Thrailkill Kathryn M, Kalaitzoglou Evangelia, Fowlkes John L
Department of Pediatrics, University of Kentucky Barnstable Brown Diabetes Center, University of Kentucky College of Medicine, Lexington, KY, United States.
Front Pediatr. 2022 Oct 11;10:1012816. doi: 10.3389/fped.2022.1012816. eCollection 2022.
In recent years, new therapies for the treatment of rare pediatric bone disorders have emerged, guided by an increasing understanding of the genetic and molecular etiology of these diseases. Herein, we review three such disorders, impacted by debilitating deficits in bone mineralization or cartilage ossification, as well as the novel disease-modifying drugs that are now available to treat these conditions. Specifically, we discuss asfotase alfa, burosumab-twza, and vosoritide, for the treatment of hypophosphatasia, X-linked hypophosphatemia and achondroplasia, respectively. For each skeletal disorder, an overview of the clinical phenotype and natural history of disease is provided, along with a discussion of the clinical pharmacology, mechanism of action and FDA indication for the relevant medication. In each case, a brief review of clinical trial data supporting drug development for each medication is provided. Additionally, guidance as to drug dosing and long-term monitoring of adverse events and pediatric efficacy is presented, to aid the clinician seeking to utilize these novel therapies in their practice, or to become familiar with the healthcare expectations for children receiving these medications through specialized multidisciplinary clinics. The availability of these targeted therapies now significantly augments treatment options for conditions in which past therapy has relied upon less specific, symptomatic medical and orthopedic care.
近年来，随着对这些罕见儿童骨骼疾病的遗传和分子病因学的认识不断加深，治疗这些疾病的新疗法应运而生。在此，我们回顾三种受骨矿化或软骨骨化严重缺陷影响的此类疾病，以及目前可用于治疗这些病症的新型疾病修正药物。具体而言，我们分别讨论了阿法骨化醇、布罗索尤单抗 - twza和维索瑞肽，它们分别用于治疗低磷血症、X连锁低磷血症和软骨发育不全。对于每种骨骼疾病，我们提供了疾病临床表型和自然史的概述，同时讨论了相关药物的临床药理学、作用机制和美国食品药品监督管理局（FDA）的适应症。在每种情况下，我们都简要回顾了支持每种药物研发的临床试验数据。此外，还介绍了药物剂量、不良事件的长期监测以及儿科疗效的指导意见，以帮助临床医生在实践中使用这些新型疗法，或熟悉通过专门的多学科诊所接受这些药物治疗的儿童的医疗期望。这些靶向疗法的出现，显著增加了过去治疗依赖于不太特异的对症医疗和骨科护理的病症的治疗选择。
