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Weight not protective against AI bone loss.

MONTREAL -- Aromatase inhibitors are proving to be better hormone-positive breast cancer treatments than tamoxifen with respect to both efficacy and tolerability, but they do take their toll on bone.

AIs lower the level of circulating estrogens, and their long-term use has been linked with both a reduction in bone mineral density (BMD) and an increased risk of osteoporosis and fracture among postmenopausal women. Two studies addressing these adverse events were presented in posters at the annual meeting of the International Bone and Mineral Society.

Dr. Eugene McCloskey of the academic unit of bone metabolism, Metabolic Bone Centre, University of Sheffield (England) and colleagues noted that a high body mass index (BMI) is associated with a reduced risk of osteoporotic fractures as a result--at least partly--of higher endogenous estrogen levels. They set out to determine whether a higher BMI could confer a protective effect against the negative effects of AIs on bone.

As part of the Letrozole, Exemestane, and Anastrozole Pharmacodynamics (LEAP) trial, 102 healthy postmenopausal women were randomized to receive one of three AIs--letrozole, exemestane, or anastrozole--on a daily basis for 24 weeks. The women's serum levels of bone formation and resorption markers were measured at baseline and 12, 24, and 36 weeks.

Prior to treatment, baseline BMI correlated significantly with circulating levels of endogenous estrogens. Both baseline BMI and circulating estradiol levels also correlated negatively with baseline markers of bone resorption and positively with levels of parathyroid hormone.

After 24 weeks of treatment, among 90 evaluable patients, baseline BMI and estradiol correlated positively with increased levels of serum C telopeptide crosslinks, a marker of bone resorption. Baseline BMI also correlated with increased serum levels of N-terminal propeptide of type I collagen, a marker of bone formation, at 24 weeks. There was no correlation, however, between changes in parathyroid hormone and BMI or estradiol at 24 weeks.

Based on these findings, the authors concluded that "during AI treatment, women with higher BMI and estradiol levels at baseline had greater increases in bone turnover compared with women with low BMI and estradiol levels. [Therefore,] a high BMI may not confer a reduced fracture risk in women with early breast cancer receiving an AI." This study was conducted in collaboration with AstraZeneca, manufacturer of anastrozole under the tradename Arimidex.

In another study of the effect of AIs on bone, Nancy Waltman, Ph.D., and colleagues from the University of Nebraska College of Nursing, in Lincoln, randomly assigned 249 postmenopausal women who had received AIs for early breast cancer, and who had a BMD T score of -1.0 standard deviations or lower, to strength/weight training exercises or to no such intervention. All participants took 35 mg of risedronate weekly plus 1,200 mg of calcium and 400 IU of vitamin D on a daily basis. The exercise program consisted of eight exercises focusing on upper and lower extremity strength-building, as well as on balance, conducted two times a week.

Overall, 223 of the 249 women completed the 24-month trial. Adherence to medication and vitamin/mineral supplementation was over 90%, but adherence to the exercise program was only about 70%. Those in the exercise group had significant improvements in their muscle strength for hip and knee flexion and extension. They also had significantly improved balance.

There were no differences between the two experimental groups with respect to BMD, but among women who were 90% or more adherent to the exercise program, there was a trend toward improved BMD at the trochanter and total hip. Since improved balance also has been shown to reduce falls and fractures, a more intensive exercise program might be beneficial for these patients, the authors suggested.

A substudy of this analysis involving 29 patients revealed that, despite taking a 400-IU vitamin D supplement, most women in this trial had insufficient levels of serum 25(OH)D levels. There was also an inverse correlation between serum D levels and musculoskeletal pain. Therefore, women on AIs may benefit from supplementation with vitamin D at much higher doses than the current standard of 400 IU, the authors wrote.


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Title Annotation:Women's Health; Aromatase inhibitors
Author:Palkhivala, Alison
Publication:Internal Medicine News
Geographic Code:1USA
Date:Oct 15, 2007
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