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|Title:||Prospective histomorphometric and DXA evaluation of bone remodeling in imatinib-treated CML patients: Evidence for site-specific skeletal effects|
|Citation:||Journal of Clinical Endocrinology and Metabolism, 2013; 98(1):67-76|
|Kate Vandyke, Stephen Fitter, Jenny Drew, Seiji Fukumoto, Christopher G. Schultz, Natalie A. Sims, David T. Yeung, Timothy P. Hughes, and Andrew C. W. Zannettino|
|Abstract:||CONTEXT: Imatinib is a tyrosine kinase inhibitor that has been successfully used to treat Philadelphia chromosome-positive chronic myeloid leukemia (CML) and Kit+ gastrointestinal stromal tumors. We have previously shown that imatinib therapy is associated with an increase in trabecular bone volume. OBJECTIVE: In the present study, we performed a prospective analysis of bone indices in imatinib-treated CML patients to determine the mechanism responsible for this altered bone remodeling. DESIGN, PATIENTS, AND INTERVENTION: This study assessed the effects of high-dose (600 mg/d) imatinib on bone parameters in newly diagnosed chronic-phase Philadelphia chromosome-positive CML patients (n = 11) enrolled in the TIDEL II study. At baseline and after 6, 12, and 24 months of treatment, serum markers of bone remodeling were quantitated, dual-energy x-ray absorptiometry analysis of bone mineral density (BMD) was carried out, and a bone biopsy was collected for histological and micro-computed tomography analysis. RESULTS: Our studies show that the increase in trabecular bone volume and trabecular thickness after imatinib treatment was associated with a significant decrease in osteoclast numbers, accompanied by a significant decrease in serum levels of a marker of osteoclast activity. In contrast, osteoblast numbers were not altered by up to 24 months of imatinib treatment. Notably, we also found that imatinib caused a site-specific decrease in BMD at the femoral neck. CONCLUSIONS: These data suggest that imatinib therapy dysregulates bone remodeling, causing a generalized decrease in osteoclast number and activity that is not counterbalanced by a decrease in osteoblast activity, leading to increased trabecular bone volume. Further long-term investigations are required to determine the causes and consequences of the site-specific decrease in BMD at the femoral neck.|
|Keywords:||Forearm; Bone and Bones; Femur Neck; Lumbar Vertebrae; Humans; Piperazines; Pyrimidines; Antineoplastic Agents; Protein Kinase Inhibitors; Absorptiometry, Photon; Bone Remodeling; Organ Specificity; Bone Density; Adult; Aged; Middle Aged; Female; Male; Leukemia, Myelogenous, Chronic, BCR-ABL Positive|
|Rights:||Copyright © 2013 by The Endocrine Society|
|Appears in Collections:||Medicine publications|
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