Sarcopenia and preserved bone mineral density in paediatric survivors of high‐risk neuroblastoma with growth failure

Abstract

Background Survival from paediatric high‐risk neuroblastoma (HR‐NBL) has increased, but cis‐retinoic acid (cis‐RA), the cornerstone of HR‐NBL therapy, can cause osteoporosis and premature physeal closure and is a potential threat to skeletal structure in HR‐NBL survivors. Sarcopenia is associated with increased morbidity in survivors of paediatric malignancies. Low muscle mass may be associated with poor prognosis in HR‐NBL patients but has not been studied in these survivors. The study objective was to assess bone density, body composition and muscle strength in HR‐NBL survivors compared with controls. Methods This prospective cross‐sectional study assessed areal bone mineral density (aBMD) of the whole body, lumbar spine, total hip, femoral neck, distal 1/3 and ultradistal radius and body composition (muscle and fat mass) using dual‐energy X‐ray absorptiometry (DXA) and lower leg muscle strength using a dynamometer. Measures expressed as sex‐specific standard deviation scores (Z‐scores) included aBMD (adjusted for height Z‐score), bone mineral apparent density (BMAD), leg lean mass (adjusted for leg length), whole‐body fat mass index (FMI) and ankle dorsiflexion peak torque adjusted for leg length (strength‐Z). Muscle‐specific force was assessed as strength relative to leg lean mass. Outcomes were compared between HR‐NBL survivors and controls using Student's t‐test or Mann–Whitney U test. Linear regression models examined correlations between DXA and dynamometer outcomes. Results We enrolled 20 survivors of HR‐NBL treated with cis‐RA [13 male; mean age: 12.4 ± 1.6 years; median (range) age at therapy initiation: 2.6 (0.3–9.1) years] and 20 age‐, sex‐ and race‐matched controls. Height‐Z was significantly lower in HR‐NBL survivors compared with controls (−1.73 ± 1.38 vs. 0.34 ± 1.12, P < 0.001). Areal BMD‐Z, BMAD‐Z, FMI‐Z, visceral adipose tissue and subcutaneous adipose tissue were not significantly different in HR‐NBL survivors compared with controls. Compared with controls, HR‐NBL survivors had lower leg lean mass‐Z (−1.46 ± 1.35 vs. − 0.17 ± 0.84, P < 0.001) and strength‐Z (−1.13 ± 0.86 vs. − 0.15 ± 0.71, P < 0.001). Muscle‐specific force was lower in HR‐NBL survivors compared with controls (P < 0.05). Conclusions Bone mineral density and adiposity are not severely impacted in HR‐NBL survivors with growth failure, but significant sarcopenia persists years after treatment. Future studies are needed to determine if sarcopenia improves with muscle‐specific interventions in this population of cancer survivors.

Novel Insight into the Relationship Between Muscle-Fat and Bone in Type 2 Diabetes Ranging from Normal Weight to Obesity

“…Other studies 3 , 13 , 14 demonstrated that skeletal muscle improved bone health and fat was harmful to bone density, similar to our findings that SMM or FFM exhibited a linear positive correlation with BMD and BFM with a negative correlation with BMD ( Figure 3 ). Interestingly, the whole BFM further divided into trunk BFM and non-trunk BFM.…”

“…Further, few data are available on individuals with type two diabetes (T2DM), though the relationship between BMD and body composition has been widely discussed in children, the elderly and obesity. 3 , 13 , 14 This is in that fragility fractures have been recognized as a crucial diabetes complication. 15 Hence, and the novelty of our study is that we firstly observe the combined effect of muscle-fat on BMD with novel non-linear covariate-adjusted penalized spline generalized additive models (GAMs) in specific T2DM individuals.…”

Reference ranges for body composition indices by dual energy X-ray absorptiometry from the Bone Mineral Density in Childhood Study Cohort

“…[ 32 ] demonstrated the loss in appendicular LSTM Index in boys with Duchenne’s muscular dystrophy, and Guo et al. [ 36 ] reported more pronounced deficits in appendicular LSTM Index (compared to total LSTM Index) in survivors of neuroblastoma. Of note, we included reference ranges for total LSTM Index and subtotal LSTM Index in supplementary tables because appendicular LSTM may not be available to all clinicians or investigators.…”

Targeting Sarcopenia as an Objective Clinical Outcome in the Care of Children with Spinal Cord-Related Paralysis: A Clinician’s View

“…Predictive techniques: skinfold, bio-electric impedance analysis (BIA) [15]; ultrasound [16], creatine excretion [17], total or partial body potassium per fat-free soft tissue [18], and neutron activation [19] • Two-component techniques and models: dual-energy x-ray absorptiometry (DXA) (Figure 1) [20,21], air displacement plethysmography [22][23][24], deuterium dilution [25], computed tomography (CT) [21,26], and magnetic resonance imaging (MRI) [27,28].…”

“…Predictive techniques: skinfold, bio-electric impedance analysis (BIA) [15 sound [16], creatine excretion [17], total or partial body potassium per fattissue [18], and neutron activation [19] • Two-component techniques and models: dual-energy x-ray absorptiometr (Figure 1) [20,21], air displacement plethysmography [22][23][24], deuterium [25], computed tomography (CT) [21,26], and magnetic resonance imagin [27,28]. While in adults, Baumgartner et al [29] proposed using Dual-energy X-ray tiometry (DXA) and bioelectrical impedance analysis (BIA) as standardized me determine lean body mass, comparing values obtained to a normal referenced po (gender-specific young adult), no such methods are uniformly adopted for chil cause of ongoing changes in body composition during childhood [15].…”