Decreased Bone Turnover Despite Persistent Secondary Hyperparathyroidism during Prolonged Treatment with Imatinib

• Published in: The journal of clinical endocrinology and metabolism 2009-04, Vol.94 (4), p.1131-1136
• Main Authors: O'Sullivan, Susannah, Horne, Anne, Wattie, Diana, Porteous, Fran, Callon, Karen, Gamble, Greg, Ebeling, Peter, Browett, Peter, Grey, Andrew
• Format: Article
• Language: English
• Subjects: Aged; Benzamides; Biological and medical sciences; Bone and Bones - drug effects; Bone and Bones - metabolism; Bone Density - drug effects; Bone Density - physiology; Calcitriol - blood; Calcium - blood; Endocrinopathies; Feeding. Feeding behavior; Female; Fibroblast Growth Factors - blood; Fundamental and applied biological sciences. Psychology; Glomerular Filtration Rate; Humans; Hyperparathyroidism, Secondary - drug therapy; Hyperparathyroidism, Secondary - metabolism; Imatinib Mesylate; Male; Medical sciences; Middle Aged; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Parathyroid Hormone - blood; Parathyroids. Parafollicular cells. Cholecalciferol. Phosphocalcic homeostasis (diseases); Phosphates - blood; Piperazines - therapeutic use; Protein Kinase Inhibitors - therapeutic use; Pyrimidines - therapeutic use; Serum Albumin - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Vitamin D - analogs & derivatives; Vitamin D - blood
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2008-2324

Context: 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. Design: This was a 2-yr prospective study. Setting: The study was performed at an academic clinical research center. Patients or Other Participants: Nine patients with bcr-abl positive chronic myeloid leukemia were included in the study. Interventions: Patients received Imatinib mesylate 400 mg/d. Main Outcome Measures: 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. Long-term therapy with imatinib mesylate leads to persistent mild secondary hyperparathyroidism, decreased bone turnover, and stable or increased bone density.