Bioactive glass S53P4 as bone graft substitute in treatment of osteomyelitis
Introduction
Osteomyelitis, first described by Chassaignac in 1852, is caused by infecting micro-organisms and defines a destructive inflammatory process in bone that is often accompanied by bone destruction [1]. The infection can arise from a variety of aetiologies [2]. Most often it is caused by trauma, but any kind of bone or soft tissue surgery where pathogens can enter the bone, may cause the infection. In diabetic patients, osteomyelitis may appear as a secondary manifestation due to vascular insufficiency and soft tissue infection [3]. Haematogenous osteomyelitis has been found in children, as well as in elderly patients [4].
Acute osteomyelitis is an infection characterized by oedema, locally decreased blood supply and pus formation. Untreated or due to treatment failure, the infection can progress to a more chronic phase, with formation of a large area of devascularized dead bone, a sequestrum. In treatment of chronic osteomyelitis, adequate debridement is mandatory. Unfortunately, this treatment often results in a poorly vascularized large bone defect, a dead space. Bacterial infection can also cause local acidosis, leading to dissolution of bone matrix mineral [5]. Many different methods have been used to treat the bone defect and the infection, including free vascularized bone grafts, local muscle flaps, antibiotic-impregnated polymethyl methacrylate (PMMA) beads, granulation formation according to the technique of Papineau and the Masquelet technique [6] or bone reconstruction based on Ilizarov technology [7].
Staphylococcus aureus and Gram-negative bacilli are the pathogens most commonly involved [7]. The bacterial colonization of host tissue or implanted materials is promoted by the ability of the bacteria to produce protein-specific adhesins on their surfaces, which is followed by interactions with host protein components, such as fibrinogen, fibronectin and collagen. Bacteria also have sophisticated methods for communication through hormone-like compounds in biofilms, making treatment with antimicrobial agents difficult [2]. Use of synthetic bone graft substitutes in treating osteomyelitis is, therefore, generally not recommended.
Bioactive glasses (BAGs) are synthetic biocompatible osteoconductive bone substitutes, with bone bonding capacity and documented antibacterial and angiogenesis-promoting properties [8], [9], [10], [11], [12], [13], [14], [15], [16]. Previous studies on atrophic rhinitis, a chronic purulent disorder often caused by Klebsiella ozaenae and difficult to treat, have shown that BAG-S53P4 does not favour adhesion or colonization of K. ozaenae on its surface. In addition, K. ozaenae cannot form biofilms on BAG-S53P4 [17].
The aim of this study was to apply the experimentally known antibacterial properties of BAG-S53P4 to clinical practice, evaluating the operative outcome using BAG-S53P4 as a bone graft substitute in treating osteomyelitis.
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Patients and methods
This is a multicentre study on patients with verified osteomyelitis in 2007–2009. Eleven patients (nine males, two females) with a radiologically diagnosed osteomyelitis participated. Osteomyelitis was verified on MRI (nine patients), or on CT scans (two patients). Osteomyelitis was localized in the lower extremity in ten cases and in the spine in one case (Fig. 1, Fig. 2). Seven of the patients had sustained a fracture: in the distal tibia (three patients), in the calcaneus (two patients), in
Results
BAG-S53P4 was well tolerated; no BAG-related adverse effects were seen in any patient. The use of BAG-S53P4 as a bone graft substitute resulted in a fast recovery, i.e. patients that had been treated with long-lasting therapies responded well to the treatment. Clinical outcome was good or excellent in nine of eleven patients. The clinical and radiological findings are summarized in Table 3.
Postoperative complications needing treatment were seen in two patients. In one patient, vascular problems
Discussion
Despite advances in antibiotic therapies and operative techniques, treatment of osteomyelitis remains challenging, expensive and time-consuming for both the doctor and the patient.
Debridement in combination with local administration of antibiotics, e.g. gentamicin-loaded PMMA beads, has for years been the method of choice in treating osteomyelitis. However, in a long-term follow-up study of 100 patients treated with gentamicin-PMMA beads, relapses were observed for 8.8% of patients with acute
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