Subclinical infection associated with orthopedic devices can be challenging to diagnose. The goal of this study was to evaluate longitudinal, microcomputed tomography (microCT) imaging in a rat model of subclinical orthopedic device-related infection caused by Staphylococcus epidermidis and four different Cutibacterium (previously Propionibacterium) acnes strains, and compare outcomes with non-inoculated and historical S. aureus-inoculated controls. Sterile screws or screws colonized with bacteria were placed in the tibia of 38 adult Wistar rats [n = 6 sterile screws; n = 6 S. epidermidis-colonized screws; n = 26 C. acnes-colonized screws (covering all three main subspecies)]. Regular microCT scans were taken over 28 days and processed for quantitative time-lapse imaging with dynamic histomorphometry. At euthanasia, tissues were processed for semiquantitative histopathology or quantitative bacteriology. All rats receiving sterile screws were culture-negative at euthanasia and displayed progressive bony encapsulation of the screw. All rats inoculated with S. epidermidis-colonized screws were culture-positive and displayed minor changes in peri-implant bone, characteristic of subclinical infection. Five of the 17 rats in the C. acnes inoculated group were culture positive at euthanasia and displayed bone changes at the interface of the screw and bone, but not deeper in the peri-implant bone. Dynamic histomorphometry revealed significant differences in osseointegration, bone remodeling and periosteal reactions between groups that were not measurable by visual observation of still microCT images. Our study illustrates the added value of merging 3D microCT data from subsequent timepoints and producing inherently richer 4D data for the detection and characterization of subclinical orthopedic infections, whilst also reducing animal use.

A significant proportion of orthopedic devices are implanted in osteoporotic patients, but it is currently unclear how estrogen deficiency and/or exposure to antiresorptive bisphosphonates (BPs) influence orthopedic device-related infection (ODRI), or response to therapy. The aim of this study is to characterize the bone changes resulting from Staphylococcus epidermidis infection in a rodent ODRI model and to determine if ovariectomy (OVX) or BP treatment influences the infection or the success of antibiotic therapy. A sterile or S. epidermidis-contaminated screw was implanted into the proximal tibia of skeletally mature female Wistar rats (n = 6-9 per group). Bone changes were monitored over 28 days using in vivo micro-computed tomography scanning. OVX was performed 12 weeks before screw implantation. The BP zoledronic acid (ZOL) was administered 4 days before screw insertion. A combination antibiotic regimen (rifampin plus cefazolin) was administered from Days 7-21. In skeletally healthy animals, S. epidermidis induced marked changes in bone, with peak osteolysis occurring at Day 9 and woven bone deposition and periosteal mineralization from Day 14 onwards. Antibiotic therapy cleared the infection in the majority of animals (2/9 infected) but did not affect bone responses. OVX did not affect the pattern of infection-induced changes in bone, nor bacterial load, but reduced antibiotic efficacy (5/9 infected). ZOL treatment did not protect from osteolysis in OVX animals, or further affect antibiotic efficacy (5/9 infected) but did significantly increase the bacterial load. This study suggests that both BPs and OVX can influence host responses to bone infections involving S. epidermidis.

Hybrid locking pancarpal arthrodesis plates were designed with either a round (RH) or an oval (OH) radiocarpal hole, the latter allowing varied screw positioning. Due to concerns about potential decreased structural properties of the OH design, our aim was to compare the mechanical behavior of the contrasting plates using combined finite element analysis (FEA) and mechanical testing. Pancarpal arthrodesis plates with RH or OH design were assigned to three fixation techniques ( n = 6 ), prebent at 20°, and fixed to canine forelimb models with simulated radius and radiocarpal and 3rd metacarpal bones. OH plates were instrumented with a radiocarpal screw inserted either most proximal (OH-P) or most distal (OH-D). Specimens were axially loaded to 300 N over 10 ramped cycles at 0.5 Hz. Plate strains were measured with strain gauges placed at areas of highest deformations as predicted by FEA under identical loading conditions. FEA predicted the highest strains (μm/m) adjacent to the radiocarpal hole (2,500 [RH], 2,900 [OH-P/OH-D]) and plate bending point (2,250 [RH], 1,900 [OH-P/OH-D]). Experimentally, peak radiocarpal hole strains were not influenced by the OH screw position ( 3,329 ± 443 [OH-P], 3,222 ± 467 [OH-D]; P = 0.550 ) but were significantly higher compared to the RH design ( 2,123 ± 154 ; P < 0.001 ). Peak strains at the bending point were significantly lower for OH-P ( 1,792 ± 174 ) and OH-D ( 1,806 ± 194 ) versus RH configurations ( 2,158 ± 114 ) ( P ≤ 0.006 ). OH plates demonstrated highest peak strains next to the radiocarpal hole and were associated with more heterogenous plate strain distribution. Structural weakening associated with radiocarpal OH plate design could result in decreased fixation strength and increased risk of plate fatigue failure.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for pain management during recovery from orthopaedic surgery. NSAID use is associated with increased risk of bone healing complications but it is currently unknown whether NSAIDs increase the risk of developing an orthopaedic-device-related infection (ODRI) and/or affects its response to antibiotic therapy. The present study aimed to determine if administration of the NSAID carprofen [a preferential cyclooxygenase-2 (COX-2) inhibitor] negatively affected Staphylococcus epidermidis (S. epidermidis) bone infection, or its subsequent treatment with antibiotics, in a rodent ODRI model. Sterile or S. epidermidis-contaminated screws (~ 1.5 x 106 CFU) were implanted into the proximal tibia of skeletally mature female Wistar rats, in the absence or presence of daily carprofen administration. A subset of infected animals received antibiotics (rifampicin plus cefazolin) from day 7 to 21, to determine if carprofen affected antibiotic efficacy. Bone changes were monitored using in vivo µCT scanning and histological analysis. The risk of developing an infection with carprofen administration was assessed in separate animals at day 9 using a screw contaminated with 102 CFU S. epidermidis. Quantitative bacteriological analysis assessed bacterial load at euthanasia. In the 28-day antibiotic treatment study, carprofen reduced osteolysis but markedly diminished reparative bone formation, although total bacterial load was not affected at euthanasia. Antibiotic efficacy was negatively affected by carprofen (carprofen: 8/8 infected; control: 2/9 infected). Finally, carprofen increased bacterial load and diminished bone formation following reduced S. epidermidis inoculum (102 CFU) at day 9. This study suggests that NSAIDs with COX-2 selectivity reduce antibiotic efficacy and diminish reparative responses to S. epidermidis ODRI.

Introduction The aim of this investigation was to better understand the differences in local bone quality at the distal femur and their correlation with biomechanical construct failure, with the intention to identify regions of importance to optimize implant anchorage. Materials and methods Seven fresh–frozen female femurs underwent high-resolution peripheral quantitative computed tomography (HR-pQCT) to determine bone mineral density (BMD) within three different regions of interest (distal, intermedium, and proximal) at the distal femur. In addition, local bone quality was assessed by measuring the peak torque necessary to break out the trabecular bone along each separate hole of a locking compression plate (LCP) during its instrumentation. Finally, biomechanical testing was performed using cyclic axial loading until failure in an AO/OTA 33 A3 fracture model. Results Local BMD was highest in the distal region. This was confirmed by the measurement of local bone quality using DensiProbe™. The most distal holes represented locations with the highest breakaway torque resistance, with the holes on the posterior side of the plate indicating higher values than those on its anterior side. We demonstrated strong correlation between the cycles to failure and local bone strength (measured with DensiProbe™) in the most distal posterior screw hole, having the highest peak torque. Conclusion The local bone quality at the distal femur indicates that in plated distal femur fractures the distal posterior screw holes seem to be the key ones and should be occupied. Measurement of the local bone strength with DensiProbe™ is one possibility to determine the risk of construct failure, therefore, thresholds need to be defined.