Bone Remodeling Markers in Children with Acute Lymphoblastic Leukemia after Intensive Chemotherapy: The Screenshot of a Biochemical Signature

Acute lymphoblastic leukemia (ALL) is the most frequent pediatric malignancy. The survival of ALL patients has reached a 90% 5-year survival rate, thanks to intensive chemotherapy regimens. Improved survival of ALL patients has led to an increase in long-term complications of chemotherapy, including adverse effects on bone, such as osteopenia/osteoporosis, osteonecrosis, and fragility fractures. Skeletal health depends on the balance between bone resorption and bone deposition, through bone remodeling coordinated by the nuclear factor kappa-B ligand (RANKL)/RANK/osteoprotegerin (OPG) and Wnt/fi-catenin pathways, respectively. There are no data on the effect of intensive chemotherapy on bone remodeling markers in ALL children. We investigated these effects and characterized the unknown biochemical signature of bone status in these patients. Our cohort of ALL children showed a biomarker profile of increased bone resorption and ineffective bone formation. This condition can expose them to the risk of osteopenia and increased bone fragility. Purpose: to investigate the effects of intensive chemotherapy and glucocorticoid (GC) treatment on bone remodeling markers in children with acute lymphoblastic leukemia (ALL). Methods: A cross-sectional study was carried out in 39 ALL children (aged 7.64 +/- 4.47) and 49 controls (aged 8.7 +/- 4.7 years). Osteoprotegerin (OPG), receptor activator of NF-kappa B ligand (RANKL), osteocalcin (OC), C-terminal telopeptide of type I collagen (CTX), bone alkaline phosphatase (bALP), tartrate-resistant acid phosphatase 5b (TRACP5b), procollagen type I N-terminal propeptide (P1NP), Dickkopf-1 (DKK-1), and sclerostin were assessed. Statistical analysis was conducted using the principal component analysis (PCA) to study patterns of associations in bone markers. Results: ALL patients showed significantly higher OPG, RANKL, OC, CTX, and TRACP5b than the controls (p <= 0.02). Considering ALL group, we found a strong positive correlation among OC, TRACP5b, P1NP, CTX, and PTH (r = 0.43-0.69; p < 0.001); between CTX and P1NP (r = 0.5; p = 0.001); and between P1NP and TRAcP (r = 0.63; p < 0.001). The PCA revealed OC, CTX, and P1NP as the main markers explaining the variability of the ALL cohort. Conclusions: Children with ALL showed a signature of bone resorption. The assessment of bone biomarkers could help identify ALL individuals who are most at risk of developing bone damage and who need preventive interventions.

Automated summary

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy with a 90% 5-year survival rate due to intensive chemotherapy. However, chemotherapy can negatively affect bone health, leading to conditions such as osteopenia and fragility fractures. This study aims to investigate the impact of intensive chemotherapy on bone remodeling in ALL children and identify biomarkers for bone damage.