Around Travel Mug 10 % of long bone fractures show inadequate bone healing resulting in non-union development.A deregulated arginine-citrulline-nitric oxide metabolism caused by a poor nutritional status of the patients is a risk factor for non-unions.Additionally, previous research in mice with a disrupted arginine to citrulline conversion showed delayed healing.The study hypothesis was that stimulating said metabolism could positively influence the healing process through promotion of collagen synthesis and angiogenesis.Adult wild-type mice underwent a femur osteotomy and plate-screw osteosynthesis.
Mice were randomly divided into three groups and received daily oral supplementation of arginine, citrulline or 0.9 % saline (control).Body weight and food intake were measured daily.After 14 d, the mice were euthanised and femora collected.Callus formation was assessed by micro-computed tomography and concentrations of amino acids and enzymes in the femora were measured.
Only citrulline-treated mice showed significantly increased bridging of the fracture gap when compared to control mice.Femur citrulline and ornithine concentrations were increased in citrulline-treated animals.qPCR showed significantly decreased expression of inflammatory markers, whereas increased expression of angiogenic and collagen-producing factors was observed in citrulline-treated mice.Although food intake did not show any difference between the Folding Ramp three groups, animals treated with citrulline showed a weight gain of 0.3 g, compared with a 0.
1 g decline in the control group.Daily oral citrulline supplementation stimulated callus formation and improved the inflammatory response, positively contributing to the enhanced healing response.Finally, the increased weight gain pointed toward a better post-operative recovery.