Altered Bone and Mineral Metabolism in Patients Receiving Imatinib Mesylate
Ellin Berman, M.D., Maria Nicolaides, M.D., Robert G. Maki, M.D., Ph.D., Martin Fleisher, Ph.D., Suzanne Chanel, R.N., Kelly Scheu, R.N., Bri-Anne Wilson, B.A., Glenn Heller, Ph.D., and Nicholas P. Sauter, M.D.
Background Imatinib mesylate inhibits several tyrosine kinases,including BCR-ABL, the C-KIT receptor, and the platelet-derivedgrowth factor receptors and , all of which are associated withdisease. We observed that hypophosphatemia developed in somepatients with either chronic myelogenous leukemia or gastrointestinalstromal tumors who were receiving imatinib.
Methods We identified 16 patients who had low serum phosphatelevels and 8 patients who had normal serum phosphate levels,all of whom were receiving imatinib. We performed the followingbiochemical measurements: whole-blood levels of ionized calcium,plasma levels of intact parathyroid hormone, and serum levelsof total calcium, phosphate, 25-hydroxyvitamin D, 1,25-dihydroxyvitaminD, magnesium, and markers of bone formation (bone alkaline phosphataseand osteocalcin) and bone resorption (N-telopeptide of collagencross-links); urinalysis; and phosphate, calcium, and creatininelevels in "spot" urine specimens.
Results Patients in the low-phosphate group (median serum phosphatelevel, 2.0 mg per deciliter [0.6 mmol per liter]; normal level,>2.5 mg per deciliter [0.8 mmol per liter]) had elevatedparathyroid hormone levels and low-to-normal serum calcium levels,were younger, and were receiving a higher dose of imatinib thanpatients in the normal-phosphate group (median level, 3.2 mgper deciliter [1.0 mmol per liter]). Both groups had high levelsof phosphate excreted in the urine and markedly decreased serumlevels of osteocalcin and N-telopeptide of collagen cross-links.
Conclusions Hypophosphatemia, with associated changes in boneand mineral metabolism, develops in a proportion of patientstaking imatinib for either chronic myelogenous leukemia or gastrointestinalstromal tumors. The drug may inhibit bone remodeling (formationand resorption), even in patients with normal serum phosphatelevels.
Source Information
From the Departments of Medicine (E.B., M.N., R.G.M., S.C., K.S., B.-A.W., N.P.S.), Clinical Laboratories (M.F.), and Epidemiology and Biostatistics (G.H.), Memorial Sloan-Kettering Cancer Center, New York.
Address reprint requests to Dr. Berman at the Leukemia Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY, 10021, or at bermane{at}mskcc.org.
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and 
, 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. 
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