Lavoie Declan C T, Robinson Marie-Eve, Johnston Donna, Pagé Marika, Konji Victor N, Rauch Frank, Ward Leanne M
Pediatric Bone Health Clinical Research Program, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
Department of Pediatrics, Division of Endocrinology, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
J Endocr Soc. 2019 Mar 11;3(5):857-864. doi: 10.1210/js.2018-00268. eCollection 2019 May 1.
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.
酪氨酸激酶抑制剂（TKIs）与接受TKI治疗的慢性粒细胞白血病（CML）患儿的骨痛和线性生长衰减有关。我们描述了一名11岁因TKI治疗的CML而患有慢性骨痛男孩的骨骼表型，包括他对静脉注射（IV）帕米膦酸盐的反应。该男孩4岁时被诊断为费城染色体阳性CML。他接受了3年的伊马替尼治疗，随后接受了4年的达沙替尼治疗。11岁时，他在一家骨骼健康诊所就诊，有4年的腿痛病史，需要定期服用非甾体抗炎药（NSAIDs），且身高百分位数下降（从第25百分位数降至第5百分位数）。经髂骨活检标本的骨体积/组织体积Z评分为+1.6，小梁数量增加（Z评分，+3.1）。小梁表面的骨形成和吸收参数在正常范围内。通过外周定量计算机断层扫描，胫骨体积骨密度（BMD）和骨几何形状正常，通过双能X线吸收法在多个骨骼部位的面积BMD Z评分平均或高于平均水平，胫骨长度Z评分降低（-2.3）。除血清碱性磷酸酶水平较低外，生长和骨骼相关的生化研究无异常。低剂量IV帕米膦酸盐治疗9个月后，他的骨痛完全缓解。该患者的主要骨骼特征是经髂骨小梁数量增加和胫骨缩短。短期IV帕米膦酸盐对减轻骨痛有效，使该男孩能够继续接受达沙替尼治疗，而无需长期使用NSAID治疗。
