Achondroplasia: From bone to bench to bedside an integrated review of medical and surgical management strategies.
The review outlines the transition from traditional management of achondroplasia to modern pharmacotherapy, including the recent approvals of vosoritide and navepegritide.
Where it sits
this study against the rest of the vosoritide corpusSummary and findings
This review examines the evolution of treatment strategies for achondroplasia, focusing on both surgical and pharmacological interventions. It highlights the FDA approval of vosoritide in 2021 and discusses other emerging agents. The paper aims to provide insights into multimodal therapy approaches for improving quality of life in affected individuals.
Abstract
Achondroplasia is the most prevalent form of human skeletal dysplasia in humans and is caused by a gain-of-function pathogenic variant in the fibroblast growth factor receptor 3 (FGFR3) gene. Historically managed through symptomatic and orthopedic interventions, the condition has entered a new therapeutic era defined by targeted molecular pharmacotherapy. This review provides a comprehensive examination of the evolution of treatment strategies-from early surgical approaches and the pioneering application of distraction osteogenesis by Gavriil Ilizarov, through empirical trials of growth hormone, to the 2021 FDA approval of vosoritide (Voxzogo), a C-type natriuretic peptide (CNP) analogue. Most recently another CNP prodrug, known as navepegritide (Yuviwel) was approved by the FDA in 2026. Emerging agents like infigratinib, dabogratinib, and aptamers are also discussed. There have been other drugs considered for clinical trials, some tried unsuccessfully that are relevant for discussion; many of them repurposed drugs. We examine the advances, limitations, and complications of surgical limb lengthening and evaluate the growing body of evidence supporting multimodal therapy that combines molecular intervention with judicious surgical management. The goal of these treatments is to improve functional quality of life, mitigate musculoskeletal and neurological complications, and achieve growth trajectories approaching normal developmental benchmarks.
Background
Achondroplasia is the most prevalent form of human skeletal dysplasia, caused by a gain-of-function variant in the FGFR3 gene. Historically, management has relied on symptomatic and orthopedic interventions. This review is significant as it highlights the transition to targeted molecular pharmacotherapy, particularly with the introduction of vosoritide and other emerging treatments.
Methods
Not reported in abstract.
Results
Not reported in abstract.
Interpretation
Not reported in abstract.
Key findings
- FDA approval of vosoritide (Voxzogo) in 2021.
- FDA approval of navepegritide (Yuviwel) in 2026.
- Emerging agents like infigratinib and dabogratinib are discussed.
Limitations
- Not reported in abstract.