Altered bone and mineral metabolism in patients receiving imatinib mesylate

Berman, E., Nicolaides, M., Maki, R. G., Fleisher, M., Chanel, S., Scheu, K., Wilson, B. A., Heller, G., Sauter, N. P. (May 2006) Altered bone and mineral metabolism in patients receiving imatinib mesylate. N Engl J Med, 354 (19). pp. 2006-13. ISSN 1533-4406 (Electronic)0028-4793 (Linking)

DOI: 10.1056/NEJMoa051140


BACKGROUND: Imatinib mesylate inhibits several tyrosine kinases, including BCR-ABL, the C-KIT receptor, and the platelet-derived growth factor receptors alpha and beta, all of which are associated with disease. We observed that hypophosphatemia developed in some patients with either chronic myelogenous leukemia or gastrointestinal stromal tumors who were receiving imatinib. METHODS: We identified 16 patients who had low serum phosphate levels and 8 patients who had normal serum phosphate levels, all of whom were receiving imatinib. We performed the following biochemical measurements: whole-blood levels of ionized calcium, plasma levels of intact parathyroid hormone, and serum levels of total calcium, phosphate, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, magnesium, and markers of bone formation (bone alkaline phosphatase and osteocalcin) and bone resorption (N-telopeptide of collagen cross-links); urinalysis; and phosphate, calcium, and creatinine levels in "spot" urine specimens. RESULTS: Patients in the low-phosphate group (median serum phosphate level, 2.0 mg per deciliter [0.6 mmol per liter]; normal level, >2.5 mg per deciliter [0.8 mmol per liter]) had elevated parathyroid hormone levels and low-to-normal serum calcium levels, were younger, and were receiving a higher dose of imatinib than patients in the normal-phosphate group (median level, 3.2 mg per deciliter [1.0 mmol per liter]). Both groups had high levels of phosphate excreted in the urine and markedly decreased serum levels of osteocalcin and N-telopeptide of collagen cross-links. CONCLUSIONS: Hypophosphatemia, with associated changes in bone and mineral metabolism, develops in a proportion of patients taking imatinib for either chronic myelogenous leukemia or gastrointestinal stromal tumors. The drug may inhibit bone remodeling (formation and resorption), even in patients with normal serum phosphate levels.

Item Type: Paper
Uncontrolled Keywords: Benzamides Biomarkers/blood Bone Remodeling/*drug effects/physiology Bone and Bones/metabolism Calcitriol/blood Calcium/blood Female Gastrointestinal Stromal Tumors/drug therapy Humans Hypophosphatemia/blood/*chemically induced Imatinib Mesylate Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy Male Middle Aged Osteocalcin/blood Parathyroid Hormone/blood Phosphates/blood Piperazines/*adverse effects/therapeutic use Protein Kinase Inhibitors/*adverse effects/therapeutic use Protein-Tyrosine Kinases/antagonists & inhibitors Pyrimidines/*adverse effects/therapeutic use Vitamin D/analogs & derivatives/blood
Subjects: diseases & disorders > bone diseses
diseases & disorders > cancer > drugs and therapies
diseases & disorders > cancer > cancer types > gastrointestinal stromal tumors
CSHL Authors:
Communities: CSHL labs > Maki lab
Depositing User: Matt Covey
Date: 11 May 2006
Date Deposited: 26 Oct 2016 19:50
Last Modified: 26 Oct 2016 19:50
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