Abstract
Bone metabolism has been rarely investigated in children affected by Neurofibromatosis type 1 (NF1). Aim of the present study was to assess bone mineral metabolism in children and adults NF1 patients, to determine the relevant factors potentially involved in the development of reduced bone mineral density (BMD), and provide possible therapeutic intervention in NF1 patients. 114 NF1 patients and sex and age matched controls were enrolled into the study. Clinical and biochemical factors reflecting bone metabolism were evaluated. Factors potentially affecting BMD were also investigated including: physical activity, sun exposure, vitamin D intake. Whenever the presence of vitamin D deficiency was recorded, cholecalciferol supplementation was started and z-score data obtained at Dual-Energy X-ray Absorptiometry (DXA) during supplementation were compared with previous ones. NF1 patients showed lower Z-scores at Dual-Energy X-ray Absorptiometry DXA than controls. Physical activity was significantly reduced in NF1 patients than in controls. Sun exposure was significantly lower in NF1 compared to control subjects. At linear regression analysis vitamin D was the most predictive factor of reduced z-score at DXA (p = 0.0001). Cholecalciferol supplementation significantly increased BMD z-score (p < 0.001). We speculated that a combination of different factors, including reduced sun exposure, possibly associated with reduced serum vitamin D levels, and poor physical activity, concur to the impaired bone status in NF1 patients. We also demonstrated that treatment with vitamin D can be effective in improving z-score value in NF1 patients, including children. In conclusion, the findings of the current study are expected to have important implications for the follow-up and prevention of osteopenia/osteoporosis in this common genetic disease.
Highlights
Bone metabolism has been rarely investigated in children affected by Neurofibromatosis type 1 (NF1)
Patients presenting with cafe-au-lait macules (CALMs), axillary freckling, Lisch nodules (LN), dermal and/or nodular NFs, and non-progressive scoliosis were classified as “mild”, those presenting with plexiform NFs, bone abnormalities, precocious or progressive scoliosis were classified as “moderate”, and patients with learning disability/mental retardation, optic pathway glioma (OPG) and/or other neoplasms, and/or cerebrovascular disease were classified as “severe”. 114 individuals diagnosed with NF1 according to National Institutes of Health criteria[2] were enrolled into the study. 69 patients were females and 45 males
This study confirmed the presence of low bone mineral density (BMD) in NF1 patients, including children
Summary
Bone metabolism has been rarely investigated in children affected by Neurofibromatosis type 1 (NF1). Factors potentially affecting BMD were investigated including: physical activity, sun exposure, vitamin D intake. NF1 patients showed lower Z-scores at Dual-Energy X-ray Absorptiometry DXA than controls. We speculated that a combination of different factors, including reduced sun exposure, possibly associated with reduced serum vitamin D levels, and poor physical activity, concur to the impaired bone status in NF1 patients. Abbreviations 25OHD 25-Hydroxy vitamin D3 BMD Bone mineral density CALMs Cafe-au-lait macules CTX C-terminal cross-linking Telopeptide of type I collagen DXA Dual-energy X-ray absorptiometry LN Lisch nodules NF Neurofibromas NF1 Neurofibromatosis type 1 OC Osteocalcin OPG Optic pathway glioma. NF1 is caused by heterozygous mutations of the NF1 gene (chromosome 17q11.2) which contains 57 constitutive and 3 alternatively spliced exons[3] and encodes neurofibromin, a protein with tumor suppressor function, ubiquitously expressed and involved in pathways affecting cell growth and development of skeletal, cardiovascular, and nervous s ystems[4]. Most intragenic mutations are truncating or intragenic copy number changes, a smaller percentage are “in frame” v ariants[12]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
