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What if a drug could stop you from getting cancer, but in the process may cause bone density loss that could lead to life-altering fractures?

Would it be worth the risk?

A growing number of women with a high probability of developing breast cancer will be asking themselves that question in light of a new study that found exemestane, a promising prevention drug, could lead to substantial bone density loss.

New hope is being funnelled into the possibility that exemestane, traditionally used as a treatment for women with existing cases of breast cancer, can be used pre-emptively to ward off the disease.

A major study published in the New England Journal of Medicine last year found that healthy women at high risk of developing breast cancer who took exemestane had a 65 per cent lower chance of getting the disease than women who took placebo. High-risk women include those who are older than 60, have a strong family history of the disease, or have had a previous mastectomy to treat non-invasive breast cancer.

The findings energized the medical community and breast cancer experts who saw it as a possible way to dramatically reduce incidence of the disease in some high-risk women.

But that initial excitement is being tempered by the new evidence showing women who take the drug may experience three times the bone density loss of women who don't take it. The study, published Monday in the Lancet Oncology journal, also found the drug worsens bone loss even when women take calcium and vitamin D supplements.

The risks shouldn't be taken lightly; bone density loss exposes individuals to osteoporosis and puts them at risk for serious fractures that can hinder quality of life and even hasten death.

"[The drug is]something women should be excited about," saidAliya Khan, professor of medicine at McMaster University and director of the Calcium Disorders Clinic at St. Joseph's Healthcare Hamilton, who was not involved in the study. "But … what's the cost of this drug? If the cost is you can increase your risk of osteoporosis, that might not be such a good decision."

It's not surprising that exemestane leads to bone loss. The drug is an aromatase inhibitor, meaning it blocks production of estrogen, leading to bone density loss . Yet, preliminary research suggested exemestane might not affect bone loss as much as other aromatase inhibitors, or that it could even offer a protective benefit by stimulating bone formation.

The new study may finally offer some clarity. It marks the first time researchers have been able to comprehensively quantify the impact of exemestane on bone health using a state-of-the-art screening mechanism known as high-resolution peripheral quantitative computed tomography. The test enables researchers to differentiate between bone loss in the outer cortical shell of the bone and the inside spongy layer, which allows better understanding of all aspects of bone fragility.

Lead author of the study Angela Cheung, who is director of the University Health Network Osteoporosis Program in Toronto, said it appears the drug causes greater loss to the outer shell of the bone. It's a serious concern because the majority of bone fractures in the elderly are linked to loss of the outer cortical bone, the authors said.

Jane Cauley, an epidemiology professor at the University of Pittsburgh who wrote a commentary published with the new study, noted that previous studiesmay have actually underestimated bone loss caused by aromatase inhibitors because they relied on less-advanced screening methods.

In total, 351 women without osteoporosis were included in the study, with half receiving exemestane and half placebo. After two years, the exemestane group had a significant decrease in bone mineral density: a nearly eight per cent decline in cortical thickness in that group compared to a one per cent decline in the placebo group.

"It is something to consider when you consider taking this medication to prevent breast cancer," Dr. Cheung said. "I think each individual has to weigh their risk and benefit."

For healthy women who face a heightened risk of breast cancer, the benefit could be sparing themselves from the disease. But the risk could be depleting bone strength, developing osteoporosis and suffering a fatal hip fracture, all to prevent a disease that may never have appeared in the first place.