Skeletal morbidity in children receiving chemotherapy for acute lymphoblastic leukemia and its association with mineral homeostasis and duration of inpatient stay.

Background: Reduced activity, older age, and abnormal bone mineral status are considered as important determinants of poor bone health in children with acute lymphoblastic leukemia (ALL). The independent contribution of these factors toward skeletal morbidity (SM) requires further investigation.

Aim: The aim of this study was to investigate the influence of activity, age, and mineral status over the first 12 months of chemotherapy on subsequent SM.

Patients And Methods: The medical records of 56 children presenting with ALL between 2003 and 2007 and treated on UKALL2003 were reviewed for the number of inpatient days over the first 12 months of chemotherapy as a surrogate marker of inactivity and lack of well-being. Data for serum Ca, albumin, Mg, and Pho were also collected over this period. SM was defined as any episode of musculoskeletal pain or fractures.

Results: The median duration of inpatient days over the first 12 months of treatment in children with no SM was 58 days (40,100), whereas the median number of inpatient days during the first 12 months in those children with any SM, musculoskeletal pain only, or fractures only was 83 days (54,131), 81 days (52,119) and 91 days (59,158), respectively (P=0.003). Children with SM and fractures particularly had lower levels of serum Ca, Mg, and Pho compared with those without SM over the first 12 months of chemotherapy. There was a higher risk of SM in those who were diagnosed after the age of 8 years (P=0.001, odds ratio=16, 95% confidence interval: 3.80). Multiple regression analysis showed that the incidence of SM only had a significant independent association with age at diagnosis (P=0.001) and the number of inpatient days (P=0.03) over the first 12 months (r=23). All children who were diagnosed after the age of 8 years with an inpatient stay of more than 75 days, in the first 12 months of the chemotherapy (n,14) children had some form of SM (odds ratio=64).

Conclusions: The incidence of SM in children receiving chemotherapy for ALL is associated with a higher likelihood of being older and having longer periods of inpatient stay. The close link between age and changes in bone mineral status may be one explanation for the increased bone morbidity in ALL children.