Sclerostin inhibits bone formation via the WNT/β-catenin pathway and is a therapeutic target in osteoporosis. Antibodies against sclerostin are currently under investigation for the treatment of osteogenesis imperfecta (OI), a rare, genetically and clinically heterogeneous bone fragility disorder. However, data on serum sclerostin levels in pediatric and adolescent patients with OI remain limited.
Design
This is a retrospective, cross-sectional analysis of serum sclerostin levels in a genetically heterogeneous cohort of children and adolescents with OI.
Patients and methods
80 serum samples from 74 OI patients (median age 8.9 years, range 0.1–20.7 years), classified by clinical severity and affected gene, were collected. Serum levels of sclerostin, osteoprotegerin (OPG), parathyroid hormone (PTH), alkaline phosphatase (AP) and 25-Hydroxy Vitamin D (25(OH)D) were measured and analyzed according to genotype and OI severity.
Results
The median serum sclerostin level in this cohort was 0.35 ng/mL (IQR 0.28–0.52). Disease severity showed an inverse correlation with serum sclerostin levels (Spearman ρ = −0.4547, 95% CI [−0.62, −0.25], P < 0.0001). Multivariable linear regression analysis revealed genotype-specific differences in sclerostin levels, particularly in patients with BMP1 or WNT1 mutations compared with other mutation subgroups. No significant correlations were found between sclerostin and OPG, PTH, 25(OH)D, or AP.
Conclusions
In this cohort of children and adolescents with OI, disease severity was inversely associated with serum sclerostin levels, and genotype-specific differences may reflect distinct pathophysiological mechanisms of bone metabolism. These findings may contribute identifying patient subgroups most likely to benefit from targeted anti-sclerostin therapies.
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