Bone Morbidity and Recovery in Children With Acute Lymphoblastic Leukemia: Results of a Six-Year Prospective Cohort Study

Abstract

Osteoporotic fractures are a significant cause of morbidity in acute lymphoblastic leukemia (ALL). Our objective was to determine the incidence and predictors of fractures and recovery from osteoporosis in pediatric ALL over 6 years following glucocorticoid initiation. 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 6 months for 4 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 2 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. 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. © 2018 American Society for Bone and Mineral Research.

Severity of reduced bone mineral density and risk of fractures in long‐term survivors of childhood leukemia and lymphoma undergoing guideline‐recommended surveillance for bone health

“…This is comparable to a prior study in 61 patients with ALL that found a 6‐fold greater risk of fracture compared with controls at the end of therapy but, in contrast to other studies, did not show an increased risk of fracture in survivors . A recent study by Ward et al restricted to vertebral fractures during the first 6 years post‐diagnosis found a significant association between low BMD and vertebral fractures, of which 71% occurred on therapy ≤2 years post‐diagnosis . Our study extends these findings to a longer follow‐up period and additional fracture sites.…”

“…21,22,44 A recent study by Ward et al restricted to vertebral fractures during the first 6 years post-diagnosis found a significant association between low BMD and vertebral fractures, of which 71% occurred on therapy ≤2 years post-diagnosis. 45 Our Cancer January 1, 2020 study extends these findings to a longer follow-up period and additional fracture sites. We considered that being underweight could be an independent risk factor for fracture separate from low BMD.…”

The Radiology of Osteoporotic Vertebral Fractures Revisited

“…In childhood, fractures often heal and the affected vertebrae may reshape and regain their original or near‐original configuration, if the threat to bone health is transient and there remains sufficient residual growth potential to effect complete or partial reshaping (because reshaping appears to be a growth‐dependent phenomenon). Pediatric radiologists may thus be afforded an advantage in that they are often provided with a retrospective “audit” of their diagnostic acumen . For diagnosis the observer may have to rely on morphometric criteria because ossification of the centrum is centripetal from a central ossification center in the centrum with mineralization only reaching the vertebral endplates in adolescence .…”

“…OVFs in children, usually due to glucocorticoid administration for serious diseases such as leukemia, chronic juvenile arthritis, renal disease, and Duchenne muscular dystrophy, among several others, require a separate understanding. (52)(53)(54)(55)(56) OVFs are a frequent manifestation of bone fragility in children, to the extent now that spine imaging for vertebral fracture detection is prioritized over BMD in the bone health assessment of at-risk children. (57,58) Routine monitoring in those at risk is paramount because OVFs in the young are frequently asymptomatic, similar to observations in at-risk adults.…”

“…Pediatric radiologists may thus be afforded an advantage in that they are often provided with a retrospective "audit" of their diagnostic acumen. (52,57,61,62) For diagnosis the observer may have to rely on morphometric criteria because ossification of the centrum is centripetal from a central ossification center in the centrum with mineralization only reaching the vertebral endplates in adolescence. (57) As a result, the ABQ methodology is of uncertain effectiveness related to plain-film radiography in children.…”