Bone Microthrombus Promotes Bone Loss in Iron Accumulation Rats

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40(5):1-8,2020

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Bone Microthrombus Promotes Bone Loss in Iron Accumulation Rats Hai-feng HANG1, 4†, Long-jia DONG1, 2†, Xin-bing TANG4, Ai-fei WANG1, Fan YANG1, 3, Hui ZHANG1, You-jia XU1, 3# 1 Department of Orthopedics, Second Affiliated Hospital of Soochow University, Suzhou 215004 , China 2 Department of Orthopedics, The Affiliated Baiyun Hospital of Guizhou Medical University, Guizhou 550014, China 3 Osteoporosis Institute, Soochow University, Suzhou 215004, China 4 Department of Orthopedics, Jiangdu People’s Hospital of Yangzhou,Yangzhou 225200, China Huazhong University of Science and Technology 2020

Summary: In the present study, we investigated the changes of the coagulation state, bone microthrombus, microvascular bed and bone density levels in iron accumulation rats. Meanwhile,the effect of anticoagulation therapy on bone mineral density was further investigated. We established two groups: a control (Ctrl) group and an iron intervention (FAC) group. Changes in coagulation function, peripheral blood cell counts, bone microthrombus, bone vessels and bone mineral density were compared between the two groups. We designed the non-treatment group and treatment group to study the changes of bone mineral density by preventing microthrombus formation with the anticoagulant fondaparinux. We found that the fibrinogen and D-dimer contents were significantly higher, whereas the thrombin time (TT) and prothrombin time (PT) were significantly shorter in the FAC group. After ink staining, the microvascular bed in the FAC group was significantly reduced compared with that in the Ctrl group. HE and Martius Scarlet Blue (MSB) staining showed microthrombus in the bone marrow of the iron accumulation rats. Following anticoagulation therapy, the bone microcirculation vascular bed areas in the treatment group rats were significantly increased. Furthermore, the bone mineral density was increased in the treatment group compared with that in the non-treatment group. Through experiments, we found that the blood in iron accumulation rat was relatively hypercoagulable; moreover, there was microthrombus in the bone marrow, and the bone vascular bed was reduced. Additionally, anticoagulation was helpful for improving bone microcirculation, reducing microthrombus and decreasing bone loss. Key words: iron accumulation; osteoporosis; coagulation state; microvascular bed; bone microthrombus; anticoagulant

As one of the essential trace elements of the human body, iron ions have specific biological functions, but excessive iron can affect cells, affect various tissues of the body, and cause damage. Excess iron can lead to tissue damage by promoting the generation of reactive oxygen species (ROS) through the Fenton reaction[1]. Although controversial, several lines of evidence suggest that iron excess may predispose to vascular disease. Elevated body iron stores were associated with an increased risk of myocardial infarction in a large cohort of Finnish men[2]. Carriers of the hemochromatosis gene may have moderate iron overload and high