In a Journal of Bone and Mineral Research study that followed 186 children with Acute Lymphoblastic Leukemia (ALL) for 6 years after initiation of chemotherapy, approximately 1 in 5 children experienced a non-vertebral fracture and 1 in 3 had a new vertebral fracture

Osteoporotic fractures are a significant cause of morbidity in acute lymphoblastic leukemia (ALL). Vertebral fractures were asymptomatic in 39 percent of the children, and approximately 25% persisted as vertebral deformities. Older children and those with more severe vertebral collapse were more likely to have the persistent vertebral deformity.

Vertebral fractures soon after diagnosis were strong predictors of both vertebral and non-vertebral fractures, and most of the fractures occurred in the first two years of treatment.

Vertebral fractures (VF) and vertebral body reshaping were assessed on annual spine radiographs, low?trauma non?VF were recorded at regular intervals, and spine bone mineral density (BMD) was captured every six months for four years and then annually.

A total of 186 children with ALL were enrolled (median age 5.3 years; range, 1.3 to 17.0 years). The cumulative fracture incidence was 32.5% for VF and 23.0% for non?VF; 39.0% of children with VF were asymptomatic. No fractures occurred in the sixth year, and 71.3% of incident fractures occurred in the first two years.

Baseline VF, cumulative glucocorticoid dose, and baseline lumbar spine (LS) BMD Z?score predicted both VF and non?VF. Vertebral body reshaping following VF was incomplete or absent in 22.7% of children.

Those with residual vertebral deformity following VF were older compared to those without (median age 8.0 years at baseline [interquartile range {IQR}, 5.5 to 9.4] versus 4.8 years [IQR, 3.6 to 6.2], p = 0.04) and had more severe vertebral collapse (median maximum spinal deformity index 3.5 [IQR, 1.0 to 8.0] versus 0.5 [IQR, 0.0 to 1.0], p = 0.01).

VF and low LS BMD Z?score at baseline, as well as glucocorticoid exposure, predicted incident VF and non?VF. Nearly 25% of children had persistent vertebral deformity following VF, more frequent in older children, and in those with more severe collapse. 

Outcome

These results suggest the need for trials addressing interventions in the first 2 years of chemotherapy, targeting older children and children with more severe vertebral collapse because these children are at greatest risk for incident VF and subsequent residual vertebral deformity.

In revealing that vertebral fractures are frequent in children with ALL on chemotherapy and that older children and those with more severe collapse are at risk for residual vertebral deformities, strategies to prevent vertebral fractures in those at greatest risk for permanent sequelae now merit further study," said lead author Dr. Leanne Ward, of Pediatrics Children's Hospital of Eastern Ontario.