Original Full Length ArticleDeficits in bone density and structure in children and young adults following Fontan palliation
Introduction
Over the four decades since its initial description, the Fontan operation has evolved as the final palliative procedure for various types of single ventricle heart disease. Through this total cavopulmonary connection, systemic venous blood flows passively to the lungs for oxygenation while the single ventricular mass supplies cardiac output to the body. Over the last 40 years, outcomes following the Fontan have improved dramatically. Surgical mortality is now less than 5% [1], [2], [3], [4], and transplant-free survival for the earliest Fontan patients is greater than 80% over a 15 to 20 year period [5]. As survival improves, focus has shifted toward the long-term consequences of this abnormal physiology characterized by elevated central venous pressure and often diminished cardiac output. These consequences are particularly important as there are now more adults than children living with congenital heart disease in the United States [6].
Fontan patients have multiple risk factors for poor growth, abnormal bone accrual, and muscle deficits, including hepatic dysfunction, vitamin D and other nutritional deficiencies, decreased weight-bearing activity, and treatment with medications including diuretics and anti-coagulants [7], [8]. Protein losing enteropathy (PLE) imposes additional risk factors; a recent report of 12 Fontan patients with PLE demonstrated a significant reduction in dual energy X-ray absorptiometry (DXA) areal bone mineral density (BMD) relative to age in association with glucocorticoid therapy and impaired growth [9].
While poor linear growth is well-documented in Fontan patients [10], [11], [12], [13], bone studies are otherwise limited to a case series of six Fontan patients, demonstrating significant deficits in distal radius volumetric BMD (vBMD) [14]. We recently demonstrated substantial growth failure and deficits in appendicular lean mass, as measured by whole body DXA, in 46 children and young adults following Fontan palliation [15]. As muscles increase during growth, bones adapt by increasing cortical dimensions, with lifelong implications for bone strength. Consistent with this functional muscle–bone unit, we have demonstrated that greater muscle mass, muscle strength, and physical activity during childhood and adolescence are independently associated with cortical bone acquisition as a consequence of greater periosteal expansion in healthy children and adolescents [16], [17]. The relationship between muscle deficits and cortical bone structure has not been addressed in the high-risk Fontan population.
Tibia peripheral quantitative computed tomography (pQCT) provides three-dimensional measures of trabecular and cortical vBMD (g/cm3) and cortical bone structure that are highly correlated with fracture load [18]. Additionally, pQCT provides measures of calf muscle and fat cross-sectional area (CSA). This technique represents an important advance over DXA measures that are subject to the confounding effects of poor growth on areal BMD (g/cm2) [19] and fail to distinguish between trabecular and cortical bone density and structure. The objectives of this pQCT study were to characterize vBMD, cortical structure, and the muscle–bone unit in children, adolescents and young adults after Fontan palliation, and to identify risk factors for musculoskeletal abnormalities.
Section snippets
Study subjects
Fontan participants > 5 years of age were prospectively enrolled in this cross-sectional study of growth, nutrition, body composition, and bone health from July 2011 through October 2013, as previously described [15]. Subjects were eligible if they had single ventricle physiology and had undergone Fontan palliation. Exclusion criteria included: pregnancy, Fontan baffle obstruction, single lung physiology, moderate to severe chronic kidney disease (estimated glomerular filtration rate < 60 mL/min/1.73 m
Subject characteristics
Table 1 summarizes the demographic and anthropometric characteristics of the 43 Fontan participants. Fontan participants had lower mean height Z-scores compared to reference participants (− 0.29 ± 1.00 vs. 0.25 ± 0.93, p < 0.001) and exhibited significantly delayed puberty, as previously described [15]. Fontan participants were older than reference participants within Tanner stages 2, 3, and 4, adjusted for sex and race (p < 0.001). BMI Z-scores did not differ in Fontan participants compared with
Discussion
This study demonstrates substantial deficits in trabecular vBMD, cortical structure, and muscle area in a population of children, adolescents, and young adults with Fontan physiology, compared to reference participants. The deficits in cortical dimensions were highly correlated with muscle deficits, consistent with our observations in multiple chronic diseases [24], [32], [33], [34], and remained significant after adjustment for these muscle deficits. This is the largest comprehensive
Acknowledgments
This study was funded by a Children's Hospital of Philadelphia Cardiac Center Grant and the Robert S. and Dolores Harrington Endowment in Pediatric Cardiology at The Children's Hospital of Philadelphia. NIH support included grants T32 HL007915 (CA), K23 HL089647 (KKW), and K24 DK076808 (MBL), and the Clinical and Translational Science Award UL1 RR024134 and UL1 TR000003.
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2019, Progress in Pediatric CardiologyCitation Excerpt :Both restrictive and obstructive lung disease have been demonstrated in a group of children undergoing screening for pulmonary processes [18]. There are also abnormalities in bone density [19] and calcium & vitamin D metabolism. Patients with Fontan physiology are at risk for chronic kidney disease, both related to serial episodes of acute kidney injury as well as chronic nephrotoxin exposure [20,21].
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Current affiliation: St. Christopher's Hospital for Children, 160 East Erie Avenue, Philadelphia, PA 19134, USA.