-dwelling healthy men and women (500 mg calcium and 700 IU cholecalciferol) [Chapuy MC. N Engl J Med.1992;327:1637-1642. Salovaara K. J Bone Miner Res. 2010;25:1487-1495.]. So we have many questions and few randomized controlled trials that address the safety and efficacy of calcium cholecalciferol. Until we have adequate data, the paper of Datta and Schwartz reminds us that — lacking solid information — one must be cautious in making broad recommendations.