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A Validated Risk Prediction Model for Bone Fragility in Children With Acute Lymphoblastic Leukemia |
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| Authors: | Emma J Verwaaijen Jinhui Ma Hester A de Groot-Kruseman Rob Pieters Inge M van der Sluis Jenneke E van Atteveld Jacqueline Halton Conrad V Fernandez Annelies Hartman Robert de Jonge Maarten H Lequin Mariël L te Winkel Nathalie Alos Stephanie A Atkinson Ronald Barr Ronald M Grant John Hay Adam M Huber Josephine Ho Jacob Jaremko Khaldoun Koujok Bianca Lang Mary-Ann Matzinger Nazih Shenouda Frank Rauch Celia Rodd Marry M van den Heuvel-Eibrink Saskia MF Pluijm Leanne M Ward The DCOG-ALL and Canadian STOPP Consortia |
| Institution: | 1. Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands;2. Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada
Contribution: Conceptualization, Data curation, Formal analysis, ?Investigation, Methodology, Supervision, Validation, Writing - original draft, Writing - review & editing;3. Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands Dutch Childhood Oncology Group, Utrecht, The Netherlands Contribution: Conceptualization, Data curation, ?Investigation, Writing - review & editing;4. Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands Contribution: Conceptualization, Data curation, ?Investigation, Supervision, Writing - review & editing;5. Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands Contribution: Data curation, ?Investigation, Writing - review & editing;6. Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada Contribution: ?Investigation, Writing - review & editing;7. Department of Pediatrics, Dalhousie University, Halifax, NS, Canada Contribution: Data curation, ?Investigation, Writing - review & editing;8. Department of Pediatric Physiotherapy, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands Contribution: Supervision, Writing - review & editing;9. Department of Clinical Chemistry, Academic Medical Center, Amsterdam, The Netherlands Contribution: Methodology, Writing - review & editing;10. Department of Radiology, University Medical Center, Amsterdam, The Netherlands Contribution: Data curation, Writing - review & editing;11. Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands Contribution: Data curation, Formal analysis, ?Investigation, Methodology, Writing - review & editing;12. Département de Pédiatrie, Université de Montréal, Montréal, QC, Canada Contribution: Data curation, ?Investigation, Writing - review & editing;13. Department of Pediatrics, McMaster University, Hamilton, ON, Canada Contribution: Data curation, ?Investigation, Writing - review & editing;14. Department of Pediatrics, University of Toronto, Toronto, ON, Canada Contribution: Data curation, ?Investigation, Writing - review & editing;15. Department of Health Sciences, Brock University, St. Catharines, ON, Canada Contribution: Data curation, ?Investigation, Methodology, Writing - review & editing;16. Department of Pediatrics, University of Calgary, Calgary, AB, Canada Contribution: Data curation, ?Investigation, Writing - review & editing;17. Department of Radiology & Diagnostic Imaging, University of Alberta, Edmonton, AB, Canada Contribution: Data curation, ?Investigation, Writing - review & editing;18. Department of Medical Imaging, University of Ottawa, Ottawa, ON, Canada Contribution: Data curation, ?Investigation, Writing - review & editing;19. Department of Pediatrics, McGill University, Montréal, QC, Canada;20. Department of Pediatrics, University of Manitoba, Winnipeg, MB, Canada Contribution: Data curation, ?Investigation, Methodology, Supervision, Writing - review & editing;21. Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands Contribution: Conceptualization, Data curation, Funding acquisition, ?Investigation, Methodology, Resources, Supervision, Writing - review & editing;22. Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands Contribution: Formal analysis, Methodology, Supervision, Writing - review & editing;23. Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada;24. Canadian Pediatric Bone Health Working Group, Ottawa, ON, Canada |
| 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 ≤ ?2.0) 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 = ?0.70) and age (β = ?0.10) 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 indicator for bone fragility, was successfully developed and validated. This can facilitate identification of future bone fragility in individual pediatric ALL patients. © 2021 American Society for Bone and Mineral Research (ASBMR). |
| Keywords: | BONE FRAGILITY BONE MINERAL DENSITY FRACTURE RISK PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA PREDICTION MODEL |