Methods: Treatment was initiated 3 days after Staphylococcus aureus inoculation and included RANK-Fc, OPG-Fc, and OPG-Fc in combination with antibiotics. Control groups were treated with antibiotics, huFc, and PBS. Joints were evaluated for clinical signs of arthritis and histologically for bone and cartilage destruction. Bone mineral density (BMD) was evaluated using a peripheral quantitative computed tomography. Circulating markers of bone metabolism, inflammatory cytokines, and chemokines were analyzed in each group.
Results: Mice treated with RANK-Fc or OPG-Fc in combination with antibiotics preserved total BMD and trabecular bone as compared to huFc or antibiotics. Treatment with RANK-Fc or OPG-Fc diminished the levels of bone resorption markers (osteocalcin, CTX-I, and TRACP5b). Neither RANK-Fc nor OPG-Fc influenced significantly the frequency and severity of arthritis.
Conclusions: Inhibition of RANKL signalling efficiently prevents bone loss in the mouse model of bacterial arthritis even when started in the overt phase of infection.