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Abstract：
BACKGROUND: The use of antiepileptic drugs and estrogen deficiency put forward higher requirements for bone defect regeneration. The present study investigated the effects of alendronate (ALN) on femoral bone defect in ovariectomized (OVX) rats under the influence of carbamazepine (CBZ).
METHODS: One hundred female SD rats at 3 months of age were either sham-operated or OVX and divided into four groups: sham control (CON); OVX control (OVX); ovariectomized rats treated with CBZ via gavage (75 mg/kg/day; CBZ); ovariectomized rats treated with CBZ plus ALN (2 mg/kg/day; CBZ-ALN). A critical-sized femoral metaphyseal bone defect was established in all female SD rats. Animals from the CBZ and CBZ-ALN groups received drugs by gavage the day after bone defect surgery was performed. After the rats were sacrificed, the defected area located in the distal femur was harvested for evaluation by microcomputed tomography (micro-CT), hematoxylin and eosin (HE) staining, and Masson\'s trichrome staining. The samples were also analyzed by biomechanics and immunohistochemical evaluation (IHC). Besides, biochemical analysis evaluates all serum samples.
RESULTS: The present study showed that ovariectomy changed the microstructural parameters of bone. The use of CBZ further decreased femur bone mass while treatment with ALN prevented bone loss. Compared to OVX and CBZ groups, CBZ-ALN group promoted bone neoformation and enhanced the ultimate load of the femur bone. However, the group of CBZ-ALN did not return to normal levels compared with the CON group. Besides, we noticed that CBZ-ALN group reduced tartrate-resistant acid phosphatase-5b (Tracp-5b) expression and had no significant effect on the expression of osteocalcin (OCN) and type I collagen (Col-I) in IHC compared with CBZ group. Biochemical analysis results presented that systemic delivery of CBZ showed pernicious effects on bone formation and resorption in ovariectomized rats, with the worse effects on C-terminal crosslinked telopeptide of type I collagen (CTX-1). Besides, a significant decrease in CTX-1 levels was observed in CBZ-ALN group as compared to the group of CBZ.
CONCLUSIONS: 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.
CONCLUSIONS: The dose of 2 mg/kg ALN improves the negative effect of prescription of CBZ at 75 mg/kg and promotes bone neoformation of femoral bony deficits.
METHODS: One hundred female SD rats at 3 months of age were either sham-operated or OVX and divided into four groups: sham control (CON); OVX control (OVX); ovariectomized rats treated with CBZ via gavage (75 mg/kg/day; CBZ); ovariectomized rats treated with CBZ plus ALN (2 mg/kg/day; CBZ-ALN). A critical-sized femoral metaphyseal bone defect was established in all female SD rats. Animals from the CBZ and CBZ-ALN groups received drugs by gavage the day after bone defect surgery was performed. After the rats were sacrificed, the defected area located in the distal femur was harvested for evaluation by microcomputed tomography (micro-CT), hematoxylin and eosin (HE) staining, and Masson\'s trichrome staining. The samples were also analyzed by biomechanics and immunohistochemical evaluation (IHC). Besides, biochemical analysis evaluates all serum samples.
RESULTS: The present study showed that ovariectomy changed the microstructural parameters of bone. The use of CBZ further decreased femur bone mass while treatment with ALN prevented bone loss. Compared to OVX and CBZ groups, CBZ-ALN group promoted bone neoformation and enhanced the ultimate load of the femur bone. However, the group of CBZ-ALN did not return to normal levels compared with the CON group. Besides, we noticed that CBZ-ALN group reduced tartrate-resistant acid phosphatase-5b (Tracp-5b) expression and had no significant effect on the expression of osteocalcin (OCN) and type I collagen (Col-I) in IHC compared with CBZ group. Biochemical analysis results presented that systemic delivery of CBZ showed pernicious effects on bone formation and resorption in ovariectomized rats, with the worse effects on C-terminal crosslinked telopeptide of type I collagen (CTX-1). Besides, a significant decrease in CTX-1 levels was observed in CBZ-ALN group as compared to the group of CBZ.
CONCLUSIONS: 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.
CONCLUSIONS: The dose of 2 mg/kg ALN improves the negative effect of prescription of CBZ at 75 mg/kg and promotes bone neoformation of femoral bony deficits.
摘要：
背景：抗癫痫药物的使用和雌激素缺乏对骨缺损的再生提出了更高的要求。本研究研究了在卡马西平（CBZ）的影响下，阿仑膦酸钠（ALN）对去卵巢（OVX）大鼠股骨骨缺损的影响。
方法：将100只3月龄的雌性SD大鼠进行假手术或OVX，分为四组：假对照（CON）；OVX对照（OVX）；通过管饲法用CBZ治疗的卵巢切除大鼠（75mg/kg/天；CBZ）；用CBZ加ALN（2mg/kg/天）治疗的卵巢切除大鼠。在所有雌性SD大鼠中都建立了临界大小的股骨干phy端骨缺损。来自CBZ和CBZ-ALN组的动物在进行骨缺损手术后的第二天通过管饲法接受药物。老鼠被处死后,采集位于股骨远端的缺损区域进行显微计算机断层扫描（micro-CT）评估，苏木精和伊红（HE）染色，和马森的三色染色。还通过生物力学和免疫组织化学评估(IHC)分析样品。此外,生化分析评估所有血清样本。
结果：本研究表明卵巢切除术改变了骨的微观结构参数。CBZ的使用进一步减少了股骨骨量，而用ALN治疗可预防骨丢失。与OVX和CBZ组相比，CBZ-ALN组促进骨新生，增强股骨极限负荷。然而,与CON组相比,CBZ-ALN组未恢复至正常水平.此外,我们注意到与CBZ组相比，CBZ-ALN组降低了抗酒石酸酸性磷酸酶-5b（Tracp-5b）的表达，对IHC中骨钙蛋白（OCN）和I型胶原（Col-I）的表达没有显着影响。生化分析结果表明，CBZ的全身递送对卵巢切除大鼠的骨形成和骨吸收具有有害作用，对I型胶原蛋白（CTX-1）的C端交联端肽的影响较差。此外,与CBZ组相比,CBZ-ALN组CTX-1水平显著下降.
结论：这些结果表明，ALN可以有效地逆转CBZ对骨骼微观结构特性的影响，因此可以对骨质疏松症大鼠的局部骨肿瘤形成产生积极影响。
结论：2mg/kgALN的剂量可以改善75mg/kgCBZ的负面影响，并促进股骨骨性缺损的骨新生。
方法：将100只3月龄的雌性SD大鼠进行假手术或OVX，分为四组：假对照（CON）；OVX对照（OVX）；通过管饲法用CBZ治疗的卵巢切除大鼠（75mg/kg/天；CBZ）；用CBZ加ALN（2mg/kg/天）治疗的卵巢切除大鼠。在所有雌性SD大鼠中都建立了临界大小的股骨干phy端骨缺损。来自CBZ和CBZ-ALN组的动物在进行骨缺损手术后的第二天通过管饲法接受药物。老鼠被处死后,采集位于股骨远端的缺损区域进行显微计算机断层扫描（micro-CT）评估，苏木精和伊红（HE）染色，和马森的三色染色。还通过生物力学和免疫组织化学评估(IHC)分析样品。此外,生化分析评估所有血清样本。
结果：本研究表明卵巢切除术改变了骨的微观结构参数。CBZ的使用进一步减少了股骨骨量，而用ALN治疗可预防骨丢失。与OVX和CBZ组相比，CBZ-ALN组促进骨新生，增强股骨极限负荷。然而,与CON组相比,CBZ-ALN组未恢复至正常水平.此外,我们注意到与CBZ组相比，CBZ-ALN组降低了抗酒石酸酸性磷酸酶-5b（Tracp-5b）的表达，对IHC中骨钙蛋白（OCN）和I型胶原（Col-I）的表达没有显着影响。生化分析结果表明，CBZ的全身递送对卵巢切除大鼠的骨形成和骨吸收具有有害作用，对I型胶原蛋白（CTX-1）的C端交联端肽的影响较差。此外,与CBZ组相比,CBZ-ALN组CTX-1水平显著下降.
结论：这些结果表明，ALN可以有效地逆转CBZ对骨骼微观结构特性的影响，因此可以对骨质疏松症大鼠的局部骨肿瘤形成产生积极影响。
结论：2mg/kgALN的剂量可以改善75mg/kgCBZ的负面影响，并促进股骨骨性缺损的骨新生。
