Skeletal morbidity in acute lymphoblastic leukemia of childhood: Effects on bone metabolism

Abstract

Background: We have previously shown that the majority of survivors treated for acute lymphoblastic leukemia (ALL) in childhood recovered their bone mineral density (BMD) despite disease effects and prolonged therapy with steroids and methotrexate. However, for a subset of patients who received higher total doses of methotrexate or prednisone, bone mass remained sub-optimal. This study’s objective was to determine whether altered bone turnover was reflected in profiles of bone biomarkers as a cause of their persistently reduced bone mass. Methods: Markers of bone metabolism were measured in 31 survivors of ALL with low BMD. The results were compared to 29 ALL survivors with normal BMD that were matched for gender, age and years since diagnosis. Blood samples obtained at the time of the scan by dual energy x-ray absorptiometry for BMD measure were assayed for 25-hydroxyvitamin D, parathyroid hormone (PTH), and serum CrossLaps. Results: No difference was found between survivors with low BMD and those with normal BMD for serum 25-OH Vitamin D, PTH or serum C-terminal telopeptide of type-1 collagen (CrossLaps). Vitamin D status was lower than accepted for normal bone health in 37% of subjects and 27% of controls. Conclusion: Survivors of childhood ALL as a whole recover normal BMD. Those that have low BMD after treatments do not have evidence of any permanent alterations in markers of bone turnover. Thus, survivors of childhood ALL who have low BMD likely do so for the same reasons as the general population, such as inadequate Vitamin D status.