Histological and biomechanical effects of zoledronate on fracture healing in an osteoporotic rat tibia model.

Abstract

This study aims to investigate the effects of zoledronate therapy on histological and biomechanical properties of bone healing via a fracture model generated on osteoporotic rat tibiae. Ovariectomized 40 Wistar-Dawley female rats weighing 300 g to 350 g were used in the study. After one week, 2 IU/g heparin injection was started subcutaneously. After four weeks of daily injections, osteoporosis was ensued proven with bone mineral density measurements. Osteoporotic rats were separated into four equal groups randomly as group A (control), group B (calcium and vitamin D), group C (0.1 mg/kg subcutaneous zoledronic acid), and group D (calcium and vitamin D / 0.1 mg/kg subcutaneous zoledronic acid). Six weeks later, all rats were sacrificed, their tibiae were resected, and histopathologic and biomechanical studies were performed. Group C (30.2±1 Nm) and group D (33.3±3 Nm) had significantly higher peak torque values than group A (21.6±6 Nm) and group B (23.6±4 Nm) (p=0.007 and p=0.005, respectively). Group C (1.8) and group D (2.0) had higher stiffness values than group A (1.4) and group B (1.7); however, the difference was not statistically significant (p>0.05 for all). According to histopathological and biomechanical test results, single dose zoledronic acid treatment improves fracture healing in an osteoporotic rat fracture model. Orally administered daily calcium and vitamin D treatment had no effect on fracture healing. There was no additional improvement in fracture healing when calcium and vitamin D treatment was added to zoledronic acid treatment. Positive effects of zoledronic acid treatment on osteoporotic fracture healing and callus quality should be shown by future clinical studies.