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Altered Bone and Mineral Metabolism in Patients Receiving Imatinib Mesylate

Ellin Berman, M.D., Nicolaides, M.D., G. Maki, M.D., Ph.D.,

Fleisher, Ph.D., Suzanne Chanel, R.N., Scheu, R.N., Bri-Anne

, B.A., Glenn Heller, Ph.D., and P. Sauter, M.D.

ABSTRACT

Background Imatinib mesylate inhibits several tyrosine kinases, including

BCR-ABL, the C-KIT receptor, and the platelet-derived growth factor

receptors {alpha} <http://content.nejm.org/math/alpha.gif> and beta

<http://content.nejm.org/math/beta.gif> , 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.

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

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