Dennis Meesters (Maastricht / NL), Levi Smeets (Maastricht / NL), Hans van Eijk (Maastricht / NL), Stephan Zeiter (Davos / CH), Nina Wijnands (Maastricht / NL), Martijn Poeze (Maastricht / NL)
Abstract text (incl. references and figure legends)
Background: Nonunion develops in up to 10% of all fractures and requires relatively complicated (surgical) treatments and significantly impairs the quality of life for the patients. Biomedical risk factors include inherited diseases, medical conditions associated with impaired vascular function, metabolic disorders and drug use. Absence of nitric oxide synthase (NOS) activity is known to facilitate nonunion development in a murine model of delayed fracture healing. Osteoglycin (OGN) was identified as a bone anabolic factor which may play an important role in nonunion formation. Here, it is investigated whether OGN is associated with NOS activity in nonunion development.
Methods: Wild type (WT), Nos2- and Nos3-deficient mice were used in a model of delayed fracture healing characterized by induction of a 0.45 mm femoral osteotomy combined with periosteal cauterization and fixation. Healing was assessed after 42 days using µCT. Inflammation was assessed using myeloperoxidase staining for neutrophil influx. For OGN expression, a new staining protocol was developed. To correlate the OGN expression with metabolic factors, amino acids related to the arginine-NO metabolism were measured using HPLC.
Results: After 42 days of fracture healing, nonunion development was present in both NOS deficient mice. OGN expression was attenuated in fracture callus collected from Nos3- deficient mice when comparing to WT. Neutrophil influx was increased in Nos2-deficient mice when compared to WT. Moderate alterations in arginine, citrulline and ornithine concentrations were found in plasma and femurs of both NOS deficient when compared to WT mice.
Discussion: OGN expression correlated with NOS activity in callus tissue and absence of both is associated with nonunion development in the current model. The relationship between osteogenic factors, inflammation and metabolism need to further elucidated in future research to assess if its value in treatment or prevention of nonunions.
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