Gera Sonia, Guo Michelle, Xie Yang, Pollock Netanya, Song Minkeun, Weber David R, Denburg Michelle, Zemel Babette, Mostoufi-Moab Sogol
Children's Hospital of Philadelphia, 3500 Civic Center Boulevard, 12th Floor, Philadelphia, PA 19104, USA.
Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA.
Bone. 2025 Jun;195:117468. doi: 10.1016/j.bone.2025.117468. Epub 2025 Mar 24.
Survival of children with high-risk neuroblastoma (HR-NBL) has increased with multimodal therapy. cis-Retinoic acid (cis-RA), cornerstone of HR-NBL therapy, can cause osteoporosis and premature physeal closure. This study utilized high-resolution peripheral quantitative computed tomography (HR-pQCT), for 3D measures of volumetric bone mineral density (BMD) and microarchitecture, to assess impact of HR-NBL therapy on skeletal structure.
We prospectively enrolled 20 HR-NBL survivors and 20 age-, sex-, and race-matched healthy reference participants. We assessed leg lean mass adjusted for leg length by DXA and strength using a Biodex dynamometer. Tibia bone microarchitecture was assessed via HR-pQCT scans at 4 % of tibia length and a cortical site at 30 %. We compared tibia length (cm), cortical and trabecular vBMD (mg HA/cm), geometric and structural parameters between groups. Linear regression models assessed group differences in bone microarchitecture adjusted for leg lean mass.
Compared to reference participants, tibia length was significantly shorter in HR-NBL survivors (31.6 cm [27.7,39.5] vs. 36.1 cm [30.4,40], p < 0.005), consistent with significantly lower height Z-score in the HR-NBL cohort (p < 0.001). HR-NBL survivors demonstrated lower cortical area (178.3mm [121.9273.5] vs. 214.6mm [159.4326.9], p < 0.05) and cortical perimeter (60.0 mm [51.9,82.5] vs. 68.8 mm [57.7,90.8], p < 0.01). After adjusting for tibia length, these differences were no longer significant. Total, cortical, and trabecular volumetric BMD, were not significantly different between groups. Cortical geometry and peak torque deficits were associated with muscle deficits when adjusted for leg lean mass (p < 0.001).
Bone density was not severely impacted in HR-NBL survivors. Muscle deficits persisted years after treatment and underscored cortical geometry deficits.
