PDF(Pubmed)
Abstract：
UNASSIGNED: Subjects with a fragility fracture have an increased risk of a new fracture and should receive effective strategies to prevent new events. The medium-term to long-term strategy should be scheduled by considering the mechanisms of action in therapy and the estimated fracture risk.
UNASSIGNED: A systematic review was conducted to evaluate the sequential strategy in patients with or at risk of a fragility fracture in the context of the development of the Italian Guidelines.
UNASSIGNED: Systematic review and meta-analysis.
UNASSIGNED: PubMed, Embase, and the Cochrane Library were investigated up to February 2021 to update the search of a recent systematic review. Randomized clinical trials (RCTs) that analyzed the sequential therapy of antiresorptive, anabolic treatment, or placebo in patients with or at risk of a fragility fracture were eligible. Three authors independently extracted data and appraised the risk of bias in the included studies. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Effect sizes were pooled in a meta-analysis using fixed-effects models. The primary outcome was the risk of refracture, while the secondary outcome was the bone mineral density (BMD) change.
UNASSIGNED: In all, 17 RCTs, ranging from low to high quality, met our inclusion criteria. A significantly reduced risk of fracture was detected at (i) 12 or 24 months after the switch from romosozumab to denosumab versus placebo to denosumab; (ii) 30 months from teriparatide to bisphosphonates versus placebo to bisphosphonates; and (iii) 12 months from romosozumab to alendronate versus the only alendronate therapy (specifically for vertebral fractures). In general, at 2 years after the switch from anabolic to antiresorptive drugs, a weighted BMD was increased at the lumbar spine, total hip, and femoral neck site.
UNASSIGNED: The Task Force formulated recommendations on sequential therapy, which is the first treatment with anabolic drugs or \'bone builders\' in patients with very high or imminent risk of fracture.
A systematic review to evaluate the sequential therapy of antiresorptive (denosumab and bisphosphonate, such as alendronate, minodronate, risedronate, and etidronate), anabolic treatment (such as romosozumab, teriparatide), or placebo in patients with or at risk of a fragility fracture in the context of the development of the Italian Guidelines Subjects with previous fragility fractures should promptly receive effective strategies to prevent the risk of subsequent events. Indeed, patients with a fragility fracture have a doubled risk of a new fracture. For this reason, it is essential to provide adequate sequential therapy based on the mechanisms and the rapidity of action. A systematic review was performed to identify the sequential strategy in patients at high- or imminent-risk of (re)fracture and to support the Panel of the Italian Fragility Fracture Guideline in formulating recommendations. Our systematic review included seventeen studies mostly focused on women and enabled us to strongly recommend the anabolic drugs as first-line treatment. Specifically, for the sequential therapy from anabolic to antiresorptive treatment, there was a significant reduction in the risk of different types of fractures after the switch from romosozumab to denosumab versus placebo to denosumab. These findings were confirmed at 24 months after the switch. Considering the sequential treatment from antiresorptive to anabolic medications, there was a decreased risk of fracture 12 months after the switch from placebo to teriparatide versus bisphosphonate or antiresorptive to teriparatide. Moreover, a greater bone mineral density increase after the switch from anabolic to antiresorptive medications was shown in the lumbar spine, total hip, and femoral neck. The results of this systematic review and meta-analysis confirm that initial treatment with anabolic drugs produces substantial bone mineral density improvements, and the transition to antiresorptive drugs can preserve or even amplify the acquired benefit. These findings support the choice to treat very high-risk individuals with anabolic drugs first, followed by antiresorptive drugs.
UNASSIGNED: A systematic review was conducted to evaluate the sequential strategy in patients with or at risk of a fragility fracture in the context of the development of the Italian Guidelines.
UNASSIGNED: Systematic review and meta-analysis.
UNASSIGNED: PubMed, Embase, and the Cochrane Library were investigated up to February 2021 to update the search of a recent systematic review. Randomized clinical trials (RCTs) that analyzed the sequential therapy of antiresorptive, anabolic treatment, or placebo in patients with or at risk of a fragility fracture were eligible. Three authors independently extracted data and appraised the risk of bias in the included studies. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Effect sizes were pooled in a meta-analysis using fixed-effects models. The primary outcome was the risk of refracture, while the secondary outcome was the bone mineral density (BMD) change.
UNASSIGNED: In all, 17 RCTs, ranging from low to high quality, met our inclusion criteria. A significantly reduced risk of fracture was detected at (i) 12 or 24 months after the switch from romosozumab to denosumab versus placebo to denosumab; (ii) 30 months from teriparatide to bisphosphonates versus placebo to bisphosphonates; and (iii) 12 months from romosozumab to alendronate versus the only alendronate therapy (specifically for vertebral fractures). In general, at 2 years after the switch from anabolic to antiresorptive drugs, a weighted BMD was increased at the lumbar spine, total hip, and femoral neck site.
UNASSIGNED: The Task Force formulated recommendations on sequential therapy, which is the first treatment with anabolic drugs or \'bone builders\' in patients with very high or imminent risk of fracture.
A systematic review to evaluate the sequential therapy of antiresorptive (denosumab and bisphosphonate, such as alendronate, minodronate, risedronate, and etidronate), anabolic treatment (such as romosozumab, teriparatide), or placebo in patients with or at risk of a fragility fracture in the context of the development of the Italian Guidelines Subjects with previous fragility fractures should promptly receive effective strategies to prevent the risk of subsequent events. Indeed, patients with a fragility fracture have a doubled risk of a new fracture. For this reason, it is essential to provide adequate sequential therapy based on the mechanisms and the rapidity of action. A systematic review was performed to identify the sequential strategy in patients at high- or imminent-risk of (re)fracture and to support the Panel of the Italian Fragility Fracture Guideline in formulating recommendations. Our systematic review included seventeen studies mostly focused on women and enabled us to strongly recommend the anabolic drugs as first-line treatment. Specifically, for the sequential therapy from anabolic to antiresorptive treatment, there was a significant reduction in the risk of different types of fractures after the switch from romosozumab to denosumab versus placebo to denosumab. These findings were confirmed at 24 months after the switch. Considering the sequential treatment from antiresorptive to anabolic medications, there was a decreased risk of fracture 12 months after the switch from placebo to teriparatide versus bisphosphonate or antiresorptive to teriparatide. Moreover, a greater bone mineral density increase after the switch from anabolic to antiresorptive medications was shown in the lumbar spine, total hip, and femoral neck. The results of this systematic review and meta-analysis confirm that initial treatment with anabolic drugs produces substantial bone mineral density improvements, and the transition to antiresorptive drugs can preserve or even amplify the acquired benefit. These findings support the choice to treat very high-risk individuals with anabolic drugs first, followed by antiresorptive drugs.
摘要：
■患有脆性骨折的受试者发生新骨折的风险增加，应接受有效的策略来预防新事件。应通过考虑治疗中的作用机制和估计的骨折风险来安排中期至长期策略。
■在制定意大利指南的背景下，进行了系统评价，以评估脆性骨折或有脆性骨折风险的患者的序贯策略。
■系统评价和荟萃分析。
■PubMed,Embase,对Cochrane图书馆进行了调查，直到2021年2月，以更新对最近的系统评价的搜索。随机临床试验（RCT）分析了抗再吸收的序贯疗法，合成代谢疗法,有脆性骨折或有脆性骨折风险的患者的安慰剂或安慰剂均符合条件.三位作者独立提取了数据，并评估了纳入研究中的偏倚风险。使用建议分级评估来评估证据质量，发展,和评价方法。使用固定效应模型在荟萃分析中汇总效应大小。主要结果是再骨折的风险，而次要结果是骨密度（BMD）的变化。
■总之，17项随机对照试验,从低质量到高质量，符合我们的纳入标准。在（i）从romosozumab转换为denosumab与安慰剂转换为denosumab后12或24个月时，发现骨折风险显着降低；（ii）从特立帕肽转换为双膦酸盐与安慰剂转换为双膦酸盐30个月；（iii）从romosozumab转换为阿仑膦酸盐与唯一的阿仑膦酸盐治疗（特别是椎体骨折）总的来说,在从合成代谢药物转向抗吸收药物的2年后，腰椎的加权骨密度增加，全髋关节,和股骨颈部位。
■工作组制定了序贯疗法的建议，这是对骨折风险非常高或迫在眉睫的患者首次使用合成代谢药物或“骨构建剂”进行治疗。
系统评价抗再吸收的序贯疗法（denosumab和双膦酸盐，比如阿仑膦酸盐，米诺膦酸盐,利塞膦酸盐,和依替膦酸盐)，合成代谢治疗(如romosozumab，特立帕肽),在制定意大利指南的背景下，患有脆性骨折或有脆性骨折风险的患者应及时接受有效的策略，以防止后续事件的风险。的确,脆性骨折患者发生新骨折的风险增加了一倍.出于这个原因,必须根据作用机制和作用速度提供适当的序贯疗法.进行了系统评价，以确定高或即将发生（重新）骨折的患者的序贯策略，并支持意大利脆性骨折指南小组制定建议。我们的系统评价包括17项主要针对女性的研究，使我们能够强烈建议合成代谢药物作为一线治疗。具体来说,对于从合成代谢到抗吸收治疗的序贯疗法，从romosozumab转换为地诺塞马后,与安慰剂转换为地诺塞马后相比,不同类型骨折的风险显著降低.这些发现在转换后24个月得到证实。考虑到从抗再吸收到合成代谢药物的序贯治疗，与双膦酸盐相比,安慰剂转用特立帕肽或抗再吸收转用特立帕肽后12个月,骨折风险降低.此外，从合成代谢药物转换为抗吸收药物后，腰椎显示出更大的骨矿物质密度增加，全髋关节,还有股骨颈.这项系统评价和荟萃分析的结果证实，使用合成代谢药物的初始治疗可以显着改善骨密度，过渡到抗再吸收药物可以保留甚至扩大获得的益处。这些发现支持选择首先使用合成代谢药物治疗非常高风险的个体，其次是抗吸收药物。
■在制定意大利指南的背景下，进行了系统评价，以评估脆性骨折或有脆性骨折风险的患者的序贯策略。
■系统评价和荟萃分析。
■PubMed,Embase,对Cochrane图书馆进行了调查，直到2021年2月，以更新对最近的系统评价的搜索。随机临床试验（RCT）分析了抗再吸收的序贯疗法，合成代谢疗法,有脆性骨折或有脆性骨折风险的患者的安慰剂或安慰剂均符合条件.三位作者独立提取了数据，并评估了纳入研究中的偏倚风险。使用建议分级评估来评估证据质量，发展,和评价方法。使用固定效应模型在荟萃分析中汇总效应大小。主要结果是再骨折的风险，而次要结果是骨密度（BMD）的变化。
■总之，17项随机对照试验,从低质量到高质量，符合我们的纳入标准。在（i）从romosozumab转换为denosumab与安慰剂转换为denosumab后12或24个月时，发现骨折风险显着降低；（ii）从特立帕肽转换为双膦酸盐与安慰剂转换为双膦酸盐30个月；（iii）从romosozumab转换为阿仑膦酸盐与唯一的阿仑膦酸盐治疗（特别是椎体骨折）总的来说,在从合成代谢药物转向抗吸收药物的2年后，腰椎的加权骨密度增加，全髋关节,和股骨颈部位。
■工作组制定了序贯疗法的建议，这是对骨折风险非常高或迫在眉睫的患者首次使用合成代谢药物或“骨构建剂”进行治疗。
系统评价抗再吸收的序贯疗法（denosumab和双膦酸盐，比如阿仑膦酸盐，米诺膦酸盐,利塞膦酸盐,和依替膦酸盐)，合成代谢治疗(如romosozumab，特立帕肽),在制定意大利指南的背景下，患有脆性骨折或有脆性骨折风险的患者应及时接受有效的策略，以防止后续事件的风险。的确,脆性骨折患者发生新骨折的风险增加了一倍.出于这个原因,必须根据作用机制和作用速度提供适当的序贯疗法.进行了系统评价，以确定高或即将发生（重新）骨折的患者的序贯策略，并支持意大利脆性骨折指南小组制定建议。我们的系统评价包括17项主要针对女性的研究，使我们能够强烈建议合成代谢药物作为一线治疗。具体来说,对于从合成代谢到抗吸收治疗的序贯疗法，从romosozumab转换为地诺塞马后,与安慰剂转换为地诺塞马后相比,不同类型骨折的风险显著降低.这些发现在转换后24个月得到证实。考虑到从抗再吸收到合成代谢药物的序贯治疗，与双膦酸盐相比,安慰剂转用特立帕肽或抗再吸收转用特立帕肽后12个月,骨折风险降低.此外，从合成代谢药物转换为抗吸收药物后，腰椎显示出更大的骨矿物质密度增加，全髋关节,还有股骨颈.这项系统评价和荟萃分析的结果证实，使用合成代谢药物的初始治疗可以显着改善骨密度，过渡到抗再吸收药物可以保留甚至扩大获得的益处。这些发现支持选择首先使用合成代谢药物治疗非常高风险的个体，其次是抗吸收药物。
