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This study was designed to investigate if local tissue and serum markers of bone remodeling reflect implant fixation following administration of lipopolysaccharide (LPS)\u2010doped polyethylene (PE) particles in a rat model. Twenty\u2010four rats received bilateral implantation of intramedullary titanium rods in the distal femur, followed by weekly bilateral intra\u2010articular injection of either LPS\u2010doped PE particles (<jats:italic>n<\/jats:italic>= 12) or vehicle that contained no particles (<jats:italic>n<\/jats:italic>= 12) for 12 weeks. The group in which the particles were injected had increased serum C\u2010terminal telopeptide of type I collagen (CTX\u2010I), decreased serum osteocalcin (OC), increased peri\u2010implant eroded surface, decreased peri\u2010implant bone volume, and decreased mechanical pull\u2010out strength compared to the controls. Implant fixation strength was positively correlated with peri\u2010implant bone volume and serum OC and inversely correlated with serum CTX\u2010I, while energy to yield was positively correlated with serum OC and inversely correlated with the number of tartrate\u2010resistant acid phosphatase positive cells at the interface and the amount of peri\u2010implant eroded surface. There was no effect on trabecular bone volume at a remote site. Thus, the particle\u2010induced impaired fixation in this rat model was directly associated with local and serum markers of elevated bone resorption and depressed bone formation, supporting the rationale of exploring both anticatabolic and anabolic strategies to treat and prevent particle\u2010related implant osteolysis and loosening, and indicating that serum markers may prove useful in tracking implant fixation. \u00a9 2012 Wiley Periodicals, Inc. 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