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Decreased Bone Turnover Despite Persistent Secondary Hyperparathyroidism during Prolonged Treatment with Imatinib

Departments of Medicine (S.O., A.H., D.W., K.C., G.G., A.G.) and Molecular Medicine and Pathology (F.P., P.B.), The University of Auckland, Auckland 1142, New Zealand; and Department of Medicine (P.E.), Western Hospital, The University of Melbourne, Parkville, Victoria 3050, Australia

Address all correspondence and requests for reprints to: Dr. O'Sullivan, Department of Medicine, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand. E-mail: s.osullivan{at}auckland.ac.nz.

Context: The tyrosine kinase inhibitor imatinib mesylate has an established role in the management of a number of malignant and proliferative conditions. Cross-sectional and short-term prospective studies have demonstrated secondary hyperparathyroidism during imatinib therapy, and variable changes in markers of bone turnover.

Objective: Our objective was to determine the biochemical and skeletal effects of imatinib during long-term therapy.

Design: This was a 2-yr prospective study.

Setting: The study was performed at an academic clinical research center.

Patients or Other Participants: Nine patients with bcr-abl positive chronic myeloid leukemia were included in the study.

Interventions: Patients received Imatinib mesylate 400 mg/d.

Main Outcome Measures: Serum and urine biochemistry, markers of bone turnover, and bone mineral density were measured.

Results: Participants developed mild secondary hyperparathyroidism, with significant decreases in serum calcium and phosphate (P < 0.05 and P < 0.0001 vs. baseline, respectively) and an increase in PTH (P < 0.0001 vs. baseline). Biochemical markers of bone turnover demonstrated a biphasic response, with an initial increase in markers of bone formation being followed by a decrease in markers of both formation and resorption. Bone density at the lumbar spine increased [mean (95% confidence interval) change from baseline 3.6% (1.6, 5.5); P = 0.003] as did that at the total body [1.4% (0.2, 2.5); P = 0.065], whereas that at the proximal femur did not change [–0.12% (–3.0, 2.7); P = 0.93]. Body weight and fat mass increased significantly (P < 0.0001 vs. baseline).

Conclusions: Long-term treatment with imatinib leads to persistent mild secondary hyperparathyroidism. Despite this, bone turnover is decreased, and bone density is stable or increased. Evaluation of the skeletal actions and safety of imatinib during longer-term therapy is warranted.

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