Dose-Related Effect of Chemotherapy on Bone Mineral Density Among Pediatric Acute Lymphoblastic Leukemia Survivors

Abstract

OBJECTIVES Reduced bone mineral density (BMD) can negatively affect lifelong skeletal health by ­increasing the risk for developing osteopenia and osteoporosis. This study evaluated the relationship between BMD and cumulative doses of intravenous (IV) methotrexate (MTX) and glucocorticoids in pediatric acute lymphoblastic leukemia (ALL) survivors. The association between BMD and vitamin D concentrations measured at the time of entry into the long-term follow-up program was also assessed. METHODS This retrospective study included pediatric ALL survivors who had received a dual-energy X-ray absorptiometry (DXA) scan after the end of therapy (EOT) or within the 6 months prior to the EOT. Low/­intermediate and high cumulative IV MTX doses were defined as doses less than 20,000 mg/m2 and ­greater than or equal to 20,000 mg/m2, respectively. Descriptive statistics, Student t test, and linear ­regression were used to analyze the data. RESULTS A total of 62 patients, with 34 patients in the low/intermediate and 28 patients in the high ­cumulative IV MTX dose groups, were analyzed. The median time from EOT to DXA scan was 2.3 years. The mean DXA lumbar spine z score was significantly lower in the high cumulative IV MTX dose group ­compared with the low/intermediate dose group (−0.86 vs −0.14; p = 0.008). Cumulative glucocorticoid doses and vitamin D concentrations were not associated with BMD. CONCLUSIONS Pediatric patients who had received cumulative IV MTX doses of greater than or equal to 20,000 mg/m2 during their ALL treatment had lower BMD than those who had received lower cumulative doses.