losartan-potassium and Fractures--Bone

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Topics: Anemia; Blood Transfusion; Bone Diseases; Calcitonin; Clodronic Acid; Diphosphonates; Erythropoietin; Fractures, Bone; Hematinics; Humans; Hypercalcemia; Imidazoles; Multiple Myeloma; Osteoporosis; Pamidronate; Recombinant Proteins; Renal Insufficiency; Zoledronic Acid

Patients with hip or pelvic fractures experience significant blood loss as a result of the fracture and from the surgery that subsequently is performed. The emergent and unplanned nature of fracture surgery precludes the use of preoperative blood donation and the optimization of chronic medical problems. Blood transfusion frequently is required to maintain adequate tissue O2 delivery in these injured patients. However, the administration of allogeneic blood causes other problems, including a well documented increase in the risk of infectious complications. Perioperative measures to minimize blood loss such as hypotensive anesthesia and red blood cell salvage are important, but often are inadequate to prevent the need for blood transfusion. Recently, erythropoietin therapy has been shown to stimulate hematopoiesis in patients with hip fractures. The authors discuss their experience with blood loss management in these patients with hip injuries, including aggressive Fe replacement therapy and the use of recombinant human erythropoietin.

Topics: Blood Loss, Surgical; Erythropoietin; Fractures, Bone; Hip Fractures; Humans; Pelvis

Little is known about the impact of multiple trauma (MT)-related systemic hypoxia on osseous protein concentration of the hypoxia transcriptome. To shed light on this issue, we investigated erythropoietin (Epo), erythropoietin receptor (EpoR), and Y-box binding protein 1 (YB-1) concentrations in the fracture zone in a porcine MT + traumatic hemorrhage (TH) model. Sixteen male domestic pigs were randomized into two groups: an MT + TH group and a sham group. A tibia fracture, lung contusion, and TH were induced in the MT + TH group. The total observation period was 72 h. YB-1 concentrations in bone marrow (BM) were significantly lower in the fracture zone of the MT + TH animals than in the sham animals. Significant downregulation of BM-localized EpoR concentration in both unfractured and fractured bones was observed in the MT + TH animals relative to the sham animals. In BM, Epo concentrations were higher in the fracture zone of the MT + TH animals compared with that in the sham animals. Significantly higher Epo concentrations were detected in the BM of fractured bone compared to that in cortical bone. Our results provide the first evidence that MT + TH alters hypoxia-related protein concentrations. The impacts of both the fracture and concomitant injuries on protein concentrations need to be studied in more detail to shed light on the hypoxia transcriptome in fractured and healthy bones after MT + TH.

Topics: Animals; Erythropoietin; Fractures, Bone; Hypoxia; Male; Multiple Trauma; Receptors, Erythropoietin; Swine

Beyond its role in the regulation of red blood cell proliferation, the glycoprotein erythropoietin (EPO) has been shown to promote cell regeneration and angiogenesis in a variety of different tissues. In addition, EPO has been indicated to share significant functional and structural homologies with the vascular endothelial growth factor (VEGF), a cytokine essential in the process of fracture healing. However, there is complete lack of information on the action of EPO in bone repair and fracture healing. Therefore, we investigated the effect of EPO treatment on bone healing in a murine closed femur fracture model using radiological, histomorphometric, immunohistochemical, biomechanical and protein biochemical analysis. Thirty-six SKH1-hr mice were treated with daily i.p. injections of 5000 U/kg EPO from day 1 before fracture until day 4 after fracture. Controls received equivalent amounts of the vehicle. After 2 weeks of fracture healing, we could demonstrate expression of the EPO-receptor (EPOR) in terminally differentiating chondrocytes within the callus. At this time point EPO-treated animals showed a higher torsional stiffness (biomechanical analysis: 39.6+/-19.4% of the contralateral unfractured femur) and an increased callus density (X-ray analysis (callus density/spongiosa density): 110.5+/-7.1%) when compared to vehicle-treated controls (14.3+/-8.2% and 105.9+/-6.6%; p<0.05). Accordingly, the histomorphometric examination revealed an increased fraction of mineralized bone and osteoid (33.0+/-3.0% versus 28.5+/-3.6%; p<0.05). Of interest, this early effect of the initial 6-day EPO treatment had vanished at 5 weeks after fracture. We conclude that EPO-EPOR signaling is involved in the process of early endochondral ossification, enhancing the transition of soft callus to hard callus.

Topics: Animals; Biomechanical Phenomena; Blotting, Western; Chondrocytes; Erythropoietin; Fractures, Bone; Hemoglobins; Immunohistochemistry; Mice; Osteogenesis; Radiography; Receptors, Erythropoietin; Signal Transduction; Wound Healing

Topics: Animals; Erythropoietin; Fracture Healing; Fractures, Bone; Rats; Rats, Sprague-Dawley

Orthopedic trauma is a major source of morbidity and mortality in the United States and other countries. Major orthopedic trauma often results in significant blood loss, which is the most common cause of shock in the trauma setting. Transfusion of allogeneic blood and blood products may be used to maintain blood pressure but may not be the most effective therapy for the acute anemia that results from trauma-induced hemorrhage. Because acute anemia can interfere with successful and timely rehabilitation of these patients, it is important to be aggressive in treating anemia. One approach is to administer Epoetin alfa to stimulate erythropoiesis. A pilot study is currently in progress to test the efficacy of this approach in major trauma patients.

Topics: Blood Transfusion; Blood Transfusion, Autologous; Epoetin Alfa; Erythropoietin; Fractures, Bone; Hematinics; Hemorrhage; Humans; Recombinant Proteins

Recombinant human erythropoietin (r-HuEPO) administration to a Jehovah's witness refusing blood transfusions increased her nadir packed cell volume from 13% to 37% and reticulocyte count from 2% to 17.7%. R-HuEPO may provide an alternative safe and effective therapy in life-threatening anemia when blood transfusions are unacceptable to the patient.

Topics: Accidents, Traffic; Acetabulum; Adult; Blood Transfusion; Christianity; Dose-Response Relationship, Drug; Erythrocyte Count; Erythropoietin; Female; Fractures, Bone; Hematocrit; Humans; Pelvic Bones; Reticulocytes; Shock, Hemorrhagic; Treatment Refusal