Abstract

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 long-term imatinib treatment in childhood CML is warranted.

Keywords: Pyrimidines - therapeutic use, Piperazines - therapeutic use, Osteocalcin - blood, Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy, Child, Preschool, Child, Calcifediol - blood, Bone and Bones - pathology, Benzamides - therapeutic use, Adolescent, Reference Values, Tumor Markers, Biological - blood