CYSTIC FIBROSIS -RELATED BONE DISEASE
DOI:
https://doi.org/10.25753/BirthGrowthMJ.v22.i4.9893Keywords:
Children, cystic fibrosis related bone diseaseAbstract
Introduction: More than seven decades have passed since the first description of cystic fibrosis as a deadly childhood disease. Since then, progress has been made to extend the lives of these patients. As a consequence, children with cystic fibrosis are living into adulthood, which was once an unexpected outcome. Nevertheless, this increased survival brought new secondary complications as well as problems caused by the long -lasting medication. Cystic fibrosis -related bone disease is a recent but common complication in long -term survivors. Since its first description in 1979, a large number of papers have been published concerning the various areas of research around this secondary complication of cystic fibrosis.
Aims: This article attempts to review the literature related to several research areas around the cystic fibrosis -related bone disease summarizing the most relevant aspects of this problem.
Development: Throughout the article the authors emphasize knowledge about the epidemiology, pathophysiology and clinical aspects, and describe the most current recommendations for the diagnosis, prevention, treatment and monitoring of cystic fibrosis -related bone disease.
Conclusions: Multifactorial aetiology and interdependence and complexity of underlying pathological mechanisms stress the need and importance of monitoring patients with cystic fibrosis- -related bone disease in specialized centers that allow a multi- -and interdisciplinary integrated and differentiated follow -up.
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References
Barreto C. Fibrose quística. In: Sociedade Portuguesa de
Pneumologia, eds. Tratado de Pneumologia. 1ª ed. Lisboa:
Permanyer Portugal; 2003. p. 927 -43.
Southern KW, Munck A, Pollitt R, Travert G, Zanolla L,
Dankert -Roelse J, et al. A survey of newborn screening
for cystic fibrosis in Europe. J Cyst Fibros 2007; 6:57 -65.
doi:10.1016/j.jcf.2006.05.008
Farrell P. The prevalence of cystic fibrosis in the European
Union. J Cyst Fibros 2008; 7:450 -3. doi:10.1016/j.
jcf.2008.03.007
Cystic Fibrosis Foundation: Patient Registry 2006 Annual
Report [Internet]. [citado 2012 Jun 15]. Disponível em:
http://www.cff.org/UploadedFiles/research/ClinicalResearch/
%20Patient%20Registry%20Report.pdf
Cystic Fibrosis Foundation: Cystic Fibrosis Foundation 2010
Annual Report [Internet]. [citado 2012 Jun 15]. Disponível
em: http://www.cff.org/UploadedFiles/aboutCFFoundation/
AnnualReport/2010 -Annual -Report.pdf
Mischler EH, Chesney PJ, Chesney RW, Mazess RB. Demineralization
in cystic fibrosis detected by direct photon absorptiometry.
Am J Dis Child 1979; 133:632 -5.
Hahn TJ, Squires AE, Halstead LR, Strominger DB. Reduced
serum 25 -hydroxyvitamin D concentration and disordered
mineral metabolism in patients with cystic fibrosis. J Pediatr
; 94:38 -42. doi:10.1016/S0022 -3476(79)80346 -7
Elkin S. Arthritis, vasculitis and bone disease. In: Bush A, Alton
EWFW, Davies JC, Griesenbach U, Jaffe A, eds. Cystic
Fibrosis in the 21st Century. Progress in Respiratory Research.
Basel: Karger; 2006. Vol. 34. p. 270 -7.
Javier RM, Jacquot J. Bone disease in cystic fibrosis: What’s
new? Joint Bone Spine 2011; 78:445 -50. doi:10.1016/j.jbspin.
11.015
Sermet -Gaudelus I, Castanet M, Retsch -Bogart G, Aris RM.
Update on cystic fibrosis -related bone disease: a special
focus on children. Paediatr Respir Rev 2009; 10:134 -42.
doi:10.1016/j.prrv.2009.05.001
Sermet -Gaudelus I, Bianchi ML, Garabédian M, Aris RM,
Morton A, Hardin DS, et al. European cystic fibrosis bone
mineralisation guidelines. J Cyst Fibros 2011; 10:S16 -23.
doi:10.1016/S1569 -1993(11)60004 -0
Cystic Fibrosis Trust: Bone mineralisation in cystic fibrosis
[Internet]. [citado 2012 Jun 15]. Disponível em: http://www.
cftrust.org.uk/aboutcf/publications/consensusdoc/Bone-
-Mineral -Booklet.pdf
Aris RM, Merkel PA, Bachrach LK, Borowitz DS, Boyle
MP, Elkin SL, et al. Guide to bone health and disease in
cystic fibrosis. J Clin Endocrinol Metab 2005; 90:1888 -96.
doi:10.1210/jc.2004 -1629
Land C, Schoenau E. Fetal and postnatal bone development:
reviewing the role of mechanical stimuli and nutrition.
Best Pract Res Clin Endocrinol Metab 2008; 22:107 -18.
doi:10.1016/j.beem.2007.09.005
World Health Organization: Assessment of fracture risk and
its application to screening for postmenopausal osteoporosis:
report of WHO study group. [Internet]. [citado 2012 Jun 15].
Acessível em:http://whqlibdoc.who.int/trs/WHO_TRS_843.pdf
Reix P, Bellon G, Braillon P. Bone mineral and body composition
alterations in paediatric cystic fibrosis patients. Pediatr
Radiol 2010; 40:301 -8. doi:10.1007/s00247 -009 -1446 -8
Legroux -Gérot I, Leroy S, Prudhomme C, Perez T, Flipo
RM, Wallaert B, et al. Bone loss in adults with cystic fibrosis:
prevalence, associated factors, and usefulness of biological
markers. Joint Bone Spine 2012; 79:73 -7. doi:10.1016/j.jbspin.
05.009
Paccou J, Zeboulon N, Combescure C, Gossec L, Cortet
B. The prevalence of osteoporosis, osteopenia and fractures
among adults with cystic fibrosis: a systematic literature
review with meta -analysis. Calcif Tissue Int 2010; 86:1 -7.
doi:10.1007/s00223 -009 -9316 -9
Sermet -Gaudelus I, Souberbielle JC, Ruiz JC, Vrielynck S,
Heuillon B, Azhar I, et al. Low bone mineral density in young
children with cystic fibrosis. Am J Respir Crit Car Med 2007;
:951 -7. doi:10.1164/rccm.200606 -776OC
Caldeira RJ, Fonseca VM, Gomes Junior SC, Chaves CR.
Prevalence of bone mineral disease among adolescents with
cystic fibrosis. J Pediatr (Rio J) 2008; 84:18 -25. doi:10.2223/
JPED.1737
Gronowitz E, Garemo M, Lindblad A, Mellstrom D, Strandvik
B. Decreased bone mineral density in normal -growing
patients with cystic fibrosis. Acta Paediatr 2003; 92:688 -93.
doi:10.1111/j.1651 -2227.2003.tb00601.x
Ujhelyi R, Treszl A, Vasarhelyi B,Holics K, Tóth M, Arató
A, et al. Bone mineral density acquisition in children and
young adults with cystic fibrosis: a follow -up study. J Ped
Gastroenterol Nutr 2004; 38:401 -6. doi:10.1097/00005176-
-200404000 -00007
Bianchi ML, Romano G, Saraifoger S, Costantini D, Limonta
C, Colombo C. BMD and body composition in children and
young patients affected by cystic fibrosis. J Bone Miner Res
; 21:388 -96. doi:10.1359/JBMR.051106
Conway SP, Oldroyd B, Brownlee KG, Wolfe SP, Truscott
JG. A cross -sectional study of bone mineral density in children
and adolescents attending a Cystic Fibrosis Centre. J
Cyst Fibros 2008; 7:469 -76. doi:10.1016/j.jcf.2008.04.004
Grey V, Atkinson S, Drury D, Casey L, Ferland G, Gundberg
C, et al. Prevalence of low bone mass and deficiencies of
vitamins D and K in pediatric patients with cystic fibrosis
from 3 canadian centers. Pediatrics 2008; 122:1014 -20. doi:
1542/peds.2007 -2336
Laursen EM, Molgaard C, Michaelsen KF, Koch C, Muller J.
Bone mineral status in 134 patients with cystic fibrosis. Arch
Dis Child 1999; 81:235 -40. doi: 10.1136/adc.81.3.235
Mortensen LA, Chan GM, Alder SC, Marshall BC. Bone mineral
status in prepubertal children with cystic fibrosis. J Pediatr
; 136:648 -52. doi:10.1067/mpd.2000.104271
Sood M, Hambleton G, Super M, Fraser WD, Adams JE, Mughal
MZ. Bone status in cystic fibrosis. Arch Dis Child 2001;
:516 -20. doi:10.1136/adc.84.6.516
Hardin DS, Arumugam R, Seilheimer DK, LeBlanc A, Ellis KJ.
Normal bone mineral density in cystic fibrosis. Arch Dis Child
; 84:363 -8. doi:10.1136/adc.84.4.363
Buntain HM, Greer RM, Schluter PJ, Wong JC, Batch JA,
Potter JM, et al. Bone mineral density in australian children,
adolescents and adults with cystic fibrosis: a controlled cross
sectional study. Thorax 2004; 59:149 -55. doi:10.1136/thorax.
006726
Kelly A, Schall JI, Stallings VA, Zemel BS. Deficits in bone mineral
contents in children and adolescents with cystic fibrosis
are related to height deficits. J Clin Densitom 2008; 11:581 -9.
doi:10.1016/j.jocd.2008.07.002
Papaioannou A, Kennedy CC, Freitag A, O’Neill J, Pui M,
Ioannidis G, et al. Longitudinal analysis of vertebral fracture
and BMD in a Canadian cohort of adult cystic fibrosis patients.
BMC Musculoskelet Disord 2008; 9:125. doi:10.1186/1471-
-2474 -9 -125
Rovner AJ, Zemel BS, Leonard MB, Schall JI, Stallings VA.
Mild to moderate cystic fibrosis is not associated with increased
fracture risk in children and adolescents. J Pediatr 2005;
:327 -31. doi:10.1016/j.jpeds.2005.04.015
Buntain HM, Schluter PJ, Bell SC, Greer RM, Wong JC, Batch
J, et al. Controlled longitudinal study of bone mass accrual
in children and adolescents with cystic fibrosis. Thorax
; 61:146 -54. doi:10.1136/thx.2005.046516
Jacquot J, Tabary O, Clement A. Hyperinflammation in airways
of cystic fibrosis patients: what’s new? Expert Rev Mol
Diagn 2008; 8:359 -63. doi:10.1586/14737159.8.4.359
Haworth CS, Selby PL, Webb AK, Martin L, Elborn JS, Sharples
LD, et al. Inflammatory related changes in bone mineral
content in adults with cystic fibrosis. Thorax 2004; 59:613 -7.
doi:10.1136/thx.2003.012047
Shead EF, Haworth CS, Barker H, Bilton D, Compston JE.
Osteoclast function, bone turnover and inflammatory cytokines
during infective exacerbations of cystic fibrosis. J Cyst
Fibros 2010; 9:93 -8. doi:10.1016/j.jcf.2009.11.007
Ionescu AA, Evans WD, Pettit RJ, Nixon LS, Stone MD, Shale
DJ. Hidden depletion of fat -free mass and bone mineral
density in adults with cystic fibrosis. Chest 2003; 124:2220 -8.
doi:10.1378/chest.124.6.2220
Kawai M, Rosen CJ. Insulin -like growth factor -I and bone: lessons
from mice and men. Pediatr Nephrol. 2009; 24:1277 -85.
doi:10.1007/s00467 -008 -1040 -6
Hillman LS, Cassidy JT, Popescu MF, Hewett JE, Kyger J,
Robertson JD. Percent true calcium absorption, mineral metabolism,
and bone mineralization in children with cystic fibrosis:
effect of supplementation with vitamin D and calcium.
Pediatr Pulmonol 2008; 43:772 -80. doi:10.1002/art.23809
Schulze KJ, O’Brien KO, Germain -Lee EL, Baer D, Leonard
ALR, Rosenstein BR. Endogenous fecal losses of calcium
compromise calcium balance in pancreatic -insufficient girls
with cystic fibrosis. J Pediatr 2003; 143:765 -71. doi:10.1067/
S0022 -3476(03)00539 -0
Schulze KJ, Cutchins C, Rosenstein BJ,Germain -Lee EL,
O’BrienKO. Calcium acquisition rates do not support age-
-appropriate gains in total body mineral content in prepuberty
and late puberty in girls with cystic fibrosis. Osteoporos Int
; 17:731 -40. doi:10.1007/s00198 -005 -0041 -6
Borowitz D, Baker RD, Stallings V. Consensus report on
nutrition for pediatric patients with cystic fibrosis. J Pediatr
Gastroenterol Nutr 2002; 35:246 -59. doi:10.1097/01.
MPG.0000025580.85615.14
Hall WB, Sparks AA, Aris RM. Vitamin D deficiency
in cystic fibrosis. Int J Endocrinol 2010; 2010:218691.
doi:10.1155/2010/218691
Fewtrell MS, Benden C, Williams JE,Chomtho S, Ginty F,
Nigdikar SV,et al. Undercarboxylated osteocalcin and bone
mass in 8 -12 year old children with cystic fibrosis. J Cyst Fibr
; 7:307 -12. doi:10.1016/j.jcf.2007.11.006
Conway SP, Wolfe SP, Brownlee KG, White H, Oldroyd B,
Truscott JG,et al. Vitamin K status among children with cystic
fibrosis and its relationship to bone mineral density and
bone turnover. Pediatrics 2005; 115:1325 -31. doi:10.1542/
peds.2004 -1242
Dodd JD, Barry SC, Barry RB, Cawood TJ, McKenna MJ,
Gallagher CG. Bone mineral density in cystic fibrosis: benefit
of exercise capacity. J Clin Densitom 2008; 11:537 -42.
doi:10.1016/j.jocd.2008.05.095
Arrigo T, De Luca F, Lucanto C, Lombardo M, Rulli I, Salzano
G, et al. Nutritional, glycometabolic and genetic factors affecting
menarcheal age in cystic fibrosis. Diabetes Nutr Metab
; 17:114 -9.
Jin R, Hodges CA, Drumm ML, Palmert MR. The Cystic fibrosis
transmembrane conductance regulator (CFTR) modulates
the timing of puberty in mice. J Med Genet 2006; 43:e29.
doi:10.1136/jmg.2005.032839
Shead EF, Haworth CS, Condliffe AM, McKeon DJ, Scott MA,
Compston JE. Cystic fibrosis transmembrane conductance
regulator (CFTR) is expressed in human bone. Thorax 2007;
:650 -1. doi:10.1136/thx.2006.075887
Aris RM, Ontjes DA, Buell HE, Blackwood AD, Lark RK, Caminiti
M, et al. Abnormal bone turnover in cystic fibrosis adults.
Osteoporos Int 2002; 13:151 -7. doi:10.1007/s001980200007
Schoenau E, Land C, Stabrey A, Remer T, Kroke A. The
bone mass concept: problems in short stature. Eur J Endocrinol
; 151:S87 -91. doi:10.1530/eje.0.151S087
Fewtrell MS,British Paediatric & Adolescent Bone Group.
Bone densitometry in children assessed by dual X ray absorptiometry:
uses and pitfalls.Arch Dis Child 2003; 88:795 -8.
doi:10.1136/adc.88.9.795
American Academy of Pediatrics. Bone Densitometry in
Children and Adolescents. Pediatrics 2011; 127:189 -94.
doi:10.1542/peds.2010 -2961
National Osteoporosis Society: A practical guide to bone densitometry
in children[Internet]. [citado 2012 Jun 30]. Disponível
em: http://www.nos.org.uk/document.doc?id=851
Nicolaidou P, Stavrinadis I, Loukou I, Papadopoulou A, Georgouli
H, Douros K, et al. The effect of vitamin K supplementation
on biochemical markers of bone formation in children and
adolescents with cystic fibrosis. Eur J Pediatr 2006; 165:540-
-5. doi:10.1007/s00431 -006 -0132 -1
Hind K, Truscott JG, Conway SP. Exercise during childhood
and adolescence: A prophylaxis against cystic fibrosis-
-related low bone mineral density? Exercise for bone health
in children with cystic fibrosis. J Cyst Fibros 2008; 7:270 -6.
doi:10.1016/j.jcf.2008.02.001
Phillipi CA, Remmington T, Steiner RD. Bisphosphonate therapy
for osteogenesis imperfecta. Cochrane Database Syst
Rev 2008; 4:CD005088. doi:10.1002/14651858.CD005088.
pub2.
Conwell LS, Chang AB. Bisphosphonates for osteoporosis
in people with cystic fibrosis. Cochrane Database Syst Rev
; 4:CD002010. doi:10.1002/14651858.CD002010.pub3.
Phung OJ, Coleman CI, Baker EL, Scholle JM, Girotto JE,
Makanji SS, et al. Recombinant human growth hormone in
the treatment of patients with cystic fibrosis. Pediatrics 2010;
:e1211 -26. doi:10.1542/peds.2010 -2007
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