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.
| Original language | English |
|---|---|
| Pages (from-to) | 1435-1443 |
| Number of pages | 9 |
| Journal | Journal of Bone and Mineral Research |
| Volume | 33 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 2018 |
Bibliographical note
Funding Information:This work was primarily supported by an operating grant from the Canadian Institutes for Health Research (CIHR) (FRN 64285). Additional funding for this work was provided to LMW by a CIHR New Investigator Award, a Canadian Child Health Clinician Scientist Career Enhancement Award, a University of Ottawa Research Chair Award, a Children’s Hospital of Eastern Ontario (CHEO) Research Institute Capacity Building Award, and the CHEO Departments of Pediatrics and Surgery. This work was also supported by the University of Alberta Women and Children’s Health Research Institute. The Canadian STOPP Consortium thanks the following individuals: The children and their families who participated in the study, the Research Associates who managed the study at the coordinating center as well as the Research Associates who recruited patients and managed the study at the various sites across Canada.
Funding Information:
This work was primarily supported by an operating grant from the Canadian Institutes for Health Research (CIHR) (FRN 64285). Additional funding for this work was provided to LMW by a CIHR New Investigator Award, a Canadian Child Health Clinician Scientist Career Enhancement Award, a University of Ottawa Research Chair Award, a Children's Hospital of Eastern Ontario (CHEO) Research Institute Capacity Building Award, and the CHEO Departments of Pediatrics and Surgery. This work was also supported by the University of Alberta Women and Children's Health Research Institute. The Canadian STOPP Consortium thanks the following individuals: The children and their families who participated in the study, the Research Associates who managed the study at the coordinating center as well as the Research Associates who recruited patients and managed the study at the various sites across Canada. The Canadian STOPP Consortium (a Pan-Canadian, Pediatric Bone Health Working Group): Principal Investigator: Leanne M. Ward (Children's Hospital of Eastern Ontario, Ottawa). Alberta Children's Hospital: Josephine Ho, Reinhard Kloiber, Victor Lewis, Julian Midgley, Paivi Miettunen, David Stephure; British Columbia Women's Hospital and Health Sciences, Vancouver: Brian C. Lentle; British Columbia Children's Hospital, Vancouver: Tom Blydt-Hansen, David Cabral, David B. Dix, Kristin Houghton, Helen R. Nadel; Brock University, St. Catharines: John Hay; Children's Hospital of Eastern Ontario, Ottawa: Janusz Feber, Jacqueline Halton, Roman Jurencak, Jinhui Ma, MaryAnn Matzinger, Johannes Roth, Nazih Shenouda, Karen Watanabe-Duffy; Children's Hospital, London Health Sciences Centre, University of Western Ontario, London: Elizabeth Cairney, Cheril Clarson, Guido Filler, Joanne Grimmer, Scott McKillop, Keith Sparrow, Robert Stein; IWK Health Center, Halifax: Elizabeth Cummings, Conrad Fernandez, Adam M. Huber, Bianca Lang, Kathy O'Brien: McMaster Children's Hospital, Hamilton: Steve Arora, Stephanie Atkinson, Ronald Barr, Craig Coblentz, Peter B. Dent, Maggie Larche; Montréal Children's Hospital, Montréal: Sharon Abish, Lorraine Bell, Claire LeBlanc, Anne Marie Sbrocchi, Rosie Scuccimarri; Ottawa Hospital Research Institute, Ottawa: David Moher, Monica Taljaard; Shriners Hospital for Children, Montréal: Frank Rauch; Ste. Justine Hospital, Montreal: Nathalie Alos, Josee Dubois, Caroline Laverdiere, Veronique Phan, Claire Saint-Cyr; Stollery Children's Hospital, Edmonton: Robert Couch, Janet Ellsworth, Jacob Jaremko, Kerry Siminoski, Beverly Wilson; Toronto Hospital for Sick Children, Toronto: Ronald Grant, Martin Charron, Diane Hebert; Université de Sherbrooke, Sherbrooke: Isabelle Gaboury; Winnipeg Children's Hospital, Winnipeg, Manitoba: Shayne Taback, Sara Israels, Kiem Oen, Maury Pinsk, Martin Reed, Celia Rodd. Authors’ roles: Study conception and design: LMW, B Lang, NA, MAM, NS, B Lentle, DS, CR, J Halton, SI, RMG, CVF, DBD, EAC, RC, EC, RB, SA, SAA, FR, DM, KS, and J Hay. Data analysis and interpretation: LMW, JM, MAM, NS, JLJ, B Lentle, FR, DM, KS, J Halton, J Ho and J Hay. Data acquisition: All authors. Recruitment of study participants: B Lang, J Halton, NA, BW, DS, RS, AMS, CR, VL, SI, RMG, CVF, DBD, EAC, RC, EC, RB, SA, and J Ho. Drafting of the manuscript: LMW and JM. Revising manuscript content: All authors. Approval of the final version of the submitted manuscript: All authors. All authors agree to be accountable for all aspects of the work. LMW is the Principal Investigator of the Canadian STOPP Study and supervised its conduct, data analysis, and data interpretation and takes responsibility for the integrity of the data analysis.
Publisher Copyright:
© 2018 American Society for Bone and Mineral Research
ASJC Scopus Subject Areas
- Endocrinology, Diabetes and Metabolism
- Orthopedics and Sports Medicine
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't
