Background. Understanding of the pathogenetic mechanisms of non-union can not ignore bone remodelling and its cascade of processes at cellular and biochemical levels culminating in an incomplete structural and functional restoration of the damaged bone.

Osteoprotegerin (OPG) is expressed by osteoblasts and functions as a decoy receptor that is able to control and to regulate osteoclastogenesis and therefore to prevent bone resorption.

The objectives of our study were: to investigate OPG serum levels in shaft fractures non-union compared to controls; to assess the use of OPG as a marker for the early identification of fracture non-unions.

Material and Methods. OPG serum levels were determined in 25 male patients (aged between 20–59 years, mean 35.44 ± 11.53) with a shaft fracture non-union at the time of minimum six months (mean 16.83 ± 10.87) since trauma and age matched with 25 male controls patients (aged 20–59 mean 35.44 ± 11.76) with a shaft fracture healed. All patients were correctly operated with different types of synthesis for complex fractures of a long bone (humerus, femur, tibia). Osteocalcin, bone isoenzyme of alkaline phosphatase and deoxypyridino-line (DPD) were also measured.

Results. OPG levels were significantly higher in non-union cases compared to age matched controls (mean 10.17 ± 3.08 vs 8.54 ± 1.18 U/L; p=0.0084). DPD level was significantly higher in cases respect to controls (mean 7.9 ± 2.74 vs 3.8 ± 1.00 nmolDPD/mmol urinary creatinine excretion; p=0.0001). ROC analysis and the classification for probability cut-off show a very good negative predictive value (84%) for a cut-off of OPG 10 U/L, indicating that all patients having OPG lower than 10 U/L are probably free of non-union. Similarly, for an increase of 1 U/L of OPG there is an increase of probability of being a case of 92%. Higher OPG levels clearly carries a higher risk of non-union, thus indicating the usefulness of OPG evaluation in the follow-up of fractured patients. Larger groups will allow the estimation of the correct level of OPG threshold by age, which we are now able to estimate of about 8 U/L for young patients and 10 U/L for older ones in our population.

Conclusion. Shaft fracture non-union may occur following appropriate osteosynthesis in consequence of a condition of altered bone osteoclastic activity. OPG could be directly involved in the pathogenesis of shaft fractures non-union and seems to be an accurate predictive marker in non-union evaluation.