A Modular Communicative Leadless Pacing-Defibrillator System.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (ICD) is associated with fewer lead-related complications than a transvenous ICD; however, the subcutaneous ICD cannot provide bradycardia and antitachycardia pacing. Whether a modular pacing-defibrillator system comprising a leadless pacemaker in wireless communication with a subcutaneous ICD to provide antitachycardia and bradycardia pacing is safe remains unknown. METHODS: We conducted a multinational, single-group study that enrolled patients at risk for sudden death from ventricular arrhythmias and followed them for 6 months after implantation of a modular pacemaker-defibrillator system. The safety end point was freedom from leadless pacemaker-related major complications, evaluated against a performance goal of 86%. The two primary performance end points were successful communication between the pacemaker and the ICD (performance goal, 88%) and a pacing threshold of up to 2.0 V at a 0.4-msec pulse width (performance goal, 80%). RESULTS: We enrolled 293 patients, 162 of whom were in the 6-month end-point cohort and 151 of whom completed the 6-month follow-up period. The mean age of the patients was 60 years, 16.7% were women, and the mean (±SD) left ventricular ejection fraction was 33.1±12.6%. The percentage of patients who were free from leadless pacemaker-related major complications was 97.5%, which exceeded the prespecified performance goal. Wireless-device communication was successful in 98.8% of communication tests, which exceeded the prespecified goal. Of 151 patients, 147 (97.4%) had pacing thresholds of 2.0 V or less, which exceeded the prespecified goal. The percentage of episodes of arrhythmia that were successfully terminated by antitachycardia pacing was 61.3%, and there were no episodes for which antitachycardia pacing was not delivered owing to communication failure. Of 162 patients, 8 died (4.9%); none of the deaths were deemed to be related to arrhythmias or the implantation procedure. CONCLUSIONS: The leadless pacemaker in wireless communication with a subcutaneous ICD exceeded performance goals for freedom from major complications related to the leadless pacemaker, for communication between the leadless pacemaker and subcutaneous ICD, and for the percentage of patients with a pacing threshold up to 2.0 V at a 0.4-msec pulse width at 6 months. (Funded by Boston Scientific; MODULAR ATP ClinicalTrials.gov NCT04798768.).

Dual-energy lattice-tip ablation system for persistent atrial fibrillation: a randomized trial.

Clinical outcomes of catheter ablation for atrial fibrillation (AF) are suboptimal due, in part, to challenges in achieving durable lesions. Although focal point-by-point ablation allows for the creation of any required lesion set, this strategy necessitates the generation of contiguous lesions without gaps. A large-tip catheter, capable of creating wide-footprint ablation lesions, may increase ablation effectiveness and efficiency. In a randomized, single-blind, non-inferiority trial, 420 patients with persistent AF underwent ablation using a large-tip catheter with dual pulsed field and radiofrequency energies versus ablation using a conventional radiofrequency ablation system. The primary composite effectiveness endpoint was evaluated through 1 year and included freedom from acute procedural failure and repeat ablation at any time, plus arrhythmia recurrence, drug initiation or escalation or cardioversion after a 3-month blanking period. The primary safety endpoint was freedom from a composite of serious procedure-related or device-related adverse events. The primary effectiveness endpoint was observed for 73.8% and 65.8% of patients in the investigational and control arms, respectively (P < 0.0001 for non-inferiority). Major procedural or device-related complications occurred in three patients in the investigational arm and in two patients in the control arm (P < 0.0001 for non-inferiority). In a secondary analysis, procedural times were shorter in the investigational arm as compared to the control arm (P < 0.0001). These results demonstrate non-inferior safety and effectiveness of the dual-energy catheter for the treatment of persistent AF. Future large-scale studies are needed to gather real-world evidence on the impact of the focal dual-energy lattice catheter on the broader population of patients with AF. ClinicalTrials.gov identifier: NCT05120193 .

Management of Lisfranc Injuries: A Critical Analysis Review.

¼: There is a spectrum of midtarsal injuries, ranging from mild midfoot sprains to complex Lisfranc fracture-dislocations. ¼: Use of appropriate imaging can reduce patient morbidity, by reducing the number of missed diagnoses and, conversely, avoiding overtreatment. Weight-bearing radiographs are of great value when investigating the so-called subtle Lisfranc injury. ¼: Regardless of the operative strategy, anatomical reduction and stable fixation is a prerequisite for a satisfactory outcome in the management of displaced injuries. ¼: Fixation device removal is less frequently reported after primary arthrodesis compared with open reduction and internal fixation based on 6 published meta-analyses. However, the indications for further surgery are often unclear, and the evidence of the included studies is of typically low quality. Further high-quality prospective randomized trials with robust cost-effectiveness analyses are required in this area. ¼: We have proposed an investigation and treatment algorithm based on the current literature and clinical experience of our trauma center.

Longitudinal QTc stability and impact of baseline cardiac rhythm on discharge dose in dofetilide-treated patients.

INTRODUCTION: Dofetilide suppresses atrial fibrillation (AF) in a dose-dependent fashion. The protective effect of AF against QTc prolongation induced torsades de pointe and transient post-cardioversion QTc prolongation may result in dofetilide under-dosing during initiation. Thus, the optimal timing of cardioversion for AF patients undergoing dofetilide initiation to optimize discharge dose remains unknown as does the longitudinal stability of QTc . The purpose of this study was to evaluate the impact of baseline rhythm on dofetilide dosing during initiation and assess the longitudinal stability of QTc-all (Bazzett, Fridericia, Framingham, and Hodges) over time. METHODS: Medical records of patients who underwent preplanned dofetilide loading at a tertiary care center between January 2016 and 2019 were reviewed. RESULTS: A total of 198 patients (66 ± 10 years, 32% female, CHADS2 -Vasc 3 [2-4]) presented for dofetilide loading in either AF (59%) or sinus rhythm (SR) (41%). Neither presenting rhythm, nor spontaneous conversion to SR impacted discharge dose. The cumulative dofetilide dose before cardioversion moderately correlated (r = .36; p = .0001) with discharge dose. Postcardioversion QTc-all prolongation (p < .0001) prompted discharge dose reduction (890 ± 224 mcg vs. 552 ± 199 mcg; p < .0001) in 30% patients. QTc-all in SR prolonged significantly during loading (p < .0001). All patients displayed QTc-all reduction (p < .0001) from discharge to short-term (46 [34-65] days) that continued at long-term (360 [296-414] days) follow-ups. The extent of QTc-all reduction over time moderately correlated with discharge QTc-all (r = .54-0.65; p < .0001). CONCLUSION: Dofetilide initiation before cardioversion is equivalent to initiation during SR. Significant QTc reduction proportional to discharge QTc is seen over time in all dofetilide-treated patients. QTc returns to preloading baseline during follow-up in patients initiated in SR.

Relationship between Surpoint Tag Index, a Radiofrequency Ablation lesion quality indicator, and Atrial wall thickness in Cavotricuspid isthmus Ablations exhibiting bidirectional block.

BACKGROUND: An RFA lesion quality indicator, Surpoint Tag Index® (TI) incorporates key factors: power, time, and contact force, impacting lesion quality. TI accurately estimates lesion depth in animal studies. However, the relationship between TI and in-vivo atrial wall thickness in patients exhibiting bidirectional block remains unknown. OBJECTIVE: To describe the relationship between atrial wall thickness and TI in CTI exhibiting bidirectional block. METHODS: Data from 492 RFA lesions from 25 patients undergoing PVI and CTI ablations in SR with point-by-point RF lesions (<45 W) utilizing a Thermocool Smarttouch® SF ablation catheter and CARTO-3 mapping were retrospectively analyzed. Operators were blinded to TI data and CTI thickness. CTI thickness was obtained using ICE images on Cartosound pre-ablation. Durable lesions were defined as part of a lesion set exhibiting bidirectional block of >30 min. RESULTS: In lesions exhibiting bidirectional block, the thinnest (1-2 mm; 5% lesions) and thickest (8-10 mm; 6% lesions) portions of the CTI correlated with the lowest (429 ± 75) and highest (516 ± 64) TI. The bulk of thickness (2-6 mm; 80%) correlated with a TI of 455 ± 72 (p = 0.001). There was a weak but positive correlation between TI and CTI thickness (r = 0.2; p ≤ 0.01). Examined in sectors, the anterior 1/3rd CTI was the thickest (4.8 ± 1.9 mm) but correlated with a similar TI value (479 ± 75 vs. 471 ± 70; p = 0.34) as the thinner middle 1/3rd (3.8 ± 1.7 mm; p ≤ 0.0001). CONCLUSION: A mean TI value of 455 correlates with bidirectional block across the bulk of CTI with lower and higher values needed for the thinner and thicker portions, respectively. Tissue composition, aside from wall thickness, influences TI values for the creation of the bidirectional block.

Impact of a dedicated atrial fibrillation clinic on diagnosis-to-ablation time.

Background: Outcomes following catheter ablation (CA) for atrial fibrillation (AF) improve as the diagnosis-to-ablation time (DAT) shortens. Use of a protocol-based integrated care model through a dedicated atrial fibrillation clinic (AFC) may serve to standardize treatment pathways and decrease DAT. Objective: To evaluate the DAT and clinical characteristics of patients with AF referred from an AFC vs a conventional electrophysiology clinic (EC). Methods: Retrospective analysis was completed in consecutive patients undergoing index AF ablation at Riverside Methodist Hospital in 2019 with minimum 1 year follow-up. Patients were categorized based off their CA referral source (AFC vs EC) and where the initial visit following index diagnosis of AF occurred (AFC vs EC). Results: A total of 182 patients (mean age 65 years, 64% male) were reviewed. Patients referred from an AFC (21%) had a median DAT of 342 days (interquartile range [IQR], 125-855 days) compared to patients referred from EC (79%) with a median DAT of 813 days (IQR, 241-1444 days; P = .01). Patients with their index visit following AF diagnosis occurring in the AFC (9%) had significantly shorter median DAT (127 days [IQR, 95-188 days]) compared to EC (91%) (789 days [IQR, 253-1503 days]; P = .002). Patients with DAT <1 year had lower AF recurrence than patients with DAT >1 year (P = .04, hazard ratio = 0.58, 95% confidence interval 0.3418-1.000). Conclusion: DAT is a modifiable factor that may affect CA outcomes. Significant reductions in DAT were observed in patients evaluated through a dedicated AF clinic.

Lead Macrodislodgement of a Subcutaneous Implantable Cardioverter-Defibrillator Results in a Reel Problem.

Lead macrodislodgement is a rare complication of cardiac implantable electronic devices associated with patient-related risk factors. This paper outlines a case of reel syndrome secondary to device manipulation 3 months after subcutaneous implantable cardioverter-defibrillator implantation and describes the challenges with lead macrodislodgement diagnosis, mechanisms, and management. (Level of Difficulty: Beginner.).

Cell-associated type I collagen in nondegenerate and degenerate human articular cartilage.

Chondrocytes with abnormal morphology are present in nondegenerate human cartilage suggesting dedifferentiation to a fibroblastic phenotype and production of a mechanically-weakened matrix of unknown composition. We determined the relationship between in situ chondrocyte morphology, chondrocyte clusters, and levels of cell-associated collagen type I. Chondrocyte morphology in fresh femoral head cartilage from 19 patients with femoral neck fracture and collagen type I labelling was identified with Cell TrackerTM fluorescence and immunofluorescence, respectively, in axial/coronal orientations using confocal microscopy with images analysed by ImarisTM . In axial images of grade 0 cartilage, 87 ± 8% were normal chondrocytes with a small (10 ± 6%) abnormal population possessing ≥1 cytoplasmic process. More normal chondrocytes (78 ± 11%) were collagen type I negative than those labelling positively (p < 0.001). For abnormal chondrocytes, 81 ± 14% labelled negatively for collagen type I compared to those labelling positively (19 ± 3%; p = 0.007; N(n)=11(3)). Overall, approximately 9% of the cells in normal cartilage labelled for collagen type I. With degeneration, the percentage of normal chondrocytes decreased (p < 0.001) but increased for abnormal cells (p = 0.036) and clusters (p = 0.003). A larger percentage of normal, abnormal and clustered chondrocytes now demonstrated collagen type I labelling (p = 0.004; p = 0.009; p = 0.001 respectively). Coronal images exhibited increased (p = 0.001) collagen type I labelling in the superficial zone of mildly degenerate cartilage with none in the mid or deep zones. These results show that collagen type I was identified around normal and abnormal chondrocytes in nondegenerate cartilage, which increased with degeneration. This suggested the presence of mechanically weak fibro-cartilaginous repair tissue in otherwise macroscopically nondegenerate human cartilage which progressed with degeneration as occurs in osteoarthritis.

Hinge location and apical drill holes in opening wedge high tibial osteotomy: A finite element analysis.

At the time of medial opening wedge high tibial osteotomy (HTO) to realign the lower limb and offload medial compartment knee osteoarthritis, unwanted fractures can propagate from the osteotomy apex. The aim of this study was to use finite element (FE) analysis to determine the effect of hinge location and apical drill holes on cortical stresses and strains in HTO. A monoplanar medial opening wedge HTO was created above the tibial tuberosity in a composite tibia. Using the FE method, intact lateral hinges of different widths were considered (5, 7.5, and 10 mm). Additional apical drill holes (2, 4, and 6 mm diameters) were then incorporated into the 10 mm hinge model. The primary outcome measure was the maximum principal strain in the cortical bone surrounding the hinge axis. Secondary outcomes included the force required for osteotomy opening, minimum principal strain, and mean cortical bone stresses (maximum principal/minimum principal/von Mises). Larger intact hinges (10 mm) were associated with higher cortical bone maximum principal strain and stress, lower minimum principal strain/stress, and required greater force to open. Lateral cortex strain concentrations were present in all scenarios, but extended to the joint surface with the 10 mm hinge. Apical drill holes reduced the mean cortical bone maximum principal strain adjacent to the hinge axis: 2 mm hole 6% reduction; 4 mm 35% reduction; and 6 mm 55% reduction. Incorporating a 4-mm apical drill hole centered 10 mm from the intact lateral cortex maintains a cortical bone hinge, minimizes cortical bone strains and reduces the force required to open the HTO; thus improving control.

Optimization and Validation of a Human Ex Vivo Femoral Head Model for Preclinical Cartilage Research and Regenerative Therapies.

OBJECTIVE: Articular cartilage is incapable of effective repair following injury or during osteoarthritis. While there have been developments in cartilage repair technologies, there is a need to advance biologically relevant models for preclinical testing of biomaterial and regenerative therapies. This study describes conditions for the effective ex vivo culture of the whole human femoral head. DESIGN: Fresh, viable femoral heads were obtained from femoral neck fractures and cultured for up to 10 weeks in (a) Dulbecco's modified Eagle's medium (DMEM); (b) DMEM + mixing; (c) DMEM + 10% human serum (HS); (d) DMEM + 10% HS + mixing. The viability, morphology, volume, and density of fluorescently labelled in situ chondrocytes and cartilage surface roughness were assessed by confocal microscopy. Cartilage histology was studied for glycosaminoglycan content using Alcian blue and collagen content using picrosirius red. RESULTS: Chondrocyte viability remained at >95% in DMEM + 10% HS. In DMEM alone, viability remained high for ~4 weeks and then declined. For the other conditions, superficial zone chondrocyte viability fell to <35% at 10 weeks with deeper zones being relatively unaffected. In DMEM + 10% HS at 10 weeks, the number of chondrocytes possessing cytoplasmic processes increased compared with DMEM (P = 0.017). Alcian blue labeling decreased (P = 0.02) and cartilage thinned (P ≤ 0.05); however, there was no change to surface roughness, chondrocyte density, chondrocyte volume, or picrosirius red labeling (P > 0.05). CONCLUSIONS: In this ex vivo model, chondrocyte viability was maintained in human femoral heads for up to 10 weeks in culture, a novel finding not previously reported. This human model could prove invaluable for the exploration, development, and assessment of preclinical cartilage repair and regenerative therapies.

Percutaneous reduction and fixation of low energy Lisfranc injuries results in better outcome compared to open reduction and internal fixation: Results from a matched case-control study with minimum 12 months follow up.

BACKGROUND: Percutaneous fixation of Lisfranc injuries is potentially less invasive to traditional open techniques but evidence of any clinical benefit is lacking. The aim of this study is to compare the clinical outcomes of percutaneous reduction and internal fixation (PRIF) of low energy Lisfranc injuries with a matched, control group of patients treated with ORIF. METHODS: Over a seven-year period (2012-2019), 16 consecutive patients with a low energy Lisfranc injury (Myerson B2-type) were treated with PRIF. Patient demographics, injury mechanism and radiological outcomes were recorded within a prospectively maintained database at the institution. This study sample was matched for age, sex and mechanism of injury to a control group of 16 patients with similar low energy Lisfranc injuries (Myerson B2-type) treated with ORIF. Clinical outcome was compared using the American Orthopaedic Foot and Ankle Society (AOFAS) midfoot score and Manchester Oxford Foot Questionnaire (MOXFQ). RESULTS: At a mean follow up of 43 months (95% CI 35.6 - 50.4), both the AOFAS and MOXFQ scores were significantly higher in the PRIF group compared to the control ORIF group (AOFAS 89.1vs 76.4, p=0.03; MOXFQ 10.0 vs 27.6, p=0.03). There were no immediate postoperative complications in either group. There was no radiological evidence of midfoot osteoarthritis in the PRIF group, three patients in the ORIF group developed midfoot osteoarthritis (p=0.2). CONCLUSIONS: PRIF of low energy Lisfranc injures is a safe, minimally invasive technique and is associated with better mid-term clinical outcomes compared to ORIF.

Editorial Commentary: Raising the Osmolarity of Arthroscopic Irrigating Solutions May Be Chondroprotective: We Must Be Kind to Joints During Arthroscopy!

The irrigation of joints during arthroscopic procedures typically uses a non-physiological solution. This replaces the natural synovial fluid and rapidly subjects the connective tissues to an alien hypo-osmotic environment in which cartilage cells are far more sensitive to iatrogenic injury. Raising the osmolarity of the irrigating solution may be a simple, safe, and effective chondroprotective strategy.

Population mobility and adult orthopaedic trauma services during the COVID-19 pandemic: fragility fracture provision remains a priority.

AIMS: This study aims to define the epidemiology of trauma presenting to a single centre providing all orthopaedic trauma care for a population of ∼ 900,000 over the first 40 days of the COVID-19 pandemic compared to that presenting over the same period one year earlier. The secondary aim was to compare this with population mobility data obtained from Google. METHODS: A cross-sectional study of consecutive adult (> 13 years) patients with musculoskeletal trauma referred as either in-patients or out-patients over a 40-day period beginning on 5 March 2020, the date of the first reported UK COVID-19 death, was performed. This time period encompassed social distancing measures. This group was compared to a group of patients referred over the same calendar period in 2019 and to publicly available mobility data from Google. RESULTS: Orthopaedic trauma referrals reduced by 42% (1,056 compared to 1,820) during the study period, and by 58% (405 compared to 967) following national lockdown. Outpatient referrals reduced by 44%, and inpatient referrals by 36%, and the number of surgeries performed by 36%. The regional incidence of traumatic injury fell from 5.07 (95% confidence interval (CI) 4.79 to 5.35) to 2.94 (95% CI 2.52 to 3.32) per 100,000 population per day. Significant reductions were seen in injuries related to sports and alcohol consumption. No admissions occurred relating to major trauma (Injury Severity Score > 16) or violence against the person. Changes in population mobility and trauma volume from baseline correlated significantly (Pearson's correlation 0.749, 95% CI 0.58 to 0.85, p < 0.001). However, admissions related to fragility fractures remained unchanged compared to the 2019 baseline. CONCLUSION: The profound changes in social behaviour and mobility during the early stages of the COVID-19 pandemic have directly correlated with a significant decrease in orthopaedic trauma referrals, but fragility fractures remained unaffected and provision for these patients should be maintained.Cite this article: Bone Joint Open 2020;1-6:182-189.

A Ghost Left Behind After Transvenous Lead Extraction: A Finding to be Feared.

BACKGROUND Following transvenous lead extraction (TLE) for infective endocarditis, a fibrinous remnant, or "ghost", that previously encapsulated the lead may remain. The main aim of this case report was to highlight the importance of identification of ghosts, their negative implications, and the importance of close monitoring. CASE REPORT A 72-year-old male with a history of heart failure with non-ischemic cardiomyopathy and remote cardiac resynchronization therapy defibrillator (CRT-D) placement as well as atrioventricular node ablation for atrial fibrillation presented following a mechanical fall. An initial evaluation revealed methicillin-resistant Staphylococcus aureus bacteremia; the suspected nidus was an indwelling chemotherapy port for non-Hodgkin's lymphoma. Echocardiography demonstrated vegetations on the aortic and mitral valves, and the right atrial device lead concerning for infective endocarditis. After TLE, a temporary transvenous wire was placed. Definitive pacing was then achieved by a Micra leadless pacemaker (LP). We opted with LP technology via the Micra device with plan for subcutaneous implantable cardioverter defibrillator (SICD) implantation to mitigate the risk of infection recurrence. After completion of 6 weeks of antibiotics, a pre-SICD transesophageal echocardiogram identified a 1.3 cm mobile echo-dense "ghost" in the right atrium. SICD was implanted as planned. Following expert consensus, no specific therapy was implemented when the ghost was identified. At 3 months, echocardiography revealed the absence of the ghost. At 1-year follow-up, no infection recurrence was noted. CONCLUSIONS The presence of ghosts after transvenous lead extraction is associated with poor outcome and infection recurrence thus requiring diligent monitoring and serial echocardiography as optimal management is yet to be defined.

Rates of Displacement and Patient-Reported Outcomes Following Conservative Treatment of Minimally Displaced Lisfranc Injury.

BACKGROUND: While surgery is indicated in Lisfranc fracture-dislocations, the natural history and optimal management of minimally displaced injures are unclear. The aim of this study was to define the rate of subsequent displacement and to determine the clinical outcome after conservative treatment of minimally displaced Lisfranc injuries. METHODS: Over a 5-year period (2011-2016), 26 consecutive patients with minimally displaced Lisfranc injuries presenting to a single university teaching hospital were identified retrospectively using hospital electronic records. Patient demographics, injury mechanism, and radiological outcomes were recorded. Patient-reported outcome scores (PROMS) were collated at least 1 year postinjury and included the American Orthopaedic Foot & Ankle Society (AOFAS) midfoot score and Manchester Oxford Foot Questionnaire (MOXFQ). RESULTS: The rate of displacement was 54% (14/26). The median time to displacement was 18 days (range, 2-141 days). Forty-six percent (12/26) of the Lisfranc injuries remained minimally displaced after 12 weeks of conservative treatment. Initial weightbearing status was not associated with the risk of subsequent displacement (P = .9). At a mean follow-up of 54 months, PROMS were comparable between patients whose injury remained minimally displaced and those that required surgery for further displacement, despite the delay to surgery (AOFAS 78.0 vs 75.9, MOXFQ 24.8 vs 26.3, P > .1). CONCLUSION: There was a high rate of displacement after initial conservative management of the minimally displaced Lisfranc injuries. Subsequent surgical management of displaced injuries resulted in outcomes comparable to those that remained minimally displaced. LEVEL OF EVIDENCE: Level III, retrospective comparative series.

Damage control articular surgery: Maintaining chondrocyte health and minimising iatrogenic injury.

Articular cartilage has limited intrinsic regenerative potential. The maintenance of healthy articular cartilage is essential to prevent joint degeneration and the morbidity associated with arthritis. In this review, we outline the structure and function of healthy articular cartilage. We summarise some of the recent literature outlining the influence of surgical factors on chondrocyte health. These factors include mechanical injury from instrumentation and drilling, drying, and the influence of irrigation fluids, antimicrobial solutions and local anaesthetics. We demonstrate that there is scope for improving cartilage viability at the time of surgery if simple chondroprotective measures are routinely adopted.

Conditional deletion of E11/podoplanin in bone protects against load-induced osteoarthritis.

BACKGROUND: Subchondral bone (SCB) thickening is one of the earliest detectable changes in osteoarthritic joints and is considered a potential trigger for subsequent articular cartilage degeneration. In this manuscript, we examine whether disruption to the SCB osteocyte network contributes to the initiation and pathogenesis of osteoarthritis. METHODS: We examined expression patterns of the glycoprotein E11/podoplanin by immunohistochemical labelling in murine, human and canine osteoarthritis models. We also examined the effects of twice-weekly administration of Bortezomib, a proteasome inhibitor which stabilises osteocyte E11 levels, to C57/BL6 wild-type male mice (1 mg/kg/day) for 8 weeks after surgical destabilisation of the medial meniscus. By inducing osteoarthritis-like changes in the right knee joint of 12-week-old male E11 hypomorphic mice (and corresponding controls) using a post-traumatic joint loading model, we also investigated whether a bone-specific E11 deletion in mice increases joint vulnerability to osteoarthritis. Articular cartilage degradation and osteophyte formation were assessed by histology and in line with the OARSI grading system. RESULTS: Our studies reveal increased E11 expression in osteocytes of human and canine osteoarthritic SCB. We found that Bortezomib administration had no effect on surgically-induced osteoarthritis, potentially due to a lack of the expected stabilisation of E11 in the SCB. We also found, in concordance with our previous work, wild-type mice exhibited significant load-induced articular cartilage lesions on the lateral femoral condyle (p < 0.01) and osteophyte formation. In contrast, E11 hypomorphic mice did not develop osteophytes or any corresponding articular lesions. CONCLUSIONS: Overall, these data suggest that an intact osteocyte network in the SCB contributes to the development of mechanically-driven osteoarthritis. Further, the data presented here indicate that the molecular pathways that preserve the osteocyte network, such as those driven by E11, may be targeted to limit osteoarthritis pathogenesis.