PARENT SESSION

(W630) EARLY OVARIAN FAILURE ACCELERATES THE RATE OF BONE MINERAL DENSITY LOSS IN AGED C57BL/6 MICE.

Rivera, Zelieann¹, Funk, Janet¹, Christian, Patricia ¹, Hoyer, Patricia¹, ¹ University of Arizona, Tucson, AZ

ABSTRACT- 4-vinylcyclohexene diepoxide (VCD) induces premature ovarian failure (OF) in mice. Previous studies in young mice have shown that VCD-induced follicle loss can cause OF within an average of 58 days after the onset of dosing, and that this is accompanied by morphological evidence of loss of bone integrity. Thus, the VCD-treated mouse is a potential model for studies related to post-menopausal osteoporosis. This study was designed to evaluate the effect of OF on bone mineral density (BMD) in older mice. Nine-month old C57BL/6 mice were dosed daily for 15 days with either vehicle control or VCD (160mg/kg; i.p.). Baseline BMD values and body composition data were determined by dual energy X-ray absorptiometry (Piximus, GE Lunar) before the onset of dosing and then every 2 weeks beginning 24h after the final dose. Body weights were recorded every 2 weeks. Estrous cycles were monitored daily by vaginal cytology to determine the onset of OF in VCD-treated mice. Average time to OF was 36.2 ± 3.6 days after the onset of dosing with VCD (n=6). At the end of the study (d171), 60% of the controls (n=3) were still cycling at an average of 5.6 ± 0.03 days/cycle and the remaining 40% (n=2) underwent OF on d152. Body weights in the control group were greater (P<0.05) only on d137 (35.5 ± 1.8 g) when compared to baseline (30 ± 0.4 g). Total body fat (TBF) of control animals did not change significantly over time. Conversely, body weights and TBF in VCD-treated mice increased significantly by d84 (35 ± 1.8 and 9.6 ± 1.2 g, respectively) and were greater than baseline (29.5 ± 0.3 and 6.2 ± 0.3 g, respectively) until the end of the study. In VCD-treated mice, BMD values decreased (P<0.05) by d84 (0.041 ± 0.003 g/cm²) when compared to baseline (0.056 ± 0.001 g/cm²) and remained low, whereas BMD values in control animals remained unchanged from baseline. Our findings demonstrate that, as has been reported in younger animals, OF also accelerates the rate of BMD loss in older animals. Collectively these observations suggest that loss of ovarian function contributes more significantly than age to the BMD loss seen in post-menopausal women. (AG021948).

KEY WORDS: menopause, ovarian failure, osteoporosis, bone mineral density