A commonly used drug exemestane taken by early breast cancer patients in India – as frequently as once a day for five years – has been found to cause significant bone loss, even when they are given adequate calcium and vitamin D intake.
The drug has been found to worsen age-related decrease in bone mineral density (BMD) by about three times, increasing chances of fractures manifold.
In a study published in the medical journal Lancet, researchers from Canada said the drug causes loss of cortical bone that comprises 80% of the human skeleton.
In the study, cortical thickness of women who took exemestane declined by almost 8% compared with a 1% decline in those who didn’t.
This finding is important because most fractures (80%) in old age are the result of greater loss of cortical bone and account for most disability.
“Exemestane worsens age-related decreases in bone mineral density by about three times, even in the setting of adequate calcium and vitamin D intake,” said lead author Angela Cheung from the University Health Network, Toronto.
Dr Bhawna Sirohi, head of medical oncology at Artemis Cancer Centre, said exemestane is considered a “wonder drug” in India, and is used very commonly to treat early breast cancer in post-menopausal women. It is also used for women whose breast cancer has worsened.
Dr Sirohi said, “Exemestane is in a class of medications called aromatase inhibitors. It works by decreasing the amount of oestrogen production. This can slow or stop the growth of some breast tumours that need estrogen to grow. Using exemestane is a standard treatment for post-menopausal women with early stage hormone-receptor-positive breast cancer.” She added almost 75% of breast cancer cases are hormone driven.
“In hormonal cancers, oestrogen feeds the cancer cells and helps it grow. Exemestane deprives the cancer cells of oestrogen. In early breast cancer patients, it decreases risk of cancer recurrence. In women with advanced stage of cancer, it keeps the disease in remission. The benefit of drug is so high that women want it even against its risk of BMD deletion,” she explained.
“Oestrogen is protective for bones. As women attain menopause, oestrogen levels dip. Exemestane reduces level of oestrogen causing bone loss,” Dr Sirohi added.
In the Lancet study, Cheung and colleagues report the results of a bone-mineral and bone structure sub-study of patients, to quantify the effect of exemestane on BMD in post-menopausal women.
The randomized trial examined the effect of exemestane at preventing breast cancer in over 4,500 healthy post-menopausal women at high risk of developing the disease (those with a family history of breast cancer).
Exemestane reduced the risk of developing breast cancer by 65% compared with placebo. Around 351 women without osteoporosis were included in the bone sub-study, 176 given exemestane and 175 given placebo. BMD was then measured.
After two years of treatment, women given exemestane had a significant loss of BMD at the distal radius (a common site for fractures related to osteoporosis) and distal tibia compared with at the start of the study.
“Women considering exemestane for the primary prevention of breast cancer should weigh their individual risks and benefits. For women taking exemestane, regular bone monitoring plus adequate calcium and vitamin D supplementation are important,” the authors cautioned.
Dr Sirohi added, “Before starting a patient on this drug, we always conduct a BMD scan and then categorize them as normal BMD, those with low BMD and osteoporotic patients. We always give calcium – 1 gram daily and Vitamin D – once a week with the drug.”
Breast cancer is the most commonly diagnosed cancer in India, and the leading cause of cancer-related death among women worldwide.