Polycythemia is associated with bone loss and reduced osteoblast activity in mice |
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| Authors: | Email author" target="_blank">P?R?OikonomidouEmail author C?Casu Z?Yang B?Crielaard J?H?Shim S?Rivella M?G?Vogiatzi |
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| Institution: | 1.Division of Pediatric Endocrinology,Weill Cornell Medical College,New York,USA;2.Division of Pediatric Hematology/Oncology,Weill Cornell Medical College,New York,USA;3.Department of Medicine, Cancer Center,Weill Cornell Medical College,New York,USA;4.Department of Pathology and Laboratory medicine,Weill Cornell Medical College,New York,USA;5.Division of Hematology, Children’s Hospital of Philadelphia,Abramson Research Center,Philadelphia,USA;6.Department of Polymer Chemistry and Bioengineering, Zernike Institute for Advanced Materials, University of Groningen,Groningen,Netherlands;7.Division of Hematology, Children’s Hospital of Philadelphia, Abramson Research Center,Philadelphia,USA;8.Division of Endocrinology, Children’s Hospital of Philadelphia,Philadelphia,USA |
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| Abstract: | SummaryIncreased fragility has been described in humans with polycythemia vera (PV). Herein, we describe an osteoporotic phenotype associated with decreased osteoblast activity in a mouse model of PV and another mouse of polycythemia and elevated circulating erythropoietin (EPO). Our results are important for patients with PV or those treated with recombinant EPO (rEPO).IntroductionPV and other myeloproliferative syndromes have been recently associated with an increased risk for fractures. However, the presence of osteoporosis in these patients has not been well documented. EPO, a hormone primarily known to stimulate erythropoiesis, has been shown recently to regulate bone homeostasis in mice. The aim of this study was to examine the bone phenotype of a mouse model of PV and compare it to that of animals with polycythemia caused by elevated circulating EPO.MethodsBone mass and remodeling were evaluated by micro-computed tomography and histomorphometry. The JAK2V617F knock-in mouse, a model of human PV, manifests polycythemia and low circulating EPO levels. Results from this mouse were compared to wild type (wt) controls and the tg6 transgenic mouse that shows polycythemia caused by increased constitutive expression of EPO.ResultsCompared to wt, both JAK2V617F and tg6 mice had a decrease in trabecular bone mass. Tg6 mice showed an additional modest decrease in cortical thickness and cortical bone volume per tissue volume (P?<?0.01) suggesting a more severe bone phenotype than JAK2V617F. Decreased osteoblast numbers and bone formation along with normal osteoclast numbers and activity were found in both mice.ConclusionsThis study indicates that PV is associated with low bone mass and decreased osteoblast activity in mice. Our results support future studies of osteoporosis in affected humans. Polycythemia caused by chronically elevated circulating EPO also results in bone loss, and implications on patients treated with rEPO should be evaluated. |
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