Comparison of the efficacy of denosumab and bisphosphonates for treating secondary osteoporosis in patients with rheumatoid arthritis

Objectives: This study aimed to investigate the efficacy of denosumab (compared with that of bisphosphonates) for preventing secondary osteoporosis and inflammation caused by excessive bone resorption in Japanese rheumatoid arthritis (RA) patients never previously treated for osteoporosis.

Methods: Ninety-eight patients with coexisting RA and osteoporosis were enrolled. The patients were subdivided by whether they were treated with denosumab (n?=?49) or traditional bisphosphonates (n?=?49). RA disease activity, bone turnover markers, and bone mineral density (BMD) were compared between the two groups before treatment, and after 6 and 12 months of treatment.

Results: There was no significant difference between the groups in any of the disease activity indices and BMD at any of the measured time points. With regard to bone metabolism, denosumab significantly reduced bone-specific alkaline phosphatase at 6 and 12 months compared with pretreatment, but had no effect on tartrate-resistant acid phosphatase 5b levels, suggesting an effect on the bone formation rate, but not on the bone resorption rate.

Conclusions: Neither denosumab nor bisphosphonates could suppress inflammation or RA disease activity, but denosumab significantly suppressed a marker of bone metabolism in Japanese RA patients never previously treated for osteoporosis.     

双膦酸盐与狄诺塞麦治疗PMOP的“药物假期”EMAS立场声明要点解读

目的为了使骨质疏松领域相关医生能够进一步了解和掌握双膦酸盐与狄诺塞麦的药物假期规律,提高临床治疗水平,本文就欧洲女性与男性更年期协会(EMAS)对双膦酸盐与狄诺塞麦治疗绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)"药物假期"的立场声明进行要点解读,供同仁参考。方法 EMAS系统性回顾分析了双膦酸盐和狄诺塞麦中止使用后在骨折风险方面的影响,同时,评估降低不良事件风险的可能性,形成立场声明。结果 (1)考虑双膦酸盐的长期疗效、安全性及骨折风险,建议采取个性化的药物假期方案;(2)药物假期时机:阿仑膦酸钠治疗超过5年,利塞膦酸钠、唑来膦酸治疗超过3年的患者,应该考虑药物假期;(3)鉴于伊班膦酸钠证据有限,狄诺塞麦停药后可能引起骨折的"反弹效应",所以,不强烈推荐伊班膦酸钠和狄诺塞麦进行药物假期;(4)药物假期时长:一般情况下,双膦酸盐药物假期为1~3年;(5)重启治疗评估内容:双膦酸盐药物假期中,每年应评估病人的特征,包括患者的年龄、跌倒史、是否有新的骨折、可能危险因素、骨密度和骨代谢生化标志物;(6)重启治疗药物:双膦酸盐、狄诺塞麦,特立帕肽,雌激素受体调节剂(selective estrogen receptor modulators,SERMs),性激素补充(menopausal hormone replacement therapy,MHT)和雷奈酸锶等,是药物假期后重启治疗的选择药物。结论双磷酸盐药物假期遵循个体化原则,不推荐狄诺塞麦药物假期。     

地诺单抗与唑来膦酸治疗恶性肿瘤伴骨转移安全性和有效性的Meta分析

目的系统评价地诺单抗与唑来膦酸治疗恶性肿瘤伴骨转移的有效性和安全性。方法利用Cochranelibrary、PubMed、OVID、SpringerLinker、ScienceDirect、EBSCO等数据库检索文献,按Cochrane风险偏倚评估工具评价纳入文献质量并提取文献数据,应用RevMan5.3软件进行Meta分析。结果纳入4项临床随机对照试验,共6029例患者,包含7篇相关文献。Meta分析结果显示,与唑来膦酸比较,地诺单抗能明显延缓骨相关事件（SREs）发生的时间,降低骨转移标志物Ⅰ型胶原交联氨基末端肽/肌酐（uNTx/Cr）、骨源性碱性磷酸酶（S-BALP）浓度,预防骨放疗,延缓疼痛加剧和干预,同时治疗后贫血、急性期反应和肾毒性的发生率更低,差异均有统计学意义（均P＜0.01）;两组患者总生存（OS）时间、疾病进展时间、预防病理性骨折、预防骨手术、预防脊髓压迫、不良事件（AEs,包括恶心、疲劳、背痛、下颌骨坏死等）的发生率等指标比较,差异均无统计学意义（均P＞0.05）。结论地诺单抗在临床有效性和安全性方面优于唑来膦酸,为恶性实体瘤伴骨转移患者的临床预防与治疗提供了新的方案。     

Gingival fibroblasts and medication-related osteonecrosis of the jaw: Results by real-time and wound healing in vitro assays

ObjectiveThis study investigated the effects of bisphosphonates and denosumab on human gingival fibroblasts (HGFs) that could influence inflammation, wound healing, and angiogenesis in medication-related osteonecrosis of the jaw (MRONJ).MethodsA real-time in vitro assay was performed on HGFs with and without the addition of bacterial lipopolysaccharide and a mononuclear cell co-culture to observe the effects of zoledronate, ibandronate, alendronate, clodronate, denosumab, and combinations of zoledronate and denosumab at varied concentrations. A wound healing assay was performed, and gene and protein expression was analyzed for inflammatory, angiogenic, and osteoclastogenic cytokines and mediators including interleukin (IL)-1β, IL-6, tumor necrosis factor alpha (TNFα), IL-8, vascular endothelial growth factor (VEGF), RANKL, and osteoprotegerin.ResultsHigher concentrations of antiresorptives resulted in impaired wound healing and HGF death, which also occurred without mechanical damage. These effects were increased with bacterial lipopolysaccharide and mononuclear cells. Increased levels of IL-1β, TNFα, IL-8, VEGF, osteoprotegerin, and decreased levels of IL-6 were observed.ConclusionsAntiresorptive exposure was associated with HGF death and delayed wound healing, which could be attributed to an elevated inflammatory response and immune dysfunction contributing to MRONJ development. There was no evidence of anti-angiogenic effects. Our experiments present the first results of denosumab with HGFs.     

Denosumab治疗绝经后骨质疏松症的临床研究进展

狄诺塞单抗(Denosumab)是首个上市的抗核因子κB受体活化因子配体(RANKL)治疗性单克隆抗体产品,主要用于治疗骨质疏松症和其他骨骼疾病.本文主要综述其近年国外治疗绝经后骨质疏松症的临床研究进展.