The Bone Phenotype and Pain Response to Pamidronate in Tyrosine Kinase Inhibitor–Treated Chronic Myelogenous Leukemia

Tyrosine kinase inhibitors (TKIs) have been linked to bone pain and linear growth attenuation in children with TKI-treated chronic myelogenous leukemia (CML). We describe the skeletal phenotype in an 11-year-old boy with chronic bone pain due to TKI-treated CML, including his response to intravenous (IV) pamidronate. This boy was diagnosed with Philadelphia chromosome-positive CML at 4 years of age. He was treated with imatinib for 3 years, followed by dasatinib for 4 years. At age 11 years, he was seen in a bone health clinic with a 4-year history of leg pains that necessitated regular nonsteroidal anti-inflammatory drugs (NSAIDS) and downward crossing of height percentiles (from the 25th to fifth). The bone volume/tissue volume Z-score was +1.6 for a trans-iliac bone biopsy specimen, with an increase in trabecular number (Z-score, +3.1). Bone formation and resorption parameters on trabecular surfaces were within normal limits. Tibia volumetric bone mineral density (BMD) and bone geometry were normal by peripheral quantitative computed tomography, areal BMD Z-scores were average or above average at multiple skeletal sites by dual-energy x-ray absorptiometry, and tibia length Z-score was reduced (−2.3). Growth- and bone-related biochemical studies were unremarkable except a low serum alkaline phosphatase level. His bone pain resolved completely after 9 months of low-dose IV pamidronate. An increase in trans-iliac trabecular number and shortened tibia were the main skeletal features in this patient. Short-term IV pamidronate was effective for mitigating bone pain, allowing this boy to continue receiving dasatinib without the need for chronic NSAID therapy.