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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.

The purpose was to observe whether local administration Strontium (Sr) and Aspirin (Asp) can enhance the efficacy of β-Tricalcium phosphate(β-TCP) in the treatment of osteoporotic bone defect. The MC3T3-E1 cells were co-cultured with β-TCP, Sr/β-TCP, Asp-Sr/β-TCP scaffold and induced to osteogenesis, and the cell viability, mineralization ability were observed by MTT, Alizarin Red staining(ARS) and Western blotting(WB). Then this scaffolds were implanted into the femoral epiphysis bone defect model of ovariectomized(OVX) rats for 8 weeks. X-ray, Micro-CT, histology and Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis were used to observe the therapeutic effect and explore the possible mechanism. MTT, ARS results show that the cell mineralization and viability of Asp-Sr/β-TCP group is significantly higher than Control group, β-TCP group and Sr/β-TCP group. Protein expression show that the osteogenic protein expression such as ALP、OP、RUNX-2、OC and COL-1 of Asp-Sr/β-TCP group is significantly higher than Control group, β-TCP group and Sr/β-TCP group. X-ray images, Micro-CT and Histological analysis evaluation show that, group Asp-Sr/β-TCP presented the strongest effect on bone regeneration and bone mineralization, when compared with β-TCP group and Sr/β-TCP group. RT-qPCR analysis show that Asp-Sr/β-TCP, β-TCP group and Sr/β-TCP group showed increased BMP2, Smad1, OPG than the OVX group(p < 0.05), while Asp-Sr/β-TCP exhibited decreased TNF-α、IFN-γ and RANKL than the OVX group(p < 0.05). Our current study demonstrated that Asp-Sr/ β-TCP is a scheme for rapid repair of femoral condylar defects, and these effects may be achieved by inhibiting local inflammation and through BMP-2/Smad1 and OPG/RANKL signaling pathway., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Parathyroid hormone (1-34, PTH) combined β-tricalcium phosphate (β-TCP) achieves stable bone regeneration without cell transplantation in previous studies. Recently, with the development of tissue engineering slow release technology, PTH used locally to promote bone defect healing become possible. This study by virtue of collagen with a combination of drugs and has a slow release properties, and investigated bone regeneration by β-TCP/collagen (β-TCP/COL) with the single local administration of PTH. After the creation of a rodent critical-sized femoral metaphyseal bone defect, β-TCP/COL was prepared by mixing sieved granules of β-TCP and atelocollagen for medical use, then β-TCP/COL with dripped PTH solution (1.0 µg) was implanted into the defect of OVX rats until death at 4 and 8 weeks. The defected area in distal femurs of rats was harvested for evaluation by histology, micro-CT, and biomechanics. The results of our study show that single-dose local administration of PTH combined local usage of β-TCP/COL can increase the healing of defects in OVX rats. Furthermore, treatments with single-dose local administration of PTH and β-TCP/COL showed a stronger effect on accelerating the local bone formation than β-TCP/COL used alone. The results from our study demonstrate that combination of single-dose local administration of PTH and β-TCP/COL had an additive effect on local bone formation in osteoporosis rats.

Previous studies have demonstrated the effect of human parathyroid hormone (1-34) (PTH) or strontium-doped hydroxyapatite coating (Sr-HA) on osteoporotic bone implantation. However, reports about effects of PTH plus Sr-HA on bone osseointegration of titanium implants in a state of osteoporosis were limited. This study was designed to investigate the effects of intermittent administration of human parathyroid hormone (1-34) on strontium-doped hydroxyapatite coating (Sr-HA) implant fixation in ovariectomized (OVX) rats. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into four groups including control group, Sr group, PTH group and PTH+Sr group. Forty OVX rats accepted implant insertion in the distal femurs, control group, and PTH group with HA implants and the Sr group and PTH+Sr group with Sr-HA implants. Animals from PTH group and PTH+Sr group then randomly received PTH (60 µg/kg, 3 times a week) until death at 12 weeks. After 12-week healing period, implants from group PTH+Sr revealed improved osseointegration compared with other treatment groups, which is manifested by the exceeding increase of bone area ratio and bone-to-implant contact, the trabecular microarchitecture and the maximal push-out force displayed by tests like histomorphometry, micro-CT, and biomechanics evaluation. These results demonstrated that PTH+ Sr-HA coatings could enhance implant osseointegration in OVX rats, and suggested the feasibility of using this method to improve implant fixation in osteoporotic bone., (© The Author(s) 2015.)

The objective of this study was to evaluate the effect of following combined treatment with parathyroid hormone (1-34) (PTH) and β-tricalcium phosphate (β-TCP) on local bone formation in a rat 3-mm critical-sized defect at the distal femur. Fourteen weeks were allowed to pass before defect surgery for the establishment of osteopenic animal models chronically fed a low-protein diet. All animals were randomly divided into four groups: group PTH; group β-TCP, group PTH + β-TCP, and a control group. All rats then underwent a surgical procedure to create bone defects in the bilateral distal femurs, and β-TCP was implanted into critical-sized defects for the groups designated as β-TCP and group PTH + β-TCP. After the defect operation, all animals from group PTH and group PTH + β-TCP received following subcutaneous injections with PTH (60 μg/kg, three times per week) until euthanasia at 4 and 8 weeks. The distal femurs and blood were collected for evaluation. The results of study showed the strongest effect on accelerating the local bone formation with treatment β-TCP and PTH at 4 weeks and 8 weeks. The results from our study demonstrate that a combination of PTH and β-TCP had an additive effect on local bone formation in osteopenic rats chronically fed a low-protein diet., (Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

In this study, we tested the effect of Teriparatide (PTH) in combination with β-tricalcium phosphate (β-TCP) as a bone void filler in an ovariectomised rat distal femoral metaphysis model.β-TCP is a completely resorbable synthetic calcium phosphate and the Teriparatide is a drug that can promote bone formation in the condition of osteoporosis. A critical size defect of 3mm in diameter, a through-hole bone defect, was drilled into each distal femur of the ovariectomised rats. The hole was filled with β-TCP and the rat was injected PTH Teriparatide (30μg/kg) in peritoneum 5 times per week. After 4and 8 weeks the animals were killed and the degree of bone healing analysed. In total, 60 animals were investigated. When the β-TCP and PTH were used, histological, biochemistry and histomor-phometric evaluations revealed significantly better bone healing in terms of quantity and quality of the newly formed bone. The Ovariectomised rats which suffer from femur metaphysis defect are cured by embedding β-tricalcuim phosphate and intermittently cured by parathyroid hormone (PTH)., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The effect of human parathyroid hormone 1-34 (PTH) and simvastatin (SIM) alone could promote bone healing in osteoporotic osseous integration of the implant, but there are no reports about the combined use of PTH and SIM for promotion of bone healing around implant in osteoporotic settings still limited. This study aims to investigate effects of PTH+SIM on osseous integration of the implant in OVX rats. Female Sprague-Dawley rats were used for this study. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into four groups: group control; group SIM; group PTH and group PTH+SIM. Afterwards, all OVX rats received hydroxyapatite (HA)-coated titanium rods (external diameter and length are 1.5mm and 20mm) in the femoral medullary canal. Subsequently, the animals from group SIM, group PTH and group PTH+SIM received human parathyroid hormone 1-34 (60μg/kg, three times a week), SIM (5mg/kg daily), or both for 12 weeks. Implants were inserted bilaterally in all animals until death at 12 weeks. The bilateral femurs of rats were harvested for evaluation. All groups increased new bone formation around the surface of titanium rods and push-out force; group PTH+SIM showed the strongest effects on new bone formation and biomechanical strength. Additionally, these are significant difference observed in bone formation and push-out force between groups SIM and PTH. This finding suggests that intermittent administration of PTH or SIM alone has an effect to increase new bone formation on the surface of HA-coated implants in the osteoporotic condition, and the additive effects of combination PTH and SIM on osseous integration of the implant in OVX rats., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The objective of this study was to evaluate local bone formation following systemic administration of parathyroid hormone (1-34), a surgically implanted synthetic β-tricalcium phosphate bone biomaterial serving as a matrix to support new bone formation. Twelve weeks after bilateral ovariectomy, all rats underwent bone defect in the distal femurs, and β-tricalcium phosphate was implanted into critical sized defects. After defect operation, all animals were randomly divided into four groups and received following subcutaneous injections until death at four and eight weeks: sham rats (group ST); sham rats + parathyroid hormone, 30 µg/kg, three times a week (group SPT); OVX rats (group OT); and OVX rats + parathyroid hormone (group OPT). The distal femurs of rats were harvested for evaluation. The treatment group demonstrating the highest levels of new bone formation was the defects treated with parathyroid hormone as assessed by micro-computed tomography, biomechanical strength, and histological analysis for sham rats. Furthermore, parathyroid hormone showed a stronger effect on accelerating the degradation of β-tricalcium phosphate. Osteoporosis can limit the function of parathyroid hormone and/or β-tricalcium phosphate. The results from our study demonstrate that combination of parathyroid hormone and β-tricalcium phosphate brings better effect to bone tissue repair in non-osteoporosis and/or osteoporosis status., (© The Author(s) 2015.)

Magnesium (Mg) and Selenium (Se) are essential elements for bone health and have been studied extensively for its powerful osteogenesis and promoting bone regeneration. The purpose was to observe whether Co-modified 3D-printed β-tricalcium phosphate with Mg and Se could promote bone defect regeneration in an ovariectomized(OVX) rat model. The MC3T3-E1 cells were co-cultured with the leachate of β-TCP, Mg-TCP, and Mg/Se-TCP and induced to osteogenesis, and the cell viability, ROS, and osteogenic activity were observed by Cell Count Kit-8(CCK-8), fluorescent probe 2′, 7′-dichlorofluorescin diacetate, Alkaline phosphatase (ALP) staining, Alizarin Red(RES) staining, western blotting(WB), and immunofluorescence. Then the β-TCP, Mg-TCP, and Mg/Se-TCP were implanted into the femoral epiphysis bone defect model of OVX rats for 12 weeks. Micro-CT and histology analysis were used to observe the therapeutic effect. In vitro results show that the cell mineralization and osteogenic activity of the Mg/Se-TCP group is significantly higher than the β-TCP group and Mg-TCP group. Protein expressions such as FOxO1, SIRT1, SOD2, Runx-2, Cola1a, and OC of the Mg/Se-TCP group are significantly higher than the Con group and the β-TCP group. The results of intracellular ROS and SIRT1 and SOD2 immunofluorescence showed that Mg/Se-TCP can restore the oxidative stress balance of osteoblasts. Micro-CT and histology analysis showed that treatment with Mg/Se-TCP showed the largest amount of bone tissue in the defect area (p < 0.05), and exhibited lower values of residual biological material (p < 0.05), compared to that of the β-TCP group and Mg-TCP group. Our research results confirm that Mg/Se-TCP can improve the activity and function of osteoblasts and enhance bone regeneration mediated by reducing intracellular ROS in OVX rat models. [ABSTRACT FROM AUTHOR]

The purpose of this study is to investigate the role of Silibinin (SIL)-modified Hydroxyapatite coating on osseointegration in diabetes in vivo and in vitro and explore the mechanism of osteogenic differentiation of MC3T3-E1. RT-qPCR, Immunofluorescence, and Western blot were used to measure the expression level of oxidative Stress Indicators and osteogenic markers proteins. Moreover, CCK-8 assay was conducted to detect cell viability in hyperglycemia. Alizarin red staining and alkaline phosphatase staining were used to examine osteogenic function and calcium deposits. The diabetic rat model receive titanium rod implantation was set up successfully and Von-Gieson staining was used to examine femoral bone tissue around titanium rod. Our results showed that intracellular oxidative stress in hyperglycemia was overexpressed, while FoxO1, SIRT1, GPX1, and SOD2 were downregulated. SIL suppressed oxidative stress to promote osteogenic differentiation. Additionally, it was confirmed that SIL promoted osteogenic differentiation of MC3T3-E1 and obviously restored the osseointegration ability of diabetic rats. Further study indicated that SIL exerted its beneficial function through activation SIRT1/SOD2 signaling pathway to restore osteoblast function, and improved the osseointegration and stability of titanium rods in vivo. Our research suggested that the SIL-modulated oxidative Stress inhibition is responsible for the activation of the process of osteogenic differentiation through activation SIRT1/SOD2 signaling pathway in hyperglycemia, providing a novel insight into improving prosthetic osseointegration in diabetic patients. [ABSTRACT FROM AUTHOR]

Surface modification techniques have been applied to generate titanium implant surfaces that promote osseointegration for the implants in cementless arthroplasty. However, its effect is not sufficient for osteoporotic bone. Strontium (Sr) promotes osteoblast proliferation and inhibits osteoclast proliferation and positively affects bone regeneration. The aim of this study was to confirm the effects of strontium-substituted hydroxyapatite (Sr-HA) coating via electrochemical deposition on implant's osseointegration in the osteoporotic condition. Female Sprague Dawley rats were used for this study. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into four groups: group HA; group 5 % Sr-HA; group 10 % Sr-HA; and group 20 % Sr-HA. Afterward, all rats from groups HA, 5 % Sr-HA, 10 % Sr-HA, and 20 % Sr-HA received implants with hydroxyapatite coating containing 0, 5, 10, and 20 % Sr. Implants were inserted bilaterally in all animals until death at 12 weeks. The bilateral femurs of rats were harvested for evaluation. All treatment groups increased new bone formation around the surface of titanium rods and push-out force; group 20 % Sr-HA showed the strongest effects on new bone formation and biomechanical strength. Additionally, these are significant differences in bone formation and push-out force was observed between groups 5 % Sr-HA and 10 % Sr-HA. This finding suggests that Sr-HA coating can improve implant osseointegration, and the 20 % Sr coating exhibited the best properties for implant osseointegration among the tested coatings in osteoporosis rats. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the effect of following combined treatment with parathyroid hormone (1-34) (PTH) and beta-tricalcium phosphate (β-TCP) on local bone formation in a rat 3-mm critical-size defect at distal femur. Twelve weeks after bilateral ovariectomy (OVX) and sham operation (sham), all animals were randomly divided into four groups: group OVX, group OVX + β-TCP, group sham, and group sham + β-TCP, then all rats underwent bone defect in the bilateral distal femurs, and β-TCP were implanted into critical-sized defects for group OVX + β-TCP and group sham + β-TCP. After defect operation, all animals were received following subcutaneous injections with PTH (60 μg/kg, three times a week) until death at 4 and 8 weeks. The defected area in distal femurs of rats was harvested for evaluation by histology, micro-CT, and biomechanics. The results of our study show that systemic usage of PTH or local usage of β-TCP can increase the healing of defects in OVX or sham rats. Furthermore, treatments with PTH and β-TCP showed a stronger effect on accelerating the local bone formation than used alone. Osteoporosis can limit the function of PTH and/or β-TCP. The results from our study demonstrate that combination of PTH and β-TCP had an additive effect on local bone formation in non-osteoporosis and/or osteoporosis rats. [ABSTRACT FROM AUTHOR]

The effect of human parathyroid hormone 1-34 (PTH) and simvastatin (SIM) alone could promote bone healing in osteoporotic osseous integration of the implant, but there are no reports about the combined use of PTH and SIM for promotion of bone healing around implant in osteoporotic settings still limited. This study aims to investigate effects of PTH+SIM on osseous integration of the implant in OVX rats. Female Sprague-Dawley rats were used for this study. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into four groups: group control; group SIM; group PTH and group PTH+SIM. Afterwards, all OVX rats received hydroxyapatite (HA)-coated titanium rods (external diameter and length are 1.5mm and 20mm) in the femoral medullary canal. Subsequently, the animals from group SIM, group PTH and group PTH+SIM received human parathyroid hormone 1-34 (60μg/kg, three times a week), SIM (5mg/kg daily), or both for 12 weeks. Implants were inserted bilaterally in all animals until death at 12 weeks. The bilateral femurs of rats were harvested for evaluation. All groups increased new bone formation around the surface of titanium rods and push-out force; group PTH+SIM showed the strongest effects on new bone formation and biomechanical strength. Additionally, these are significant difference observed in bone formation and push-out force between groups SIM and PTH. This finding suggests that intermittent administration of PTH or SIM alone has an effect to increase new bone formation on the surface of HA-coated implants in the osteoporotic condition, and the additive effects of combination PTH and SIM on osseous integration of the implant in OVX rats. [ABSTRACT FROM AUTHOR]

In this study, we tested the effect of Teriparatide (PTH) in combination with β-tricalcium phosphate (β-TCP) as a bone void filler in an ovariectomised rat distal femoral metaphysis model.β-TCP is a completely resorbable synthetic calcium phosphate and the Teriparatide is a drug that can promote bone formation in the condition of osteoporosis. A critical size defect of 3mm in diameter, a through-hole bone defect, was drilled into each distal femur of the ovariectomised rats. The hole was filled with β-TCP and the rat was injected PTH Teriparatide (30μg/kg) in peritoneum 5 times per week. After 4and 8 weeks the animals were killed and the degree of bone healing analysed. In total, 60 animals were investigated. When the β-TCP and PTH were used, histological, biochemistry and histomor-phometric evaluations revealed significantly better bone healing in terms of quantity and quality of the newly formed bone. The Ovariectomised rats which suffer from femur metaphysis defect are cured by embedding β-tricalcuim phosphate and intermittently cured by parathyroid hormone (PTH). [ABSTRACT FROM AUTHOR]