SUN-023 Changes in Microct Bone Density and Reduced Bone Formation in a “Postmenopausal” PCOS Rat Model

Abstract

Polycystic ovary syndrome (PCOS) affects women during their entire lifespan. Evidence from the literature suggests an association of PCOS with decreased bone formation markers (osteocalcin and P1NP), although no conclusive data about the incidence of fractures exist. In the present study, we investigated the consequences of androgenization in rats on bone markers and femur microCT and the changes in these parameters after ovariectomy. This study was approved by the local Animal Ethics Committee. Briefly, Wistar rats (n= 38) were divided in 4 groups: 1) “Control OVX” (single dose of corn oil s.c. at day 5 of life and ovariectomy at day 100, n=9); 2) “Control SHAM” (n=9); 3) “Androgenized OVX”(single dose of testosterone propionate 1.25 mg s.c. at day 5 of life and ovariectomy at day 100, n=10); and 4) “Androgenized SHAM” (n=10). Full characterization of estrous cycles and weight was performed during growth, and all animals were euthanized at day 180 during metestrus/diestrous. Evaluation of glucose levels, lipids, estradiol, P1NP levels (a marker of bone formation), and analysis of the femur micro CT Skyscan 1174 (Aartselaar, Belgium) was performed in at least eight animals of each group. Ovariectomy increased the weight of Androgenized OVX rats on day 180: these animals were heavier than Control OVX, Control SHAM, or Androgenized SHAM (ANOVA p<0.001). However, metabolic changes were observed in ovary-intact Androgenized SHAM rats who exhibited higher total cholesterol (ANOVA p<0.001), increased LDL (ANOVA p=0.03), and elevated TyG index, a marker of insulin resistance (ANOVA p<0.001) against all other three groups. This group (Androgenized SHAM rats)also exhibited an increase in MicroCt bone density (g/cm-3) (mean + SEM) of 1.117 + 0.06 against the other - Control SHAM 0.8433 + 0.03, Control OVX 0.5527 + 0.001, and Androgenized OVX 0.6284 + 0.02 (ANOVA p< 0.001). Although the values of bone density between Control OVX and Androgenized OVX groups were similar, gonadal removal produced a different pattern of bone density reduction between Control OVX and Androgenized OVX (Two-Way ANOVA p=0.001). Moreover, we found P1NP levels significantly decreased in the Androgenized OVX group (mean + SEM) of 58.57 + 4.41 ng/ml against 88.02 + 8.49 ng/ml in Control OVX versus (ANOVA p<0.0001) indicating lower bone formation. Our results suggest that bone and metabolic features of Androgenized rats are affected by ovariectomy with a negative impact on bone formation.