Investigation of the effects of aromatase inhibitors letrazole and anastrazole on bone turnover markers and bone mineral density in female intact rats.

2. ABSTRACTInvestigation of the Effects of Aromatase Inhibitors Letrazole andAnastrazole on Bone Turnover Markers and Bone Mineral Density in FemaleIntact Rats.Aromatase inhibitors have recently been in use with new indications inreproductive period. The present study was designed to investigate effects of twoaromatase inhibitors on bone mineral density and turnover markers in intact femalerats. Effects of letrazole and anastrazole at two different dose levels wereinvestigated on weights of ovary and uterus, and effects on serum levels of estradiol,androstenedione, testosterone, dehydroepiandrostendion (DHEA), DHEA-sulfate(DHEA-S) and osteocalcin and pyridinoline levels as bone turnover markers.A total of 50 intact female rats were obtained from the ExperimentalResearch Center at Firat University Medical School (FUTDAM). They were dividedin five groups, and oral gavage was applied for a period of 16 weeks. The groupswere formed as follows:Group 1 (n=10): Control 2 ml salineGroup 2 (n=10): Letrazole 1 mg/kgGroup 3 (n=10): Letrazole 2 mg/kgGroup 4 (n=10): Anastrazole 0.1 mg/kgGroup 5 (n=10): Anastrazole 0.2 mg/kgOne-Way ANOVA, followed by post hoc Tukey?s HSD was performed ondata. SPSS 11.0 for Windows was utilized for statistical analysis. P<0.05 wasconsidered to be statistically significant.xivBoth doses of letrazole and anastrazole did not change femur and vertebrabone mineral density, but different doses of both agents significantly decreaseduterus weight (p<0.001). As both letrazole doses enhanced ovarian weight (p<0.001),anastrazole had no such effect. Serum estrogen levels were reduced by different at alldose levels by both agents (p<0.001). All androgen levels were significantly elevatedby letrazole (p<0.05) although anastrazole positively affected only androstenedionelevels (p<0.05). Higher dose of letrazole increased osteocalcin levels (p<0.05) whilepyridinoline levels were increased (p<0.05) by higher dose of anastrazole.Our results indicate that using of letrazole and anastrazole had no cleareffects on bone density in the intact rats. However, it is thought that effects ofletrazole on bone formation and anastrozole on bone rezorption and mineral densityremain to be further investigated.Keywords: rat, letrazole, anastrazole, bone mineral density, osteocalcin,pyridinolinexv