The effect of angiotensin ii type 1 receptor blockage on biomechanical and histomorphometrical alterations by experimental osteoporosis rat femur

Renin angiotensin system (RAS) is operating not only systemically but also locally in several tissues, have been also studied in bone microenvironments. Osteoblasts and osteoclasts are known to express Ang II type I (AT1) receptor in cell cultures, suggesting the existence of local RAS in bone. Our study was designed to investigate the effects of losartan on overiectomized rats? femur, since the effect of AT1 receptor blocker on biomechanical parameters and histomorphometric alterations of osteoporotic bone has not been studied yet.In this study, 120 female Wistar rats were used. The animals were divided into ight groups as Control (n=15) (CONT), sham operated (n=15) (SHAM), losartan treated control (n=15) (CONT+LOS), overiectomized (n=15) (OVX), losartan treated overiectomized (n=15) (OVX+LOS), overiectomized (12 weeks) (n=15) (OVX-1), losartan treated control from first day (12 weeks) (n=15) (CONT-1-LOS) and losartan treated overiectomized from first day of overiectomized (12 weeks) (n=15) (OVX-1-LOS).Losartan as AT1 receptor blocker was administered via oral gavage for 8 weeks. Bone mineral density was measured using dual energy X-ray absorbsiometry, while tensile and three-point bending tests were performed for evaluation of biomechanical properties of bone. The structural properties were analyzed by scanning electron microscopy and the captured images were quantified using image analysis software. There was a significant decrease in BMD values of OVX group which were reversed by losartan treatment. According to tensile test results; ultimate tensile strength and strain values of OVX+LOS group increased and decreased respectively when compared to that of OVX group. Losartan treatment also caused a significant recovery in flexural strength and modulus parameters regarding respective control values, which means OVX+LOS group had more force tolerance until break than OVX group. Histomorphological results revealed that; the ratio of alveolar cavities of OVX rat femurs was significantly higher than CONT rat femurs and it was significantly decreased after losartan treatment. There was no significant difference between OVX-1-LOS and OVX-1 according to BMD values and the ratio of alveolar cavities. There was a significant increase in all biomechanical parameters (fleksural strength, fleksural modulus, tensile strength, stifness, young modulus and EAC) of OVX-1-LOS according to OVX-1 group.In conclusion, losartan increased strength, mass and trabecular connections of ovariectomized rat femurs. Therefore, it is tempting to speculate that drugs including AT1 receptor blocker may be used for treatment of osteoporosis or reduction of detrimental effects governed by in the future.