title: Digital image analysis as a tool to assess the effects of imatinib on trabecular bone in patients with chronic myelogenous leukemia.
abstract: Skeletal integrity is sustained by osteoblast-osteoclast interactions, controlled by several signaling pathways that include tyrosine kinases. Imatinib is a tyrosine kinase inhibitor with an extended therapeutic range based on its ability to differentially bind to receptor and nonreceptor tyrosine kinases. In this study, we used digital image analysis to assess changes in trabecular bone surface area within bone marrow biopsy specimens of 34 patients with chronic phase chronic myelogenous leukemia treated with single-agent imatinib. These patients were 25 men and 9 women with a median age of 59 years. We selected representative areas of paired bone marrow biopsy specimens obtained at baseline and within the subsequent 48 months. Computer-assisted analysis was performed to calculate trabecular bone area (TBA) within the sample by using the equation TBA% = sum of trabecular area/total biopsy specimen area. Percentage changes were defined as ΔTBA% and were arbitrarily subdivided into marked (>50%), moderate (10%-50%), and mild (<10%). During the study interval, TBA% increased in 24 patients (71%) and decreased in 10 patients (29%). Overall, there was a significant increase in TBA% (P = .02). No correlation was found between changes in trabecular bone area and either clinical or cytogenetic response (P = .25). The results show that imatinib therapy can alter trabecular bone in bone marrow biopsy specimens of chronic myelogenous leukemia patients, most often resulting in an increase in TBA%.
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. dhoehn@mdanderson.org
authors.forename: Daniela
authors.initials: D
authors.lastname: Hoehn
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Bueso-Ramos
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001549:Benzamides; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006706:Homeostasis; D006801:Humans; D007091:Image Processing, Computer-Assisted; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate