Effects of the steroidal aromatase inhibitor exemestane and the nonsteroidal aromatase inhibitor letrozole on bone and lipid metabolism in ovariectomized rats
| Autor: | Maria Mendes, Shangle Qi, Angela M. Cheung, Haiqing Hu, Paul E. Goss, Kenneth P.H. Pritzker |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Cancer Research
medicine.medical_specialty medicine.drug_class Ovariectomy Osteocalcin Injections Intramuscular Bone resorption Bone and Bones Rats Sprague-Dawley chemistry.chemical_compound Exemestane Internal medicine Nitriles medicine Animals Femur Aromatase Amino Acids Bone mineral Pyridinoline Aromatase inhibitor Lumbar Vertebrae biology business.industry Aromatase Inhibitors Letrozole Cholesterol LDL Triazoles Lipid Metabolism Rats Androstadienes Endocrinology Cholesterol Oncology chemistry Ovariectomized rat biology.protein Female Steroids business medicine.drug |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 10(17) |
| ISSN: | 1078-0432 |
| Popis: | Purpose: Exemestane (EXE) and letrozole (LET) are third-generation aromatase inhibitors currently prescribed for postmenopausal hormone-dependent breast cancer. The impact on end organs of estrogen depletion in menopausal women is of significant clinical importance. We studied the effects of EXE, its principal metabolite, 17-hydroexemestane (17-H-EXE), and LET on bone and lipid metabolism in ovariectomized (OVX) rats. Experimental Design: OVX rats were treated by weekly intramuscular injection for 16 weeks with 20, 50, and 100 mg/kg EXE, 20 mg/kg 17-H-EXE, and daily oral gavage of 1 mg/kg LET. At the end of the treatment period, bone mineral density (BMD), the bone resorption marker serum pyridinoline, the bone formation marker serum osteocalcin, bone mechanical properties, histomorphometry, and serum lipid concentrations were determined. Results: Lumbar vertebral and femoral BMD, bending strength of the femur, compressive strength of the fifth lumbar vertebra, and trabecular bone volume were significantly higher in OVX animals given EXE and 17-H-EXE than in OVX controls. EXE and 17-H-EXE significantly reduced an ovariectomy-induced increase in serum pyridinoline and serum osteocalcin. EXE and 17-H-EXE given to OVX rats caused significant reductions of serum cholesterol and low-density lipoprotein cholesterol. In contrast, OVX rats treated with LET had BMD, bone biomarkers, mechanical failure properties, and lipid levels similar to those of OVX controls. Conclusions: EXE and 17-H-EXE significantly prevent bone loss, enhance bone mechanical strength, and lower serum cholesterol and low-density lipoprotein levels in OVX rats. These protective effects on end-organ function are not seen with the nonsteroidal inhibitor LET. |
| Databáze: | OpenAIRE |
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