Objectives. To study bone mineral density (BMD) in cystic fibrosis (CF) children and adults with the CFTR I1234V mutation associated with pancreatic sufficiency. Methods. Lumbar spine, total hip, and whole-body mineral density were measured by dual-energy radiographic absorptiometry (DEXA) scan. Z score was used for those less than 21 years and T score was used for those 21 years or older. Results. Twenty-one CF patients were younger than 21 years and 5 CF patients were 21 years or older. Mean age was 17.29？±？4.95 years, ranging from 10 to 33 years. The mean BMD Z scores for patients younger than 21 years were ？0.69？±？0.96 (lumbar spine = L1–L4), ？0.48？±？0.92 (total hip), and ？0.38？±？0.86 (total body). The mean T scores for patients 21 years or older were 0.14？±？0.7 (L1–L4), 0.38？±？1 (total hip), and 0.52？±？1.03 (total body). BMD reduction less than ？1 was found in 7 (26.9%) CF patients. Vitamin D deficiency in 20 CF patients (76.9%) tended to be lower in CF patients with low BMD. BMD was significantly correlated with FEV1; however, no significant association was observed with P. aeruginosa colonization. Conclusion. BMD reduction does occur in patients with mild CFTR mutation associated with pancreatic sufficiency. 1. Introduction CF is one of the most common inherited diseases among Caucasians [1]. It is caused by mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a transmembrane glycoprotein [2, 3]. The CF transmembrane conductance regulator has been shown to function as a cyclic adenosine monophosphate- (cAMP-) regulated chloride channel at the apical membrane of epithelial cells [4]. One of the main consequences of mutations in the CFTR gene is a dysfunction of ion channels resulting in elevated sweat chloride concentrations, pancreatic insufficiency, and progressive lung disease [5]. Newly introduced therapies and aggressive management have led to a median expected survival age of 36 years [6]. However, new clinical problems that need to be identified and therapeutically addressed may become evident as the population ages. A number of reports have documented CF-related low BMD in both adults and children with CF [7–9]. CF-related bone disease (CFRBD) is multifactorial in etiology, primarily related to imbalanced bone deposition and resorption [10]. Other factors influencing CFRBD include low body mass index, vitamins D and K insufficiency, poor Ca2+ absorption and excessive Ca2+ secretion in the gastrointestinal tract, low levels of insulin-like growth factor 1, chronic bacterial infection with associated
References
[1]
F. Ratjen and G. D？ring, “Cystic fibrosis,” The Lancet, vol. 361, no. 9358, pp. 681–689, 2003.
[2]
J. Walkowiak, K.-H. Herzig, M. Witt et al., “Analysis of exocrine pancreatic function in cystic fibrosis: one mild CFTR mutation does not exclude pancreatic insufficiency,” European Journal of Clinical Investigation, vol. 31, no. 9, pp. 796–801, 2001.
[3]
D. N. Sheppard and M. J. Welsh, “Structure and function of the CFTR chloride channel,” Physiological Reviews, vol. 79, supplement 1, pp. S23–S45, 1999.
[4]
M. J. Welsh and A. E. Smith, “Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis,” Cell, vol. 73, no. 7, pp. 1251–1254, 1993.
[5]
D. J. Davidson and D. J. Porteous, “The genetics of cystic fibrosis lung disease,” Thorax, vol. 53, no. 5, pp. 389–397, 1998.
[6]
J. A. Dodge, P. A. Lewis, M. Stanton, and J. Wilsher, “Cystic fibrosis mortality and survival in the UK: 1947–2003,” European Respiratory Journal, vol. 29, no. 3, pp. 522–526, 2007.
[7]
D. T. Gibbens, V. Gilsanz, M. I. Boechat, D. Dufer, M. E. Carlson, and C. Wang, “Osteoporosis in cystic fibrosis,” The Journal of Pediatrics, vol. 113, no. 2, pp. 295–300, 1988.
[8]
L. K. Bachrach, C. W. Loutit, and R. B. Moss, “Osteopenia in adults with cystic fibrosis,” The American Journal of Medicine, vol. 96, no. 1, pp. 27–34, 1994.
[9]
R. C. Henderson and C. D. Madsen, “Bone density in children and adolescents with cystic fibrosis,” Journal of Pediatrics, vol. 128, no. 1, pp. 28–34, 1996.
[10]
T. J. Hahn, A. E. Squires, L. R. Halstead, and D. B. Strominger, “Reduced serum 25-hydroxyvitamin D concentration and disordered mineral metabolism in patients with cystic fibrosis,” Journal of Pediatrics, vol. 94, no. 1, pp. 38–42, 1979.
[11]
S. P. Conway, A. M. Morton, B. Oldroyd et al., “Osteoporosis and osteopenia in adults and adolescents with cystic fibrosis: prevalence and associated factors,” Thorax, vol. 55, no. 9, pp. 798–804, 2000.
[12]
R. M. Aris, P. A. Merkel, L. K. Bachrach et al., “Consensus statement: guide to bone health and disease in cystic fibrosis,” Journal of Clinical Endocrinology and Metabolism, vol. 90, no. 3, pp. 1888–1896, 2005.
[13]
I. Sermet-Gaudelus, M. L. Bianchi, M. Garabédian et al., “European cystic fibrosis bone mineralisation guidelines,” Journal of Cystic Fibrosis, vol. 10, no. 2, pp. S16–S23, 2011.
[14]
A. Abdul Wahab, G. Al Thani, S. T. Dawod, M. Kambouris, and M. Al Hamed, “Heterogeneity of the cystic fibrosis phenotype in a large kindred family in Qatar with cystic fibrosis mutation (I1234V),” Journal of Tropical Pediatrics, vol. 47, no. 2, pp. 110–112, 2001.
[15]
H. Banjar, M. Kambouris, B. F. Meyer, A. Al-Mehaidib, and I. Mogarri, “Geographic distribution of cystic fibrosis transmembrane regulator gene mutations in Saudi Arabia,” Annals of Tropical Paediatrics, vol. 19, no. 1, pp. 69–73, 1999.
[16]
M. R. Miller, J. Hankinson, V. Brusasco, et al., “ATS/ERS Task Force: standardisation of spirometry,” European Respiratory Journal, vol. 26, pp. 319–338, 2005.
[17]
R. J. Knudson, M. D. Lebowitz, C. J. Holberg, and B. Burrows, “Changes in the normal maximal expiratory flow-volume curve with growth and aging,” American Review of Respiratory Disease, vol. 127, no. 6, pp. 725–734, 1983.
[18]
E. Gronowitz, M. Garemo, A. Lindblad, D. Mellstr？m, and B. Strandvik, “Decreased bone mineral density in normal-growing patients with cystic fibrosis,” Acta Paediatrica, vol. 92, no. 6, pp. 688–693, 2003.
[19]
M. V. F. Donadio, G. C. de Souza, G. Tiecher et al., “Bone mineral density, pulmonary function, chronological age, and age at diagnosis in children and adolescents with cystic fibrosis,” Jornal de Pediatria, vol. 89, no. 2, pp. 151–157, 2013.
[20]
I. Sermet-Gaudelus, J. C. Souberbielle, J. C. Ruiz et al., “Low bone mineral density in young children with cystic fibrosis,” American Journal of Respiratory and Critical Care Medicine, vol. 175, no. 9, pp. 951–957, 2007.
[21]
K. Douros, I. Loukou, P. Nicolaidou, A. Tzonou, and S. Doudounakis, “Bone mass density and associated factors in cystic fibrosis patients of young age,” Journal of Paediatrics and Child Health, vol. 44, no. 12, pp. 681–685, 2008.
[22]
A. A. Wahab, A. Soliman, and M. O. A. Rahman, “Growth parameters and calcium homeostasis in cystic fibrosis patients with CFTR I1234V mutation,” Annals of Saudi Medicine, vol. 29, no. 6, pp. 487–488, 2009.
[23]
J. Robertson and K. MacDonald, “Prevalence of bone loss in a population with cystic fibrosis,” British Journal of Nursing, vol. 19, no. 10, pp. 636–639, 2010.
[24]
V. Grey, S. Atkinson, D. Drury et al., “Prevalence of low bone mass and deficiencies of vitamins D and K in pediatrics patients with cystic fibrosis from 3 Canadian centers,” Pediatrics, vol. 122, no. 5, pp. 1414–1020, 2008.
