RANKL-mediated osteoclast formation is required for bone loss in a murine model of Staphylococcus aureus osteomyelitis

• DOI: 10.1016/j.bone.2024.117181
• Publication Date: 2024-07-01T06:36:07Z
• Authors: Mara J. Campbell; Cecile Bustamante...; Qiang Fu; Karen E. Beenken; Humberto Reyes-Pardo; Mark S. Smeltzer; Charles A. O'Brien
• Keywords: Denosumab; Bone Infection

Staphylococcus aureus osteomyelitis leads to extensive bone destruction. Osteoclasts are resorbing cells that often increased in infected with S. aureus. The cytokine RANKL is essential for osteoclast formation under physiological conditions but vitro evidence suggests inflammatory cytokines may by-pass the requirement RANKL. goal of this study was determine whether RANKL-dependent loss occurs a murine model osteomyelitis. To end, humanized-RANKL mice were by direct inoculation into unicortical defect femur. Mice treated vehicle or denosumab, human monoclonal antibody inhibits RANKL, both before and during 14-day infection period. severe cortical destruction caused completely prevented denosumab administration even though bacterial burden femur not affected. abundant near site vehicle-treated absent denosumab-treated mice. In situ hybridization demonstrated potently stimulated expression marrow stromal cells. reactive also reduced administration. Lastly, there notable lack osteoblasts suggesting normal coupling resorption disrupted infection. These results demonstrate RANKL-mediated required suggest disruption contribute condition.