Decreased bone turnover despite persistent secondary hyperparathyroidism during prolonged treatment with imatinib.
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.
O'Sullivan
Susannah
S
Department of Medicine, The University of Auckland, Private Bag, Auckland, New Zealand. s.osullivan@auckland.ac.nz
Horne
Anne
A
Wattie
Diana
D
Porteous
Fran
F
Callon
Karen
K
Gamble
Greg
G
Ebeling
Peter
P
Browett
Peter
P
Grey
Andrew
A
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
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