Toronto (Feb. 6, 2012) - Exemestane, a drug used in the prevention of breast cancer in postmenopausal women, has a negative effect on bone density and structure in these women, despite calcium and vitamin D supplements.

Dr Angela Cheung imageThis first-ever study examined the effect of this drug on women's bone health and found that on three major outcome measures, taking exemestane for two years worsens age-related bone loss in postmenopausal women. The results are in an article entitled, "Bone Density and Structure in Healthy Postmenopausal Women treated with Exemestane for the Primary Prevention of Breast Cancer: a nested substudy of the MAP.3 trial", published Online First in The Lancet Oncology.

"The study is important because of the potential for wide-spread use of this medication by women at increased risk of developing breast cancer," said Dr. Lianne Tile, one of the authors of the study, Medical Director of the Osteoporosis Clinic and Staff General Internist at University Health Network (UHN).

The first author is Dr. Angela Cheung, Director of the Centre of Excellence in Skeletal Health Assessment and the Osteoporosis Program, holder of the Lillian Love Chair in Women's Health at the UHN, Staff, General Internal Medicine and Endocrinology. Other authors at UHN include: Dr. Savannah Cardew, Dr. George Tomlinson, Dr. Moira Kapral, Dr. Christine Elser, Dr. Marta Erlandson, Judy Scher, Hanxian Hu, and Alice Demaras.

In addition, Dr. David McCready, Dr. Ruth Heisey, Irene Ho, Suzanne Cohen, Alexandra Tse, Queenie Wong, Gail Jefferson, Diana Yau and Karen Stratton at UHN also contributed to the study.

This study was a nested safety substudy of the MAP.3 trial of exemestane for the primary prevention of breast cancer. The drug is a member of the class of drugs known as aromatase inhibitors. It works by decreasing the amount of estrogen circulating in the body. This can slow or stop the growth of some breast tumors that need estrogen to grow. Studies have shown that treating women at high-risk of developing breast cancer with this drug can cut their risk of developing the disease by two-thirds.

In the substudy, 351 postmenopausal women, with a median age of 61.3, from five North American centres, including Toronto General Hospital, Mount Sinai Hospital and Women's College Hospital in Toronto, participated in a two-year follow-up with the drug. These women were not osteoporotic, not on bone medications, and were supplemented to a total daily intake of 1200-1500mg calcium and 800IU vitamin D. All had baseline lumbar spine, total hip and femoral neck T-scores above -2.0. T-scores indicate how much your bone mass compares to the average bone mass of a healthy adult. A T-score of less than or equal to -2.5 indicates osteoporosis.

Osteoporosis is a condition that causes bones to become weaker, thereby increasing the risk of fracture or breakage. The most common sites of osteoporotic fracture are the wrist, spine and hip.

The main outcome measured was bone mineral density (BMD) by low-radiation, high resolution peripheral quantitative computed tomography (HRpQCT), an assessment of how dense or strong bones are. At the distal radius or wrist, a common site for fractures, the change in BMD was - 6.1% in the exemestane group, and -1.8% in the placebo group at two years. At the distal tibia or ankle, the BMD change was -5.0% in the medication group, and -1.3% in the non-medication or placebo group.

Cortical bone (or compact bone) comprises 80% of the human skeleton and is the major determinant of bone structural strength. The HRpQCT, one of the most advanced imaging technologies for measuring bone structure and density, can measure the thickness of the cortical bone or the outer shell of bones, with images like a "virtual biopsy". The change in thickness was -7.9% in the exemestane group, and -1.1% in the placebo group at two years.

Dual-energy X-ray absorptiometry, the most widely used and most thoroughly studied bone density measurement, was also used to assess bone mineral density at the lumbar spine and hip. Both body sites showed a decline compared to placebo (-2.4% vs. - .5% in the spine and -1.8% vs. -0.6% in the hip).

"We found that exemestane worsens age-related bone loss by about three-fold, even in women who take adequate calcium and vitamin D," concluded Dr. Tile. "Our findings suggest that we need to weigh the individual risks and benefits when considering exemestane for the primary prevention of breast cancer. For women taking this medication, it is a good idea to have regular bone monitoring, and adequate calcium and vitamin D."

Dr. Cheung also recommended that in addition to calcium and vitamin D, women do regular weight-bearing exercises such as walking, dancing, or exercising with small weights, to preserve muscle mass, maintain balance and prevent osteoporotic fractures.

For more information about the Osteoporosis Program at University Health Network, please visit http://www.uhn.ca/Arthritis/Clinics/Osteoporosis_Clinic, which includes information about the Osteoporosis Exercise Guide, demonstrating and explaining the most beneficial exercises in building bone strength and guidelines in preventing injuries and fractures.

This study was supported by the Canadian Breast Cancer Research Alliance, the Canadian Cancer Society, Canadian Institutes of Health and Pfizer Inc.

Bone Density image 

About University Health Network

University Health Network consists of Toronto General, Toronto Western and Princess Margaret Hospitals, and Toronto Rehabilitation Institute. The scope of research and complexity of cases at University Health Network has made it a national and international source for discovery, education and patient care. It has the largest hospital-based research program in Canada, with major research in complex care, cardiology, transplantation, neurosciences, oncology, surgical innovation, infectious diseases, genomic medicine and rehabilitation medicine. University Health Network is a research hospital affiliated with the University of Toronto.

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