Abstract

Osteogenesis imperfecta (OI) is a genetic disorder characterized by increased bone fragility largely caused by defects in structure, synthesis, or post-translational processing of type I collagen. Drugs currently used to improve skeletal health in OI were initially developed to treat osteoporosis and clinical trials are ongoing to study their effectiveness in OI adults. Additionally, novel bone-protective agents are in preclinical studies and various phases of OI clinical trials. This review summarizes current knowledge on available pharmacologic agents and current drug trials involving OI participants. A PubMed online database search of all study types published in the English language using the terms “osteogenesis imperfecta,” “OI,” and “brittle bone disease” was performed in August 2022. Articles screened were restricted to adults. A ClinicalTrials.gov database search of all studies involving “osteogenesis imperfecta” was performed in August 2023. Although clinical trial data are limited, bisphosphonates and teriparatide may be useful in improving bone mineral density. As of yet, no clinical trials are available that adequately evaluate the usefulness of current therapies in reducing fracture risk. Several therapeutics, including teriparatide, setrusumab, anti-TGF-β antibodies, and allogeneic stem cells, are being studied in clinical trials. Preclinical studies involving Dickkopf-1 antagonists present promising data in non-OI bone disease, and could be useful in OI. Research is ongoing to improve therapeutic options for adults with OI and clinical trials involving gene-editing may be possible in the coming decade.

中文翻译：

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当前和正在开发的用于改善成骨不全成人骨骼健康的药物

摘要

成骨不全症 (OI) 是一种遗传性疾病，其特征是骨脆性增加，这主要是由 I 型胶原蛋白的结构、合成或翻译后加工缺陷引起的。目前用于改善成骨不全症骨骼健康的药物最初是为了治疗骨质疏松症而开发的，目前正在进行临床试验以研究它们对成骨不全症成人的有效性。此外，新型骨保护剂正处于临床前研究和成骨不全临床试验的各个阶段。本综述总结了现有药物的最新知识以及涉及 OI 参与者的当前药物试验。2022 年 8 月，使用术语“成骨不全”、“成骨不全”和“脆骨病”对以英语发表的所有研究类型进行了 PubMed 在线数据库搜索。筛选的文章仅限于成人。2023 年 8 月，ClinicalTrials.gov 数据库检索了所有涉及“成骨不全症”的研究。尽管临床试验数据有限，但双磷酸盐和特立帕肽可能有助于改善骨矿物质密度。迄今为止，还没有临床试验能够充分评估当前疗法在降低骨折风险方面的有效性。包括特立帕肽、setrusumab、抗 TGF-β 抗体和同种异体干细胞在内的几种疗法正在临床试验中进行研究。涉及 Dickkopf-1 拮抗剂的临床前研究在非 OI 骨病方面提供了有希望的数据，并且可能对 OI 有用。正在开展研究以改善成人成骨不全症的治疗选择，并且涉及基因编辑的临床试验可能在未来十年内实现。