A drug widely used to prevent breast cancer in postmenopausal women highly prone to developing the disease appears to significantly worsen age-related bone loss, a new Canadian study has claimed.
The study, published in The Lancet Oncology, found that exemestane, the standard drug for postmenopausal women with early stage hormone-receptor-positive breast cancer, worsens the bone-mineral density (BMD) compared to those who don't take the drug.
"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 here.
According to researchers, exemestane, also known as the aromatage inhibitors, work by suppressing oestrogen production in postmenopausal women prone to developing breast cancer.
But despite being generally well-tolerated, concerns have been raised about their effects on bone loss and increased fracture risk.
There was, however, no clear evidence of the problem as most studies have been done with tamoxifen, which has beneficial effects on bone in postmenopausal women.
In the latest study, Cheung and colleagues carried out a bone-mineral and bone structure substudy of patients included in the Mammary Prevention 3 (MAP-3) trial, to quantify the effect of exemestane on BMD and structure in postmenopausal women.
The MAP-3 trial examined over 4500 healthy postmenopausal women at high risk of developing the disease (with a family history of breast cancer) and found that exemestane reduced the risk of developing breast cancer by 65 per cent compared with placebo.
In the substudy involving 351 women without osteoporosis, 176 were given exemestane and 175 given placebo.
After 2 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.
Additionally, in the exemestane group, cortical thickness and area declined by almost eight per cent compared with a one per cent decline in the placebo group, the researchers said. Exemestane substantially affected the loss of cortical bone compared with trabecular bone.
This finding is important because most fractures (80 per cent) in old age are the result of greater loss of cortical rather than trabecular bone and account for most disability, they said.
The authors cautioned that 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. Long-term studies are needed to assess the effect of our findings on fracture risk," they added.
In an accompanying comment, Jane Cauley of the University of Pittsburgh, Pennsylvania, said: "Most bone loss occurs after 65 years of age, within the cortical compartment. Thus, if aromatase inhibitors increase cortical porosity, this effect could be a key cause of bone loss strength and non-vertebral fractures associated with their use."
"Thus, one might not be too reassured about the use of exemestane in the prevention setting."
