<p><strong>BACKGROUND: </strong>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.</p>

<p><strong>METHODS: </strong>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.</p>

<p><strong>RESULTS: </strong>We enrolled 20 survivors of HR-NBL treated with cis-RA [13 male; mean age: 12.4&nbsp;±&nbsp;1.6&nbsp;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&nbsp;±&nbsp;1.38 vs. 0.34&nbsp;±&nbsp;1.12, P&nbsp;&lt;&nbsp;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&nbsp;±&nbsp;1.35 vs. -&nbsp;0.17&nbsp;±&nbsp;0.84, P&nbsp;&lt;&nbsp;0.001) and strength-Z (-1.13&nbsp;±&nbsp;0.86 vs. -&nbsp;0.15&nbsp;±&nbsp;0.71, P&nbsp;&lt;&nbsp;0.001). Muscle-specific force was lower in HR-NBL survivors compared with controls (P&nbsp;&lt;&nbsp;0.05).</p>

<p><strong>CONCLUSIONS: </strong>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.</p>