losartan-potassium and Femoral-Fractures

Fracture healing in the elderly is associated with a declined healing potential caused by multiple factors including a delay of vascularization. Erythropoietin (EPO) has been demonstrated to improve vascularization and fracture healing in adult mice. We, therefore, hypothesized that EPO in aged mice also improves fracture healing. For this purpose, EPO was given daily in a femoral fracture model in aged mice and compared to vehicle-treated controls using radiological, biomechanical, histomorphometric and Western blot techniques. Blood analyses revealed significantly higher concentrations of hemoglobin and a higher hematocrit in EPO-treated animals at 14 and 35 days after fracture. Micro-computed tomography (μCT) indicated that the fraction of bone volume/tissue volume within the callus did not differ between the two groups. However, μCT showed a 3-fold increased tissue mineral density (TMD) in the callus of EPO-treated animals compared to controls. The callus TMD of the EPO-treated animals was also 2-fold higher when compared to the TMD of the unfractured contralateral femur. Interestingly, biomechanical analyses revealed a reduced bending stiffness in femurs of EPO-treated animals at day 35. The histomorphometrically analyzed callus size and callus composition did not show significant differences between the study groups. However, Western blot analyses exhibited an increased expression of osteoprotegerin (OPG), but in particular of receptor activator of NF-κB ligand (RANKL) in the callus of the EPO-treated animals. Further histological analyses of the callus tissue showed that this was associated with an increased number of newly formed blood vessels and a higher number of tartrate-resistant acid phosphatase (TRAP)

Topics: Aging; Animals; Biomechanical Phenomena; Bone Remodeling; Bony Callus; Erythropoietin; Female; Femoral Fractures; Fracture Healing; Hemoglobins; Male; Mice; Osteoprotegerin; RANK Ligand; X-Ray Microtomography

To evaluate preoperative application of recombinant human erythropoietin (rHuEPO) in reducing transfusion requirements in elderly patients undergoing elective surgery for femoral intertrochanteric fractures.. From January 2011 to December 2013,442 cases of elderly patients with femoral intertrochanteric fracture were retrospectively reviewed. According to inclusion and exclusion criteria, 119 cases were eventually included and divided into the treatment group and the control group. There were 12 males and 40 females, with a mean age (71.4 ± 12.8) years old, and the patients received preoperative administration of rHuEPO 10,000 U qod combined with iron dextran 200 mg (3 times each day). While 16 males and 51 females in control group, with a mean age (70.9 ± 16.2) years old, and the patients only received preoperative administration of iron dextran 200 mg (3 times each day). All the patients received closed reduction and PFNA-II or Internal fixation surgeries. The perioperative blood transfusion rate, average amount of blood transfusion, postoperative complications, the length of hospital stay and mortality within 30 days were compared between the two groups.. There were no statistical differences between two groups in the baseline indexes (P > 0.05). Overall,71 of 119 patients (59.7%) received at least one unit allogeneic blood transfusion (ABT). However,there were significant differences in perioperative ABT rates (48.1% vs 68.7%, χ2 = 4.77, P < 0.05) and the average amount of blood transfusion between treatment group and control group, which were (1.8 ± 0.4) U/pte vs (3.6 ± 1.1) U/pte (t = 2.244, P < 0.05). Postoperative hemoglobin (Hb) on postoperative days 7 and 30 was higher in treatment group than that in control group. In addition, in treatment group, Hb levels were higher on postoperative day 30 than those on admission, which were (128.2 ± 20.6) g/L vs (118.2 ± 18.9) g/L (t = 2.133, P < 0.05). There were no statistical differences in postoperative complications, the length of hospital stay and mortality within 30 days.. For elderly patients with femoral intertrochanteric fractures undergoing elective surgery, preoperative application of rHuEPO can significantly reduce perioperative transfusion requirements, and is likely to reduce ABT-related infection, but its long-term safety remains to be evaluated.

Topics: Aged; Aged, 80 and over; Blood Transfusion; Case-Control Studies; Erythropoietin; Female; Femoral Fractures; Fracture Fixation, Internal; Hemoglobins; Hip Fractures; Humans; Male; Preoperative Care; Retrospective Studies

Erythropoietin (EPO)/erythropoietin receptor (EPOR) signaling is involved in the development and regeneration of several non-hematopoietic tissues including the skeleton. EPO is identified as a downstream target of the hypoxia inducible factor-α (HIF-α) pathway. It is shown that EPO exerts a positive role in bone repair, however, the underlying cellular and molecular mechanisms remain unclear. In the present study we show that EPO and EPOR are expressed in the proliferating, pre-hypertrophic and hypertrophic zone of the developing mouse growth plates as well as in the cartilaginous callus of the healing bone. The proliferation rate of chondrocytes is increased under EPO treatment, while this effect is decreased following siRNA mediated knockdown of EPOR in chondrocytes. EPO treatment increases biosynthesis of proteoglycan, accompanied by up-regulation of chondrogenic marker genes including SOX9, SOX5, SOX6, collagen type 2, and aggrecan. The effects are inhibited by knockdown of EPOR. Blockage of the endogenous EPO in chondrocytes also impaired the chondrogenic differentiation. In addition, EPO promotes metatarsal endothelial sprouting in vitro. This coincides with the in vivo data that local delivery of EPO increases vascularity at the mid-stage of bone healing (day 14). In a mouse femoral fracture model, EPO promotes cartilaginous callus formation at days 7 and 14, and enhances bone healing at day 28 indexed by improved X-ray score and micro-CT analysis of microstructure of new bone regenerates, which results in improved biomechanical properties. Our results indicate that EPO enhances chondrogenic and angiogenic responses during bone repair. EPO's function on chondrocyte proliferation and differentiation is at least partially mediated by its receptor EPOR. EPO may serve as a therapeutic agent to facilitate skeletal regeneration.

Topics: Animals; Bone Regeneration; Bony Callus; Cell Differentiation; Cell Proliferation; Cells, Cultured; Chondrocytes; Erythropoietin; Femoral Fractures; Femur; Growth Plate; Metatarsal Bones; Mice, Inbred C57BL; Neovascularization, Physiologic; Primary Cell Culture; Proteoglycans; Receptors, Erythropoietin

A 20-year-old Jehovah's witness patient experienced a femur fracture, with a section of the femoral artery and vein. On admission, haemoglobin concentration was 5.6 g.dL-1 and haematocrit 17%. Because of aponevrotomy, blood losses persisted. As the patient refused blood transfusion, recombinant human erythropoietin and parenteral iron were administered, associated with mild hypothermia, sedation and mechanical ventilation. After 21 days, the haemoglobin concentration increased to 10.9 g.dL-1 and haematocrit to 33% Recombinant human erythropoietin and parenteral iron may provide an alternative safe and effective therapy in life-threatening anaemia when blood transfusions are not accepted by the patient.

Topics: Acute Disease; Adult; Anemia, Hypochromic; Blood Loss, Surgical; Christianity; Erythropoietin; Femoral Artery; Femoral Fractures; Femoral Vein; Hemoglobins; Humans; Male; Recombinant Proteins; Time Factors