sildenafil-citrate and Femoral-Fractures

This study aims to investigate whether tadalafil accelerates fracture healing with an efficiency equal to that of sildenafil.. Fracture healing was studied using a rat closed femur fracture model. Forty-eight male Wistar albino rats (mean age 13 weeks; range 12 to 14 weeks) were divided into three groups: 16 received sildenafil (5 mg/kg/day per oral), 16 received tadalafil (1 mg/kg/day per oral), and 16 (control group) received saline daily. After two and five weeks, eight rats from each group were euthanized and bone healing was evaluated using radiographic, histologic, and histomorphometric analyses.. At second week, radiologic score of tadalafil group was higher than the sildenafil treated groups and the sildenafil and tadalafil groups both had higher radiographic scores than the control group, all groups had similar scores at fifth week. The sildenafil and tadalafil treated group exhibited smaller callus diameter at the second week comparing to control group but the difference was not statistically significant, while callus diameter was significantly smaller in tadalafil group when compared to the control group in fifth week. Compared with the control group, cartilage percentage of the callus was lower in the sildenafil group at two weeks and lower in both the tadalafil and sildenafil groups at five weeks. There were no differences between the tadalafil and sildenafil groups regarding the radiographic scores, callus size, cartilage and osseous callus percentage, and the qualitative bridging scores at second or fifth week.. This study demonstrated that tadalafil accelerates fracture healing by enhancing osseous tissue formation similar to sildenafil.

Topics: Animals; Biomechanical Phenomena; Bony Callus; Femoral Fractures; Fracture Healing; Male; Phosphodiesterase 5 Inhibitors; Radiography; Rats; Rats, Wistar; Sildenafil Citrate; Tadalafil; Treatment Outcome

Sildenafil, a cyclic guanosine monophosphate (cGMP)-dependent phospodiesterase-5 inhibitor, has been shown to be a potent stimulator of angiogenesis through upregulation of pro-angiogenic factors and control of cGMP concentration. Herein, we determined whether sildenafil also influences angiogenic growth factor expression and bone formation during the process of fracture healing. Bone healing was studied in a murine closed femur fracture model using radiological, biomechanical, histomorphometric, and protein biochemical analysis at 2 and 5 weeks after fracture. Thirty mice received 5 mg/kg body weight sildenafil p.o. daily. Controls (n  = 30) received equivalent amounts of vehicle. After 2 weeks of fracture healing sildenafil significantly increased osseous fracture bridging, as determined radiologically and histologically. This resulted in an increased biomechanical stiffness compared to controls. A smaller callus area with a slightly reduced amount of cartilaginous tissue indicated an accelerated healing process. After 5 weeks the differences were found blunted, demonstrating successful healing in both groups. Western blot analysis showed a significantly higher expression of the pro-angiogenic and osteogenic cysteine-rich protein (CYR) 61, confirming the increase of bone formation. We show for the first time that sildenafil treatment accelerates fracture healing by enhancing bone formation, most probably by a CYR61-associated pathway.

Topics: Animals; Biomechanical Phenomena; Blotting, Western; Drug Evaluation, Preclinical; Femoral Fractures; Femur; Fracture Healing; Intercellular Signaling Peptides and Proteins; Mice; Osteogenesis; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Radiography; Sildenafil Citrate; Sulfones