Operative Unit of Rheumatology, San Pietro Fateebenefratelli Hospital, Rome, Italy.
Curr Med Res Opin. 2012 Mar;28(3):467-73. doi: 10.1185/03007995.2012.659724. Epub 2012 Feb 16.
The recent development of compounds with anabolic action on bone have increased the range of therapeutic options for the treatment of osteoporosis and the prevention of fractures. Two major PTH analogs, the synthetic full-length 1-84 PTH molecule and the recombinant 1-34 N-terminal fragment (teriparatide), are available for the treatment of osteoporosis in many countries. There have bee no comparative trials on the bone anabolic effects of these compounds.
In this study we applied a mixed treatment comparison (MTC) to compare the efficacy of teriparatide versus PTH 1-84 for the prevention of vertebral and non-vertebral fractures in women with severe osteoporosis. With this approach the relative treatment effect of one intervention over another can be obtained in the absence of head-to-head comparison. Among the candidate papers selected for analysis, two randomized controlled trials investigating the effects of teriparatide and PTH 1-84 met the selection criteria and underwent MTC analysis.
Based on a fixed-effect MTC model analysis of data from two RCTs, teriparatide (20 µg/day) showed a 70% and 94% probability of being the best treatment for the prevention of vertebral and non-vertebral fractures, respectively. Together with a lack of statistical significance, this study has additional limitations. Some differences in trial procedures and populations exist; another limitation concerns the impossibility of carrying out a randomized-effect model MTC, due to sample exiguity. Furthermore, in order to consider unknown or unmeasured differences of covariates across trials, a random-effects approach would be preferred in order to assess the presence of heterogeneity across comparisons. In contrast, in our analysis a fixed-effect MTC model only was used.
Teriparatide is expected to provide a greater efficacy over PTH 1-84 with both vertebral and non-vertebral fracture prevention in postmenopausal women with severe osteoporosis.
具有促进骨骼合成代谢作用的化合物的最新发展增加了治疗骨质疏松症和预防骨折的治疗选择范围。两种主要的甲状旁腺激素(PTH)类似物,即合成全长 1-84 PTH 分子和重组 1-34 氨基端片段(特立帕肽),已在许多国家用于治疗骨质疏松症。目前还没有关于这些化合物在促进骨骼合成代谢方面的疗效比较试验。
在这项研究中,我们应用混合治疗比较(MTC)来比较特立帕肽与 PTH 1-84 预防绝经后严重骨质疏松症妇女椎骨和非椎骨骨折的疗效。通过这种方法,可以在没有头对头比较的情况下获得一种干预措施相对于另一种干预措施的相对治疗效果。在选定进行分析的候选论文中,有两项随机对照试验符合选择标准并进行了 MTC 分析,调查了特立帕肽和 PTH 1-84 的效果。
基于对两项 RCT 数据的固定效应 MTC 模型分析,特立帕肽(20μg/天)预防椎骨和非椎骨骨折的最佳治疗概率分别为 70%和 94%。此外,这项研究还存在一些局限性,如缺乏统计学意义。试验程序和人群存在一些差异;另一个限制是由于样本量不足,不可能进行随机效应模型 MTC。此外,为了考虑到试验之间未知或未测量的协变量差异,为了评估比较之间是否存在异质性,倾向于使用随机效应方法。相反,在我们的分析中,仅使用了固定效应 MTC 模型。
在绝经后严重骨质疏松症妇女中,特立帕肽预防椎骨和非椎骨骨折的疗效预计优于 PTH 1-84。