ATLANTA — Anastrozole decreased bone mineral density by an average of 6.1% in the lumbar spine and 7.2% in the hip over the 5 years that postmenopausal breast cancer patients were enrolled in a study presented by Dr. Robert E. Coleman at the annual meeting of the American Society of Clinical Oncology.
Osteoporosis risk appeared limited to women who were osteopenic before starting treatment with anastrozole (Arimidex), an aromatase inhibitor. Less clear was the likelihood of progression to osteopenia in women who started out with normal bone mineral density (BMD).
All the women who became osteoporotic—four treated with anastrozole and one who was treated with tamoxifen—were osteopenic before they began adjuvant hormonal therapy in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial.
“No patient with normal bone at baseline became osteoporotic after 5 years of treatment,” Dr. Coleman, a professor of medical oncology at Weston Park Hospital in Sheffield, England, said in his report on a subset of 167 women who were tracked for bone loss.
Among 81 patients tracked in the anastrozole arm of the trial, just 13 had normal BMD after 5 years. All but one had been classified as having normal bone before the study started.
The group of patients identified as osteopenic after 5 years was more mixed, comprising 14 women who entered the study with normal BMD and 21 who were osteopenic at the outset. Dr. Coleman calculated that 17% of patients on anastrozole progressed from normal BMD to osteopenia during the study.
About a third of the anastrozole patients had not reached 5 years of follow-up, however. They were categorized as “not recorded” in Dr. Coleman's analysis.
In a discussion of the trial, Dr. Julie Gralow, of the University of Washington, Seattle, excluded the 27 unrecorded patients, 6 of whom started out with normal BMD, from a recalculation of the data. When she looked only at patients for whom 5-year data were available, she found that 53% of the women who started with normal BMD became osteopenic on anastrozole.
That anastrozole caused bone loss was no surprise to Dr. Coleman and his coinvestigators. The 9,366-patient ATAC trial reported that the aromatase inhibitor was more effective than tamoxifen at preventing breast cancer recurrences and had fewer side effects overall. Fractures were an exception, however, occurring in 11% of women on anastrozole but in only 7.7% of those on tamoxifen (Lancet 2005;365:60-2).
“Anastrozole suppresses postmenopausal estradiol levels by about 97%, so one would anticipate it would have an effect on bone health,” Dr. Coleman said, noting that the bone-loss study was planned when the trial was designed.
Tamoxifen increases estradiol levels and was associated with significantly less bone loss for 86 women in the other arm of the study. Their average BMD loss was just 2.8% in the lumbar spine and 0.7% in the hip.
Despite greater bone loss with anastrozole, he said its “superior efficacy and better overall tolerability, compared with tamoxifen” would continue to give anastrozole the advantage in a risk-benefit analysis.
AstraZeneca provided research funds and honoraria.