Fractures in Children With Neurofibromatosis Type 1 From Two NF Clinics

Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
American Journal of Medical Genetics Part A (Impact Factor: 2.16). 05/2013; 161A(5). DOI: 10.1002/ajmg.a.35541
Source: PubMed


Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder with osseous abnormalities occurring in up to one-third of patients. Several studies have documented osteopenia in both children and adults with NF1; however, the significance of lower bone mineral density (BMD) in relationship to fracture incidence is not well elucidated in NF1, particularly in children. We undertook a retrospective study to determine prevalence and location of fractures in children and adolescents with NF1, ages 5-20 years, using a standardized questionnaire. We surveyed 256 individuals with NF1 from two multidisciplinary NF centers and 178 controls without NF1 of similar ages and sex. Participants with known long bone dysplasia (LBD) were analyzed separately. Data collected included numbers and location of fractures, dietary calcium intake, and physical activity levels. There was no difference in prevalence of ever having a fracture between the NF1 group without LBD (22%) and the control group (25%); median number of fractures also did not differ. There were significant differences in fracture location with a higher frequency of fractures of the lower extremities in NF1 individuals without LBD compared to controls. Both NF1 cohorts had lower rates of physical activity than controls (P < 0.0001). Our data demonstrate that the likelihood of having had a fracture is not higher in young NF1 individuals without LBD in comparison to healthy controls. The lower physical activity level may have a "protective effect" for those with NF1, thus keeping their fracture incidence lower than expected for their relative degree of osteopenia. © 2013 Wiley Periodicals, Inc.

15 Reads
  • Source

  • [Show abstract] [Hide abstract]
    ABSTRACT: This article is a selection of the most significant developments in the field of pediatric dermatology through an analysis of the articles published between October 2012 and October 2013. In the field of vascular anomalies, propranolol remains a topic of interest for infantile hemangiomas. New clinical concepts appear in the field of vascular malformations in parallel to genetic progress in this area. New epidemiological data or new pathophysiological concepts apply to atopic dermatitis. Congenital or atypical nevi of the child benefit from genetic progress or improvement of clinical knowledge. Although rare, melanoma of the child concerns by its increasing incidence and its misleadingclinical characteristics. Other data reported here relate to infectious skin of the child, morpheas, neurofibromatosis type 1, psoriasis and other commonly seen dermatoses in children.
    Annales de Dermatologie et de Vénéréologie 11/2013; 140 Suppl 3:S273-82. DOI:10.1016/S0151-9638(13)70143-1 · 0.92 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This is the first prospective follow-up study to describe the effects of oral alendronate medication on neurofibromatosis 1 (NF1)-related osteoporosis. NF1 is a neurocutaneous skeletal syndrome associated with increased fracture risk and high frequency of osteopenia and osteoporosis. Alendronate is a bisphosphonate drug which inhibits the function of bone-resorbing osteoclasts, ultimately leading to an increase in bone mineral density (BMD) and reduction in fracture risk. However, in vitro studies have shown that NF1 osteoclasts display insensitivity to apoptotic signals caused by bisphosphonates. Our aim was to monitor the effects of alendronate medication in patients with NF1. Five men and one woman, aged 28-76 years, with NF1-related osteoporosis were enrolled to the study. Study participants did not have other conditions and were not taking any medication known to affect bone. The medication included a weekly dose of 70 mg alendronate and a daily 20 μg vitamin D supplementation. After 23 months of follow-up, BMD was increased in five out of six patients, but the increase was not statistically significant. Serum levels of the bone turnover markers CTX and PINP were reduced, suggesting slower bone remodeling, as expected. An unexpected result was that serum levels of the osteoclast activity marker TRAP5b did not change during the follow-up. One new stress fracture of the tibia was documented during the alendronate therapy. Even though the study group was small, the findings of the current study (one new fracture and one patient with decreased BMD) call for a larger study to assess the efficacy of bisphosphonates in NF1-related osteoporosis.
    Calcified Tissue International 01/2014; 94(6). DOI:10.1007/s00223-013-9835-2 · 3.27 Impact Factor
Show more