Elsevier

Bone

Volume 77, August 2015, Pages 12-16
Bone

Original Full Length Article
Deficits in bone density and structure in children and young adults following Fontan palliation

https://doi.org/10.1016/j.bone.2015.04.012Get rights and content

Highlights

  • Patients with single ventricle heart disease are at risk for impaired bone accrual.

  • Quantitative CT was used to assess bone in Fontan participants and controls.

  • Fontan participants had lower trabecular density and smaller cortical dimensions.

  • Calf muscle area was also significantly lower in Fontan participants.

  • Lower muscle area was associated with smaller periosteal circumference.

Abstract

Background

Survival of patients with congenital heart disease has improved such that there are now more adults than children living with these conditions. Complex single ventricle congenital heart disease requiring Fontan palliation is associated with multiple risk factors for impaired bone accrual. Bone density and structure have not been characterized in these patients.

Methods

Tibia peripheral quantitative computed tomography (pQCT) was used to assess trabecular and cortical volumetric bone mineral density (vBMD), cortical dimensions, and calf muscle area in 43 Fontan participants (5–33 years old), a median of 10 years following Fontan palliation. pQCT outcomes were converted to sex- and race-specific Z-scores relative to age based on > 700 healthy reference participants. Cortical dimensions and muscle area were further adjusted for tibia length.

Results

Height Z-scores were lower in Fontan compared to reference participants (mean ± SD: − 0.29 ± 1.00 vs. 0.25 ± 0.93, p < 0.001); BMI Z-scores were similar (0.16 ± 0.88 vs. 0.35 ± 1.02, p = 0.1). Fontan participants had lower trabecular vBMD Z-scores (− 0.85 ± 0.96 vs. 0.01 ± 1.02, p < 0.001); cortical vBMD Z-scores were similar (− 0.17 ± 0.98 vs. 0.00 ± 1.00, p = 0.27). Cortical dimensions were reduced with lower cortical area (− 0.59 ± 0.84 vs. 0.00 ± 0.88, p < 0.001) and periosteal circumference (− 0.50 ± 0.82 vs. 0.00 ± 0.84, p < 0.001) Z-scores, compared to reference participants. Calf muscle area Z-scores were lower in the Fontan participants (− 0.45 ± 0.98 vs. 0.00 ± 0.96, p = 0.003) and lower calf muscle area Z-scores were associated with smaller periosteal circumference Z-scores (R = 0.62, p < 0.001). Musculoskeletal deficits were not associated with age, Fontan characteristics, parathyroid hormone or vitamin D levels.

Conclusions

Children and young adults demonstrate low trabecular vBMD, cortical structure and muscle area following Fontan. Muscle deficits were associated with smaller periosteal dimensions. Future studies should determine the fracture implications of these deficits and identify interventions to promote musculoskeletal development.

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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    Current affiliation: St. Christopher's Hospital for Children, 160 East Erie Avenue, Philadelphia, PA 19134, USA.

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