Prospective histomorphometric and DXA evaluation of bone remodeling in imatinib-treated CML patients: Evidence for site-specific skeletal effects

Kate Vandyke, Stephen Fitter, Jenny Drew, Seiji Fukumoto, Christopher G. Schultz, Natalie A. Sims, David T. Yeung, Timothy P. Hughes, Andrew C W Zannettino

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18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)67-76
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume98
Issue number1
DOIs
Publication statusPublished or Issued - Jan 2013

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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