Bisphosphonates offer protection against prosthetic joint infections caused by Staphylococcus aureus and Staphylococcus epidermidis biofilms

Abstract Medical device-associated osteomyelitis is a complication in orthopedic surgery, and often caused by Staphylococcus aureus and Staphylococcus epidermidis biofilms. There is an urgent need for the discovery of biodegradable therapies with bone restoring properties, which can additionally hamper biofilms development. Bisphosphonates inhibit osteoclastic bone resorption and are used e.g. in the treatment of osteoporosis. In turn, bioactive glass is a biodegradable material, which is used to resolve infection-induced bone defects due to its anti-biofilm and osteostimulative properties. Combining bioactive glass with bisphosphonates has attracted interest due to their synergistic effects on improved bone formation in orthopedic and dental applications. Our previous study showed that the addition of bisphosphonates (alendronate, etidronate, risedronate and zoledronate) improves the anti-biofilm effect of bioactive glass (S53P4; BAG) against periodontal biofilms ( Aggregatibacter actinomycetemcomitans ). In the present study, we studied the anti-biofilm effects of these bisphosphonate-BAG combinations on Staphylococcus aureus and Staphylococcus epidermidis biofilms as a plausible therapeutic alternative for the treatment of medical device-associated osteomyelitis. It was demonstrated that alendronate, etidronate and risedronate displayed anti-biofilm activity either when used alone or in combination with BAG. Overall, these results support a promising role of bisphosphonates in managing medical device-associated osteomyelitis, which it is worth exploring further.