Addition of bisphosphonate to antibiotic and anti-inflammatory treatment reduces bone resorption in experimental Staphylococcus aureus-induced arthritis

• 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.

Keyword

Animals

Anti-Bacterial Agents/*therapeutic use

Anti-Inflammatory Agents/*therapeutic use

Arthritis

Experimental/drug therapy

Arthritis

Infectious/*drug therapy

Bone Density Conservation Agents/pharmacology/*therapeutic use

Bone Resorption/blood/*drug therapy

Diphosphonates/pharmacology/*therapeutic use

Drug Therapy

Combination

Female

Imidazoles/pharmacology/*therapeutic use

Interleukin-6/blood

Mice

Osteoclasts/drug effects

Osteoporosis/prevention & control

Staphylococcal Infections/*drug therapy

Staphylococcus aureus

Publication and Content Type

ref (subject category)

art (subject category)