Bone metabolism in patients with type 1 neurofibromatosis: key role of sun exposure and physical activity

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.

Endocrine system involvement in patients with RASopathies: A case series

“…However, additional factors that could contribute to the increased bone resorption markers (e.g., inactivity, hypotonia, and poor motor function) should be considered. Consistently, recent study confirms 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 ( 61 ).…”

“…Reduced BMD in presence of normal bone mineralization marker has previously been reported in NS ( 44 ). Low 25-OH vitamin D concentration has been documented in NF1 patients ( 60 , 61 ) and circumstantially in other RASopathies. However, no clear correlation between vitamin D levels and BMD was reported ( 45 ).…”

Vitamin D and Bone Metabolism in Adult Patients with Neurofibromatosis Type 1

“…This study provides an assessment of vitamin D levels and bone metabolism in a monocentric cohort of adult NF1 patients, analyzing potential correlations with clinical phenotype. Low levels of 25OHD in individuals with NF1 had already been reported [ 12 , 14 , 17 , 20 ] and treatment with vitamin D have been proven to be effective in improving DEXA data in NF1 young patients, including children [ 11 ]. Our results confirm and strengthen the evidence of a very high prevalence of low 25OHD levels in adult NF1 patients.…”

“…Conflicting data exists regarding calcium-phosphate metabolism in NF1 [ 11 , 20 , 33 ]. We did not find any statistically significant difference between patients and controls regarding the relationship between corrected calcium, PTH levels and low 25OHD.…”

“…Furthermore, bone manifestations in NF1 are frequent and may result in significant morbidity [ 10 ]. Consequently, the impairment of bone metabolism has emerged as a relevant issue, alongside with the role of vitamin D [ 11 ]. Diverse skeletal abnormalities, including scoliosis, are commonly described [ 10 ] and NF1 patients have a higher prevalence of osteoporosis and osteopenia than general population [ 12 , 13 , 14 ].…”