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Preventive breast cancer drug boosts age-related bone loss threefold

Cortical bone, associated with most old-age fractures, worst affected, study shows

Caroline White

Tuesday, 07 February 2012

A drug that can stave off breast cancer in postmenopausal women at high risk of developing the disease, and which is poised for widespread use, seems to increase age-related bone loss threefold, suggests a small study published online in The Lancet Oncology.

Previous preliminary research has suggested that exemestane, a third generation steroidal aromatase inhibitor, might cause less bone loss than other aromatase inhibitors and could even stimulate bone formation.

Aromatase inhibitors, which suppress oestrogen production, are the standard treatment for postmenopausal women with early stage hormone receptor positive breast cancer.

But concerns have been raised about their effects on bone loss and increased fracture risk. Most studies looking into this issue have used tamoxifen as the comparison treatment; this drug is known to protect bone health in postmenopausal women.

The researchers of this study report the results of a bone mineral and bone structure substudy of patients included in the Mammary Prevention 3 (MAP.3) randomised trial, to quantify the effect of exemestane on bone health.

The MAP.3 trial assessed how well exemestane prevented breast cancer in over 4500 healthy postmenopausal women with a family history of the disease. Exemestane cut the risk by 65% compared with placebo.

Some 351 women without osteoporosis were included in the bone substudy, 176 of whom were given exemestane (25 mg/day) and 175 given placebo. Bone mineral density was measured by conventional dual-energy x-ray absorptiometry and new high-resolution peripheral quantitative computed tomography.

After 2 years of treatment, women in the exemestane group had a significant loss of bone mineral density at the distal radius, a common site for fractures related to osteoporosis, and distal tibia.

Furthermore, cortical thickness and area fell by almost 8% compared with a 1% decline in the placebo group. And exemestane substantially affected the loss of cortical bone compared with trabecular bone.

This finding is important, say the authors, because 80% of fractures in old age are the result of greater loss of cortical, rather than trabecular, 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”, explains lead author Angela Cheung from the University Health Network, Toronto, Canada.

In an accompanying Comment, Jane Cauley from the University of Pittsburgh, Pennsylvania, USA, says: “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.”

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