Abstract | CONTEXT: 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.
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Authors | Kate Vandyke, Stephen Fitter, Jenny Drew, Seiji Fukumoto, Christopher G Schultz, Natalie A Sims, David T Yeung, Timothy P Hughes, Andrew C W Zannettino |
Journal | The Journal of clinical endocrinology and metabolism
(J Clin Endocrinol Metab)
Vol. 98
Issue 1
Pg. 67-76
(Jan 2013)
ISSN: 1945-7197 [Electronic] United States |
PMID | 23144472
(Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Benzamides
- Piperazines
- Protein Kinase Inhibitors
- Pyrimidines
- Imatinib Mesylate
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Topics |
- Absorptiometry, Photon
- Adult
- Aged
- Antineoplastic Agents
(pharmacology, therapeutic use)
- Benzamides
- Bone Density
(drug effects)
- Bone Remodeling
(drug effects, physiology)
- Bone and Bones
(diagnostic imaging, drug effects, pathology)
- Female
- Femur Neck
(diagnostic imaging, drug effects, pathology)
- Forearm
(diagnostic imaging, pathology)
- Humans
- Imatinib Mesylate
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
(diagnostic imaging, drug therapy, metabolism, physiopathology)
- Lumbar Vertebrae
(diagnostic imaging, drug effects, pathology)
- Male
- Middle Aged
- Organ Specificity
(drug effects)
- Piperazines
(pharmacology, therapeutic use)
- Protein Kinase Inhibitors
(pharmacology, therapeutic use)
- Pyrimidines
(pharmacology, therapeutic use)
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