Neurofibromatosis 1-Related Osteopenia Often Progresses to Osteoporosis in 12 Years
Tóm tắt
The current study is based on our earlier investigation carried out in 1999, where bone mineral density (BMD) of 35 neurofibromatosis type 1 (NF1) patients was measured and osteoporosis was shown to be common in NF1. The findings have been confirmed by a number of later publications. The purpose of the current longitudinal study was to assess the bone health of these 35 NF1 patients 12 years after the initial study. A total of 28 patients were reached, and BMD of 19 patients was subsequently remeasured. Fracture history of 28/35 NF1 patients who were reached was verified from the medical records. Six NF1 patients had osteoporosis in 1999, and three of them had an osteoporotic fracture between 1999 and 2011, showing an increased fracture risk compared to NF1 patients without osteoporosis. BMD of 19 patients was remeasured in 2011, and four patients who had osteopenia in 1999 had osteoporosis in 2011. The decrease in BMD was not explained by changes in smoking habits, physical activity, sunlight exposure, body mass index, or laboratory parameters, even though secondary hyperparathyroidism was common. Osteoporosis was found in 2011 in patients aged 37 years or older, both men and women. The results showed that NF1-related osteopenia often progresses to osteoporosis since BMD decreases with aging even in young patients. Even though our sample size was 19 patients, we recommend follow-up of NF1 patients with osteopenia and consideration of prophylactic measures to prevent osteoporosis and associated fracture risk.
Tài liệu tham khảo
Riccardi VM, Eichner JE (1992) Neurofibromatosis: phenotype, natural history and pathogenesis. Johns Hopkins University Press, Baltimore
Lammert M, Friedman J, Kluwe L, Mautner V (2005) Prevalence of neurofibromatosis 1 in German children at elementary school enrollment. Arch Dermatol 141:71–74
Jouhilahti EM, Peltonen S, Heape AM, Peltonen J (2011) The pathoetiology of neurofibromatosis 1. Am J Pathol 178:1932–1939
Xu G, O’Connell P, Viskochil D, Cawthon R, Robertson M, Culver M, Dunn D, Stevens J, Gesteland R, White R (1990) The neurofibromatosis type 1 gene encodes a protein related to GAP. Cell 62:599–608
Stumpf D, Annergers J, Brown S, Conneally P, Housman D, Leppert M, Miller J, Moss M, Pileggi A, Rapin I, Strohman R, Swanson L, Zimmersman A (1988) Neurofibromatosis. conference statement. National Institutes of Health Consensus Development Conference. Arch Neurol 45:575–578
Huson S (2008) The neurofibromatosis: classification, clinical features and genetic counselling. In: Kaufmann D (ed) Neurofibromatoses. Karger, Basel, pp 1–20
Friedman J, Riccardi VM (1999) Clinical and epidemiological features. In: Gutmann D, MacCollin M, Riccardi VM (eds) Neurofibromatosis: phenotype, natural history, and pathogenesis. John Hopkins University Press, Baltimore, pp 26–86
Heervä E, Koffert A, Jokinen E, Kuorilehto T, Peltonen S, Aro HT, Peltonen J (2012) A controlled register-based study of 460 neurofibromatosis 1 patients: increased fracture risk in children and adults over 41 years of age. J Bone Miner Res. doi:10.1002/jbmr.1685
Elefteriou F, Kolanczyk M, Schindeler A, Viskochil DH, Hock JM, Schorry EK, Crawford AH, Friedman JM, Little D, Peltonen J, Carey JC, Feldman D, Yu X, Armstrong L, Birch P, Kendler DL, Mundlos S, Yang FC, Agiostratidou G, Hunter-Schaedle K, Stevenson DA (2009) Skeletal abnormalities in neurofibromatosis type 1: approaches to therapeutic options. Am J Med Genet A 149:2327–2338
Evans DG, O’Hara C, Wilding A, Ingham SL, Howard E, Dawson J, Moran A, Scott-Kitching V, Holt F, Huson SM (2011) Mortality in neurofibromatosis 1: in North West England: an assessment of actuarial survival in a region of the UK since 1989. Eur J Hum Genet 19:1187–1191
Duong TA, Sbidian E, Valeyrie-Allanore L, Vialette C, Ferkal S, Hadj-Rabia S, Glorion C, Lyonnet S, Zerah M, Kemlin I, Rodriguez D, Bastuji-Garin S, Wolkenstein P (2011) Mortality associated with neurofibromatosis 1: a cohort study of 1895 patients in 1980–2006 in France. Orphanet J Rare Dis 6:18
NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy (2001) Osteoporosis prevention, diagnosis, and therapy. JAMA 285:785–795
Lewiecki EM, Gordon CM, Baim S, Binkley N, Bilezikian JP, Kendler DL, Hans DB, Silverman S, Bishop NJ, Leonard MB, Bianchi ML, Kalkwarf HJ, Langman CB, Plotkin H, Rauch F, Zemel BS (2008) Special report on the 2007 adult and pediatric position development conferences of the International Society for Clinical Densitometry. Osteoporos Int 19:1369–1378
Kuorilehto T, Pöyhönen M, Bloigu R, Heikkinen J, Väänänen K, Peltonen J (2005) 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
Brunetti-Pierri N, Doty SB, Hicks J, Phan K, Mendoza-Londono R, Blazo M, Tran A, Carter S, Lewis RA, Plon SE, Phillips WA, O’Brian Smith E, Ellis KJ, Lee B (2008) Generalized metabolic bone disease in neurofibromatosis type I. Mol Genet Metab 94:105–111
Seitz S, Schnabel C, Busse B, Schmidt HU, Beil FT, Friedrich RE, Schinke T, Mautner VF, Amling M (2010) High bone turnover and accumulation of osteoid in patients with neurofibromatosis 1. Osteoporos Int 21:119–127
Tucker T, Schnabel C, Hartmann M, Friedrich RE, Frieling I, Kruse HP, Mautner VF, Friedman JM (2009) Bone health and fracture rate in individuals with neurofibromatosis 1 (NF1). J Med Genet 46:259–265
Stevenson DA, Moyer-Mileur LJ, Murray M, Slater H, Sheng X, Carey JC, Dube B, Viskochil DH (2007) Bone mineral density in children and adolescents with neurofibromatosis type 1. J Pediatr 150:83–88
Heervä E, Peltonen S, Svedström E, Aro HT, Väänänen K, Peltonen J (2012) Osteoclasts derived from patients with neurofibromatosis 1 (NF1) display insensitivity to bisphosphonates in vitro. Bone 50:798–803
Pöyhönen M, Kytölä 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
Vasikaran S, Eastell R, Bruyère O, Foldes AJ, Garnero P, Griesmacher A, McClung M, Morris HA, Silverman S, Trenti T, Wahl DA, Cooper C, Kanis JA, Group I-IBMSW (2011) Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int 22:391–420
