Bone morphogenetic proteins - 7 and - 2 in the treatment of delayed osseous union secondary to bacterial osteitis in a rat model.

BACKGROUND: Bone infections due to trauma and subsequent delayed or impaired fracture healing represent a great challenge in orthopedics and trauma surgery. The prevalence of such bacterial infection-related types of delayed non-union is high in complex fractures, particularly in open fractures with additional extensive soft-tissue damage. The aim of this study was to establish a rat model of delayed osseous union secondary to bacterial osteitis and investigate the impact of rhBMP-7 and rhBMP-2 on fracture healing in the situation of an ongoing infection. METHODS: After randomization to four groups 72 Sprague-Dawley rats underwent a transverse fracture of the midshaft tibia stabilized by intramedullary titanium K-wires. Three groups received an intramedullary inoculation with Staphylococcus aureus (103 colony-forming units) before stabilization and the group without bacteria inoculation served as healing control. After 5 weeks, a second surgery was performed with irrigation of the medullary canal and local rhBMP-7 and rhBMP-2 treatment whereas control group and infected control group received sterile saline. After further 5 weeks rats were sacrificed and underwent biomechanical testing to assess the mechanical stability of the fractured bone. Additional micro-CT analysis, histological, and histomorphometric analysis were done to evaluate bone consolidation or delayed union, respectively, and to quantify callus formation and the mineralized area of the callus. RESULTS: Biomechanical testing showed a significantly higher fracture torque in the non-infected control group and the infected rhBMP-7- and rhBMP-2 group compared with the infected control group (p < 0.001). RhBMP-7 and rhBMP-2 groups did not show statistically significant differences (p = 0.57). Histological findings supported improved bone-healing after rhBMP treatment but quantitative micro-CT and histomorphometric results still showed significantly more hypertrophic callus tissue in all three infected groups compared to the non-infected group. Results from a semiquantitative bone-healing-score revealed best bone-healing in the non-infected control group. The expected chronic infection was confirmed in all infected groups. CONCLUSIONS: In delayed bone healing secondary to infection rhBMP treatment promotes bone healing with no significant differences in the healing efficacy of rhBMP-2 and rhBMP-7 being noted. Further new therapeutic bone substitutes should be analyzed with the present rat model for delayed osseous union secondary to bacterial osteitis.

Initial peri- and postoperative antibiotic treatment of infected nonunions: results from 212 consecutive patients after mean follow-up of 34 months.

PURPOSE: Infected nonunions of the long bones belong to the most feared complications in the field of orthopedic and trauma surgery. Optimal antibiotic therapy should start early with the first revision surgery. Therefore, the aim of this study was to evaluate our peri- and postoperative antibiotic regime in context with the microbial spectrum and antibiotic resistances of patients with infected nonunions and to assess the possible impact on healing rates. METHODS: We included all patients with first revision surgery during 2010-2015 due to nonunion of long bones with a clinical history of infection treated with radical debridement, local application of a gentamicin-impregnated bone cement, and systemic cefuroxime. Mean follow-up was 34.2 months. Data collection was performed retrospectively using a computerized databank with information about microbial species from intraoperatively acquired tissue samples and respective antibiograms. Bone fusion rates were evaluated based on findings of the latest X-rays and computed tomography scans. RESULTS: Two hundred and twelve patients with nonunion and history of infection were selected; 171 patients had positive intraoperative microbial evidence of infection. Bacterial testing was mostly positive in fractures of the tibia (47.4%) and the femur (27.5%). Coagulase-negative Staphylococcus spp. were the most frequently detected (44.4%) followed by mixed infections (18.7%) and Staphylococcus aureus (10.5%). Antibiograms revealed that 62.6% of our cases were cefuroxime sensitive; 87.7% were gentamicin sensitive. Only 10.5% showed resistance to both cefuroxime and gentamicin. There was no statistically significant difference of fusion rates between patients with different microbial species or different antibiograms. CONCLUSION: Our data suggest that besides the high variety of different detected species, initial antibiotic treatment with a combination of systemic cefuroxime and local gentamicin-loaded bone cement is effective and in almost 90% the later determined microbial infection was sensitive to this treatment. Therefore, we recommend initial treatment according to this algorithm until specific antibiograms are available from intraoperatively acquired tissue samples.

Mitochondrial diversity in mountain horse population from the South-Eastern Europe.

It is believed that population structure of mountain horse breeds is preserved from any genetic introgression, because of their geographical isolation and specific semi-wild life style of husbandry. Till date there are no molecular data for the Balkan horses. In this study we try to give information about some autochthonous mountain horse breeds from Bulgaria. A total of 121 horses from three different mountain massifs are presented: Stara Planina (the Balkan mountain), the Rhodopes and Rila-Pirin massif were genotyped according to mitochondrial D-loop region. The results showed huge diversity of all known haplogroups with exception of C, F and R. West Eurasian haplogroups B, D, M and L were with the highest frequencies. Haplogroups A, J, I, O'P and Q were also observed with the highest frequencies, but not equally distributed among the three populations. Analyses of the horse breeds reveal preserved genetic profile of the Balkan and the Rhodopes mountains populations. In contrast, a Rila-Pirin breed unexpectedly showed mixed profile - a massive genetic introgression with an Asiatic-type haplogroups. A similar mixed Euro-Asiatic haplotype profile possessed the Carpathian mountain pony, although both populations are separated geographically and historically. The genetic pool of three Bulgarian mountain horse populations is highly heterogenic and because of that these breeds should be preserved.

A new animal model for delayed osseous union secondary to osteitis.

BACKGROUND: The treatment of infection-related delayed bone unions is still very challenging for the orthopedic surgeon. The prevalence of such infection-related types of osteitis is high in complex fractures, particularly in open fractures with extensive soft-tissue damage. The aim of this study was to develop a new animal model for delayed union due to osteitis. METHODS: After randomization to infected or non-infected groups 20 Sprague-Dawley rats underwent a transverse fracture of the midshaft tibia. After intramedullary inoculation with staphylococcus aureus (10(3) CFU) fracture stabilization was done by intramedullary titanium K-wires. After 5 weeks all rats were euthanized and underwent biomechanical testing to evaluate bone consolidation or delayed union, respectively. Micro-CT scans were additionally used to quantitatively evaluate the callus formation by the score of Lane and Sandhu. Blood samples were taken to analyze infectious disease markers (day 1, 14 and 35). RESULTS: Biomechanical testing showed a significant higher maximum torque in the non-infected group 5 weeks postoperatively compared with the infected group (p < 0.001). According to the Lane and Sandhu score a significantly higher callus formation was found in the non-infected group (p < 0.001). Similarly, the leucocyte count in the infected group was significantly higher than in the non-infected group (p < 0.05). CONCLUSIONS: Here we have established a new animal model for delayed osseous union secondary to osteitis. The animal model appears to be appropriate for future experimental studies to test new therapeutic strategies in these difficult to treat bone healing complications.