Implant infection is an increasing problem in orthopedic surgery, especially due to progressive antibiotic resistance and an aging population with rising numbers of implantations. As a consequence, new strategies for infection prevention are necessary. In the previous study it was hypothesized that laser-structured implant surfaces favor cellular adhesion while hindering bacterial ongrowth and therewith contribute to reduce implant infections. Cuboid titanium implants (0.8 × 0.8 × 12 mm. 3. , n=34) were used. Seventeen were laser-structured by ultra-short pulsed laser ablation to create a spike structure; the others were polished and served as controls. In general anesthesia, implants were inserted in rat tibiae and infected with a S. aureus suspension. During a 21 day postoperative follow-up, daily clinical control was performed. Radiographs were taken at day 14 and day 21. After euthanasia, bacterial load and biofilm formation on the implant surface was evaluated semi quantitatively by confocal laser scanning microscopy and computational acquisition of bacteria and cells by Imaris®-software. Additionally, histology of the surrounding bone was performed. Clinically, no differences were observed between the groups. However, contrary to our hypothesis, bacterial load was increased in the laser-structured implant group although cellular adhesion was even more pronounced. Radiographical and histological evaluations showed increased bone alterations in the group with laser-structured implants compared to the control group. These findings did not confirm prior in vitro studies, where a reduction of bacterial load was found for similar surfaces and demonstrate the necessity of in vivo trials prior to the clinical use of new materials

Little is known on how sensory nerves and osteoclasts affect degenerative processes in subchondral bone in osteoarthritis (OA). Substance P (SP) effects on bone are ambivalent but physiological levels are critical for proper bone quality whereas α-calcitonin gene-related peptide (αCGRP) has anabolic effects. Here, we aimed to analyse the influence of an altered sensory neuropeptide microenvironment on subchondral bone in murine OA. Transection of the medial meniscotibial ligament (DMM) of the right hind leg induced joint instability leading to development of OA. Subchondral bone of tibiae from wildtype (WT), alendronate-treated WT (ALN, osteoclast inhibition), αCGRP- and SP- (Tachykinin (Tac)1) knockout mice was analysed by micro-computed tomography 4 and 12 weeks after DMM or sham surgery. Bone resorption marker CTX-I was measured in serum. We observed osteophytosis in all DMM groups and ALN sham mice 4 weeks after surgery but also in sham groups 12 weeks after surgery. In subchondral bone, bone volume density (BV/TV) increased from 4 to 12 weeks after surgery in DMM WT and Tac1-/− mice. DMM WT mice additionally had increased trabecular numbers (Tb.N.) and decreased trabecular space (Tb.Sp.) over time. Sham mice also showed time-dependent alterations in subchondral bone. In sham WT and αCGRP-/− mice specific bone surface (BS/BV) decreased and trabecular thickness (Tb.Th.) increased from 4 to 12 weeks after surgery while subchondral BV/TV of αCGRP-/− mice increased. Comparison of subchondral bone parameters at each time point showed elevated BV/TV in ALN DMM compared to WT DMM mice 4 weeks after surgery. In addition, both ALN sham and DMM mice showed a reduced BS/BV compared to WT. 4 weeks after sham surgery Tb.Th. was highest in ALN mice. In DMM WT mice Tb.Sp. was higher compared to ALN and αCGRP-/−. 12 weeks after surgery (late OA stage), BS/BV of ALN sham mice was significantly reduced in relation to ALN DMM, WT and Tac1-/− sham, while Tb.Th. increased compared to WT. DMM significantly decreased Tb.N. and increased Tb.Sp. in Tac1-/− compared to sham 12 weeks after surgery. CTX-I concentrations were significantly higher in ALN compared to Tac1-/− mice 4 weeks after sham surgery. 12 weeks after sham surgery CTX-I concentrations of WT mice were increased compared to αCGRP-/− and Tac1-/− mice. Over time, DMM induced stronger changes in subchondral bone of WT mice compared to knockout strains. WT and αCGRP-/− sham mice also show alterations in bone parameters over time indicating age-related effects on bone structure. SP deficiency enhanced DMM-induced structural bone alterations in late stage OA emphasizing the importance of SP under pathophysiological conditions. Osteoclast inhibition with alendronate proved to be preservative for time-dependent changes of subchondral bone observed in both, DMM and sham mice. Interestingly, ALN treatment did not reduce bone turnover marker CTX-I, and additionally promoted early osteophyte formation in sham mice

Knee osteoarthritis (OA) affects an estimated 250 million people worldwide, with a cure yet to be found. Consequently, there is an urgent need to improve our understanding of OA physiopathology. While knee OA has long been mostly described as a loss of cartilage thickness (CTh) and research has focused on this characteristic, the role of bone alterations is rapidly gaining in interest. Analyzing subchondral bone mineral density (sBMD) is particularly interesting because this could inform on the mechanical environment at the knee. However, there is a paucity of data on sBMD in literature mainly because of the lack of prior methods to measure this parameter. A method for 3D sBMD assessment based on computed tomography (CT) scans was recently proposed, thus allowing testing for sBMD differences in knee OA. This study aimed at comparing non-OA and medial OA knees in terms of tibial sBMD and CTh. Specifically, it was hypothesized that sBMD and CTh differ with OA. Ten knees with severe medial OA and 10 matched non-OA knees were analyzed after ethical approval (50% male; 60 ± 3 years old). The arthro-CT scans of the 20 knees were segmented using custom software to build 3D mesh models of the tibial bone and cartilage. CTh maps were obtained by calculating the distance between cartilage and bone meshes, while sBMD maps were calculated based on the intensity of the CT in the first 3mm of bone. For each knee, the average CTh and sBMD values over the entire medial and lateral compartments were calculated and used to determine the medial-to-lateral (M/L) CTh and sBMD ratios. Unpaired t-tests and receiver operating characteristic (ROC) were used for statistical analysis. The M/L sBMD ratio was significantly higher in OA compared to non-OA knees (1.14 ± 0.04 vs. 1.08 ± 0.03; p<0.01), whereas the CTh ratio was not significantly different between groups (0.70 ± 0.21 vs. 0.85 ± 0.10; p=0.06). No significant differences were found between OA and non-OA knees for the average medial CTh and sBMD (p>0.4). High classification performance was obtained for the sBMD ratio and low performance for the average sBMD in the medial compartment (areas under the ROC curve of 0.9 and 0.6, respectively). CTh ratio and medial compartment average provided medium classification performances (areas under the curve of 0.7). This study showed that sBMD differed between non-OA and severe medial OA knees and that sBMD M/L ratio was more sensitive to OA severity than CTh variables. These results brought new insights into the pathogenesis of knee OA, by supporting the idea that sBMD is altered with OA and suggesting that sBMD could play a role in disease development. Indeed, the mechanical stresses on the cartilages are related to the mechanical characteristics of the bones. Indirectly, this study also demonstrated the value of arthro-CT scans to simultaneously assess sBMD and CTh. Additional studies with larger cohorts of patients at different stages of the disease are necessary to better understand when changes in sBMD occur

The accurate positioning of the total knee arthroplasty affects the survival of the implants(1). Alignment of the femoral component in relation to the native knee is best determined using pre- and post-operative 3D-CT reconstruction(2). Currently, the scans are visualised on separate displays. There is a high inter- and intra-observer variability in measurements of implant rotation and translation(3). Correct alignment is required to allow a direct comparison of the pre- and post-operative surfaces. This is prevented by the presence of the prostheses, the bone shape alteration around the implant, associated metal artefacts, and possibly a segmentation noise. The aim is to create a novel method to automatically register pre- and post-operative femora for the direct comparison of the implant and the native bone. The concept is to use post-operative femoral shaft segments free of metal noise and of surgical alteration for alignment with the pre-operative scan. It involves three steps. Firstly, using principal component analysis, the femoral shafts are re-oriented to match the X axis. Secondly, variants of the post-operative scan are created by subtracting 1mm increments from the distal femoral end. Thirdly, an iterative closest point algorithm is applied to align the variants with the pre-operative scan. For exploratory validation, this algorithm was applied to a mesh representing the distal half of a 3D scanned femur. The mesh of a prosthesis was blended with the femur to create a post-operative model. To simulate a realistic environment, segmentation and metal artefact noise were added. For segmentation noise, each femoral vertex was translated randomly within +−1mm,+−2mm,+−3mm along its normal vector. To create metal artefact random noise was added within 50 mm of the implant points in the planes orthogonal to the shaft. The alignment error was considered as the average distance between corresponding points which are identical in pre- and post-operative femora. These preliminary results obtained within a simulated environment show that by using only the native parts of the femur, the algorithm was able to automatically register the pre- and post-operative scans even in presence of the implant. Its application will allow visualisation of the scans on the same display for the direct comparison of the perioperative scans. This method requires further validation with more realistic noise models and with patient data. Future studies will have to determine if correct alignment has any effect on inter- and intra-observer variability

We investigated the effect of locally administered bisphosphonate on distraction osteogenesis in a rabbit model and evaluated its systemic effect. An osteotomy on the right tibia followed by distraction for four weeks was performed on 47 immature rabbits. They were divided into seven equal groups, with each group receiving a different treatment regime. Saline and three types of dosage of alendronate (low, 0.75 μg/kg; mid, 7.5 μg/kg and high 75 μg/kg) were given by systemic injection in four groups, and saline and two dosages (low and mild) were delivered by local injection to the distraction gap in the remaining three groups. The injections were performed five times weekly during the period of distraction.

After nine weeks the animals were killed and image analysis and mechanical testing were performed on the distracted right tibiae and the left tibiae which served as a control group. The local low-dose alendronate group showed a mean increase in bone mineral density of 124.3 mg/cm³ over the local saline group (analysis of variance, p < 0.05) without any adverse effect on the left control tibiae.

The findings indicate that the administration of local low-dose alendronate could be an effective pharmacological means of improving bone formation in distraction osteogenesis.