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Early characteristics of bone deficits in children with Fontan palliation

Published online by Cambridge University Press:  20 February 2020

Kyriakie Sarafoglou ,
Anna Petryk ,
Pooja E. Mishra ,
Lynda E. Polgreen ,
Angela Panoskaltsis-Mortari ,
Roland Brown ,
Bradley S. Marino ,
David Gremmels ,
Charles Shepard  and
Aaron S. Kelly
...Show all authors
Kyriakie Sarafoglou
Affiliation:
Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA
Anna Petryk
Affiliation:
Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA
Pooja E. Mishra
Affiliation:
Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA
Lynda E. Polgreen
Affiliation:
The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
Angela Panoskaltsis-Mortari
Affiliation:
Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA
Roland Brown
Affiliation:
Division of Biostatistics, School of Public Health Biostatistical Design and Analysis Center, Clinical and Translational Science Institute, University of Minnesota, Minneapolis, MN, USA
Bradley S. Marino
Affiliation:
Department of Pediatrics, Northwestern University, Feinberg School of Medicine, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA
David Gremmels
Affiliation:
The Children’s Heart Clinic at Children’s Hospitals and Clinics of Minnesota, Minneapolis, MN, USA
Charles Shepard
Affiliation:
The Children’s Heart Clinic at Children’s Hospitals and Clinics of Minnesota, Minneapolis, MN, USA
Aaron S. Kelly
Affiliation:
Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA Department of Pediatrics, Center for Pediatric Obesity Medicine, University of Minnesota, Minneapolis, MN, USA
Bradley S. Miller
Affiliation:
Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA
Kyle Rudser
Affiliation:
Division of Biostatistics, School of Public Health Biostatistical Design and Analysis Center, Clinical and Translational Science Institute, University of Minnesota, Minneapolis, MN, USA
Courtney McCracken
Affiliation:
Department of Pediatrics, Emory University, Atlanta, GA, USA
Lazaros K. Kochilas*
Affiliation:
Department of Pediatrics, Emory University, Atlanta, GA, USA
*
Author for correspondence: L. Kochilas, MD, MSCR, Department of Pediatrics, Emory University, 1760 Haygood Drive, Health Sciences Research Building (HSRB), W-468, Atlanta, GA30322, USA. Tel: +1 404 694 1687; Fax: +770-488-9431. E-mail: [email protected]
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Abstract

Background:

This is a cross-sectional study aiming to understand the early characteristics and background of bone health impairment in clinically well children with Fontan circulation.

Methods:

We enrolled 10 clinically well children with Fontan palliation (operated >5 years before study entrance, Tanner stage ≤3, age 12.1 ± 1.77 years, 7 males) and 11 healthy controls (age 12.0 ± 1.45 years, 9 males) at two children’s hospitals. All patients underwent peripheral quantitative CT. For the Fontan group, we obtained clinical characteristics, NYHA class, cardiac index by MRI, dual x-ray absorptiometry, and biochemical studies. Linear regression was used to compare radius and tibia peripheral quantitative CT measures between Fontan patients and controls.

Results:

All Fontan patients were clinically well (NYHA class 1 or 2, cardiac index 4.85 ± 1.51 L/min/m2) and without significant comorbidities. Adjusted trabecular bone mineral density, cortical thickness, and bone strength index at the radius were significantly decreased in Fontan patients compared to controls with mean differences −30.13 mg/cm3 (p = 0.041), −0.31 mm (p = 0.043), and −6.65 mg2/mm4 (p = 0.036), respectively. No differences were found for tibial measures. In Fontan patients, the mean height-adjusted lumbar bone mineral density and total body less head z scores were −0.46 ± 1.1 and −0.63 ± 1.1, respectively, which are below the average, but within normal range for age and sex.

Conclusions:

In a clinically well Fontan cohort, we found significant bone deficits by peripheral quantitative CT in the radius but not the tibia, suggesting non-weight-bearing bones may be more vulnerable to the unique haemodynamics of the Fontan circulation.

Keywords

Fontan circulationperipheral quantitative CTbone mineral density
Type
Original Article
Information
Cardiology in the Young , Volume 30 , Issue 4 , April 2020 , pp. 468 - 475
Copyright
© The Author(s), 2020. Published by Cambridge University Press

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Footnotes

†

Current address: Alexion Pharmaceuticals, Inc., Boston, MA, USA

References

Oster, ME, Lee, KA, Honein, MA, Riehle-Colarusso, T, Shin, M, Correa, ATemporal trends in survival among infants with critical congenital heart defects. Pediatrics. 2013; 131: e1502–e1508.CrossRefGoogle ScholarPubMed
Anderson, PA, Sleeper, LA, Mahony, L, et al.Contemporary outcomes after the Fontan procedure: a Pediatric Heart Network multicenter study. J Am Coll Cardiol. 2008; 52: 85–98.CrossRefGoogle ScholarPubMed
Dennis, M, Zannino, D, du Plessis, K, et al.Clinical outcomes in adolescents and adults after the Fontan procedure. J Am Coll Cardiol. 2018; 71: 1009–1017.CrossRefGoogle ScholarPubMed
d’Udekem, Y, Iyengar, AJ, Galati, JC, et al.Redefining expectations of long-term survival after the Fontan procedure: twenty-five years of follow-up from the entire population of Australia and New Zealand. Circulation. 2014; 130:S32–S38.CrossRefGoogle ScholarPubMed
Khairy, P, Fernandes, SM, Mayer, JE Jr., et al.Long-term survival, modes of death, and predictors of mortality in patients with Fontan surgery. Circulation. 2008; 117: 85–92.CrossRefGoogle ScholarPubMed
Pundi, KN, Johnson, JN, Dearani, JA, et al.40-Year follow-up after the Fontan operation: long-term outcomes of 1,052 patients. J Am Coll Cardiol. 2015; 66:1700–1710.CrossRefGoogle ScholarPubMed
Avitabile, CM, Goldberg, DJ, Zemel, BS, et al.Deficits in bone density and structure in children and young adults following Fontan palliation. Bone. 2015; 77: 12–16.CrossRefGoogle Scholar
Bendaly, EA, DiMeglio, LA, Fadel, WF, Hurwitz, RABone density in children with single ventricle physiology. Pediatr Cardiol. 2015; 36: 779–785.CrossRefGoogle ScholarPubMed
Goldberg, DJ, Dodds, K, Avitabile, CM, et al.Children with protein-losing enteropathy after the Fontan operation are at risk for abnormal bone mineral density. Pediatr Cardiol. 2012; 33: 1264–1268.CrossRefGoogle ScholarPubMed
Witzel, C, Sreeram, N, Coburger, S, Schickendantz, S, Brockmeier, K, Schoenau, E.Outcome of muscle and bone development in congenital heart disease. Eur J Pediatr. 2006; 165: 168–174.CrossRefGoogle ScholarPubMed
D’Ambrosio, P, Tran, D, Verrall, CE, et al. Prevalence and risk factors for low bone density in adults with a Fontan circulation. Congenit Heart Dis. 2019.CrossRefGoogle Scholar
Khan, KM, Gonzalez-Bolanos, MT, Holm, T, Miller, BS, Sarafoglou, K.Use of automated bone age for critical growth assessment. Clin Pediatr (Phila). 2015; 54: 1038–1043.CrossRefGoogle ScholarPubMed
Kuczmarski, RJ, Ogden, CL, Grummer-Strawn, LM, et al.CDC growth charts: United States. Adv Data. 2000: 1–27.Google ScholarPubMed
Tanner, JM.Assessment of Skeletal Maturity and Prediction of Adult Height (TW2 method). Academic Press, London, 1975.Google Scholar
Greulich, WW, Pyle, SIRadiographic Atlas of Skeletal Development of the Hand and Wrist, 2nd edn. Stanford University Press, Stanford, CA, 1959.CrossRefGoogle Scholar
Steinberger, J, Daniels, SR, Hagberg, N, et al.Cardiovascular health promotion in children: challenges and opportunities for 2020 and beyond: a scientific statement from the American Heart Association. Circulation. 2016; 134: e236–e255.CrossRefGoogle ScholarPubMed
Zemel, BS, Leonard, MB, Kelly, A, et al.Height adjustment in assessing dual energy x-ray absorptiometry measurements of bone mass and density in children. J Clin Endocrinol Metab. 2010; 95: 1265–1273.CrossRefGoogle ScholarPubMed
Petryk, A, Polgreen, LE, Grames, M, Lowe, DA, Hodges, JS, Karachunski, PFeasibility and tolerability of whole-body, low-intensity vibration and its effects on muscle function and bone in patients with dystrophinopathies: a pilot study. Muscle Nerve 2017; 55: 875–883.CrossRefGoogle ScholarPubMed
Zemel, B, Bass, S, Binkley, T, et al.Peripheral quantitative computed tomography in children and adolescents: the 2007 ISCD Pediatric Official Positions. J Clin Densitom 2008; 11: 59–74.CrossRefGoogle ScholarPubMed
R Core Team. A language and environment for statistical computing. R Foundation for Statistical Computing 2013, http://www.R-project.org/.Google Scholar
King, MT, Stockler, MR, Cella, DF, et al.Meta-analysis provides evidence-based effect sizes for a cancer-specific quality-of-life questionnaire, the FACT-G. J Clin Epidemiol 2010; 63: 270–281.CrossRefGoogle ScholarPubMed
Singh, M, Brookes, M.Bone growth and blood flow after experimental venous ligation. J Anat 1971; 108: 315–322.Google ScholarPubMed
Fujimoto, H, Fujimoto, K, Ueda, A, Ohata, M.Hypoxemia is a risk factor for bone mass loss. J Bone Miner Metab 1999; 17: 211–216.CrossRefGoogle ScholarPubMed
Zahm, AM, Bucaro, MA, Srinivas, V, Shapiro, IM, Adams, CSOxygen tension regulates preosteocyte maturation and mineralization. Bone 2008; 43: 25–31.CrossRefGoogle ScholarPubMed
Arnett, TR, Gibbons, DC, Utting, JC, et al.Hypoxia is a major stimulator of osteoclast formation and bone resorption. J Cell Physiol 2003; 196: 2–8.CrossRefGoogle ScholarPubMed
Avgeri, M, Papadopoulou, A, Platokouki, H, et al.Assessment of bone mineral density and markers of bone turnover in children under long-term oral anticoagulant therapy. J Pediatr Hematol Oncol 2008; 30: 592–597.CrossRefGoogle ScholarPubMed
Mazziotti, G, Canalis, E, Giustina, A.Drug-induced osteoporosis: mechanisms and clinical implications. Am J Med 2010; 123: 877–884.CrossRefGoogle ScholarPubMed
Mahle, WT, Wernovsky, G, Bridges, ND, Linton, AB, Paridon, SM.Impact of early ventricular unloading on exercise performance in preadolescents with single ventricle Fontan physiology. J Am Coll Cardiol 1999; 34: 1637–1643.CrossRefGoogle ScholarPubMed
Cordina, R, O’Meagher, S, Gould, H, et al.Skeletal muscle abnormalities and exercise capacity in adults with a Fontan circulation. Heart 2013; 99: 1530–1534.CrossRefGoogle ScholarPubMed
Lee, D, Levin, A, Kiess, M, et al.Chronic kidney damage in the adult Fontan population. Int J Cardiol 2018; 257: 62–66.CrossRefGoogle ScholarPubMed
Cheng, HH, Carmona, F, McDavitt, E, et al.Fractures related to metabolic bone disease in children with congenital heart disease. Congenit Heart Dis. 2016; 11: 80–86.CrossRefGoogle ScholarPubMed
Borer, KT.Physical activity in the prevention and amelioration of osteoporosis in women : interaction of mechanical, hormonal and dietary factors. Sports Med. 2005; 35: 779–830.CrossRefGoogle ScholarPubMed
Frost, HM, Schonau, EThe “muscle-bone unit” in children and adolescents: a 2000 overview. J Pediatr Endocrinol Metab 2000; 13: 571–590.CrossRefGoogle ScholarPubMed
Szulc, P, Boutroy, S, Chapurlat, R.Prediction of fractures in men using bone microarchitectural parameters assessed by high-resolution peripheral quantitative computed tomography-the prospective STRAMBO Study. J Bone Miner Res 2018; 33: 1470–1479.CrossRefGoogle ScholarPubMed
Sornay-Rendu, E, Boutroy, S, Duboeuf, F, Chapurlat, RD.Bone microarchitecture assessed by HR-pQCT as predictor of fracture risk in postmenopausal women: the OFELY Study. J Bone Miner Res 2017; 32: 1243–1251.CrossRefGoogle ScholarPubMed
Vilayphiou, N, Boutroy, S, Sornay-Rendu, E, et al.Finite element analysis performed on radius and tibia HR-pQCT images and fragility fractures at all sites in postmenopausal women. Bone 2010; 46: 1030–1037.CrossRefGoogle ScholarPubMed
Denhardt, DT, Noda, M, O’Regan, AW, Pavlin, D, Berman, JSOsteopontin as a means to cope with environmental insults: regulation of inflammation, tissue remodeling, and cell survival. J Clin Invest 2001; 107: 1055–1061.CrossRefGoogle ScholarPubMed
Nagao, M, Feinstein, TN, Ezura, Y, et al.Sympathetic control of bone mass regulated by osteopontin. Proc Natl Acad Sci U S A 2011; 108: 17767–17772.CrossRefGoogle ScholarPubMed
Lambert, E, d’Udekem, Y, Cheung, M, et al.Sympathetic and vascular dysfunction in adult patients with Fontan circulation. Int J Cardiol 2013; 167: 1333–1338.CrossRefGoogle ScholarPubMed
Tromp, J, Khan, MAF, Mentz, RJ, et al.Biomarker Profiles of Acute Heart Failure Patients With a Mid-Range Ejection Fraction. JACC Heart Fail. 2017;5:507–517.CrossRefGoogle ScholarPubMed
Saiki, H, Eidem, BW, Ohtani, T, Grogan, MA, Redfield, MM.Ventricular-arterial function and coupling in the adult Fontan circulation. J Am Heart Assoc 2016; 5: e003887.CrossRefGoogle ScholarPubMed
Simonet, WS, Lacey, DL, Dunstan, CR, et al.Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 1997; 89: 309–319.CrossRefGoogle ScholarPubMed
Khosla, SMinireview: the OPG/RANKL/RANK system. Endocrinology 2001; 142: 5050–5055.CrossRefGoogle ScholarPubMed
Cheung, TF, Cheuk, KY, Yu, FW, et al.Prevalence of vitamin D insufficiency among adolescents and its correlation with bone parameters using high-resolution peripheral quantitative computed tomography. Osteoporos Int 2016; 27: 2477–2488.CrossRefGoogle ScholarPubMed
Yao, P, Bennett, D, Mafham, M, et al.Vitamin D and calcium for the prevention of fracture: a systematic review and meta-analysis. JAMA Netw Open 2019; 2: e1917789.CrossRefGoogle ScholarPubMed
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