Neurofibromatosis type I (NF1) and bone involvement in a pediatric setting: insights from FGF23 levels

Neurofibromatosis type I (NF1) is an autosomal dominant disorder characterized by extremely different phenotypes, sometimes including reduced bone mass. The underlying cause of bone impairment in these patients remains poorly understood, especially in children. Previous studies in mice and single reports in NF1 patients with osteomalacia have shown elevated serum FGF23 levels. The aim of this study was to explore for the first time these results in NF1 pediatric patients to eventually provide biological insight into bone involvement in NF1.

This is an observational, cross-sectional, single-centre study evaluating FGF23/αKlotho levels, as well as other markers of bone metabolism and densitometric parameters in 31 children affected by NF1 and comparing them to 21 age- and sex-matched controls.

We enrolled 31 patients with NF1(M/F 13/18; 11.7 ± 2.9 years). After correction for bone age, BMAD Z-score was < -2SDS in 5/31 patients (16.1%). No difference was found between FGF23 and αKlotho between NF1 patients and controls. No association was found between auxological, biochemical, genetic and radiological parameters and FGF23 values.

In conclusion, this represents the first study assessing FGF23 levels in NF1 children and its possible relationship with decreased bone mineral density. Contrarily to previous observations, no significant differences were found between NF1 patients and controls regarding FGF23 and αKlotho levels. Additionally, there was no clear association between FGF23 and bone involvement, thus suggesting that this phenomenon is not FGF23-driven or FGF23 derangements might occur later in life. Further research is needed to understand the multifactorial mechanisms and determine optimal intervention strategies.