Effects of zoledronic acid on osteonecrosis and acute lymphoblastic leukemia treatment efficacy in preclinical models

Background Osteonecrosis is a devastating side effect of acute lymphoblastic leukemia (ALL) therapy. Associations between bone density loss and osteonecrosis have sparked interest in using bisphosphonates to reduce this complication. Procedure We assessed the impact of zoledronic acid (ZA) on the de...

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Bibliographic Details
Published in:Pediatric blood & cancer 2021-10, Vol.68 (10), p.e29183-n/a
Main Authors: Janke, Laura J., Kim, Jieun, Payton, Monique A., Jenkins, David A., Cai, Xiangjun, Finch, Emily R., Liu, Yiwei, Relling, Mary V., Karol, Seth E.
Format: Article
Language:English
Subjects:
Acute lymphoblastic leukemia
Animal models
Animals
Bisphosphonates
Bone Density
Bone Density Conservation Agents - therapeutic use
Bone loss
Chemotherapy
Computed tomography
Diphosphonates
Femur
Hematology
Imidazoles
Immunocompetence
Leukemia
Lymphatic leukemia
Mice
Oncology
Osteonecrosis
Osteonecrosis - diagnostic imaging
Osteonecrosis - drug therapy
Osteonecrosis - prevention & control
Pediatrics
Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy
Treatment Outcome
X-Ray Microtomography
Xenografts
Zoledronic acid
Zoledronic Acid - therapeutic use
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Summary:Background Osteonecrosis is a devastating side effect of acute lymphoblastic leukemia (ALL) therapy. Associations between bone density loss and osteonecrosis have sparked interest in using bisphosphonates to reduce this complication. Procedure We assessed the impact of zoledronic acid (ZA) on the development of osteonecrosis in murine models when used either throughout therapy (continuous administration) or late in therapy after vascular lesions have developed but before osteonecrosis has occurred. Effects on bone density were measured using microcomputed tomography (μCT)‐assessed tibial cortical thickness, while osteonecrosis was assessed histologically in the distal femur. Effects on antileukemic efficacy of chemotherapy were evaluated in both immunocompetent/syngeneic and patient‐derived xenograft (PDX) models. Results Continuous administration of ZA with chemotherapy prevented chemotherapy‐associated bone loss (p 
ISSN:1545-5009
1545-5017
DOI:10.1002/pbc.29183