Bone morphogenetic proteins − 7 and − 2 in the treatment of delayed osseous union secondary to bacterial osteitis in ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-07-27

AUTHORS

Lars Helbig, Georg W. Omlor, Adriana Ivanova, Thorsten Guehring, Robert Sonntag, J. Philippe Kretzer, Susann Minkwitz, Britt Wildemann, Gerhard Schmidmaier

ABSTRACT

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. More... »

PAGES

261

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12891-018-2203-7

DOI

http://dx.doi.org/10.1186/s12891-018-2203-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1105865417

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30049273


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26 schema:description 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 (10<sup>3</sup> 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 &lt; 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.
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33 schema:keywords Additional micro-CT analysis
34 Micro-CT analysis
35 Sprague-Dawley rats
36 Staphylococcus aureus
37 Union
38 additional extensive soft-tissue damage
39 aim
40 analysis
41 area
42 aureus
43 bacteria inoculation
44 bacterial infection-related types
45 bacterial osteitis
46 biomechanical testing
47 bone
48 bone consolidation
49 bone healing
50 bone infection
51 bone morphogenetic protein
52 bone substitute
53 callus
54 callus formation
55 callus tissue
56 canal
57 challenges
58 chronic infection
59 complex fractures
60 consolidation
61 control
62 control group
63 damage
64 differences
65 efficacy
66 extensive soft tissue damage
67 findings
68 formation
69 fracture healing
70 fracture torque
71 fractured bone
72 fractures
73 great challenge
74 group
75 groups 72 Sprague-Dawley rats
76 healing
77 healing control
78 healing efficacy
79 higher fracture torque
80 histological findings
81 histomorphometric analysis
82 histomorphometric results
83 hypertrophic callus tissue
84 impact
85 infected control group
86 infected group
87 infection
88 infection-related types
89 inoculation
90 intramedullary inoculation
91 intramedullary titanium K
92 irrigation
93 mechanical stability
94 medullary canal
95 micro-CT
96 midshaft tibia
97 mineralized areas
98 model
99 morphogenetic proteins
100 new therapeutic bone substitutes
101 non-infected control group
102 non-infected group
103 ongoing infection
104 open fractures
105 orthopedics
106 osseous union
107 osteitis
108 present rat model
109 prevalence
110 promotes bone
111 protein
112 quantitative micro-CT
113 randomization
114 rat model
115 rats
116 results
117 rhBMP treatment
118 rhBMP-2
119 rhBMP-7
120 saline
121 scores
122 second surgery
123 significant differences
124 situation
125 soft tissue damage
126 stability
127 stabilization
128 sterile saline
129 study
130 substitute
131 such bacterial infection-related types
132 surgery
133 testing
134 therapeutic bone substitutes
135 tibia
136 tissue
137 titanium K
138 torque
139 transverse fractures
140 trauma surgery
141 treatment
142 treatment promotes bone
143 types
144 underwent biomechanical testing
145 weeks
146 weeks rats
147 wire
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