Altered Bone and Mineral Metabolism in Patients Receiving Imatinib Mesylate
Open Access
- 11 May 2006
- journal article
- research article
- Published by Massachusetts Medical Society in New England Journal of Medicine
- Vol. 354 (19), 2006-2013
- https://doi.org/10.1056/nejmoa051140
Abstract
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. 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. 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. 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.Keywords
This publication has 24 references indexed in Scilit:
- Vitamin D deficiency: new perspectives on an old diseaseCurrent Opinion in Endocrinology, Diabetes and Obesity, 2004
- Imatinib as a Paradigm of Targeted TherapiesAdvances in Cancer Research, 2004
- Imatinib Compared with Interferon and Low-Dose Cytarabine for Newly Diagnosed Chronic-Phase Chronic Myeloid LeukemiaNew England Journal of Medicine, 2003
- Efficacy and Safety of a Specific Inhibitor of the BCR-ABL Tyrosine Kinase in Chronic Myeloid LeukemiaNew England Journal of Medicine, 2001
- Preanalytical Variability of Biochemical Markers of Bone TurnoverOsteoporosis International, 2000
- Application of a New Serum Assay for Type I Collagen Cross-Linked N-Telopeptides: Assessment of Diurnal Changes in Bone Turnover With and Without Alendronate TreatmentCalcified Tissue International, 1998
- The Parathyroid Hormone Circadian Rhythm Is Truly Endogenous--A General Clinical Research Center StudyJournal of Clinical Endocrinology & Metabolism, 1997
- An Introduction to the BootstrapPublished by Springer Science and Business Media LLC ,1993
- Severe hypophosphatemia in hospitalized patientsArchives of Internal Medicine, 1988
- The Effect of Anticonvulsant Therapy on Serum Levels of 25-Hydroxy-Vitamin D, Calcium, and Parathyroid HormoneJournal of Clinical Endocrinology & Metabolism, 1975