Abstract
In children with acute lymphoblastic leukemia (ALL), skeletal complications are well documented, but their exact origin remains unclear. In the present study we investigated bone mineralization density distribution by quantitative back-scattered electron imaging (qBEI) and bone histomorphometry by light microscopy in pediatric ALL patients at diagnosis, before any cancer treatment. In our one-center LELU study, we obtained bone marrow biopsies from the posterior iliac crest in 11 boys and 15 girls (median age 4.3; range 2.6–15.8 years) in connection with ALL diagnostic sampling. Blood samples were drawn for biochemistry and BMD was measured by DXA. Despite normal DXA-derived BMD, qBEI revealed undermineralization of bone matrix in our ALL-patient cohort. The average degree of mineralization was reduced (− 8%) and the proportion of lowly mineralized bone area was increased compared to pediatric reference values (+ 152%, both p < 0.0001). Bone histomorphometry revealed normal osteoid thickness, but markedly reduced osteoblast and eroded surface. Bone marrow fibrosis was observed in 24/26 samples. Neither BMD nor serum 25-OH-vitamin D correlated with bone matrix mineralization or histomorphometric parameters. In conclusion, our study showed a marked hypomineralization of the bone matrix in children at ALL diagnosis, prior to cancer treatment. These data suggest an early and significant impact of the ALL-disease process on bone homeostasis and material quality.