Objective: Primary objective is to study the arginine-NO metabolism during fracture healing and dysfunctional fracture healing. Secondary objective: to investigate if differences or decreased arginine and NO concentrations in bone healing form a prognostic marker for non-union development Hypothesis: Early detection of disturbances in the Arginine and nitric oxide metabolism during fracture healing are a good prognostic marker for non-union development.

Study design: Prospective observational study. Study population: All acute fracture patients (age >18 years), with a fracture of the tibia or femur attending the Department of General Surgery, to investigate the Arginine -NO metabolism during normal fracture healing and possible dysfunctional healing. In total 100 patients will be included during this study.

Main study parameters/endpoints:

Primary endpoints are arginine and Nitric Oxide levels in the plasma during normal and dysfunctional fracture healing the bone in patients with and without non-union Secondary endpoints are levels of Nitric Oxide citrulline, ornithine and other amino acids in bone and in plasma Other parameters: baseline demography details will be obtained, including possible confounders, such as bodyweight, smoking, alcohol abuse, which may interfere with the outcome of this study.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The extent of the burden and risk associated with participation is expected to be low during this study. In total, 7 blood samples will be taken during this study (45ml, in total). During the primary (and possible secondary) surgical procedure, bone debris will be taken. Bone debris is usually discarded but will be used for analysis in this study. There is no extra surgical procedure necessary to obtain the bone debris.

Inclusion Criteria:

• Written informed consent
• Age > 18 years
• Patient with a fracture of the femur or tibia for which a surgical procedure providing bone debris is performed as therapy

Exclusion Criteria:

• Patients with another bone fracture in their recent medical history
• Infectious complications, such as infected pseudo-arthrosis
• Use of chronic corticosteroids or nitrovasodilating medication
• Patients with severe metabolic disturbances (liver, and renal insufficiency, diabetes).
• Patients with metastases, haematological malignancies or chemotherapy

Patients with an acute fracture of the femur or tibia