Allegri Anna Elsa Maria, Bedeschi Maria Francesca, Bocchi Maria Beatrice, Camurri Valentina, Gonfiantini Michaela Veronika, Leoni Chiara, Mariani Milena, Palmacci Osvaldo, Porro Matteo, Riganti Simone, Tedesco Caterina, Rinaldi Berardo, Scarano Emanuela, Schiavariello Concetta, Selicorni Angelo, Stagi Stefano, Verdoni Fabio, Zampino Giuseppe, Maghnie Mohamad, Onesimo Roberta
Paediatric Endocrinology Unit, Department of Paediatrics, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Medical Genetic Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
Orphanet J Rare Dis. 2025 Jul 17;20(1):369. doi: 10.1186/s13023-025-03853-7.
Achondroplasia is the most common form of disproportionate short stature and can lead to serious medical complications, including foramen magnum and spinal stenosis. Until 2021, there were no precision treatments available, and in some countries, elective surgery was considered a standard approach to increase height, improve body proportions, enhance functionality, and correct deformities in a selected group of patients. Recently, C-type natriuretic peptide (CNP) has been explored as a potential treatment, aiming to counteract the molecular activity driven by FGFR3. Although post-market and real-world data on the drug are still limited, many questions remain about the potential for combining pharmacological and surgical therapies and how this might influence patient outcomes. Concerns have also been raised regarding the potential impact of drugs on bone healing. However, anecdotal evidence from orthopaedic practice suggests that the two ossification processes do not interfere with one another. The aim of this study was to describe the first real-world case series in which vosoritide treatment was integrated with limb surgery in children and adolescents with achondroplasia.
Sixteen paediatric patients with molecular confirmation of achondroplasia were included in the study. All patients underwent combined vosoritide therapy and limb surgeries (13 for lower limb lengthening and 3 for varus correction through epiphysiodesis).The complementary roles of vosoritide therapy and surgery were highlighted, with treatment outcomes aligning closely with expectations.
This report provides the first clinical description of the combination of precision therapy with limb surgery in a relatively large multicentre cohort of paediatric patients with achondroplasia. These findings support continued exploration of the integration of different therapeutic approaches.
软骨发育不全是身材不成比例矮小最常见的形式，可导致严重的医学并发症，包括枕大孔和椎管狭窄。直到2021年，尚无精准治疗方法，在一些国家，择期手术被视为在特定患者群体中增加身高、改善身体比例、增强功能和矫正畸形的标准方法。最近，C型利钠肽（CNP）已被探索作为一种潜在治疗方法，旨在抵消由FGFR3驱动的分子活性。尽管该药物的上市后和真实世界数据仍然有限，但关于联合药物治疗和手术治疗的潜力以及这可能如何影响患者预后仍有许多问题。也有人对药物对骨愈合的潜在影响表示担忧。然而，骨科实践中的轶事证据表明这两个骨化过程不会相互干扰。本研究的目的是描述首例在软骨发育不全的儿童和青少年中将维索瑞肽治疗与肢体手术相结合的真实世界病例系列。
16例经分子确诊为软骨发育不全的儿科患者纳入研究。所有患者均接受了维索瑞肽联合治疗和肢体手术（13例下肢延长手术，3例通过骨骺阻滞进行内翻矫正手术）。维索瑞肽治疗和手术的互补作用得到凸显，治疗结果与预期密切相符。
本报告首次对相对较大的多中心软骨发育不全儿科患者队列中精准治疗与肢体手术联合应用进行了临床描述。这些发现支持继续探索不同治疗方法的整合。
