Osteogenic protein-1 induces bone formation in the presence of bacterial infection in a rat intramuscular osteoinduction model

Objective: Evaluate the ability of osteogenic protein-1 to induce formation of de novo bone in the presence of bacterial infection and metal in an intramuscular osteoinduction model in the rat. Design: Prospective experimental design with assessment time points of up to 4 weeks. Setting: Intramuscular pocket surgically created along each side of the spine. Animals: One-hundred-twenty adult male Sprague-Dawley rats. Interventions: Each intramuscular pocket received 0, 10, or 25 mug of osteogenic protein-1 combined with a lyophilized collagen carrier, and 0 or 5 x 105 colony-forming units of Staphylococcus aureus. Pockets in 48 animals received a metal implant. Animals were killed at 1, 2, 3, or 4 weeks. Main Outcome Measurements: High-resolution radiographs of resulting nodules of bone/soft tissue were digitized, and areas of newly formed bone were quantified using an image analysis workstation. The nodules were decalcified for histology, and calcium content of the decalcifying solution was quantified by flame atomic absorption spectrophotometry. Results: There were minimal levels of calcium and area of new bone formation in nodules from pockets containing collagen carrier without osteogenic protein-1, for both infection and noninfection conditions. Calcium content and area of newly formed bone were significantly greater: 1) in infected pockets with osteogenic protein-1, compared to infected pockets without osteogenic protein-1; and 2) in noninfected pockets with osteogenic protein-1, compared to infected pockets with osteogenic protein-1. The presence of metal did not have a significant effect. Conclusion: Osteogenic protein- I maintained its osteoinductive capability in a contaminated intramuscular pocket in the rat, albeit at a lower level than without infection. This finding supports further study using a more clinically realistic model.