Fracture Rate and Location in Adults with Neurofibromatosis Type 1 at Two Sites

Neurofibromatosis 1 (NF1) is one of the most common autosomal dominant syndromes, affecting 1 in 3,000 individuals worldwide. The multisystem condition is caused by an inactivating mutation in NF1 gene on the long arm of chromosome 17. NF1 encodes for tumor suppressor protein neurofibromin, involved in the Ras-pathway, aiding in regulation of cellular proliferation. The phenotypic expressions from mutated NF1 are easily identifiable, and skeletal abnormalities affect over 1/3 of NF1 patients. Abnormalities are both generalized—affecting the entire system—and focal. NF1 patients are NF1⁺/NF1^- and in a haploinsufficient state for neurofibromin. Double inactivation of NF1 leads to the focal bone abnormalities like tibial pseudarthrosis. However, we hypothesize that NF1 haploisufficiency predisposes NF1 patients for generalized bone health issues like osteoporosis. Neurofibromin is found in osteoclasts, but its role is not well understood. Studies show NF1 osteoclast hyperactivity, suggesting a bone-remodeling imbalance and theoretically resulting in lower bone mineral density (BMD) for the NF1 afflicted. Low BMD increases the possibility for individuals to fracture, so we hypothesize adults with NF1 will have higher fracture rates and in locations that differ from normal controls. We are currently collecting the fracture histories, health histories, calcium intake surveys, and activity level surveys NF1 adults lacking focal bone abnormalities and healthy control adults. A multi-linear statistical analysis will be performed, correcting for factors like health conditions, medicines, calcium intake, age, sex, physical activity, and muscle strength. We predict that the NF1 group will show higher fracture rates and in different locations than controls.