Interventions for Improving Bone Mineral Density and Reducing Fracture Risk in Osteogenesis Imperfecta: A Mixed Treatment Comparison Network Meta-analysis of Randomized Controlled Clinical Trials.

IF 3.2 Q2 Pharmacology, Toxicology and Pharmaceutics
Kannan Sridharan, Gowri Sivaramakrishnan
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引用次数: 3

Abstract

Background: Osteogenesis imperfecta is a rare metabolic disorder associated with reduced mineralization of bone and corresponds to increased fracture risk. We carried out the present network meta-analysis comparing all the medical interventions for osteogenesis imperfecta.

Method: Electronic databases were searched for randomized controlled clinical trials evaluating the use of drugs in patients with osteogenesis imperfecta. Percent change in BMD was the primary and fracture risk reduction and adverse events were the secondary outcome measures. The weighted mean difference was the pooled estimate for primary outcome and odds ratio with 95% confidence interval for the secondary outcome measures. Direct and mixed treatment comparisons between the interventions were carried out by inverse heterogeneity model. Sub-group analyses were carried out on children, adults and within bisphosphonate groups. The trial sequential analysis was carried out for the comparison of oral bisphosphonates with placebo.

Results: A total of 16 studies were included evaluating oral and intravenous bisphosphonates, teriparatide, anti-sclerostin antibody, high dose vitamin D and recombinant growth hormone (rGH) combined with intravenous bisphosphonates. Oral bisphosphonates and teriparatide were observed with a statistically significant increase in BMD compared to placebo. Also, only oral bisphosphonates were associated with significant reduction in the fracture risk but when the alpha error was adjusted for the information accrued till date as well as when the results of a trial were excluded, no significant difference was observed. Either low or very low quality was observed for pooled estimates of the key comparisons.

Conclusion: Oral bisphosphonates and teriparatide significantly increase BMD but are not associated with fracture risk reduction. Of the available interventions, oral bisphosphonates could perform better than others in osteogenesis imperfecta. This evidence should be considered preliminary and may change with future head-to-head clinical trials.

改善骨密度和降低成骨不全骨折风险的干预措施:一项随机对照临床试验的混合治疗比较网络荟萃分析。
背景:成骨不全是一种罕见的代谢性疾病,与骨矿化减少有关,并与骨折风险增加有关。我们进行了网络荟萃分析,比较了所有针对成骨不全的医疗干预措施。方法:检索电子数据库中评价成骨不全患者用药的随机对照临床试验。骨密度变化百分比是主要指标,骨折风险降低和不良事件是次要指标。加权平均差是主要结果和次要结果的比值比(95%置信区间)的汇总估计值。通过逆异质性模型对干预措施之间的直接治疗和混合治疗进行比较。对儿童、成人和双膦酸盐组进行亚组分析。对口服双膦酸盐与安慰剂的比较进行了试验序列分析。结果:共纳入16项研究,评估口服和静脉注射双膦酸盐、特立帕肽、抗硬化蛋白抗体、大剂量维生素D和重组生长激素(rGH)联合静脉注射双膦酸盐的疗效。与安慰剂相比,口服双膦酸盐和特立帕肽可显著提高骨密度。此外,只有口服双膦酸盐与骨折风险的显著降低有关,但当根据迄今累积的信息调整α误差以及排除试验结果时,没有观察到显著差异。对于关键比较的汇总估计,观察到低质量或非常低质量。结论:口服双膦酸盐和特立帕肽可显著增加骨密度,但与骨折风险降低无关。在现有的干预措施中,口服双膦酸盐治疗成骨不全的效果优于其他干预措施。这一证据应被认为是初步的,并可能随着未来的正面临床试验而改变。
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来源期刊
Current clinical pharmacology
Current clinical pharmacology PHARMACOLOGY & PHARMACY-
CiteScore
3.60
自引率
0.00%
发文量
0
期刊介绍: Current Clinical Pharmacology publishes frontier reviews on all the latest advances in clinical pharmacology. The journal"s aim is to publish the highest quality review articles in the field. Topics covered include: pharmacokinetics; therapeutic trials; adverse drug reactions; drug interactions; drug metabolism; pharmacoepidemiology; and drug development. The journal is essential reading for all researchers in clinical pharmacology.
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