Heterotopic ossification (HO) is a debilitating sequela of high-energy
injuries. It frequently requires surgical excision once symptomatic and there is no practical prophylaxis for combat-injured patients. In this study, we examined the effect of local
vancomycin powder on HO formation in a small animal model of blast-related, post-traumatic HO. Male Sprague-Dawley rats were subjected to a polytraumatic extremity injury and
amputation with or without methicillin-resistant Staphylococcus aureus
infection. Animals were randomized to receive a single local application of
vancomycin (20 mg/kg) at the time of injury (POD-0, n = 34) or on postoperative day-3 (POD-3, n = 11). Quantitative volumetric measurement of ectopic bone was calculated at 12-weeks post-injury by micro-CT. Bone marrow and muscle tissues were also collected to determine the bacterial burden. Blood for serum
cytokine analysis was collected at baseline and post-injury.
Vancomycin treatment on POD-0 suppressed HO formation by 86% and prevented bone marrow and
soft tissue infections. We concurrently observed a marked reduction histologically in nonviable tissue, chronic inflammatory cell infiltrates, bone
infection, fibrous tissue, and areas of
bone necrosis within this same cohort.
Delayed treatment was significantly less efficacious. Neither treatment had a marked effect on the production of pro-inflammatory
cytokines. Our study demonstrates that local
vancomycin treatment at the time of injury significantly reduces HO formation in both the presence and absence of
infection, with decreased efficacy if not given early. These findings further support the concept that the therapeutic window for prophylaxis is narrow, highlighting the need to develop early treatment strategies for clinical management. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2397-2406, 2017.