Effect of tamoxifen and aromatase inhibitors on the risk of fractures in women with breast cancer.

We studied risk of fractures among women who had used tamoxifen or aromatase inhibitors compared to nonusers in a case-control study. There were 64,548 fracture cases and 193,641 age- and gender-matched controls. Adjustment was made for comorbidity, social factors, and use of other drugs. Use of tamoxifen in general was not associated with any significant change in the risk of any fracture, wrist fractures, and spine fractures. A significantly decreasing relative risk of fractures was seen with increasing dose, although the risk never declined statistically significantly below that in nonusers. An increased risk of hip fractures was seen, but the increase was limited to patients who had used low average doses (<20 mg of tamoxifen/day) and were prior users (i.e., had not used tamoxifen within the last year). Aromatase inhibitors were associated with significant increases in overall risk of fractures and risk of hip fractures. Tamoxifen does not seem to be bone-protective in such a degree that the risk of fractures decreases below that of nonusers. Tamoxifen per se does not seem to increase the risk of fractures. Aromatase inhibitors were associated with a significant increase in the risk of fractures. In women at high risk of fractures, supplementary measures, i.e., bisphosphonates, may be considered.