Bone mineral density at diagnosis determines fracture rate in children with acute lymphoblastic leukemia treated according to the DCOG-ALL9 protocol

Abstract Purpose To elucidate incidence and risk factors of bone mineral density and fracture risk in children with Acute Lymphoblastic Leukemia (ALL). Methods Prospectively, cumulative fracture incidence, calculated from diagnosis until one year after cessation of treatment, was assessed in 672 patients. This fracture incidence was compared between subgroups of treatment stratification and age subgroups (Log-Rank test). Serial measurements of bone mineral density of the lumbar spine (BMD LS ) were performed in 399 ALL patients using dual energy X-ray absorptiometry. We evaluated risk factors for a low BMD (multivariate regression analysis). Osteoporosis was defined as a BMD LS  ≤ − 2 SDS combined with clinical significant fractures. Results The 3-year cumulative fracture incidence was 17.8%. At diagnosis, mean BMD LS of ALL patients was lower than of healthy peers (mean BMD LS  = − 1.10 SDS, P LS  = − 1.10 SDS, P LS  = − 1.27 SDS, P LS  = − 0.95 SDS, P LS at diagnosis. After correction for weight, height, gender and immunophenotype, stratification to the high risk (HR)-protocol arm and older age lead to a larger decline of BMD LS (HR group: β  = − 0.52, P β  = − 0.16, P LS during treatment than those without fractures. Treatment-related bone loss was similar in patients with and without fractures (respectively: ΔBMD LS  = − 0.36 SDS and ΔBMD LS  = − 0.12 SDS; interaction group time, P  = 0.30). Twenty of the 399 patients (5%) met the criteria of osteoporosis. Conclusion Low values of BMD LS at diagnosis and during treatment, rather than the treatment-related decline of BMD LS , determine the increased fracture risk of 17.8% in children with ALL.