Dr. Angela Cheung, director of the osteoporosis program at Toronto's University Health Network. THE CANADIAN PRESS/HO-University Health Network
TORONTO - A drug shown to be highly effective in preventing breast cancer in postmenopausal women at high risk for the disease appears to worsen age-related bone loss, despite regular ingestion of calcium and vitamin D, researchers have discovered.
In a study published last June, the drug exemestane was found to be "very effective in preventing breast cancer in women," said Dr. Angela Cheung. "So it was a good option for women who have a high risk because of their family history, if their mother had it or their sister had it."
That study of 4,560 postmenopausal women found exemestane decreased the risk of breast cancer by 65 per cent.
Exemestane has been used along with other drugs in its class, known as aromatase inhibitors, to prevent recurrence in women already treated for breast cancer. But the drug has not yet been approved by Health Canada for preventing the disease in women who have not had breast cancer but are at high risk.
In an analysis of 351 women in the study, published Monday in the online edition of the journal Lancet Oncology, researchers found many experienced bone loss.
The finding was unexpected, as exemestane is a slightly different form of aromatase inhibitor that was thought to be "bone-neutral," said Cheung, director of the osteoporosis program at Toronto's University Health Network and the substudy's principal investigator.
Still, "we wanted to take a look a little bit more in detail at the bone side of things because we know that estrogen, the female hormone, is actually beneficial to bone," she said, explaining that aromatase inhibitors lower circulating estrogens in the body.
The women in the substudy, with a median age of 61, did not have osteoporosis and had not been prescribed bone-building medications. But they were taking daily supplements of 1,200 to 1,500 milligrams of calcium and 800 international units of vitamin D, which are recommended to preserve bone health.
Osteoporosis is a condition that causes bones to become weaker, increasing the risk of fracture. The most common sites of such fractures are the wrist, spine and hip.
"At the end of two years, what we found was that despite people taking calcium and vitamin D, there were mild decreases in bone density at the hip and spine," said Cheung.
But when the researchers used a sophisticated machine to measure the integrity of the bone ? both the outer component, called cortical bone, and the spongy inner core ? they found there had been significant changes among some of the women's bones.
"Not everyone had bone loss," said Cheung, noting that 65 per cent were affected, while the other 35 per cent were "very stable."
Researchers found the average change in bone destiny at the wrist, a common site for fractures, was a reduction of 6.1 per cent in the exemestane group and 1.8 per cent in the placebo group. At the ankle, those taking the drug had a five per cent bone density loss on average compared with 1.3 per cent in the placebo group.
Cortical, or compact, bone comprises 80 per cent of the human skeleton and is the major determinant of bone structural strength.
The advanced imaging test, called a high-resolution peripheral quantitative CT, found bone thickness was also diminished among those taking exemestane ? almost eight per cent versus about one per cent given a dummy treatment.
"We found that exemestane worsens age-related bone loss by about three-fold, even in women who take adequate calcium and vitamin D," co-author Dr. Lianne Tile, medical director of the osteoporosis clinic at UHN, added in a statement.
"Our findings suggest that we need to weigh the individual risks and benefits when considering exemestane for the primary prevention of breast cancer," she said. "For women taking this medication, it is a good idea to have regular bone monitoring, and adequate calcium and vitamin D."
Dr. Karen Gelmon, a medical oncologist at the B.C. Cancer Agency who was not involved in the study, said while the tests showed changes in the bone, "what we have no idea about is what the clinical significance of those changes are."
She said the study did not identify increased rates of osteoporosis ? which is defined by a particular level of bone density loss ? or fractures among the affected women.
"In this study, we're not seeing what we would call classical clinical osteoporosis," Gelmon said, suggesting that women taking the drug would need to be tested over a longer period to see if osteoporosis develops and subsequent fractures occur.
All the women in the study began with normal bone densities, she said Monday from Vancouver. "What we don't know is what about women with abnormal bone densities. Does it (the drug) cause less harm, more harm, the same?"
Gelmon said all drugs have side-effects to some degree, even ASA tablets, so women would have to balance the benefit of the drug in preventing breast cancer with the risk of potentially serious bone loss.
"What this study does is it gives us yet another indication that we should all be diligent whenever we're taking anything. I think that's what it really tells us."
In a commentary accompanying the article, epidemiologist Dr. Jane Cauley of the University of Pittsburgh called results from the study important because it is the first to study bone health and aromatase inhibitors using high-resolution peripheral quantitative CT.
Cauley, who studies aspects of women's health and was not involved in the research, said the results suggest that effects of the drugs on bone strength may have been significantly underestimated because all previous data relied on commonly used and less sophisticated bone density tests.
"Assessment of the use of aromatase inhibitors in patients, especially in the prevention setting, needs to consider the risks to the microarchitectural strength of bone mass," she writes, suggesting that "one might not be too reassured" by the use of exemestane for breast cancer prevention.