A Validated Risk Prediction Model for Bone Fragility in Children With Acute Lymphoblastic Leukemia

Abstract

Although bone fragility may already be present at diagnosis of pediatric acute lymphoblastic leukemia (ALL), routine performance of dual-energy X-ray absorptiometry (DXA) in every child is not universally feasible. The aim of this study was to develop and validate a risk prediction model for low lumbar spine bone mineral density (LS BMD Z-score ≤ À2.0) at diagnosis, as an important indicator for fracture risk and further treatment-related BMD aggravation. Children with ALL (4-18 years), treated according to the Dutch Childhood Oncology Group protocol (DCOG-ALL9; model development; n = 249) and children from the Canadian Steroid-Associated Osteoporosis in the Pediatric Population cohort (STOPP; validation; n = 99) were included in this study. Multivariable logistic regression analyses were used to develop the prediction model and to confirm the association of low LS BMD at diagnosis with symptomatic fractures during and shortly after cessation of ALL treatment. The area under the receiver operating characteristic curve (AUC) was used to assess model performance. The prediction model for low LS BMD at diagnosis using weight (β = À0.70) and age (β = À0.10) at diagnosis revealed an AUC of 0.71 (95% CI, 0.63-0.78) in DCOG-ALL9 and 0.74 (95% CI, 0.63-0.84) in STOPP, and resulted in correct identification of 71% of the patients with low LS BMD. We confirmed that low LS BMD at diagnosis is associated with LS BMD at treatment cessation (OR 5.9; 95% CI, 3.2-10.9) and with symptomatic fractures (OR 1.7; 95% CI, 1.3-2.4) that occurred between diagnosis and 12 months following treatment cessation. In meta-analysis, LS BMD at diagnosis (OR 1.6; 95% CI, 1.1-2.4) and the 6-month cumulative glucocorticoid dose (OR 1.9; 95% CI, 1.1-3.2) were associated with fractures that occurred in the first year of treatment. In summary, a prediction model for identifying pediatric ALL patients with low LS BMD at diagnosis, as an important

Safety and Efficacy of Alendronate to Treat Osteopenia in Children During Therapy for Acute Lymphoblastic Leukemia: A Retrospective Cohort Study of Sequential Outcomes

“…A recent Dutch-Canadian collaborative study has demonstrated the predictive value of age and weight at diagnosis in relation to LS aBMD and to subsequent development of symptomatic fractures in children with ALL, 43 complementing our established practice of HAW correction of Z scores for aBMD of the lumbar spine. 27 The results of bone morphometry and measures of bone strength, determined by peripheral quantitative computed tomography (pQCT) 44 in our study of long-term survivors of ALL (more than 10 y from diagnosis), have been reported separately.…”

“…The results in the small number of subjects (n=9) reported here, who were studied more than a decade after diagnosis, are intriguing, being suggestive of late improvement in LS aBMD, but longitudinal examination of a larger cohort will be required to evaluate this observation. A recent Dutch-Canadian collaborative study has demonstrated the predictive value of age and weight at diagnosis in relation to LS aBMD and to subsequent development of symptomatic fractures in children with ALL,43 complementing our established practice of HAW correction of Z scores for aBMD of the lumbar spine 27…”

Epidemiological Trends in Pediatric Osteoporosis

“…Future fractures are substantially predicted by VFs in the first two years following diagnosis. In order to identify asymptomatic VFs, forecast future fracture risk, prevent vertebral abnormalities, and reduce long-term morbidity, lateral spine imaging is advised for up to 45% of children with VFs [18]. A paediatric bone specialist must monitor Duchenne muscular dystrophy patients due to immobility, extended steroid use, and hypogonadism [19].…”

Osteoporosis in children and adolescents: when to suspect and how to diagnose it

“…The risk of fractures is the highest in the first two years of diagnosis and the presence of VFs at diagnosis is highly predictive of future fractures. Up to 45% of children presenting with VFs at the diagnosis can be asymptomatic; therefore, lateral spine imaging is advised to detect asymptomatic VFs, predict the risk of future fractures, and prevent vertebral deformities and long-term morbidity [ 58 – 60 ].…”