title: Addition of bisphosphonate to antibiotic and anti-inflammatory treatment reduces bone resorption in experimental Staphylococcus aureus-induced arthritis.
abstract: Bacterial arthritis is a disease with high morbidity leading to rapidly progressive bone resorption. We have shown earlier that treatment with antibiotics in combination with corticosteroids decreases joint inflammation and mortality but does not significantly affect bone/cartilage destruction of the joints. This study was performed to assess the effect of treatment with bisphosphonate [zoledronic acid (ZA)] in combination with antibiotics and corticosteroids, on the course and outcome of Staphlococcus aureus-induced arthritis. Three days after intravenous inoculation with S. aureus, mice were treated with antibiotics alone, ZA alone, ZA and antibiotics, or ZA combined with antibiotics and corticosteroids, respectively. One group served as controls and received PBS. Clinical assessment of arthritis was performed as well as histological analysis of bone and cartilage destruction in the joints. One femur from each mouse was collected for bone mineral density (BMD) analysis. In addition, serum levels of type I collagen fragments (RatLaps), and osteocalcin, markers for osteoclastic and osteoblastic activity, respectively, were analyzed. Mice treated with ZA and antibiotics or with ZA in combination with antibiotics and corticosteroids lost significantly less in trabecular bone density compared to infected control mice. Furthermore, the addition of corticosteroids to animals treated with ZA and antibiotics, significantly decreased serum levels of RatLaps and osteocalcin, compared to animals treated with ZA and antibiotics or ZA alone. Treatment with bisphosphonates in combination with antimicrobial agents and corticosteroids significantly decreases the activity of osteoclasts in septic arthritis, thereby reducing the risk of skeletal destruction.
authors.affiliation: Department of Rheumatology and Inflammation Research at the Sahlgrenska Academy, Guldhedsgatan 10A, S-41346, Göteborg, Sweden. margareta.verdrengh@rheuma.gu.se
authors.forename: Margareta
authors.initials: M
authors.lastname: Verdrengh
authors.forename: Hans
authors.initials: H
authors.lastname: Carlsten
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
authors.forename: Andrej
authors.initials: A
authors.lastname: Tarkowski
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy; D001170:Arthritis, Infectious / Q000188:drug therapy*; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001862:Bone Resorption / Q000097:blood / Q000188:drug therapy*; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood; D051379:Mice; D010010:Osteoclasts / Q000187:drug effects; D010024:Osteoporosis / Q000517:prevention & control; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus; D000077211:Zoledronic Acid
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D015850:Interleukin-6; D000077211:Zoledronic Acid