Decreased bone mineral density and content in neurofibromatosis type 1: Lowest local values are located in the load-carrying parts of the body

Abstract

Neurofibromatosis type 1 (NF1) is a dominantly inherited disease. Skeletal ailments such as short stature, kyphoscoliosis, tibial bowing and pseudarthrosis are common osseous manifestations of NF1. Previously, a correlation with scoliosis and decreased bone mineral density (BMD) of the lumbar spine has been reported in 12 NF1 patients. A total of 35 NF1 patients and 26 healthy controls were included in the present study. Of the participants over 20 years of age (26 NF1 patients and all controls) 14 were male and 12 were female, seven of whom were premenopausal. The controls were matched for age, sex and body mass index (BMI). Physical activity and medical history of NF1 patients were evaluated to screen the fractures and osseous manifestations of the disease and to rule out the factors that effect BMD. BMD and bone mineral content (BMC) were measured with DXA, using a total body program. The present study detected a lowered bone mineral density (p =0.028) and content (p <0.001) in NF1 patients of both sexes. The results of the present study also show that NF1 patients have an increased risk for osteoporosis. Among NF1 patients seven cases of osteoporosis and 13 cases of osteopenia were detected. In controls, one case of osteoporosis and 13 cases of osteopenia were detected. The location of the lowest local BMD was clustered to the load-carrying parts of the body in NF1 patients. Physical activity and the medical history of the NF1 patients did not explain the decreased BMD and BMC. The findings of the present and previous studies suggest that the pathogenesis of the osseous manifestations in NF1 may involve impaired development of the skeletal system and impaired maintenance of bone structure.

Neurofibromatosis 1

“…6,25 Orthopaedic problems Orthopaedic complications result from intrinsic defects of the skeletal system and from a disruption of bone structure maintenance. 29 Bone mineral density is decreased in Nf1 patients, mainly in the load bearing parts. Pseudoarthrosis, a false joint in a long bone, affects 2% of Nf1 patients.…”

Skeletal abnormalities in neurofibromatosis type 1: Approaches to therapeutic options

“…Decreased BMD in both sexes at an early age has been reported in up to 50% of individuals with NF1 [Illes et al, 2001;Kuorilehto et al, 2004b;Lammert et al, 2005;Dulai et al, 2007;Stevenson et al, 2007;Yilmaz et al, 2007;Brunetti-Pierri et al, 2008;Duman et al, 2008]. This may be related to an inadequate increase in bone remodeling observed by both bone histomorphometry and changes in circulating bone markers [Stevenson et al, 2008;Seitz et al, 2009].…”

Variable expression of neurofibromatosis 1 in monozygotic twins

“…There is increasing evidence from animal models and human data that the heterozygous NF1 state can cause generalized bone abnormalities such as osteopenia [Kuorilehto et al, 2004;Lammert et al, 2005;Stevenson et al, 2007;Brunetti-Pierri et al, 2008]. Other skeletal complications occur with a great deal of variability of expression; some such as tibial dysplasia/pseudarthrosis occur very rarely, with an incidence of only 3-5% of NF1 patients.…”