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.
Similar content being viewed by others
References
Gutmann DH, Aylsworth A, Carey JC, Korf B, Marks J, Pyeritz RE, Rubenstein A, Viskochil D (1997) The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA 278:51–57
Friedman JM (2002) Neurofibromatosis 1: clinical manifestations and diagnostic criteria. J Child Neurol 17:548–554
Crawford AH Jr, Bagamery N (1986) Osseous manifestations of neurofibromatosis in childhood. J Pediatr Orthop 6:72–88
Jacquemin C, Mullaney P, Bosley TM (2001) Abnormal development of the lesser wing of the sphenoid with microphthalmos and microcephaly. Neuroradiology 43:178–82
Friedman JM, Birch PH (1997) Type 1 neurofibromatosis: a descriptive analysis of the disorder in 1,728 patients. Am J Med Genet 70:138–143
Huson SM (1994) Neurofibromatoses 1: a pathogenetic and clinical overview. In: Huson SM, Hughes RAC (eds) The neurofibromatoses: a pathogenetic and clinical overview 7. Chapman & Hall Medical, London, pp 160–203
Poyhonen M (2000) A clinical assessment of neurofibromatosis type 1 (NF1) and segmental NF in northern Finland. J Med Genet 37:E43
Kim HW, Weinstein SL (1997) Spine update. The management of scoliosis in neurofibromatosis. Spine 22:2770–2776
Hefti F, Bollini G, Dungl P, Fixsen J, Grill F, Ippolito E, Romanus B, Tudisco C, Wientroub S (2000) Congenital pseudarthrosis of the tibia: history, etiology, classification, and epidemiologic data. J Pediatr Orthop B 9:11–15
Gutmann DH, Wood DL, Collins FS (1991) Identification of the neurofibromatosis type 1 gene product. Proc Natl Acad Sci U S A 88:9658–9662
Marchuk DA, Saulino AM, Tavakkol R, Swaroop M, Wallace MR, Andersen LB, Mitchell AL, Gutmann DH, Boguski M, Collins FS (1991) cDNA cloning of the type 1 neurofibromatosis gene: complete sequence of the NF1 gene product. Genomics 11:931–940
Daston MM, Scrable H, Nordlund M, Sturbaum AK, Nissen LM, Ratner N (1992) The protein product of the neurofibromatosis type 1 gene is expressed at highest abundance in neurons, Schwann cells, and oligodendrocytes. Neuron 8:415–428
Huynh DP, Nechiporuk T, Pulst SM (1994) Differential expression and tissue distribution of type I and type II neurofibromins during mouse fetal development. Dev Biol 161:538–551
Kuorilehto T, Nissinen M, Koivunen J, Benson MD, Peltonen J (2004) NF1 tumor suppressor protein and mRNA in skeletal tissues of developing and adult normal mouse and NF1-deficient embryos. J Bone Miner Res 19:983–989
Illes T, Halmai V, de Jonge T, Dubousset J (2001) Decreased bone mineral density in neurofibromatosis-1 patients with spinal deformities. Osteoporos Int 12:823–827
Cummings SR, Bates D, Black DM (2002) Clinical use of bone densitometry: scientific review. JAMA 288:1889–1897
Kanis JA, Melton LJ 3rd, Christiansen C, Johnston CC, Khaltaev N (1994) The diagnosis of osteoporosis. J Bone Miner Res 9:1137–1141
Poyhonen M, Kytola S, Leisti J (2000) Epidemiology of neurofibromatosis type 1 (NF1) in northern Finland. J Med Genet 37:632–636
Kujala UM, Kaprio J, Sarna S, Koskenvuo M (1998) Relationship of leisure-time physical activity and mortality: the Finnish twin cohort. JAMA 279:440–444
Heaney RP, Abrams S, Dawson-Hughes B, Looker A, Marcus R, Matkovic V, Weaver C (2000) Peak bone mass. Osteoporos Int 11:985–1009
Douchi T, Kuwahata R, Matsuo T, Uto H, Oki T, Nagata Y (2003) Relative contribution of lean and fat mass component to bone mineral density in males. J Bone Miner Metab 21:17–21
Gafni RI, Baron J (2004) Overdiagnosis of osteoporosis in children due to misinterpretation of dual-energy X-ray absorptiometry (DEXA). J Pediatr 144:253–257
Acknowledgements
We would like to thank the patients and their families for excellent cooperation and Oulu Deaconess Institute, Oulu, Finland. This study was supported by grants from the Cancer Society of Finland, Oulu University Hospital, grant # H01139, Academy of Finland and The Finnish Medical Foundation
Author information
Authors and Affiliations
Corresponding author
Additional information
T. Kuorilehto and M. Pöyhönen contributed equally to the study
Rights and permissions
About this article
Cite this article
Kuorilehto, T., Pöyhönen, M., Bloigu, R. et al. Decreased bone mineral density and content in neurofibromatosis type 1: Lowest local values are located in the load-carrying parts of the body. Osteoporos Int 16, 928–936 (2005). https://doi.org/10.1007/s00198-004-1801-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00198-004-1801-4