Zosia Chustecka

June 06, 2007

June 6, 2007 (Chicago) — One of the worst adverse effects of treatment with aromatase inhibitors in breast cancer — drug-induced bone loss of around 2% each year — can be prevented by the use of a bisphosphonate, a new study has shown. Postmenopausal women with hormone-positive breast cancer taking anastrozole (Arimidex, AstraZeneca) who had low bone-mineral density (BMD) and who also took a once-monthly oral formulation of 150-mg ibandronate (Bondronat, Roche) were protected against bone loss and showed significant increases in BMD.

The finding comes from the 1-year results from the ARIBON study, and details were reported in a poster presentation here at the American Society of Clinical Oncology (ASCO) 43rd Annual Meeting that won an ASCO Merit Award.

“The key issue is the bone-mineral density at the beginning,” lead researcher James Lester, MD, from the cancer research center at Weston Park Hospital, in Sheffield, United Kingdom, told Medscape. “If a woman already has osteoporosis when starting anastrozole treatment, there is no question that she should also take ibandronate at the same time,” he said. “If the woman is osteopenic, then it is also worth taking ibandronate, as it can prevent the osteopenia from developing into osteoporosis. However, if the BMD is normal before starting treatment, the woman is unlikely to develop osteoporosis while taking anastrozole.”

Ibandronate is already marketed in Europe, but not in the United States, and is not licensed for this use. Oral and intravenous formulations are marketed, and the drug was approved by the European Commission in October 2003 for the prevention of skeletal effects in patients with breast cancer and bone metastases.

The ARIBON study involved 131 patients taking the study medications for at least 1 year. Baseline bone densitometry showed that 13 patients were osteoporotic (mean age, 71 years), 50 were osteopenic (mean age, 67 years), and 68 had normal BMD measures (mean age, 63.5 years). Three patients were withdrawn during the yearlong study, 2 osteopenic patients because of joint pains, and 1 woman with osteoporosis who was put on long-term steroids.

Bone densitometry was repeated after 1 year. In the group of women who were osteopenic to begin with, there was a fall in BMD in the placebo group at both the lumbar spine (-2.61%) and the hip
(-2.34%), while the group taking ibandronate showed an increase in BMD at both sites (+2.78 at lumbar spine and +1.35% at the hip). The differences between the 2 groups were statistically significant at both sites (P < .001). Five patients who were in the ibandronate group began the study with osteopenia at 1 site ended with normal BMD measures at that site.

In women who were osteoporotic to begin with, the increase in BMD seen with ibandronate was even higher: +5.05% at the lumbar spine and +2.62% at the hip. Seven patients who were osteoporotic at 1 site ended up with the milder state of osteopenia at that site.

In the group who had normal BMD at the beginning of the study, 2-year data were presented for 20/68 patients. These showed a fall in BMD over the 2 years, -4% at the lumbar spine and -3.2% at the hip, but despite these changes, no patients developed osteoporosis, the researchers commented.

Two patients lost more than 10% BMD and were withdrawn from the study and unblinded; both had been taking placebo and were then offered open-label ibandronate.

The team concluded that in patients who were osteoporotic and osteopenic, the addition of once-monthly ibandronate at the start of anastrozole treatment prevents anastrozole-induced bone loss and results in significant increases in BMD at the lumbar spine and hip. In comments to Medscape, Dr. Lester added that these results were obtained specifically with ibandronate and anastrozole, and so they should not be generalized to all bisphosphonates and all aromatase inhibitors. There may be a class effect, but the aromatase inhibitors in particular do differ from one another, he pointed out.

American Society of Clinical Oncology 43rd Annual Meeting: Abstract 553. Presented June 2, 2007.


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