백서모델에서 장기간 파미드로네이트 투여가 골 강도와 골절 치유에 미치는 영향

Abstract

Background: Increased bone mineral density and resuced fracture incidences have been achieved by using bisphosphonates in osteoporosis and osteogenesis imperfecta. However, they cannot eliminate fracture episodes completely, Therefore, it is important to determine whether the long-term administration of strong antiresorptive agents compromises bone strength and the fracture healing procedure. So, We investigated the effects of the long-term administration of pamidronate on long bone strength and fracture healing in rat osteoporosis model Methods:We performed bilateral ovariectomy in sixty-six Sprague-Dawley female rats, average age is 3-month old. Three months after ovariectomy, animals were randomized inro rwo froups (n=33). Disodium pamidronate (0.5 mg/kg) was injected every month for 6 months in the treated group, and physiologic saline was administered in the control group. After the six-month administarion periods, the left femoral shaft was fractured by the Bonnarens and Einhorn technique after intramedullary nailing with 1.14 mm nonthreaded K-wire. Five weeks after fracture, rats were euthanized and both femurs were removed. We checked the mechanical properties of normal (right) and fractured (left) femurs and the bone mineral density of the right femoral head. Pamidronate concentration in bone was checked by high-performance liquid chromatography. Results: the maximum strngth of right femora was 154.4±17.5 N in the pamidronate-treated group and 129.7±28.0 N in the control group (p=0.0002), and stiffness was 452.5±122.8 N/mm in the pamidronate-treated group and 378.6±126.2 N/mm in the control group (p=0.036). Maximum strength of the callus was 22.7±7.2% compared to right femur in the pamidronate-treated group and 29.7±13.5% in the control group (p=0.025). The mean bone mineral denisty of the right femoral head was 230±9 mg/cm² in pamidronate-treated group and 219±13 mg/cm² in the control group (p=0.0007). The mean pamidronate concentration in bone was 62.3±15.2 ng/mg. A tendency toward a negative relationship between pamidronate concentration and the maximum strength of the femur normalized by animal body weight was observed, but this was not statistically significant (p=0.067). Conclusion: Pamidronate effectively protects the femur from bone resorption and preserves strength and stiffness after ovariectomy. However, fracture healing was impaired during the early stage of healing agter long-term administration of pamidronate