Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
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European journal of pediatrics
Efficacy and safety of vosoritide in children with achondroplasia: a systematic review and meta-analysis
UNLABELLED: Achondroplasia is caused by a gain-of-function mutation in the FGFR3 gene. Vosoritide activates the NPR-B receptor to inhibit the overactive FGFR3 signaling pathway. We aim to pool the efficacy and safety outcomes of vosoritide in children with genetically confirmed achondroplasia who are receiving the approved dose of 15 μg/kg/day. We searched five databases up to February 10, 2026. A systematic review and single-arm meta-analysis were conducted in accordance with the PRISMA guidelines. The primary outcomes were annualized growth velocity (AGV), height gain, and change in height Z-score. Three quality assessment tools were used to assess different study designs of the included studies. All analyses were conducted using OnlineMeta V1.1. Thirteen studies on vosoritide treatment in children with achondroplasia were included, comprising randomized controlled trials, cohort studies, case reports, and case series. A meta-analysis showed that vosoritide was associated with an AGV of 5.72 cm/year (95% CI: 5.51-5.94) at 12 months. The mean height Z-score improvement at 12 months after sensitivity analysis was 0.28 (95% CI: 0.16-0.4), with no significant difference between sexes. Overall, the most common adverse events were injection site reactions (51%) and gastrointestinal symptoms (50%). CONCLUSION: One-year treatment with vosoritide is associated with increased growth velocity, height gain, and a modest improvement in height Z-score, accompanied by a high incidence of mild to moderate adverse events. Larger, longer-term studies are necessary to confirm the treatment's safety and efficacy. WHAT IS KNOWN: • Achondroplasia is a skeletal dysplasia caused by a mutation in the FGFR3 gene, which leads to inhibit endochondral ossification and bone growth. • Vosoritide is a recombinant C-type natriuretic peptide analogue designed to counteract overactive FGFR3 signaling and was approved by the FDA and EMA. WHAT IS NEW: • One-year treatment with vosoritide in achondroplasia children is associated with increased growth velocity and improvement in height Z-score with reported minor adverse events.
26 Apr 2026
Read appraisal →The Journal of clinical endocrinology and metabolism
Effect of Vosoritide Therapy on IGF-I and Endogenous C-Type Natriuretic Peptide in Hypochondroplasia
CONTEXT: Insulin-like growth factor-1 (IGF-1) and C-type natriuretic peptide (CNP) promote endochondral bone growth. We previously reported that vosoritide, a CNP analogue, increases annualized growth velocity (AGV) and height SD in prepubertal children with hypochondroplasia (HCH). OBJECTIVE: We hypothesized that IGF-1 and CNP will be inversely associated at baseline and will respond differentially during a single-arm, unblinded, standardized 12-month phase 2 clinical trial of vosoritide in prepubertal patients aged 3 to 11 years with HCH and height less than -2.25 SD. Participants were followed for a baseline 6-month observation period and then received a dose of 15 μg/kg/day of vosoritide subcutaneous daily injections for 12 months. Anthropometrics, IGF-1, and NTproCNP were measured every 6 months. Longitudinal changes in IGF-1 and NTproCNP as well as the correlations between these 2 analytes and changes in height SD and AGV were analyzed. RESULTS: Baseline IGF-1 values are reduced in children with HCH and increased throughout the study, but IGF-1 SD did not change significantly. NTproCNP was raised at baseline and declined throughout the study, with NTproCNP SD significantly lower at months 6 and 12 on treatment. Change in height SD or AGV were not correlated to IGF-1 or NTproCNP SD at 12 months. The change in IGF-1 concentrations at 12 months was positively correlated with the change in NTproCNP plasma concentrations (ρ = 0.57; P = .024). CONCLUSION: In children with HCH, IGF-1 levels are reduced and NTproCNP levels are elevated at baseline. A correlation between changes in these levels during treatment suggests a possible interaction between IGF-1 and CNP signaling.
24 Apr 2026
Read appraisal →European journal of pediatrics
The impact of growth hormone therapy on ocular structural parameters in idiopathic short stature: a systematic review and meta-analysis
This study aimed to conduct a systematic review and meta-analysis of the effects of growth hormone (GH) therapy on ocular structures and biometric parameters in children with idiopathic short stature (ISS), synthesizing existing evidence for future research. We systematically searched PubMed, EMBASE, the Cochrane Library, CNKI, Wanfang, and VIP databases from inception to September 2025. Randomized controlled trials and observational studies comparing the effects of GH therapy versus control on ocular biometric and refractive outcomes in children with ISS were included. Study quality was assessed using the Cochrane Risk of Bias Tool (RoB 2) and the NOS. Meta-analysis was performed using R software version 4.3.2, with effect sizes expressed as MD or SMD and 95% CI. Nine studies were included (4 RCTs, 5 cohort studies). Meta-analysis showed no significant association of GH therapy with corneal curvature (SMD = 0.13, 95% CI: -0.34 to 0.61). For axial length, the random-effects model showed no significant difference (MD = 0.72, 95% CI: -0.36 to 1.81), with high heterogeneity (I2 = 91.7%). Similarly, no significant association was found for intraocular pressure (MD = 1.38, 95% CI: -0.66 to 3.43; I2 = 95.9%). However, a significant association was observed for refractive status (MD = 0.53, 95% CI: 0.20 to 0.86; I2 = 0.0%). Sensitivity analysis showed robust results for corneal curvature and refractive outcomes, while axial length and intraocular pressure results were influenced by individual studies. Funnel plots and Egger's test indicated no significant publication bias.Conclusion: The associations between GH therapy and ocular biometric parameters in children with ISS remain uncertain. Current evidence suggests a possible link with refractive changes but shows no significant associations with axial length or intraocular pressure when accounting for high heterogeneity. The findings are inconsistent and should be regarded as hypothesis-generating, insufficient to recommend changes in clinical monitoring practice. Future large-sample, long-term studies are required.
17 Apr 2026
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