Bone manifestations in NF1 affect approximately 50% of patients and include osteoporosis, bone dysplasia, pseudarthrosis, cranial anomalies, and spine deformities. We characterized the Prss56-Nf1 KO mouse model, which faithfully recapitulates key NF1-associated features, and identified a neural crest-derived progenitor population contributing to tibial pseudarthrosis and spinal deformities. Blocking RAS signaling prevented tibial pseudarthrosis and spine deformity in this mouse model.

Treatment of CPT is an ongoing challenge with high rates of non-union and re-fracture reported in the literature. New treatment approaches combine biological and biomechanical factors to improve healing and prevent re-fracture. Removal of the hamartoma, instillation of bone morphogenic protein, maximizing bone diameter, and intramedullary stabilization are the key steps of today’s surgical treatment. Despite this multilevel approach bracing until skeletal maturity is mandatory.

Background: Skeletal abnormalities are a diagnostic feature of neurofibromatosis type 1 (NF1), yet their full anatomical spectrum remains incompletely defined. We aimed to map skeletal lesion distribution and to examine associations with plexiform neurofibromas (PNF).

Methods: We retrospectively analyzed 269 patients with NF1 with available whole body computed tomography data. Skeletal abnormalities were recorded across 6 anatomical regions and individual skeletal elements, classified by morphology, and matched with regional PNF involvement. For lesion level and clustering analyses, patients with isolated scoliosis were excluded, leaving 193 patients with 668 lesions. Patient-level patterns were explored using clustering.

Results: Skeletal abnormalities were common and widely distributed, most frequently involving the spine (78.07%), lower limbs (24.91%), and pelvis (20.45%). Sphenoid defects were most frequent (n=18). Regional correlations were observed between PNF and specific skeletal phenotypes, including cortical irregularity in the upper limbs (φ=0.33, p<0.001), skull defects in craniofacial PNF (φ=0.27, p<0.001), and cortical thickening in lower limb PNF (φ=0.16, p=0.013). Clustering analysis identified 4 distinct skeletal patterns, demonstrating marked heterogeneity. Lower limb cortical thickening predominantly involved the tibia and was associated with greater skeletal burden and clinical characteristics including age, height, weight, and BMI.

Conclusion: Skeletal abnormalities in NF1 form a structured, regionally organized skeletal phenotype. Whole-skeleton mapping reveals site specific PNF-bone relationships and highlights lower limb cortical thickening as an underrecognized long bone phenotype.

Introduction: Neurofibromatosis type 1 (NF1) affects approximately 1:3,000 individuals, with about 5% of children developing tibial dysplasia. This congenital ossification disorder causes cortical thickening, medullary canal narrowing, and anterolateral bowing, potentially leading to fractures and congenital pseudarthrosis. While radiography remains the diagnostic gold standard, radiation concerns preclude its use for screening in asymptomatic children with tumor predisposition syndromes. Quantitative Ultrasound Imaging of Bone (QUSIB) offers a radiation-free alternative capable of assessing cortical bone microstructure and material properties.
Methods: This prospective 36-month study at the Vienna Pediatric NF1 Center will enroll 40 patients: 10 each from age groups 0–18 months, 18 months–6 years, and 6–18 years, plus 5–10 patients with known tibial dysplasia. Bilateral tibial QUSIB will assess cortical thickness (Ct.Th), compression wave velocity (Ct.n11), porosity (Ct.Po), frequency-dependent backscatter and attenuation coefficients (BSC(f), α(f)), and pore size distribution (Ct.Po.Dm.D). Measurements will occur at diagnosis and annually for three years thereafter. X-rays will be performed when clinically indicated. Descriptive and multivariate analyses will correlate QUSIB parameters with radiological findings and clinical outcomes.
Results: Data collection is ongoing. We hypothesize that side-to-side differences and deviations from the NF1 cohort in viscoelastic and microstructural parameters may identify tibial dysplasia and predict fracture risk.
Conclusion: QUSIB may provide a sensitive, specific, and radiation-free screening method for early detection of tibial dysplasia in NF1, potentially enabling timely intervention and fracture prevention.

Background: Individuals with neurofibromatosis type 1 (NF1) are at risk for skeletal complications including low bone mass for age and skeletal fragility. The MEK inhibitor (MEKi) Selumetinib is approved to treat plexiform neurofibromas (PN) in NF1. The effect of selumetinib on NF1 bony manifestations is unknown. We assessed changes in bone mineral density (BMD) in patients receiving selumetinib for NF1-PN.
Methods: Participants enrolled in the SPRINT study (NCT01362803) at the NCI were included in this analysis if baseline and comparable long-term follow-up (≥5-years) dual-energy x-ray absorptiometry (DXA) scans were obtained. We calculated whole-body subtotal height-adjusted Z-scores (HaZs) and reviewed patient charts for information about fractures.
Results: Twenty of 51 participants met inclusion criteria. 10 participants had comparable follow-up exams, 10 were excluded from analysis due to amputation (N=1), change in orthopedic hardware (N=2), or no HaZs available (N=7). In 9 participants (90%), HaZs decreased from baseline to follow-up (baseline median HaZs; -0.235 (range -7.01 to -0.53), follow up median; -1.765 (range = -1.54 to 1.88). Fractures were detected in 4 participants (2 incidental, 2 traumatic) on study.
Conclusions: Contrary to an expected increase in BMD with normally developing children and adolescents, we observed a decrease in most participants with NF1 receiving MEKi. The relationship of changes in BMD to selumetinib is unclear, as the natural history of BMD changes in NF1 has not been described to date. Longitudinal follow up on SPRINT is ongoing and we are currently analyzing changes in BMD and clinical features in NF1-Natural-History-Study participants who did not receive selumetinib.

Neurofibromatosis type 1 (NF1) is a bone disease. The skull base of NF1 patients exhibits subtle changes that are both constitutional and tumor associated. The Sella turcica (ST) is a transitional region between neural crest and notochord. This study investigates changes in the ST identifiable in NF1.
Material and methods: Lateral cephalograms (LC) from 166 NF1 patients were examined and compared with LCs of age and sex matched healthy individuals. The patients were further subdivided based on the type of facial neurofibroma (facial plexiform neurofibroma (FPNF) vs. disseminated cutaneous neurofibroma (DCNF)). Standard ST parameters were measured (entrance, length, diagonal, depth, area) and statistically analyzed with SPSS-29TM.
Results: NF1 patients show significant differences for the entrance (MD 1.85 mm, g = 0.68), length (MD 2.42 mm, g = 1.01), diagonal (MD 2.11 mm, g = 0.80), depth (MD 0.99 mm, g = 0.55) and area (MD 26.11 mm², g = 0.77) compared with controls. FPNF patients show significantly higher values for all these parameters when compared with DCNF patients. Set in relation to the difference between DCNF patients and controls, the difference between FPNF and DCNF patients was most pronounced for the area (188 %) and depth (202 %). The presence of NF1 does also effect the relation of the anterior and posterior skull base lengths, but not their sum.
Discussion and conclusion: NF1 affects shape and size of ST. NF1 has both tumor-associated and constitutive effects on ST. ST-changes in NF1 also affect dorsal regions, which are considered notochord derivatives.