Angiogenic gene therapy as a potential therapeutic agent in chronic osteomyelitis

Bacterial osteomyelitis is common, and outcomes are often poor. Standard therapies fail in 31% of cases, and lower extremity amputation and loss of independent functional status are common. Innovative therapies are desperately needed, particularly in diabetic patients with peripheral vascular disease at high risk for bad outcomes. Angiogenic gene therapy is a novel, logical and promising approach in these patients. Adult bone is not well vascularized. Host inflammation and bacterial toxin production result in further loss of vascularity, and produce bone necrosis. Dead bone acts as a foreign body, and is permissive for persistent infection. Poor blood supply prevents remodeling of dead bone, delivery of antibiotics, and phagocytosis of bacteria. Therefore, angiogenic gene therapy may be a useful therapeutic agent in osteomyelitis. It is reasonable to pursue studies of angiogenic agents in established animal models of chronic osteomyelitis, not only with vascular endothelial growth factor (VEGF), but also with the powerful bone angiogenic agent, placental growth factor, as well as other agents with tissue regenerative and angiogenic potential, such as sonic hedgehog, bone morphogenetic proteins, matrix metalloproteinase-9, secretoneurin, and perhaps pluripotent stem cells. If successful, animal studies could lead to pilot studies of one or more of these agents as adjunctive therapy, in addition to antibiotics, in diabetic patients with chronic osteomyelitis who have failed conventional treatment.