title: Decreased bone turnover despite persistent secondary hyperparathyroidism during prolonged treatment with imatinib.
abstract: BACKGROUND
  The tyrosine kinase inhibitor imatinib mesylate has an established role in the management of a number of malignant and proliferative conditions. Cross-sectional and short-term prospective studies have demonstrated secondary hyperparathyroidism during imatinib therapy, and variable changes in markers of bone turnover.
  
  
  OBJECTIVE
  Our objective was to determine the biochemical and skeletal effects of imatinib during long-term therapy.
  
  
  METHODS
  This was a 2-yr prospective study.
  
  
  METHODS
  The study was performed at an academic clinical research center.
  
  
  METHODS
  Nine patients with bcr-abl positive chronic myeloid leukemia were included in the study.
  
  
  METHODS
  Patients received Imatinib mesylate 400 mg/d.
  
  
  METHODS
  Serum and urine biochemistry, markers of bone turnover, and bone mineral density were measured.
  
  
  RESULTS
  Participants developed mild secondary hyperparathyroidism, with significant decreases in serum calcium and phosphate (P < 0.05 and P < 0.0001 vs. baseline, respectively) and an increase in PTH (P < 0.0001 vs. baseline). Biochemical markers of bone turnover demonstrated a biphasic response, with an initial increase in markers of bone formation being followed by a decrease in markers of both formation and resorption. Bone density at the lumbar spine increased [mean (95% confidence interval) change from baseline 3.6% (1.6, 5.5); P = 0.003] as did that at the total body [1.4% (0.2, 2.5); P = 0.065], whereas that at the proximal femur did not change [-0.12% (-3.0, 2.7); P = 0.93]. Body weight and fat mass increased significantly (P < 0.0001 vs. baseline).
  
  
  CONCLUSIONS
  Long-term treatment with imatinib leads to persistent mild secondary hyperparathyroidism. Despite this, bone turnover is decreased, and bone density is stable or increased. Evaluation of the skeletal actions and safety of imatinib during longer-term therapy is warranted.
authors.affiliation: Department of Medicine, The University of Auckland, Private Bag, Auckland, New Zealand. s.osullivan@auckland.ac.nz
authors.forename: Susannah
authors.initials: S
authors.lastname: O'Sullivan
authors.forename: Anne
authors.initials: A
authors.lastname: Horne
authors.forename: Diana
authors.initials: D
authors.lastname: Wattie
authors.forename: Fran
authors.initials: F
authors.lastname: Porteous
authors.forename: Karen
authors.initials: K
authors.lastname: Callon
authors.forename: Greg
authors.initials: G
authors.lastname: Gamble
authors.forename: Peter
authors.initials: P
authors.lastname: Ebeling
authors.forename: Peter
authors.initials: P
authors.lastname: Browett
authors.forename: Andrew
authors.initials: A
authors.lastname: Grey
mesh_terms: D000368:Aged; D001549:Benzamides; D015519:Bone Density / Q000187:drug effects / Q000502:physiology*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000097:blood; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D005919:Glomerular Filtration Rate; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000378:metabolism; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012709:Serum Albumin / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D001549:Benzamides; D010281:Parathyroid Hormone; D010710:Phosphates; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D012709:Serum Albumin; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D000068877:Imatinib Mesylate; C104450:25-hydroxyvitamin D; D002117:Calcitriol; D002118:Calcium