Abstract
In patients with neurofibromatosis type 1 (NF1), decreased bone mineral density (BMD) and low levels of 25-hydroxy vitamin D3 (25OHD) have been reported. Recently, the trabecular bone score (TBS) measurement has been proposed as index of bone microarchitecture and fracture risk. In 74 NF1 patients (48 females, 26 males, age 41 ± 12), we measured TBS and investigated clinical stage, lifestyle, vitamin D, serum bone turnover markers, vertebral and femoral BMD. A homogenous cohort of 61 healthy subjects was used as control group. TBS was lower in NF1 patients (1.266 ± 0.113 vs. 1.346 ± 0.105) without differences between sexes. No correlations with 25OHD, low exercise, low calcium intake, reduced sun exposure, and number of skin neurofibromas were observed. As expected, hypovitaminosis D was common (98.6%), as well as BMD reduction in hip and spine sites: In NF1 patients, bone texture evaluated by TBS was low in both sexes without any correlation with clinical or metabolic parameters, suggesting a direct role of the fibromin mutation.
Highlights
Type 1 neurofibromatosis (NF1) is an autosomal dominant disorder, involving approximately until one subject every 2000 [1]
No associations among trabecular bone score (TBS) and 25OH-vitamin D (25OHD), age, low exercise, reduced sun exposure, Riccardi scale, and number of skin neurofibromas were observed by linear regression analysis
Several studies supported the accuracy of TBS analysis in the assessment of trabecular bone microarchitecture and fracture risk in different disorders, no data on TBS in neurofibromatosis type 1 (NF1) patients are available yet
Summary
Type 1 neurofibromatosis (NF1) is an autosomal dominant disorder, involving approximately until one subject every 2000 [1]. The NF1 gene is an oncosuppressor with 60 exons, spanning 350 kb on 17q11.2 region. It encodes for neurofibromin, an ubiquitously expressed protein involved in Marcello Filopanti and Uberta Verga contributed to this study. Neurofibromin is a member of the GTPase-activating protein gene family and can modulate adenylyl cyclase activity and protein kinase A (PKA), regulators of osteoblasts, and osteoclasts cell function. Decreased expression of neurofibromin is correlated with dose-dependent elevation of intracellular RAS-activity and increasing expression of intracellular signaling pathways, such as mitogen-activated protein kinase (MAPK), phosphatidil inositol-3-phosphate kinase (PI-3K), and decreasing expression of c-fos, a crucial regulator in osteoblast differentiation [3]
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