ALENDRONATE ENHANCES ANTIBIOTIC-IMPREGNATED BONE GRAFTS IN THE TREATMENT OF OSTEOMYELITIS

Abstract

Bisphosphonates are systemically used for the treatment of metabolic bone diseases such as osteoporosis or aseptic loosening after joint replacement surgeries, and there are limited studies on their effects when applied locally. Furthermore, effects of biphosphonates in osteomyelitis treatment are not well-known. A prospective longitudinal randomised controlled study was designed for the rat tibia to test the efficacy of local or systemically administered bisphosphonates for controlling the localised osteolytic reactions and possible effects on local infection control.

Osteomyelitis was induced in the tibia of 72 Wistar albino rats with S. aureus ATCC 25923 strain. All rats in all treatment groups were given curettage and debridement surgery. Rats in Group I were left without any bone grafting. In Group II, dead space was grafted with plain bone graft, while in Group III rats were treated with vancomycin-loaded bone grafts. In group IV, defects were filled with vancomycin-loaded bone grafts, and this was combined with weekly subcutaneous alendronate application at a dose of 240 μg/kg/wk. At Group V defects were grafted with alendronate impregnated bone graft. Finally, rats in Group VI received vancomycin + alendronate impregnated grafts. Dependent variables were groups (n=6) and time (n=2) whereas independent variables were swab cultures, radiology, quantitative computerised tomography, dual energy X-ray absorptiometry and histopathology.

Within three weeks, S.aureus was isolated in all groups. Within six weeks, S.aureus was eradicated in Groups II and IV according to the results of swab cultures. Radiological diaphyseal widening was significantly lower (p=0.037) in Group VI at three weeks. Bone deformation, diaphyseal widening and osteolysis scores were lower in this group at six weeks. Bone mineral content and density measured by quantitative computerised tomography were significantly higher (p=0.001) in Groups IV and VI at six weeks. Bone mineral density measured by dual energy X-ray absorptiometry was significantly higher in Group IV at six weeks. Histology revealed marked osteoblastic activity in Groups IV and VI at six weeks.