Aim: 

Aromatase inhibitors (AI) are used in treatment of early and advanced breast cancer. Low estradiol levels in women are associated with decreased bone mineral density and increased fracture risk. In this study, we aimed to investigate effects of an AI, letrazole, on femur fracture and serum estradiol levels.

Methods: 

Total 40 adult Sprague-Dawley female rats were divided into five groups (n = 8). Controls received saline alone. Letrazole was administered to the animals in the second and third groups by daily oral gavage at 0.2 and 1 mg/kg doses, respectively, for six weeks. Another group of letrazole (1mg/kg)-treated rats were allowed to recovery for two weeks. The last group of rats was ovariectomized. At the end, all animals were decapitated and the femur rapidly removed. Serum estradiol levels were determined by ELISA. A universal testing machine was used for determination of biomechanical properties (bending characteristics, stiffness and toughness) on the femur samples.

Results: 

Serum estradiol levels were significantly reduced by letrazole in a dose-dependent manner (p < 0.01) which returned to control values following two weeks of recovery (p < 0.05). Following three point bending tests, it was observed that a slight increase (p < 0.05) in the strength of samples occurred for the letrazole-treated rats depending on given doses with respect to those of control group, however, a significant increase (p < 0.01) in the brittleness and even stiffness was observed.

Conclusion: 

The present findings suggest that long-term use of letrazole may increase risk of osteoporosis and fracture. It is advised that bone mineral density should be measured in patients taking AI and anti-resorptive therapy be commenced if osteoporosis is already present.