# The role of PD-1/PD-L1 in overshooting osteoclastogenesis in periprosthetic joint infections

## TL;DR

This study shows that PD-1/PD-L1 signaling contributes to excessive bone destruction in joint infections, and blocking PD-1 may help prevent this.

## Contribution

The study identifies PD-1/PD-L1 signaling as a novel driver of osteoclastogenesis in periprosthetic joint infections.

## Key findings

- PD-1 positive monocytes and soluble PD-L1 levels are elevated in periprosthetic joint infections.
- PD-L1 stimulation enhances osteoclast formation, while PD-1 inhibition with nivolumab reverses this effect.
- The impact of PD-1 signaling is more pronounced in infected joints compared to controls.

## Abstract

Periprosthetic joint infection (PJI) is a critical complication following arthroplasty, leading to increased prosthesis failure rates post-treatment. This study explores the role of PD-1/PD-L1 signaling in osteoclastogenesis associated with PJI. Peripheral blood, bone, and bone marrow of 65 patients (20 primary osteoarthritis, 21 PJI septic explantation, 24 PJI prosthesis reimplantation) were analyzed for their bone microstructure and cell composition. Immunocytochemistry, RT-qPCR, flow cytometry, bone resorption assay, ELISA, and RNA sequencing were performed to investigate the effects of PD-1 stimulation and blockade on osteoclast formation. PD-1 positive monocytes and sPD-L1 levels were elevated in PJI. Stimulation with PD-L1 enhanced osteoclastogenesis, while PD-1 inhibitor nivolumab reversed these effects. Impact of PD-1 and nivolumab was significantly more pronounced in PJI compared to the control. Our study suggests PD-1/PD-L1 signaling plays a significant role in PJI-related osteoclastogenesis. These findings highlight the potential of PD-1 inhibitors as a novel approach to manage this challenging clinical condition.

PD-1/PD-L1 signaling drives osteoclastogenesis in PJI. PD-1+ monocytes and sPD-L1 were elevated in PJI, enhancing osteoclast formation. Nivolumab reversed this effect, suggesting PD-1 inhibitors as a potential treatment for PJI-related bone loss.