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BACKGROUND: Mitogen-activated protein kinase signaling pathway participates in the differentiation of osteoblasts and osteoclasts, closely related to subchondral bone reconstruction and play a key role in the occurrence and development of osteoarthritis. Bisphosphonates as bone resorption inhibitor is used to treat osteoporosis. OBJECTIVE: To observe the effect of sodium ibandronate on the knee osteoarthritis in rats, and changes of mitogen-activated protein kinase signaling pathway. METHODS: The study was approved by the Laboratory Animal Ethical Committee of the First Affiliated Hospital of South China University. Thirty female Sprague-Dawley rats were randomly divided into sham, model, and treatment groups. The rats in the latter two groups underwent ovariectomy bilaterally, and anterior cruciate ligament resection, and rats in the sham group received the fatty tissue surrounding the ovaries removed only. After 1 week of surgery, the rats in the treatment group were given intraperitoneal injection of 10 pg/kg sodium ibandronate, rats in the model group were injected with normal saline, and the sham group received no intervention. Twelve weeks late, the rats were killed to perform histological examination of cartticular cartilage and Mankin scores were detected. Micro-CT of subchondral bone and quantitative analysis of the bone microstructure were conducted. The protein and mRNA expression levels of extracellular signal regulated protein kinase and c-Jun N-terminal kinase in mitogen-activated protein kinase signaling pathway were measured. RESULTS AND CONCLUSION: (1) The cartilage structure in the model group was significantly damaged, the Mankin score was significantly higher than that in the sham group, and the Mankin score in the treatment group was significantly lower than that in the model group (P < 0.01). (2) The bone mineral density, trabecular bone volume ratio, trabecular number in the model group were significantly lower than those in the sham group (P < 0.01), and trabecular separation was higher than that in the sham group (P < 0.01). Compared with the model group, the treatment group had higher bone mineral density, trabecular bone volume ratio, trabecular number, and lower trabecular separation (P < 0.01). (3) The mRNA and protein expression levels of extracellular signal regulated protein kinase and c-Jun N-terminal kinase in the model group were significantly higher than those in the sham group (P < 0.05, P < 0.01), and the levels in the treatment group were significantly lower than those in the model group (P < 0.05). (4) To conclude, sodium ibandronate may inhibit subchondral bone loss and articular cartilage degeneration in rat models of osteoarthritis by inhibiting extracellular signal regulated protein kinase and c-Jun N-terminal kinase in mitogen-activated protein kinase signaling pathway.
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BACKGROUND: Bisphosphonates are a novel inhibitor of bone resorption that can inhibit the activity and function of osteoclasts. OBJECTIVE: To observe the effects of sodium ibandronate on the expression of dentin matrix protein 1, Caspace3, Bcl-2 and Bax in condylar cartilage in osteoporosis rats. METHODS: Thirty-six female rats were randomly divided into sham group, osteoporosis group and sodium ibandronate group, twelve in each group. The sham group did not excise ovaries during surgery. Bilateral ovaries of rats were removed in the osteoporosis and sodium ibandronate groups. On the 7th day after operation, rats in the sodium ibandronate group were intraperitoneally given sodium ibandronate 10 µg/kg, once every 7 days. After 90 days, the rat ovaries were taken. Bone mineral density was measured in each group. The changes of condylar cartilage were observed by toluidine blue staining and TUNEL staining. The expression of dentin matrix protein 1 protein was detected by immunohistochemistry. The levels of Caspase3, Bcl-2 and Bax were detected by western blot assay. The study protocol was approved by the Animal Ethics Committee of Nanhua Hospital in China with the approval No. SLXD_201804010. RESULTS AND CONCLUSION: Compared with the sham group or sodium ibandronate group, the bone mineral density in the osteoporosis group was significantly decreased (P < 0.05). The results of toluidine blue staining showed that the hypertrophic layer of condylar cartilage in the sodium ibandronate group was significantly thicker than that in the osteoporosis group. Compared with the sham group or sodium ibandronate group, the number of apoptotic cells in condylar cartilage and subchondral bone increased significantly in the osteoporosis group (P < 0.05). The expression of dentin matrix protein 1 protein was significantly lower in the osteoporosis group than the sham group, but it increased after treatment with sodium ibandronate (P < 0.05). Compared with the sham group, the expression of Caspase 3 and Bax in the osteoporosis group increased significantly, and the expression of Bcl-2 decreased. However, treatment with sodium ibandronate decreased the expression of Caspase 3 and Bax and increased the expression of Bcl-2 significantly. Overall, our findings reveal that sodium ibandronate can inhibit the apoptosis of condylar chondrocytes and the number of osteoclasts in osteoporotic state, which may be related to the regulation of Caspase 3, Bcl-2, Bax and dentin matrix protein 1 expression.
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ObjectiveTo retrospectively evaluate the efficacy and safety of zoledronic acid and sodium ibandronate in treating bone metastasis in breast cancer patients.MethodsThe study included 47 patients who were treated with zoledronic acid and sodium ibandronate respectively from Aug.2006 to Mar.2011. KaplanMeier curve and Log rank test were adopted to detect the difference in survival time of skeletal related event (SRE) and survival rate between patients treated with different medicine,and x2 test was uscd to rcveal thc rate difference of pain killing effects and adverse effects.Results 1.The total effective rate of pain killing was 88.9％ and 85％ respectively.The difference had no statistical significance(P =0.467).2.The 1,2 and 3-year-survival rate in zoledronic acid group and sodium ibandronate group was 88.7％,44.4％,24.2％vs 94.7％,40.5％,5.8％.The difference had no statistical significance(P =0.744).3.The 2,3,and 4-year-survival rate in zoledronic acid group and sodium ibandronate group was 70.4％,40.7％,23.1％ vs 85％,46.7％,17.5％.The difference had no statistical significance( P =0.994).4.The 1,2 and 3-year SRE-free overall survival rate of the group with metastasis first to bone only was 92％,50.8％,and 23.8％,while the rate of the group with first metastasis to visceral organs was 85.4％,21.4％,and 5.3％ ( P =0.012).5.The 2 and 3-year overall survival rate of the group with metastasis first to bone only was 95.8％ and 74.2％ respectively,while the rate of the group with first metastasis to visceral organs was 56.5％ and 10.1％ ( P ＜0.001 ).The difference of 4 and 5 had statistical significance.The difference of zoledronic acid group and sodium ibandronate group in rate of adverse effects had no statistical significance.Conclusions Compared to sodium ibandronate,zoledronic acid has no superiority in either delaying the occurrence of SRE or improving overall survival rate.The -2are similar in incidence of adverse effects and pain control.The prognosis of patients whose first presentation is complicated by metastasis to other organs is poor.
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Objective To evaluate the palliative effect on pain relief in patients with multiple bone metastases treated with 89SrCl2 together with Sodium Ibandronate,Sodium Ibandronate alone and 89SrCl2 alone. Methods Eighty-four patients with bone pain secondary to bone metastases were divided into three groups. Thirty patients were treated with combined 89SrCl2 and Sodium Ibandronate,26 with 89SrCl2 alone and 28 with Sodium Ibandronate alone. The x2 test was used in data analysis. Results The overall palliative pain relief rate in the combined treatment group was 96.6 % (29/30). For the groups using Sodium Ibandronate or 89SrCl2 only,the palliative rates were 71.4% (20/28) and 73.1% (19/26),respectively. There are statistically significant differences between the combined treatment group and the other 2 groups with single treatment modalities in the overall palliative pain relief rate (x2 = 7.497 ),in terms of improvement in (1) whole body Karnofsky performance status (KPS) score (80.0% (24/30) vs 50.0% (14/28)/53.8% (14/26),x2 =35.476) and (2) focal palliative rate (47.6% (50/105) vs 11.2% (11/98)/22.2% (20/90),x2 =6. 564,all P ＜ 0. 05 ). Conclusions Combined treatment with 89 SrCl2 and Sodium Ibandronate is more effective than single treatment modalities to relieve bone pain seccondary to multiple bone metastases.
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[Objective]Titanium particle induced mouse calvarial osteolysis model was used to investigate the effects and mechanisms of sodium ibandronate on osteolysis.[Methods]Twenty-four Kunming species mice were randomly divided into 4 groups,6 in each group.Control group received sham operation.Titanium particle group received 30 mg titanium particle implantation onto the calvariae.One unit sodium ibandronate group and 10 units sodium ibandronate group received 10 mg and 100mg sodium ibandronate ip injection separately on the next day of titanium particles implantation.Ten days later,mice calvariae were harvested for pathology analysis.[Results]In control group osteolysis area was(0.070?0.009)mm2 and osteolysis was not apparent.In titanium particle group osteolysis area(0.369?0.050)mm2 was bigger than that of control group(P