Changes in bone metabolic parameters in children with chronic myeloid leukemia on imatinib treatment

摘要

Background: Imatinib is a highly effective drug in up-front treatment of chronic myeloid leukemia (CML). In children impaired longitudinal growth has been reported as side effect exerted by this drug under prolonged therapy. We therefore prospectively evaluated alterations of bone biochemical markers in pediatric patients with CML under ongoing imatinib exposure. Material/Methods: Bone metabolic markers (calcium, phosphate, magnesium, parathyroid hormone, vitamin D, procollagen type l N propeptide PINP, and C-terminal cross-linking telopeptide of collagen CTX-I, osteocalcin OC; pyridinoline PYD, and desoxypyridinoline DPD) were determined in 17 patients with CML aged 4-17 years under imatinib treatment in three-month intervals over a 2.5 year period. Results: Hyperparathyroidism developed in 8/17 patients and low 25-hydroxyvitamin-D3 levels were found in 15/17 patients. Increased OC levels were detected in 58 of all specimen showing a linear significant decline of -0.30 μg OC per l per week (p=0.04). Serum PINP was lowered in 25 and serum CTX-I was above the normal range in 57 of the specimen originating exclusively from prepupertal patients. Urine PYD and Urine DPD levels were above the normal range in 10 and 9, respectively, of all specimen collected and a statistically significant linear decline of -0.16 nmol DPD/mg creatinine/week was calculated (p=0.01). Conclusions: Bone remodeling may be dysregulated by imatinib. Data suggest that impaired bone formation exceeds that of decreased bone resorption. Regular evaluation of the skeletal actions during longterm imatinib treatment in childhood CML is warranted.