Altered bone and mineral metabolism in patients receiving imatinib mesylate Journal Article
| Authors: | Berman, E.; Nicolaides, M.; Maki, R. G.; Fleisher, M.; Chanel, S.; Scheu, K.; Wilson, B. A.; Heller, G.; Sauter, N. P. |
| Article Title: | Altered bone and mineral metabolism in patients receiving imatinib mesylate |
| Abstract: | BACKGROUND: Imatinib mesylate inhibits several tyrosine kinases, including BCR-ABL, the C-KIT receptor, and the platelet-derived growth factor receptors α and β, 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. Copyright © 2006 Massachusetts Medical Society. All rights reserved. |
| Keywords: | controlled study; middle aged; osteolysis; major clinical study; dose response; hypophosphatemia; chemical analysis; biological markers; imatinib; gastrointestinal stromal tumors; calcium; calcium blood level; calcitriol; pyrimidines; protein kinase inhibitors; vitamin d; collagen; protein-tyrosine kinases; ossification; bone and bones; piperazines; urinalysis; parathyroid hormone; parathyroid hormone blood level; bone remodeling; phosphate; phosphates; magnesium; amino terminal telopeptide; bone metabolism; calcium ion; phosphate blood level; 25 hydroxyvitamin d; leukemia, myeloid, chronic; alkaline phosphatase bone isoenzyme; osteocalcin; potassium dihydrogen phosphate; mineral metabolism; phosphate excretion |
| Journal Title: | New England Journal of Medicine |
| Volume: | 354 |
| Issue: | 19 |
| ISSN: | 0028-4793 |
| Publisher: | Massachusetts Medical Society |
| Date Published: | 2006-05-11 |
| Start Page: | 2006 |
| End Page: | 2013 |
| Language: | English |
| PUBMED: | 16687713 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 108" - "Export Date: 4 June 2012" - "CODEN: NEJMA" - "Source: Scopus" |
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