JAC pp493-98 MW3291

In the bone microenvironment, tumour necrosis factor (TNF) has long been established as a stimulator of osteoclasts, hence leading to bone resorption, yet it also induces osteoblasts, the bone-forming cells, to proliferate, which may have longer term influences on bone formation. A disturbance in the finely balanced processes of bone resorption and formation, termed remodelling, results in a disordered state. The effects of TNF during diseases such as rheumatoid arthritis, osteoporosis and arthritis are dramatic, the presence of TNF being linked to the accelerated bone resorption associated with these bone disorders. Levels of TNF in bone also appear to be elevated in bone infections. At the time of surgical intervention, TNF is elevated in bone tissues and transiently elevated in the serum of acute (but not chronic) post-traumatic osteomyelitis patients. This may be a direct result of infection as several bacterial components can cause bone resorption. Many of these components are likely to be released during antibiotic-induced lysis and are capable of inducing the formation of cytokines, including TNF. Some surface-associated proteins of Staphylococcus aureus are capable of inducing cells within bone to release several bone-resorbing factors including TNF, although these proteins can also act independently of TNF to induce osteolysis. The combination of azithromycin and rifampicin was previously shown to be a particularly effective treatment regime for experimental acute S. aureus osteomyelitis. Chronic osteomyelitis is generally more difficult to treat than acute osteomyelitis and part of the purpose of this study was to evaluate the combination of azithromycin and rifampicin in a model of chronic osteomyelitis. In this study, we have also investigated the effect of antibacterial therapy on bone TNF activity and TNF mRNA levels and examined the damage caused within bone during experimentally induced chronic osteomyelitis.