Conjugation with bisphosphonates for targeted antibiotic delivery to bone tissue for the treatment of osteomyelitis: a scoping review protocol.

Chronic osteomyelitis (CO), a chronic infectious process affecting the bones, is a disease with high morbidity. The standard treatment for chronic osteomyelitis and those associated with implants is the combination of surgical approach to the focus of infection, with its different modalities, associated with systemic antibiotic therapy, with or without local antibiotic therapy. Systemic antibiotics often fail to achieve sustained bactericidal concentrations at the bone-bacteria interface. Local strategies (e.g., bone cement or impregnated absorbable bone substitutes) can increase local concentrations, but have limitations: heterogeneous distribution, inadequate release into bone microcracks, and ineffectiveness against bacteria deeply lodged in bone tissue. One therapeutic strategy that has been explored to circumvent this phenomenon in preclinical studies is the conjugation of bisphosphonates (BPs) with antibiotics. BPs act by inhibiting bone resorption, and are classically used in the treatment of osteoporosis. Bisphosphonates can be conjugated to antibiotics through a chemical ligand, which would target the antibiotic specifically to the RCA, and kill the bacteria after the release of the active antibiotic at the site of infection, in a "target and release" strategy. The aim of this study is to conduct a scoping review mapping the existing literature, answering the question: What are the strategies, evidence, and gaps in the literature regarding the use of antibiotics conjugated or associated with bisphosphonates for the treatment of osteomyelitis?