Effects of intra-articular injection of dimethyl itaconate combined with systemic vancomycin on periprosthetic joint infection in rats

Aims

This investigation aimed to evaluate the efficacy and safety of intra-articular dimethyl itaconate (DI) combined with systemic vancomycin (Van) for the treatment of periprosthetic joint infections (PJI) induced by Staphylococcus aureus .

Methods

The fifty rats were divided into five groups: Control (Con), PJI, PJI + DI, PJI + Van, and PJI + Van + DI. After three weeks, systemic and local inflammation, osteolysis, bone histomorphometry, bacterial load, and biofilm formation were analyzed. Tartrate-resistant acid phosphatase (TRAP) staining was used to evaluate osteoclast inhibition by DI and vancomycin, and Alizarin Red staining was used to assess its effect on osteogenic differentiation.

Results

In vivo, the combination therapy demonstrated superior mitigation of bone loss and intra-articular synovial inflammation compared to Van monotherapy. Furthermore, the co-administration of DI and vancomycin effectively facilitated bacterial and biofilm clearance within the joint, further alleviating the dysregulation between bone resorption and remodelling. Compared to the DI and vancomycin monotherapy group, the Van + DI group showed reduced bacterial counts in implants, bone tissue, and soft-tissue. However, intra-articular DI alone was insufficient for complete eradication of S. aureus -induced PJI. Safety assessments indicated that neither DI monotherapy nor its combination with vancomycin elicited hepatic or renal toxicity in rats. In vitro, it was validated that DI exerts a promotive effect on osteoblast function while concurrently inhibiting osteoclast formation.

Conclusion

Intra-articular injection of DI combined with systemic vancomycin appears to be a safe and effective therapeutic strategy for PJI in our current rat model.

Cite this article: Bone Joint Res  2026;15(6):739–751.