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.
Osteoporosis-induced impaired bone regeneration would result in compromised osseointegration of hydroxyapatite-coated titanium and high rate of implant failure. Local administration of aspirin promotes osteoblast proliferation and inhibits osteoclast proliferation, and positively affects bone regeneration in osteoporotic condition. We hypothesized that reduced osteogenesis may account for poor osseointegration of hydroxyapatite-coated titanium which could be ameliorated by using local aspirin. The aim of this study was to confirm the effect of the local incorporation of aspirin into hydroxyapatite-coated titanium implants in the osteoporotic and normal condition. Twelve-week-old female Sprague–Dawley rats were used for this study. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into three groups: group Sham, group OVX and group OVX + ASP, and the rats from OVX and Sham received hydroxyapatite-coated implants and animals belong to group OVX + ASP received aspirin-hydroxyapatite-coated implants until death at 12 weeks, respectively. After 12-week healing period, local treatment with aspirin revealed improved osseointegration compared to OVX, with significant improvement of the bone area ratio and bone-to-implant contact in histomorphometry, the bone mass and trabecular architecture in micro-CT evaluation, and the maximal push-out force in push out test. Moreover, group OVX + ASP presented the strongest effect on Jagged1, Notch1, and Hes-1(P < 0.05). These results demonstrated that local administration of aspirin could enhance hydroxyapatite-coated titanium implant osseointegration in OVX rats by activation Wnt signaling pathway to improve implant fixation in osteoporotic bone.
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