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Bone & Joint Research
Vol. 13, Issue 12 | Pages 790 - 792
17 Dec 2024
Mangwani J Brockett C Pegg E

Cite this article: Bone Joint Res 2024;13(12):790–792.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_20 | Pages 18 - 18
12 Dec 2024
Rai A Nanda R Ponugoti N Saunders M
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Objectives. Distal humerus fractures in elderly population are often comminuted and presents multiple challenges. When managed with fixation the results are often complicated with stiffness, pain, and reduced function while total elbow replacement is fraught with lifelong restrictions on load bearing which can significantly affect elderly patients who rely assistive devices for ambulation. Elbow hemiarthroplasty however, presents a viable alternative in these cases. This series evaluates the results of the distal humerus hemiarthroplasty in a single centre. Designs and methods. Data was collected retrospectively. Comprehensive case reviews were done to collect demographic, intra-operative and post-operative data. Fractures were classified as per AO classification. The primary outcome was functional outcome and range of motion (ROM). The secondary outcomes were complications and patient satisfaction. Results. 22 cases were included in this study from 2016 – 2023 majority being females (n=18). Mean age was 74years (SD −11.2). Majority fractures were AO type C3 (n=15) with two A2 type fractures managed for non-union. Pre-existing bone on bone arthritis was present in 3 cases and CT scan was done for 12 patients to assess fracture configuration. Excluding those treated for non- union the median time between fracture and surgery was 8.5 days. Follow-up of more than 6 months was available for 16 patients with median follow-up of 18 months. ROM was available for 17 patients with 13 (50%) patients having functional ROM. No patients had full extension and there was a mean lag of 20. 0. Mean flexion was 118.2. 0. Nearly 2/3. rd. patients (73%- n=16) were satisfied with the surgery with no problems in activity of daily living. Complications seen were ulnar neuropathy (n=3), heterotopic ossification(n=2) and periprosthetic fracture (n=1). Conclusion. This single centre study suggests good outcomes following distal humerus hemiarthroplasty. It is a reasonable alternative to fixation and total elbow arthroplasty in complex fractures


Bone & Joint Research
Vol. 13, Issue 12 | Pages 716 - 724
4 Dec 2024
Cao S Chen Y Zhu Y Jiang S Yu Y Wang X Wang C Ma X

Aims

This cross-sectional study aimed to investigate the in vivo ankle kinetic alterations in patients with concomitant chronic ankle instability (CAI) and osteochondral lesion of the talus (OLT), which may offer opportunities for clinician intervention in treatment and rehabilitation.

Methods

A total of 16 subjects with CAI (eight without OLT and eight with OLT) and eight healthy subjects underwent gait analysis in a stair descent setting. Inverse dynamic analysis was applied to ground reaction forces and marker trajectories using the AnyBody Modeling System. One-dimensional statistical parametric mapping was performed to compare ankle joint reaction force and joint moment curve among groups.


Bone & Joint Research
Vol. 13, Issue 12 | Pages 703 - 715
3 Dec 2024
Raza IGA Snelling SJB Mimpen JY

Aims

Extracellular matrix (ECM) is a critical determinant of tissue mechanobiology, yet remains poorly characterized in joint tissues beyond cartilage in osteoarthritis (OA). This review aimed to define the composition and architecture of non-cartilage soft joint tissue structural ECM in human OA, and to compare the changes observed in humans with those seen in animal models of the disease.

Methods

A systematic search strategy, devised using relevant matrix, tissue, and disease nomenclature, was run through the MEDLINE, Embase, and Scopus databases. Demographic, clinical, and biological data were extracted from eligible studies. Bias analysis was performed.


The Bone & Joint Journal
Vol. 106-B, Issue 12 | Pages 1416 - 1425
1 Dec 2024
Stroobant L Jacobs E Arnout N Van Onsem S Tampere T Burssens A Witvrouw E Victor J

Aims

Approximately 10% to 20% of knee arthroplasty patients are not satisfied with the result, while a clear indication for revision surgery might not be present. Therapeutic options for these patients, who often lack adequate quadriceps strength, are limited. Therefore, the primary aim of this study was to evaluate the clinical effect of a novel rehabilitation protocol that combines low-load resistance training (LL-RT) with blood flow restriction (BFR).

Methods

Between May 2022 and March 2024, we enrolled 45 dissatisfied knee arthroplasty patients who lacked any clear indication for revision to this prospective cohort study. All patients were at least six months post-surgery and had undergone conventional physiotherapy previously. The patients participated in a supervised LL-RT combined with BFR in 18 sessions. Primary assessments included the following patient-reported outcome measures (PROMs): Knee injury and Osteoarthritis Outcome Score (KOOS); Knee Society Score: satisfaction (KSSs); the EuroQol five-dimension five-level questionnaire (EQ-5D-5L); and the pain catastrophizing scale (PCS). Functionality was assessed using the six-minute walk Test (6MWT) and the 30-second chair stand test (30CST). Follow-up timepoints were at baseline, six weeks, three months, and six months after the start.


The Bone & Joint Journal
Vol. 106-B, Issue 12 | Pages 1426 - 1430
1 Dec 2024
Warne CN Ryan S Yu E Osmon DR Berry DJ Abdel MP

Aims

Cutibacterium acnes (C. acnes; previously known as Propionibacterium acnes or P. acnes) periprosthetic hip and knee infections are under-reported. While culture contamination with C. acnes occurs, true infections are important to recognize and treat. We sought to describe the demographics and treatment outcomes of patients with C. acnes periprosthetic joint infections (PJIs) of the hip and knee.

Methods

Patients with C. acnes PJI between January 2005 and December 2018 were retrospectively reviewed utilizing the institutional total joint registry. Patients with monomicrobial PJI and two or more positive cultures were considered to have true C. acnes PJI. Patients with polymicrobial infection or with only one positive culture were excluded. This resulted in 35 PJIs (21 hips and 14 knees); the patients’ mean age was 63 years (35 to 84) and 15 (43%) were female. Mean follow-up was five years (1 to 14).


Bone & Joint 360
Vol. 13, Issue 6 | Pages 23 - 26
1 Dec 2024

The December 2024 Foot & Ankle Roundup360 looks at: Tibiotalar sector and lateral ankle instability; Isolated subtalar fusion and correction of progressive collapsing foot deformity; Diabetic control and postoperative complications following ankle fracture fixation; Are insoles of any benefit for plantar fasciitis?; Postoperative foot shape and patient-reported outcome following surgery for progressing collapsing foot deformity; Calcaneo-stop procedure for symptomatic flexible flatfoot in children.


The Bone & Joint Journal
Vol. 106-B, Issue 12 | Pages 1477 - 1484
1 Dec 2024
Wang Y Shen L Xie D Long H Chen H Wei J Zeng C Lei G

Aims

For displaced femoral neck fractures (FNFs) in geriatric patients, there remains uncertainty regarding the effect of total hip arthroplasty (THA) compared with hemiarthroplasty (HA) in the guidelines. We aimed to compare 90-day surgical readmission, in-hospital complications, and charges between THA and HA in these patients.

Methods

The Hospital Quality Monitoring System was queried from 1 January 2013 to 31 December 2019 for displaced FNFs in geriatric patients treated with THA or HA. After propensity score matching, which identified 33,849 paired patients, outcomes were compared between THA and HA using logistic and linear regression models.


The Bone & Joint Journal
Vol. 106-B, Issue 12 | Pages 1431 - 1442
1 Dec 2024
Poutoglidou F van Groningen B McMenemy L Elliot R Marsland D

Lisfranc injuries were previously described as fracture-dislocations of the tarsometatarsal joints. With advancements in modern imaging, subtle Lisfranc injuries are now more frequently recognized, revealing that their true incidence is much higher than previously thought. Injury patterns can vary widely in severity and anatomy. Early diagnosis and treatment are essential to achieve good outcomes. The original classification systems were anatomy-based, and limited as tools for guiding treatment. The current review, using the best available evidence, instead introduces a stability-based classification system, with weightbearing radiographs and CT serving as key diagnostic tools. Stable injuries generally have good outcomes with nonoperative management, most reliably treated with immobilization and non-weightbearing for six weeks. Displaced or comminuted injuries require surgical intervention, with open reduction and internal fixation (ORIF) being the most common approach, with a consensus towards bridge plating. While ORIF generally achieves satisfactory results, its effectiveness can vary, particularly in high-energy injuries. Primary arthrodesis remains niche for the treatment of acute injuries, but may offer benefits such as lower rates of post-traumatic arthritis and hardware removal. Novel fixation techniques, including suture button fixation, aim to provide flexible stabilization, which theoretically could improve midfoot biomechanics and reduce complications. Early findings suggest promising functional outcomes, but further studies are required to validate this method compared with established techniques. Future research should focus on refining stability-based classification systems, validation of weightbearing CT, improving rehabilitation protocols, and optimizing surgical techniques for various injury patterns to ultimately enhance patient outcomes.

Cite this article: Bone Joint J 2024;106-B(12):1431–1442.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 10 - 10
14 Nov 2024
Zderic I Kraus M Rossenberg LV Puls L Pastor T Gueorguiev B Richards G Pape HC Pastor T
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Introduction. The main postoperative complications in fixation of ulna shaft fractures are non-union and implant irritation using currently recommended 3.5-mm locking compression plates. An alternative approach using a combination of two smaller plates in orthogonal configuration has been proposed. The aim of this study was to compare the biomechanical properties of a single 3.5-mm locking compression plate versus double plating using one 2.5-mm and one 2.0-mm mandible plate in a human ulna shaft fracture model. Method. Eight pairs human ulnar specimens with a standardized 10-mm fracture gap were pairwise assigned for instrumentation with either a single 3.5-mm plate placed posteriorly, or for double plating using a 2.5-mm and a 2.0-mm mandible plate placed posteriorly under the flexor muscles and laterally under the extensor muscles. All constructs were initially non-destructively biomechanically tested in axial compression, torsion, and bending, which was followed by cyclic torsional loading to failure. Interfragmentary movements were monitored by means of optical motion tracking. Result. There were no significant differences between the two plating techniques for axial stiffness (p=0.335), torsional stiffness in supination (p=0.462), torsional stiffness in pronation (p=0.307), medio-lateral bending stiffness (p=0.522), and antero-posterior bending stiffness (p=0.143). During cyclic torsional loading over the first 3000 cycles, there were no significant differences between the two plating techniques for shear displacement across the fracture gap, p=0.324. The numbers of cycles until clinically relevant failure of 5° angular deformation were 1366±685 for double plating and 2024±958 for single plating, which was statistically non-significantly different, p>0.05. The constructs treated with both plating techniques failed due to bone breakage at the most distal screw. Conclusion. From a biomechanical perspective double plating of ulna shaft fractures using a 2.5-mm and a 2.0-mm locking mandible plate demonstrated equivalent fixation strength as conventional plating using a single 3.5-mm locking compression plate


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 41 - 41
14 Nov 2024
Soubrier A Kasper H Alini M Jonkers I Grad S
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Introduction. Intervertebral disc degeneration has been associated with low back pain (LBP) which is a major cause of long-term disability worldwide. Observed mechanical and biological modifications have been related to decreased water content. Clinical traction protocols as part of LBP management have shown positive outcomes. However, the underlying mechanical and biological processes are still unknown. The study purpose was to evaluate the impact of unloading through traction on the mechanobiology of healthy bovine tail discs in culture. Method. We loaded bovine tail discs (n=3/group) 2h/day at 0.2Hz for 3 days, either in dynamic compression (-0.01MPa to -0.2MPa) or in dynamic traction (-0.01MPa to 0.024MPa). In between the dynamic loading sessions, we subjected the discs to static compression loading (-0.048MPa). We assessed biomechanical and biological parameters. Result. Over the 3 days of loading, disc height decreased upon dynamic compression loading but increased upon unloading. The neutral zone was restored for all samples at the end of the dynamic unloading. Upon dynamic compression, the stiffness increased over time while the hysteresis decreased. Upon dynamic unloading, sulfated glycosaminoglycan (sGAG) release in the medium was lower at the endpoint. In the outer annulus fibrosus (AFo), we saw a higher water/sGAG of at least 30%. In the nucleus pulposus, COL2 mRNA was expressed more highly upon dynamic unloading while MMP3, iNOS and TRPV4 expression levels were lower. In the AFo of the unloading group, COL2 expression was higher but COL1 was lower. Conclusion. The biomechanical and biological results consistently indicate that dynamic unloading of healthy bovine discs in culture facilitates water uptake and promotes an anti-catabolic response which reflects a function optimization of the disc. This work combines biomechanical and biological results and opens the door to evidence-based improvement of regenerative protocols for degenerated discs and conservative LBP management. This study is funded by AO Foundation and AO Spine


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 54 - 54
14 Nov 2024
Pann P Taheri S Schilling AF Graessel S
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Introduction. Osteoarthritis (OA) causes pain, stiffness, and loss of function due to degenerative changes in joint cartilage and bone. In some forms of OA, exercise can alleviate symptoms by improving joint mobility and stability. However, excessive training after joint injury may have negative consequences for OA development. Sensory nerve fibers in joints release neuropeptides like alpha-calcitonin gene-related peptide (alpha-CGRP), potentially affecting OA progression. This study investigates the role of alpha-CGRP in OA pathogenesis under different exercise regimen in mice. Method. OA was induced in C57Bl/6J WT mice and alpha-CGRP KO mice via surgical destabilization of the medial meniscus (DMM) at 12 weeks of age (N=6). Treadmill exercise began 2 weeks post-surgery and was performed for 30 minutes, 5 days a week, for 2 or 6 weeks at intense (16 m/min, 15° incline) or moderate (10 m/min, 5° incline) levels. Histomorphometric assessment of cartilage degradation (OARSI scoring), serum cytokine analysis, immunohistochemistry, and nanoCT analysis were conducted. Result. OARSI scoring confirmed OA induction 4 weeks post-DMM surgery, with forced exercise exacerbating cartilage degradation regardless of intensity. No significant genotype-dependent differences were observed. Serum analysis revealed elevated cytokine levels associated with OA and inflammation in KO mice compared to WT mice 4 and 8 weeks post-surgery (VEGF-A, MCP-1, CXCL10, RANTES, MIP1-alpha, MIP1-beta, and RANKL). The observed effects were often exacerbated by intense exercise but rarely by DMM surgery. NanoCT analysis demonstrated increased sclerotic bone changes after 6 weeks of forced exercise in KO mice compared to WT mice. Conclusion. Our results suggest an OA promoting effect of exercise in early disease stages of posttraumatic OA. Intense exercise induced inflammatory processes correlated to increased cytokine levels in the serum that might exacerbate OA pathogenesis in later stages. The neuropeptide alpha-CGRP might play a role in protecting against these adverse effects


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 37 - 37
14 Nov 2024
Zderic I Kraus M Axente B Dhillon M Puls L Gueorguiev B Richards G Pape HC Pastor T Pastor T
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Introduction. Distal triceps tendon rupture is related to high complication rates with up to 25% failures. Elbow stiffness is another severe complication, as the traditional approach considers prolonged immobilization to ensure tendon healing. Recently a dynamic high-strength suture tape was designed, implementing a silicone-infused core for braid shortening and preventing repair elongation during mobilization, thus maintaining constant tissue approximation. The aim of this study was to biomechanically compare the novel dynamic tape versus a conventional high-strength suture tape in a human cadaveric distal triceps tendon rupture repair model. Method. Sixteen paired arms from eight donors were used. Distal triceps tendon rupture tenotomies and repairs were performed via the crossed transosseous locking Krackow stitch technique for anatomic footprint repair using either conventional suture tape (ST) or novel dynamic tape (DT). A postoperative protocol mimicking intense early rehabilitation was simulated, by a 9-day, 300-cycle daily mobilization under 120N pulling force followed by a final destructive test. Result. Significant differences were identified between the groups regarding the temporal progression of the displacement in the distal, intermediate, and proximal tendon aspects, p<0.001. DT demonstrated significantly less displacement compared to ST (4.6±1.2mm versus 7.8±2.1mm) and higher load to failure (637±113N versus 341±230N), p≤0.037. DT retracted 0.95±1.95mm after each 24-hour rest period and withstood the whole cyclic loading sequence without failure. In contrast, ST failed early in three specimens. Conclusion. From a biomechanical perspective, DT revealed lower tendon displacement and greater resistance in load to failure over ST during simulated daily mobilization, suggesting its potential for earlier elbow mobilization and prevention of postoperative elbow stiffness


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 94 - 94
14 Nov 2024
Koh J Mungalpara N Chang N Devi IMP Hutchinson M Amirouche F
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Introduction. Understanding knee joint biomechanics is crucial, but studying Anterior cruciate ligament (ACL) biomechanics in human adolescents is challenging due to limited availability cadaveric specimens. This study aims to validate the adolescent porcine stifle joint as a model for ACL studies by examining the ACL's behavior under axial and torsion loads and assessing its deformation rate, stiffness, and load-to-failure. Methods. Human knee load during high-intensity sports can reach 5-6 times body weight. Based on these benchmarks, the study applied a force equivalent to 5-times body weight of juvenile porcine samples (90 pounds), estimating a force of 520N. Experiments involved 30 fresh porcine stifle joints (Yorkshire breed, Avg 90 lbs, 2-4 months old) stored at -22°C, then thawed and prepared. Joints were divided into three groups: control (load-to-failure test), axially loaded, and 30-degree torsion loaded. Using a servo-hydraulic material testing machine, the tibia's longitudinal axis was aligned with the load sensor, and specimens underwent unidirectional tensile loading at 1 mm/sec until rupture. Data on load and displacement were captured at 100 Hz. Results. One-way ANOVA showed statistically significant differences in maximum failure force among loading conditions (p = 0.0039). Post hoc analysis indicated significant differences between the control and 500N (non-twisted) groups (p = 0.014) and between the control and 500N (twisted) groups (p = 0.003). However, no significant difference was found between 500N (non-twisted) and 500N (twisted) groups (p = 0.2645). Two samples broke from the distal femur growth plates, indicating potential growth plate vulnerability in adolescent porcines. Conclusions. The study validates the adolescent porcine stifle joint as a suitable model for ACL biomechanical research, demonstrating that torsional loads are as damaging to the ACL's integrity as equivalent axial loads. It also highlights the potential vulnerability of growth plates in younger populations, reflected in the porcine model


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 29 - 29
14 Nov 2024
Dhillon M Klos K Lenz M Zderic I Gueorguiev B
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Introduction. Tibiocalcaneal arthrodesis with a retrograde intramedullary nail is an established procedure considered as a salvage in case of severe arthritis and deformity of the ankle and subtalar joints [1]. Recently, a significant development in hindfoot arthrodesis with plates has been indicated. Therefore, the aim of this study was to compare a plate specifically developed for arthrodesis of the hindfoot with an already established nail system [2]. Method. Sixteen paired human cadaveric lower legs with removed forefoot and cut at mid-tibia were assigned to two groups for tibiocalcaneal arthrodesis using either a hindfoot arthrodesis nail or an arthrodesis plate. The specimens were tested under progressively increasing cyclic loading in dorsiflexion and plantar flexion to failure, with monitoring via motion tracking. Initial stiffness was calculated together with range of motion in dorsiflexion and plantar flexion after 200, 400, 600, 800, and 1000 cycles. Cycles to failure were evaluated based on 5° dorsiflexion failure criterion. Result. Initial stiffness in dorsiflexion, plantar flexion, varus, valgus, internal rotation and external rotation did not differ significantly between the two arthrodesis techniques (p ≥ 0.118). Range of motion in dorsiflexion and plantar flexion increased significantly between 200 and 1000 cycles (p < 0.001) and remained not significantly different between the groups (p ≥ 0.120). Cycles to failure did not differ significantly between the two techniques (p = 0.764). Conclusion. From biomechanical point of view, both tested techniques for tibiocalcaneal arthrodesis appear to be applicable. However, clinical trials and other factors, such as extent of the deformity, choice of the approach and preference of the surgeon play the main role for implant choice. Acknowledgements. This study was performed with the assistance of the AO Foundation


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 106 - 106
14 Nov 2024
Bliddal H Beier J Hartkopp A Conaghan P Henriksen M
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Introduction. Polyacrylamide hydrogel (iPAAG. 1. ), is CE marked for treating symptomatic knee osteoarthritis (OA), meeting the need for an effective, long-lasting, and safe non-surgical option. This study evaluates the efficacy and safety of a single 6 ml intra-articular injection of iPAAG in participants with moderate to severe knee OA over a 5-year post-treatment period, presenting data from the 4-year follow up. Method. This prospective multicentre study (3 sites in Denmark) involved 49 participants (31 females) with an average age of 70 (range 44 – 86 years). They received a single 6 mL iPAAG injection. All participants provided informed consent and re-consented to continue after 1 year. The study followed GCP principles and was approved by Danish health authorities and local Health Research Ethics committees. Twenty-seven participants completed the 4-year follow-up. The study evaluated WOMAC pain, stiffness, function, and Patient Global Assessment (PGA) of disease impact. Changes from baseline were analysed using a mixed model for repeated measurement (MMRM). Sensitivity analyses were applied on the extension data, where the MMRM analysis was repeated only including patients in the extension phase and an ANCOVA model was used, replacing missing values at 4-years with baseline values (BOCF). Results. The planned MMRM analysis (n=49) revealed a statistically significant decrease in WOMAC pain subscale scores (-22.0; 95%CI: -29.5; -14.4) from baseline to 4-years. Analysis of the extension phase (n=27) showed similar results (-21.8; 95%CI: -29.0; -14.6) compared to the initial analysis. Furthermore, BOCF analysis indicated a statistically significant reduction in WOMAC pain subscale scores from baseline (-13.0 units). Four new adverse events were reported between the 3-year and 4-year visits; none were related to treatment. Conclusions. This study shows that single injections of 6 ml intra-articular iPAAG were well tolerated and continued to provide clinically important effectiveness at 4-years after treatment. Acknowledgements. The study was sponsored by Contura International A/S


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 30 - 30
14 Nov 2024
Schröder M Gens L Arens D Giger N Gehweiler D Nehrbass D Zderic I Zeiter S Stoddart M Wehrle E
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Introduction. Immunomodulation represents a novel strategy to improve bone healing in combination with low doses of bone morphogenetic growth factors like BMP-2. This study aims to investigate the effect and timing of monoclonal anti-IL-1ß antibody administration with 1μg BMP-2 on bone healing over 14 weeks in a rat femur segmental defect model. Method. 2 mm femoral defects were created in 22-27 weeks-old female Fischer F344 rats, internally fixed with a plate (animal license: GR/19/2022) using established protocols for analgesia and anesthesia. Animals (n=4/group) received either a collagen sponge, a collagen sponge+1μg BMP-2 (InductOs, Medtronic) or a collagen sponge+1μg BMP-2 with a monoclonal anti-IL-1ß antibody (BioXCell, 10 mg/ml), administered intravenously under anesthesia every third day until day 15, from day 0 or 3. In vivo micro-CT was performed after surgery and at 2, 3, 4, 6, 8, 10 and 14-weeks post-OP. Mechanical properties of the operated femurs were assessed by 4-point bending (Instron5866) and compared to contralateral femurs (one-way ANOVA, GraphPad Prism8). Histopathological analysis was performed semi-quantitatively on Giemsa-Eosin-stained sections (Olympus BX63) using a six-grade severity grading scale. Result. Operated femurs with BMP-2 reached an average stiffness of 91±37% of contralateral femurs, femurs in IL-1ß groups 105±11% (day 0) and 111±12% (day 3). Administration of anti-IL-1ß+1μg BMP-2 led to faster cortical bridging (3/4 femurs bridged by week 4 for day 0, 4/4 for day 3) than 1μg BMP-2 alone (0/4 by week 4). Micro-CT results confirmed histopathological evaluation, as collagen sponge alone led to non-union, complete bicortical bridging was observed for 3/4 femurs in the BMP-2 group and for 4/4 femurs in the IL-1β groups after 14 weeks. Conclusion. Anti-IL-1ß had a beneficial effect on late fracture healing with faster cortical bridging and new bone formation than 1μg BMP-2 alone. Acknowledgments. AO foundation. We thank Andrea Furter, Alisa Hangartner and Thomas Krüger for technical support


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 119 - 119
14 Nov 2024
Rösch G Rapp AE Tsai PL Kohler H Taheri S Schilling AF Zaucke F Slattery D Lanzl ZJ
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Introduction. Osteoarthritis (OA) is a chronic degenerative disease of the entire joint leading to joint stiffness and pain (PMID:33571663). Recent evidence suggests that the sympathetic nervous system (SNS) plays a role in the pathogenesis of OA (PMID:34864169). A typical cause for long-term hyperactivity of the SNS is chronic stress. To study the contribution of increased sympathetic activity, we analyzed the progression of OA in chronically stressed mice. Method. We induced OA in male C57BL/6J mice by destabilizing the medial meniscus (DMM)(PMID:17470400) and exposed half of these mice to chronic unpredictable mild stress (CUMS)(PMID:28808696). Control groups consisted of sham-operated mice with and without CUMS exposure. After 12 weeks, CUMS efficacy was determined by assessing changes in body weight gain and activity of mice, measuring splenic norepinephrine and serum corticosterone levels. OA progression was studied by histological analysis of cartilage degeneration and synovitis, and by μCT to evaluate changes in calcified cartilage and subchondral bone microarchitecture. A dynamic weight-bearing system was used to assess OA-related pain. Result. CUMS resulted in significantly decreased body weight gain and activity, as well as increased splenic norepinephrine and serum corticosterone concentrations compared to the respective controls. Surprisingly, already DMM alone resulted in elevated stress hormone levels. CUMS significantly exacerbated cartilage degeneration and synovial inflammation and increased OA pain in DMM mice. The underlying cellular and molecular mechanisms are currently being analyzed using FACS, single cell RNAseq, and spatial proteomics. Conclusion. Overall, chronic stress exacerbates OA severity and pain. Moreover, increased levels of stress hormones were observed in OA mice without CUMS induction, suggesting a complex bi-directional interaction between the SNS and OA. Targeting the autonomic nervous system, such as attenuating the SNS but also stimulating the activity of the parasympathetic nervous system, as a counterpart of the SNS, may therefore be promising for novel preventive or causal treatments of OA


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 100 - 100
14 Nov 2024
Castorena JG Riester R Ornelas MG Guilak F Danalache M
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Introduction. Piezo1 is a mechanosensitive Ca. 2+. ion channel that has been shown to transduce hyper-physiologic mechanical loads in chondrocytes. In osteoarthritic cartilage, Piezo1 expression was shown to be upregulated by interleukin-1 alpha (IL-1α) and resulted in altered calcium dynamics and actin cytoskeleton rarefication. Together these studies highlight the importance of Piezo1 channels during joint injury. However, the mechanism by which Piezo1 regulates chondrocyte physiology and mechanotransduction during homeostasis is still largely unknown. In this study, we investigate the impact of Piezo1 activation on nuclear mechanics and chromatin methylation state. Methods. Porcine chondrocytes (n=3-5 pigs) were treated with Yoda1, a Piezo1-specific agonist, for either 2, 5, 15 or 180 minutes. To characterize chromatin state, we monitored the abundance of a chromatin methylation marker (H3K9Me3) using immunofluorescence (IF). Atomic force microscopy (AFM, 25 nm cantilever) was employed to quantify the nuclear elastic modulus (NEM) of individual cell nuclei. To explore the interplay between cytoskeletal dynamics and nuclear mechanics, chondrocytes were treated with Latrunculin A (LatA), an actin polymerization inhibitor. Result. IF experiments showed chromatin methylation was the lowest 2 minutes post Yoda1 activation of Piezo1 (p=0.027). Additionally, we found that 2 or 5 minutes post-Piezo1 activation resulted in a significantly lower NEM when compared to the control (p<0.00001). The observed decrease in NEM at 2 and 5 minutes post-Piezo1 activation was not observed after knocking down Piezo1 (p>0.99). In LatA treated cells, the elevated NEM persisted even after Piezo1 activation with Yoda1 (p>0.75). Conclusion. These findings illuminate the mechanism by which Piezo1 activation and actin remodeling regulate transient mechanotransduction during homeostasis. Further research into the transient decrease in nuclear stiffness and chromatin methylation observed during the initial 5 minutes of Piezo1-induced Ca2+ signaling, may contribute to a better understanding of the role of Piezo1 channels in joint injury and development of therapeutic interventions for osteoarthritis


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 102 - 102
14 Nov 2024
Strack D Mesbah M Rayudu NM Baum T Kirschke J Subburaj K
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Introduction. Functional Spine Units (FSUs) play a vital role in understanding biomechanical characteristics of the spine, particularly bone fracture risk assessment. While established models focus on simulating axial compression of individual bones to assess fracture load, recent models underscore the importance of understanding fracture load within FSUs, offering a better representation of physiological conditions. Despite the limited number of FSU fracture studies, they predominantly rely on a linear material model with an annulus fibrosus Young's modulus set at 500 MPa, significantly higher than stiffness values (ca. 4 MPa) utilized in other FSU and spine section biomechanical models. Thus, this study aims to study the effect of varying annulus fibrosus stiffness on FSU fracture load, aiming to identify physiologically relevant biomechanical parameters. Method. Subject-specific geometry and material properties of bones were derived from computed tomography (CT) image data of five human cadaveric FSU specimens. The annulus fibrosus and nucleus pulposus were manually recreated and assigned linear elastic material properties. By subjecting the model to axial compression, the fracture load of the FSU was deduced from the peak of the force-displacement graph. To explore the effect of stiffness of the annulus fibrosus on simulated fracture load, we conducted a parameter study, varying stiffness values from the high 500 MPa to a more physiologically relevant 25 MPa, aiming to approximate values applied in FSU kinematic models while achieving bone fracture. Result. Significant reductions in fracture load were observed, ranging from 23% to 46%, as annulus stiffness decreased from 500MPa to 25MPa. Additionally, a discernible, gradual decline in fracture load was observed with a decrease in stiffness values. Conclusion. The stiffness of the annulus fibrosus significantly influences the simulated fracture load of an FSU. Future investigations should prioritize biomechanically accurate modeling of the intervertebral disc, ensuring alignment with experimental findings regarding FSU fracture load while maintaining biomechanical fidelity