Reductions in Bone Mineral Density Are Apparent Early in Children With Prevalent Osteonecrosis Lesions Following Leukemia Therapy

Jacqueline M Halton; Jinui Ma; Paul Babyn; Mary Ann Matzinger; Sue C Kaste; Maya Scharke; Conrad V Fernandez; Paivi Miettunen; Josephine Ho; Nathalie Alos; Sharon Abish; Ronald Barr; Elizabeth Cairney; David B Dix; Ronald M Grant; Sara Israels; Victor Lewis; Beverly Wilson; Stephanie Atkinson; David Cabral; Elizabeth Cummings; Celia Rodd; Robert Stein; Anne Marie Sbrocchi; Jacob L Jaremko; Khaldoun Koujok; Nazih Shenouda; Frank Rauch; Kerry Siminoski; Leanne M Ward; Canadian STOPP Consortium

doi:10.1002/jbmr.4870

Reductions in Bone Mineral Density Are Apparent Early in Children With Prevalent Osteonecrosis Lesions Following Leukemia Therapy

J Bone Miner Res. 2023 Aug;38(8):1104-1115. doi: 10.1002/jbmr.4870. Epub 2023 Jul 10.

Authors

Jacqueline M Halton¹, Jinui Ma², Paul Babyn³, Mary Ann Matzinger⁴, Sue C Kaste⁵, Maya Scharke⁶, Conrad V Fernandez⁷, Paivi Miettunen⁸, Josephine Ho⁸, Nathalie Alos⁹, Sharon Abish¹⁰, Ronald Barr¹¹, Elizabeth Cairney¹², David B Dix¹³, Ronald M Grant¹⁴, Sara Israels¹⁵, Victor Lewis⁸, Beverly Wilson¹⁶, Stephanie Atkinson¹¹, David Cabral¹³, Elizabeth Cummings⁷, Celia Rodd¹⁵, Robert Stein¹², Anne Marie Sbrocchi¹⁰, Jacob L Jaremko¹⁷, Khaldoun Koujok⁴, Nazih Shenouda⁴, Frank Rauch¹⁰, Kerry Siminoski¹⁷, Leanne M Ward¹; Canadian STOPP Consortium

Affiliations

¹ Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada.
² Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.
³ Department of Medical Imaging, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
⁴ Department of Medical Imaging, University of Ottawa, Ottawa, Ontario, Canada.
⁵ Department of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
⁶ The Ottawa Pediatric Bone Health Research Group, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
⁷ Department of Pediatric Hematology and Oncology, Dalhousie University, Halifax, Nova Scotia, Canada.
⁸ Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada.
⁹ Département de Pédiatrie, Université de Montréal, Montréal, Quebec, Canada.
¹⁰ Department of Pediatrics, McGill University, Montreal, Quebec, Canada.
¹¹ Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
¹² Department of Paediatrics, Western University, London, Ontario, Canada.
¹³ Department of Pediatrics, University of British Columbia, Vancouver, British of Columbia, Canada.
¹⁴ Department of Pediatrics, University of Toronto, Toronto, Canada.
¹⁵ Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada.
¹⁶ Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
¹⁷ Department of Radiology and Diagnostic Imaging, University of Alberta, Edmonton, Alberta, Canada.

PMID: 37326443
DOI: 10.1002/jbmr.4870

Abstract

Osteonecrosis (ON) is a serious complication of childhood acute lymphoblastic leukemia. We determined the prevalence of osteonecrotic lesions in our patient population by a one-time multisite magnetic resonance imaging (MRI) more than 1 year following leukemia therapy. MRI findings were evaluated in relationship to clinical factors (including longitudinal changes in bone mineral density [BMD]). Eighty-six children enrolled in the Steroid Associated Osteoporosis in the Pediatric Population (STOPP) study were evaluated for ON at 3.1 ± 1.3 years following therapy. Thirty children had a total of 150 confirmed ON lesions (35%). Lumbar spine (LS) BMD Z-scores (mean ± SD) were low at diagnosis and similar between patients with and without ON (-1.09 ± 1.53 versus -1.27 ± 1.25, p = 0.549). LS BMD Z-scores declined from baseline to 12 months in children with ON (-0.31 ± 1.02) but not in those without (0.13 ± 0.82, p = 0.035); the hip BMD Z-scores from baseline to 24 months declined in both groups, but to a greater extent in those with ON (-1.77 ± 1.22) compared to those without (-1.03 ± 1.07, p = 0.045). At the time of the MRI, mean total hip and total body (TB) BMD Z-scores were lower in children with ON (hip -0.98 ± 0.95 versus -0.28 ± 1.06, p = 0.010; TB -1.36 ± 1.10 versus -0.48 ± 1.50, p = 0.018). Pain occurred in 11/30 (37%) with ON versus 20/56 (36%) without, p = 0.841. In multivariable models, older age at diagnosis (odds ratio [OR] 1.57; 95% confidence interval [CI], 1.15-2.13; p = 0.004), and hip BMD Z-score at MRI (OR 2.23; 95% CI, 1.02-4.87; p = 0.046) were independently associated with ON. Overall, one-third of children demonstrated ON after leukemia therapy. Those with ON had greater reductions in spine and hip BMD Z-scores in the first 1 and 2 years of therapy, respectively. Older age and lower hip BMD Z-scores at MRI were significantly associated with prevalent, off-therapy ON. These data assist in identifying children at risk of ON. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Keywords: BONE MINERAL DENSITY; CHILDREN AND ADOLESCENTS; LEUKEMIA; MRI SCREENING; OSTEONECROSIS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Absorptiometry, Photon / methods
Bone Density
Child
Humans
Leukemia*
Lumbar Vertebrae
Osteonecrosis* / chemically induced
Osteonecrosis* / diagnostic imaging
Osteoporosis*

Grants and funding

FRN64285/CIHR/Canada