Effect Of Alendronate On The Femoral Metaphyseal Defect Under Carbamazepine In Ovariectomized Rats

Objective: Osteoporosis(OP)is a common chronic bone disease,OP patients are usually accompanied by a high risk of fracture or bone defect.Based on this,the long-term use of antiepileptic drugs puts forward higher requirements for new bone regeneration in OP patients with bone defects.The purpose of this experiment was to investigate the effect of alendronate and carbamazepine on femoral defect in osteoporosis rats.Methods: All 100 female SD rats were first divided into normal control group(CON,N=30)and osteoporosis group(N=70),After 1 week of adaptive culture,all osteoporosis rats were treated with bilateral ovariectomy.Three months later,10 rats were randomly selected from the normal control group and the osteoporosis group,and the femoral specimens were sacrificed for Micro-CT two-dimensional and three-dimensional evaluation and H&E histology of the femoral metaphysis.The remaining 60 ovariectomized rats were divided into three groups,that is,osteosong model group(OVX,N=20 group,osteoporosis carbamazepine single drug group(75mg/kg/day,CBZ,N=20)and osteoporosis carbamazepine combined with alendronate sodium double drug group(ALN-CBZ,2mg/kg/day,N=20).A circular bone defect about 1.5 mm in diameter was subsequently created at the metaphysis of the right femur of all surviving rats using a small medical direct current drill.From the second day after the femoral defect operation,the experimental rats in the single drug group and the double drug group received gavage drugs.after 8 weeks,all rats were sacrificed.Subsequently,the defect area of distal femur was taken for Mico-CT tomography(Mico-CT),hematoxylin and eosin staining(H&E),Ma Song trichrome staining evaluation(Masson)and immunohistochemical staining evaluation(IHC).At the same time,the femoral tissue samples were analyzed by three-point bending test.The OC、CTX-1 and P1 NP levels of all serum samples obtained from the rat abdominal aorta were also evaluated by enzyme linked immunosorbent assay(Elisa).Results: Bone mineral density results showed that compared with the normal control group,the bone microparameters of the model group and the single drug group were significantly deteriorated,and the single drug group was more serious(P<0.05).Compared with the single drug group,the bone microparameters of the double drug group were improved(P<0.05).Compared with the model group,the limit load of femur was also significantly reduced in the single drug group.Compared with the single drug group,the double drug group promoted the regeneration of femur bone and enhanced the limit load of femur(P<0.05).The results of biochemical analysis showed that the systemic administration of carbamazepine,an antiepileptic drug,had adverse effects on bone formation and absorption in ovariectomized bone pine rats.The serum OC and P1 NP levels were significantly reduced and the CTX-1 level was increased(P<0.05).Meanwhile,it can be observed that the CTX-1 level of the double drug group was significantly lower than that of the single drug group(P<0.05).The results showed that although significantly lower than that in the control group(P<0.05),there was no significant difference in OCN and Col-I expression between the single drug group and the double drug group(PP<0.05).The expression of Tracp-5b was significantly higher in the single drug group than in the control group and the normal control group(P<0.05).The Tracp-5b expression in the double drug group was significantly lower than that in the single drug group(P<0.05).Conclusion: These results demonstrated that ALN can effectively reverse the effects of CBZ on the microarchitectural properties of bone,and thus can have a positive effect on local bone neoformation in rats with osteoporosis.