Background: Micro-structural changes associated with ultra high molecular weight polyethylene particle (UHMWPE) induced osteolysis, the most frequent cause of aseptic loosening, have been intensively investigated in the mammalian calvarian model by histomorphometry and micro-computed tomography. However, little is known regarding the serological changes that occur during this process. Methods: Serological parameters for bone metabolism [calcium, phosphate, osteocalcin (OCN), deoxypyridinoline (DPD)/creatinine, alkaline phosphatase, osteoprotegerin and receptor activator of nuclear factor-κB] were analyzed in this animal model for particle induced osteolysis. Ten C57BL/6 mice were divided at random into sham operated and UHM-WPE implanted groups. Blood and urine samples were collected prior to and at 14 days after surgery. Results: Implantation of UHMWPE lead to a significant decrease in bone volume (p=0.027). Both groups (sham/UHMWPE) showed a significant increase in calcium (p=0.004/p=0.027) and phosphate (p=0.001/p=0.001), without correlation to particle implantation. Significantly higher concentrations of DPD/creatinine (p=0.034) and OCN (p=0.022) were found after implantation of UHM-WPE. In addition, parameters could not be correlated to particle induced osteolysis. Conclusions: DPD can be regarded as a valuable parameter for detecting UHMWPE induced osteolysis in the calvarian model. Further studies of serum parameters should focus on the clinical relevance in aseptic prosthetic loosening.