Effect of a High Bone Turnover State Induced by Estrogen Deficiency on the Development and Progression of Breast Cancer Metastases
Abstract
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 Al therapy. Four-week-old female nude mice were treated with letrozole (10 mcg/d) zoledronic acid (ZA) (5 mcg/kg twice weekly) letrozole + ZA or control. Mice treated with letrozole alone had lower BMD compared to control (p<0.0001; total body spine femur and tibia). Mice treated with ZA alone had higher BMD compared to control (p<0.0001; total body spine femur and tibia). MicroCT analysis of the tibia showed no difference in trabecular bone volume (BV/TV) or trabecular number thickness or spacing in mice treated with letrozole compared to control. Treatment with ZA (+1- letrozole) resulted in a significant increase in BV/TV and trabecular number and thickness and the structural model index indicated that the bone structure was unusually solid. ZA prevented Al-induced bone loss but microCT and dynamic bone histomorphometry suggest reduced bone remodeling. BPs may be useful to prevent Al-induced bone loss but further studies are needed to assess the effects of these treatments on bone quality.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2007
- Accession Number
- ADA472923
Entities
People
- Wende M. Kozlow
Organizations
- University of Virginia