From Mice to Patients: Preventing Joint Destruction with Anti-RANKL in Septic Arthritis

Septic arthritis presents a significant challenge in modern medicine, often leading to permanent joint dysfunction and necessitating joint replacement surgery.

Our hypothesis focuses on monocyte differentiation into bone-damaging osteoclasts as a primary driver of rapid joint destruction.

We propose targeting receptor activator of nuclear factor-κB-ligand (RANKL), the key mediator of osteoclast activation, to reach substantial treatment improvements.Our specific aims involve elucidating the molecular mechanisms underlying the efficacy of anti-RANKL therapy, assessing safety implications through national patient registry analysis, and evaluating combination therapy with antibiotics and a RANKL inhibitor in a randomized controlled clinical trial.To achieve our goals, we will employ monocytic fate-mapping techniques in vivo to trace the differentiation of infiltrating monocytes into osteoclast-like cells.

Additionally, we will identify septic arthritis patients and controls in Sweden to analyze safety implications associated with anti-RANKL treatment.

Finally, a randomized controlled trial will be conducted to assess combination therapy efficacy, with the primary endpoint being the need for prosthetic joint replacement in affected knees within five years post-septic arthritis.Our proposed therapy has the potential to revolutionize treatment modalities, offering better outcomes for patients with septic arthritis.