Effect of alendronate on the femoral metaphyseal defect under carbamazepine in ovariectomized rats

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. 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. Clinical relevance 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.

Experimental study on the effects of simvastatin in reversing the femoral metaphyseal defects induced by sodium valproate in normal and ovariectomized rats

“…In patients over 40 years of age, bisphosphonates can improve bone mineral density in patients with epilepsy [24]. In our research group, Ruotian Zhang et al found that alendronate significantly increased bone mineral density in ovariectomized rats treated with antiepileptic drugs [26]. For phenytoin users, vitamin K supplementation improves bone density [27].…”

“…In our research group, Ruotian Zhang et al. found that alendronate significantly increased bone mineral density in ovariectomized rats treated with antiepileptic drugs [ 26 ]. For phenytoin users, vitamin K supplementation improves bone density [ 27 ].…”

A biomimetic and bioactive scaffold with intelligently pulsatile teriparatide delivery for local and systemic osteoporosis regeneration

“…S16 ). To the best of our knowledge, the variety of biomaterials for treating osteoporotic bone defects is usually focused on only the skull [ [50] , [51] , [52] , [53] ] or femur [ 12 , [54] , [55] , [56] , [57] , [58] , [59] , [60] ] [ [61] , [62] , [63] , [64] , [65] , [66] , [67] ]. Even when both the skull and femur were evaluated, they were rarely reported for a cranial BV/TV beyond 27.16% while maintaining a femoral BV/TV of 28.33% as well as a relatively short experimental period [ 68 ].…”

Intermittent administration sodium valproate has a protective effect on bone health in ovariectomized rats

“…Estrogen de ciency was shown to downregulate the expression of Runx2, resulting in bone loss and increased fracture risk [27]. In this study, female SD rats were used to establish an osteoporosis model after bilateral ovariectomy and mimics bone loss in the physiological state of female postmenopausal estrogen de ciency [28,29]. In this mature animal model, we con rmed that decreased BMD and bone loss by DEXA and Micro-CT occurred in femur at 12 weeks following OVX, consistent with our previous observation [22,30].…”