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Introduction: Periprosthetic joint infection (PJI) is a severe complication of joint arthroplasty and a leading cause of implant loosening, with rates compounded by prior revision surgery. Persistent low-grade infection drives chronic inflammation, in which overexpression of proinflammatory cytokines promotes bone loss through direct osteoclast activation and RANK-L-mediated bone resorption. Staphylococcus aureus, is a predominant causative organism that further accelerates this process by stimulating osteoclastogenesis and reducing osteoblast viability.

Intermittent parathyroid hormone (iPTH) is a potent anabolic agent that promotes osteoblast proliferation and inhibits osteoblast apoptosis, with demonstrated efficacy in preventing periprosthetic bone loss in osteoporotic patients. However, its role in infection-associated osteolysis and in combination with antibiotics remains unexplored. This study investigates the effects of iPTH, alone and combined with antibiotics, on bone preservation and remodeling in a murine PJI model.

Methods: Using an established PJI mouse model, a titanium wire was implanted retrograde into the distal femur and inoculated with bioluminescent Staphylococcus aureus or sterile saline. Infection was monitored longitudinally over 60 days via bioluminescence imaging (BLI). Beginning on postoperative day 14, mice were assigned to one of four treatment groups: subcutaneous sterile saline, vancomycin, iPTH, or combined vancomycin and iPTH. Bone loss was assessed by micro-computed tomography (micro-CT), and bacterial burden was quantified by BLI.

Results: Infected mice treated with iPTH alone or in combination with antibiotics demonstrated significantly reduced bone loss compared to infected controls and antibiotic-only groups. Micro-CT analysis revealed greater bone volume and attenuated osteolysis in iPTH-treated groups. No significant differences in BLI signal were observed among infected groups regardless of treatment.

Conclusions: Intermittent PTH, administered alone or adjunctively with antibiotics, significantly mitigated bone loss in a murine PJI model. These findings support iPTH as a promising adjunctive therapy for preserving bone integrity and improving clinical outcomes in the setting of PJI.