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Effect of a High Bone Turnover State Induced by Estrogen Deficiency on the Development and Progression of Breast Cancer Bone Metastases

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Annual summary rept. 28 Mar 2005-27 Mar 2006

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Aromatase inhibitors AIs, effective treatment for breast cancer, block estrogen synthesis. Increased bone resorption and decreased bone mineral density BMD are predicted consequences. We hypothesized that bisphosphonates BPs may prevent bone loss from AI therapy. Four-week-old female nude mice were treated with letrozole 10 mcgd, zoledronic acid ZA 5 mcgkg twice weekly, letrozole ZA or control. Mice treated with letrozole alone had lower BMD compared to control p0.0001 total body, spine, femur and tibia. Mice treated with ZA alone had higher BMD compared to control p0.0001 total body, spine, femur and tibia. MicroCT analysis of the tibia showed no difference in trabecular bone volume BVTV or trabecular number, thickness or spacing in mice treated with letrozole compared to control. Treatment with ZA - letrozole resulted in a significant increase in BVTV and trabecular number and thickness, and the structural model index indicated that the bone structure was unusually solid. ZA prevented AI-induced bone loss, but microCT and dynamic bone histomorphometry suggest reduced bone remodeling. BPs may be useful to prevent AI-induced bone loss, but further studies are needed to assess the effects of these treatments on bone quality.

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  • Biochemistry
  • Biology
  • Anatomy and Physiology

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