Altered bone and mineral metabolism in patients receiving imatinib mesylate

N Engl J Med. 2006 May 11;354(19):2006-13. 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.

MeSH terms

  • Benzamides
  • Biomarkers / blood
  • Bone Remodeling / drug effects*
  • Bone Remodeling / physiology
  • Bone and Bones / metabolism
  • Calcitriol / blood
  • Calcium / blood
  • Female
  • Gastrointestinal Stromal Tumors / drug therapy
  • Humans
  • Hypophosphatemia / blood
  • Hypophosphatemia / 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*
  • Piperazines / therapeutic use
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Pyrimidines / adverse effects*
  • Pyrimidines / therapeutic use
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood


  • Benzamides
  • Biomarkers
  • Parathyroid Hormone
  • Phosphates
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Osteocalcin
  • Vitamin D
  • Imatinib Mesylate
  • 25-hydroxyvitamin D
  • Protein-Tyrosine Kinases
  • Calcitriol
  • Calcium