Differential effects of zoledronic acid on trabecular and cortical bone in ovariectomized rats

Abstract

Zoledronic acid (ZA) is the bisphosphonate of highest antiresorptive potency used in the treatment of osteoporosis. Its effects on trabecular bone are clear; on the other hand, its effects on cortical bone are controversial and poorly understood. The aim of this work was to study the effects of ZA on trabecular and cortical bone in ovariectomized (OVX) rats with osteoporosis. For this, sixteen female Sprague Dawley rats of 70 days old underwent OVX. Eight rats were used as control of ovariectomy (Sham group). After 30 days, necessary for the development of osteoporosis, a group of OVX rats received 0.15 mg/100g body weight/weekly of ZA (OVX+ZA) or vehicle (OVX) subcutaneously. One month after treatment, the % of trabecular bone volume (%BV/TV) was measured by histomorphometry and bone mineral density (BMD) of the tibia was determined. In the femur, cortical structural parameters and mechanical properties of the diaphysis and metaphysis were evaluated. Results showed that ZA increased BMD at 7,71±2,17% compared with OVX. The % BV/TV was decreased by OVX and was reversed by ZA (Sham: 31,2±3,43%, OVX: 13,7±1,68% *, OVX+ZA: 27,4±2,98% *, p<0.05). Ovariectomy decreased the fracture strength while treatment partially restored these values.(Sham: 60.8±10,1 N, OVX: 27.2±7.79 N *, OVX+ZA: 36.9±4.03 N, p <0,05). Neither ovariectomy nor treatment with zoledronic acid modified cortical structural variables of the femoral shaft and their biomechanical properties. This work shows that zoledronic acid produces differential effects on the trabecular and cortical bone: recovers the trabecular bone loss induced by ovariectomy and partially correcting the mechanical damage, while not change the studied properties on cortical bone.