Prescribing calcium and vitamin D supplements for men at risk of bone loss from hormonal treatment for prostate cancer seems like good medicine.
But new research from epidemiologists at Wake Forest Baptist Medical Center showed that this type of supplementation did not prevent bone loss and, in fact, may increase the risk of cardiovascular disease and aggressive prostate cancer.
"It wouldn't be so bad if there simply was no obvious benefit," said Gary Schwartz, an epidemiologist at Wake Forest Baptist and lead author of the study published in the journal The Oncologist, in a statement.
"The problem is that there is evidence that calcium supplements increase the risk of cardiovascular disease and aggressive prostate cancer, the very disease that we are trying to treat."
Androgen deprivation therapy (ADT) is the mainstay treatment for men with advanced prostate cancer.
It reduces serum levels of androgens on which most prostate cancers depend. Like women undergoing menopause, a side effect of ADT in men is bone loss, or osteoporosis.
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Consequently, many physicians recommend calcium and vitamin D supplements to help reduce fracture risk in these men, which can be a significant problem. One in 10 of these men will experience a fracture within two years of therapy.
"Calcium and/or vitamin D supplementation to prevent loss of bone mineral density in these men seems so logical that no one had questioned whether it works," said Mridul Datta, co-author of the study and a postdoctoral fellow who works with Schwartz at Wake Forest Baptist.
In the study, the researchers reviewed guidelines for calcium and/or vitamin D supplementation. They also reviewed the results of 12 clinical trials of supplemental calcium and/or vitamin D in a total of 2,399 men with prostate cancer undergoing ADT, as well as the measurements of bone mineral density before and after ADT.
"We used these data to determine whether calcium and vitamin D supplements prevented bone loss in these men," Datta said. "The answer clearly is, 'No.'" The study showed that at the doses commonly recommended -- 500 to 1,000 mg of calcium and 200 to 500 IU of vitamin D per day -- men undergoing ADT lost bone mineral density.
The lack of an obvious benefit is worrisome because other data show an association between increased dietary calcium and an increased risk of aggressive prostate cancer and heart disease, Schwartz said.
Further research is needed to verify these findings, he said, by comparing a calcium and vitamin D supplement treated group vs. a non-supplemented group and looking not only at the potential benefits – in bone mineral density and in the risk of fracture -- but also at the possible risks, including unwanted cardiovascular effects and the effects on prostate cancer itself.
"The wakeup call of these findings is that the presumption of benefit from calcium and vitamin D supplements that have been routinely recommended to these men must be rigorously evaluated," said Datta.
According to cancer research UK, the strongest known risk factor for prostate cancer is age, with very low risk in men under 50 and rising risk with increasing age thereafter. Three-quarters of prostate cancer cases are diagnosed in men aged over 65 years. The older the man, the higher the risk and this ties in with post-mortem results where approximately 80% of men by age 90 were shown to have cancer cells in their prostate.
A family history of prostate cancer is one of the strongest known risk factors for this disease. It has been estimated that 5-10% of all prostate cancer cases and 30-40% of early-onset cases (men diagnosed after the age of 55 years) are caused by inherited susceptibility genes.
Variation in incidence rates around the world and within countries, suggests that risk is affected by ethnicity. In the UK, black Caribbean and black African men have approximately two to three times the risk of being diagnosed or dying from prostate cancer than white men, while Asian men generally 12 have a lower risk than the national average.
Diet has been extensively researched because of the large variation in prostate cancer incidence between different cultures and their traditional diets around the world, particularly the Asian versus 'western' diet. A variety of factors have been looked at but much of the research is at present inconclusive. A recent review of the evidence concluded that foods containing lycopenes and selenium probably have a protective effect while diets high in calcium may increase risk.
Lycopene, found principally in tomatoes and tomato-based products, may reduce the risk of prostate cancer. Cooked and processed tomatoes, such as tomato sauce, are a better source of lycopene than fresh tomatoes. A meta-analysis of 21 studies published from 1966-2003, showed that men with the highest intake of cooked tomato products had a 20% reduced risk of prostate cancer compared to men with the lowest intake. Since then, three studies including the European Investigation into Cancer and Nutrition (EPIC) study 18-20 have shown a significant protective effect with higher intake of lycopene, although three other studies showed no association.