title: The generalized bone phenotype in children with neurofibromatosis 1: a sibling matched case-control study.
abstract: People with neurofibromatosis 1 (NF1) have low bone mineralization, but the natural history and pathogenesis are poorly understood. We performed a sibling-matched case-control study of bone mineral status, morphology, and metabolism. Eighteen children with NF1 without focal bony lesions were compared to unaffected siblings and local population controls. Bone mineral content at the lumbar spine and proximal femur (dual energy X-ray absorptiometry (DXA)) was lower in children with NF1; this difference persisted after adjusting for height and weight. Peripheral quantitative computed tomography (pQCT) of the distal tibia showed that trabecular density was more severely compromised than cortical. Peripheral QCT-derived estimates of bone strength and resistance to bending and stress were poorer among children with NF1 although there was no difference in fracture frequencies. There were no differences in the size or shape of bones after adjusting for height. Differences in markers of bone turnover between cases and controls were in the directions predicted by animal studies, but did not reach statistical significance. Average serum calcium concentration was higher (although within the normal range) in children with NF1; serum 25-OH vitamin D, and PTH levels did not differ significantly between cases and controls. Children with NF1 were less mature (assessed by pubertal stage) than unaffected siblings or population controls. Children with NF1 have a generalized difference of bone metabolism that predominantly affects trabecular bone. Effects of decreased neurofibromin on bone turnover, calcium homeostasis, and pubertal development may contribute to the differences in bone mineral content observed among people with NF1.
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada. llarmstrong@cw.bc.ca
authors.forename: Linlea
authors.initials: L
authors.lastname: Armstrong
authors.forename: Kimberly
authors.initials: K
authors.lastname: Jett
authors.forename: Patricia
authors.initials: P
authors.lastname: Birch
authors.forename: David L
authors.initials: DL
authors.lastname: Kendler
authors.forename: Heather
authors.initials: H
authors.lastname: McKay
authors.forename: Erica
authors.initials: E
authors.lastname: Tsang
authors.forename: David A
authors.initials: DA
authors.lastname: Stevenson
authors.forename: David A
authors.initials: DA
authors.lastname: Hanley
authors.forename: Deetria
authors.initials: D
authors.lastname: Egeli
authors.forename: Melonie
authors.initials: M
authors.lastname: Burrows
authors.forename: J M
authors.initials: JM
authors.lastname: Friedman
mesh_terms: D015502:Absorptiometry, Photon; D000293:Adolescent; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015519:Bone Density; D001842:Bone and Bones / Q000503:physiopathology*; D002118:Calcium / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging; D008297:Male; D009456:Neurofibromatosis 1 / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D010641:Phenotype; D012016:Reference Values; D012044:Regression Analysis; D035781:Siblings; D014057:Tomography, X-Ray Computed; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D002118:Calcium