Title: Prospective Histomorphometric and DXA Evaluation of Bone Remodeling in Imatinib-Treated CML Patients: Evidence for Site-Specific Skeletal Effects
Authors: Vandyke, K
Fitter, S
Drew, J
Fukumoto, S
Schultz, CG
Sims, NA
Yeung, DT
Hughes, TP
Zannettino, ACW
Issue Year: 2013
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. (J Clin Endocrinol Metab 98: 67-76, 2013)
URI: https://publications.svi.edu.au/publications/1665
Other Identifiers 10.1210/jc.2012-2426
Publication type Article
Grant ID GNT1019703
Find it online http://press.endocrine.org/doi/10.1210/jc.2012-2426?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed