Fracture healing is an ordered process that restores the structural integrity of the bone. Soluble receptor activator of nuclear factor-kB (sRANK), its ligand (sRANKL) and osteoprotegerin (OPG) are involved in bone remodelling, thus they may play a role in fracture repair. OPG, soluble RANK and RANKL levels were measured in plasma and in drainage fluid, collected from pre-surgery phase to healing in ten patients of both genders (age range 26-65 years) with proximal humerus fracture needing osteosynthesis. All patients showed fracture healing. No significant modifications in the concentrations of sRANKL and OPG were observed, while sRANK showed a significant increase in drainage fluid 24 hours post-surgery compared with intra-surgery time. OPG levels were higher in plasma and drainage fluid than sRANK and sRANKL at each time point. Since there are no published data about sRANK involvement in fracture healing, our study represents the first preliminary indication about a local increase of this marker concentration immediately after surgery.