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Bone & Joint Research
Vol. 11, Issue 4 | Pages 214 - 225
20 Apr 2022
Hao X Zhang J Shang X Sun K Zhou J Liu J Chi R Xu T

Aims. Post-traumatic osteoarthritis (PTOA) is a subset of osteoarthritis (OA). The gut microbiome is shown to be involved in OA. However, the effect of exercise on gut microbiome in PTOA remains elusive. Methods. A total of 18 eight-week Sprague-Dawley rats were assigned into three groups: Sham/sedentary (Sham/Sed), PTOA/sedentary (PTOA/Sed), and PTOA/treadmill-walking (PTOA/TW). PTOA model was induced by transection of the anterior cruciate ligament (ACLT) and the destabilization of the medial meniscus (DMM). Treadmill-walking (15 m/min, 30 min/d, five days/week for eight weeks) was employed in the PTOA/TW group. The response of cartilage, subchondral bone, serology, and gut microbiome and their correlations were assessed. Results. Eight-week treadmill-walking was effective at maintaining the integrity of cartilage-subchondral bone unit and reducing the elevated systematic inflammation factors and microbiome-derived metabolites. Furthermore, 16S ribosomal ribonucleic acid (rRNA) sequencing showed disease-relevant microbial shifts in PTOA animals, characterized by the decreased abundance of phylum TM7 and the increase of phylum Fusobacteria. At the genus level, the abundance of Lactobacillus, Turicibacter, Adlercreutzia, and Cetobacterium were increased in the PTOA animals, while the increase of Adlercreutzia and Cetobacterium was weakened as a response to exercise. The correlation analysis showed that genus Lactobacillus and Adlercreutzia were correlated to the structural OA phenotypes, while phylum Fusobacteria and genus Cetobacterium may contribute to the effects of exercise on the diminishment of serological inflammatory factors. Conclusion. Exercise is effective at maintaining the integrity of cartilage-subchondral bone unit, and the exercise-induced modification of disease-relevant microbial shifts is potentially involved in the mechanisms of exercise-induced amelioration of PTOA. Cite this article: Bone Joint Res 2022;11(4):214–225


Bone & Joint Research
Vol. 13, Issue 9 | Pages 513 - 524
19 Sep 2024
Kalsoum R Minns Lowe CJ Gilbert S McCaskie AW Snow M Wright K Bruce G Mason DJ Watt FE

Aims. To explore key stakeholder views around feasibility and acceptability of trials seeking to prevent post-traumatic osteoarthritis (PTOA) following knee injury, and provide guidance for next steps in PTOA trial design. Methods. Healthcare professionals, clinicians, and/or researchers (HCP/Rs) were surveyed, and the data were presented at a congress workshop. A second and related survey was then developed for people with joint damage caused by knee injury and/or osteoarthritis (PJDs), who were approached by a UK Charity newsletter or Oxford involvement registry. Anonymized data were collected and analyzed in Qualtrics. Results. Survey responses (n = 19 HCP/Rs, 39 PJDs) supported studies testing pharmacological agents preventing PTOA. All HCP/Rs and 30/31 (97%) PJDs supported the development of new treatments that improved or delayed knee symptoms and damage to knee structure. PJDs thought that improving structural knee damage was more important than knee symptoms. Both groups found studies more acceptable as expected future benefit and risk of PTOA increased. All drug delivery routes were acceptable. Workshop participants (around n = 60) reflected survey views. Discussions suggested that stratifying using molecular testing for likely drug response appeared to be more acceptable than using characteristics such as sex, age, and BMI. Conclusion. Our findings supported PTOA drug intervention studies, including situations where there is low risk of disease, no expected benefit of treatment, and frequent treatment administration. PJDs appeared less risk-averse than HCP/Rs. This work reinforces the benefits of consensus and involvement work in the co-creation of PTOA drug trial design. Involvement of key stakeholders, such as PJDs with different risks of OA and regulatory representatives, are critical for trial design success. Cite this article: Bone Joint Res 2024;13(9):513–524


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_9 | Pages 44 - 44
17 Apr 2023
Wang M Lu X Li G
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To evaluate the therapeutic effect of Pulsed Electromagnetic Field (PEMF) in the treatment of meniscal tears in the avascular region. Seventy-two twelve-week-old male Sprague-Dawley rats with full-thickness longitudinal medial meniscal tears in the avascular region were divided into 3 groups: control group (G. con. ), treated with classic signal PEMF (G. classic. ), and high slew rate signal PEMF(G. HSR. ). The HSR signal has the same pulse and burst frequencies as the classic signal, but with a higher slew rate. Macroscopic observation and histological analysis of the meniscus and articular cartilage were performed to evaluate the meniscal healing and progressions of osteoarthritis. The synovium was harvested for histological and immunofluorescent analysis to assess the intra-articular inflammation. The meniscal healing, articular cartilage degeneration, and synovitis were quantitatively evaluated according to their respective scoring system. Dramatic degenerative changes of the meniscus and articular cartilage were noticed during gross observation and histological evaluation in the control group at 8 weeks. However, the menisci in the two treatment groups were restored to normal morphology with a smooth surface and shiny white color. Particularly, the HSR signal remarkably enhanced the fibrochondrogenesis and accelerated the remodeling process of the regenerated tissue. The meniscal healing scores of PEMF treatment groups were significantly higher than those in the control group at 8 weeks. Specifically, the HSR signal showed a significantly higher meniscal repair score than the classic signal at week 8 (P < .01). The degeneration score (G. con. versus G. classic. : P < .0001; Gcon versus G. HSR. : P < .0001) and synovitis score (G. con. versus Gclassic: P < .0001; G. con. versus G. HSR. : P = .0002) of the control groups were significantly higher than those in the two treatment groups. PEMF promoted the healing of meniscal tears in the avascular region and restored the injured meniscus to its structural integrity in a rat model. Compared to the classic signal, the HSR signal showed the increased capability to promote fibrocartilaginous tissue formation and modulate the inflammatory environment and therefore protected the knee joint from post-traumatic osteoarthritis development


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 249 - 249
1 Jul 2011
Hurtig M Fischer L Cruz A David F
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Purpose: To determine if an adenovirus vector expressing BMP-7 can alter the progression of post-traumatic osteoarthritis. Method: Preliminary dose-response studies were done in ovine metacarpal-phalangeal joints using 10^9, 10^10, and 10^11 virus particles (VP). In-vitro transfection efficiency studies were done using ovine synovial cells, chondrocytes and HEK293 cells. In-vivo studies were conducted in 16 sheep that underwent surgery to create bilateral contusive impact injuries to the medial femoral condyle. One week later 10^9 VP were injected into one joint of each sheep, while four sheep remained untreated bilateral controls. Three months later the sheep were sacrificed for assessments including histological scoring, cartilage glycosaminoglycan assays, and immunostaining for Col2 3/4 short collagen fragments that are generated by metalloproteinases during OA progression. Results: Transfection with 10^9 VP produced slightly longer expression than higher concentrations of VP. HEK293 cells expressed BMP-7 quickly but synoviocytes and chondrocytes expressed this protein at 48 and 96 hours. Knee joints that received Ad5-BMP-7 produced up to 2.5 ng of BMP-7 between day seven and 21. These joints had reduced cartilage degneration at the injury sites and less centrifugal progression of OA across the femoral condyle. Histological scores were reduced as was Col2 C3/4 short immunostaining. Conclusion: BMP-7 has a homeostatic role in cartilage and can be used therapeutically. 1. Ad5-BMP-7 transfection of synovial tissue produced sufficient BMP-7 to stop the progression of degenerative changes after trauma that would usually lead to OA. Adenoviral vectors can create inflammation and neutralizing antibodies but these complications were minimized by using a low (10^9) dose. Human trials using similar vectors are ongoing and the outcome of these will determine whether gene therapy will become a useful tool when patients are at risk of post-traumatic OA


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 282 - 282
1 Sep 2012
Lustig S Parratte S Servien E Argenson J Neyret P
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Introduction. It is documented in the literature the very good results of lateral unicompartmental knee arthroplasty (UKA) when the standard accepted indications are followed. In our experience these indications can be extended to include post-traumatic osteoarthritis (OA) with malunion secondary to tibial plateau fracture. We report our results concerning 15 UKAs in these particular situations. Material and methods. From 1985 to 2009, we performed 15 lateral UKAs in 15 patients for post traumatic OA secondary to malunion following a tibial plateau fracture. 7 were female and 8 male. The mean age of the patients at the time of the index procedure was 45±17 years and the mean delay from initial trauma was 5.4 years. The average follow-up was 108 months (range 12–265 months). Results. Twelve patients (12 over 15) were satisfied or very satisfied (80%). At follow up 2 had undergone a second operation: 1 osteosynthesis for patellar fracture and 1 conversion to TKA for progression of OA (at 13.7 years after UKA) and one remained unsatisfied. No revision surgery was necessary for wear or infection. The average femoral-tibial alignment was 4° valgus (range −6° to 8°). The mean IKS knee score was 95.3 points and mean IKS function score was 92 points. Discussion. Our results in the medium term are excellent. They support that the selection criteria for UKA can be extended to include these indications. A longer follow up is required before they can be routinely included in the conventional selection criteria for UKA


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 330 - 330
1 Jul 2014
Olewinski R Gupta M Wimmer M Hakimiyan A Margulis A Rappoport L Pacione C Chubinskaya S
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Summary. The ideal therapy for post-traumatic osteoarthritis (PTOA) must be mechanism-based and target multiple anabolic and catabolic pathways. Our results suggest an innovative combination of known pro-anabolic and anti-catabolic biologics to treat post-traumatic cartilage degeneration. Introduction. Untreated joint injuries can result in cartilage wear and the development of PTOA. Previous studies identified the mechanisms that may govern the progression to PTOA. Here we hypothesised that targeted biologic interventions combined based on the type/time of cellular responses may constitute an effective novel treatment algorithm to arrest PTOA. Methods. Eleven human donor normal tali, age 19–71 yo, from the Gift of Hope Organ & Tissue Donor Network were impacted using a 4mm cylindrical indenter with the impulse of 1N as discribed. 8mm cartilage explants (4mm impacted core + 4mm non-impacted adjacent ring) were removed from the joint and cultured for 14 days in 5% fetal bovine serum with or without selected biologics. Treatment groups consisted of 1) Impacted control (IC), 2) Un-impacted control (UIC); 3–5) Impaction + three combinations of BMP-7/OP-1 (100ng/ml), P188 (8 ug/ml) and tumor necrosis factor-α (TNF-α) antagonist (100ng/ml) defined as Combo1, Combo2, and Combo3. All treatments were administered according to previously reported post-injury cellular responses. Combo1: P188 administered at day 0 for 48hrs + BMP-7 administered at day 0 for 48hrs and at days 7–14 + anti-TNF-α administered at days 0–7; Combo2: All three agents administered at day 0 for 48hrs and anti-TNF-α and BMP-7 administered again at day 7 for 48hrs; Combo3: All agents administered simultaneously at day 0 for 48hrs. Tissue and media were collected on days 0, 2, 7, and 14 and analyzed for cell viability, Safranin O staining, and proteoglycan (PG) synthesis. Results. A single impact to articular cartilage resulted in cell death within the superficial layer of impacted region, which if untreated, expanded to the adjacent non-impacted area. It reduced cell viability by more than 2-fold (p<0.01) and triggered elevation of pro-inflammatory mediators within the first 24–48 hrs and again around day 10. Initial anabolic responses characterised by the synthesis of superficial zone protein, endogenous BMP-7 and PGs were initiated at days 5–7. Cell survival in the superficial layer was improved under the individual or combined treatments with the most pronounced sustained effect under Combo1 & 2 (∼1.5-fold increase vs IC, p<0.05). Combo1 and to a lesser extend Combo 2 markedly improved cell survival in the entire cartilage thickness, which increased from 59% in IC to 84% in Combo1, p=0.006. Both Combo1 & 2 had a stronger effect on Safranin O staining and preservation of matrix integrity than Combo 3. Contrary, Combo3 exhibited the highest effect on PG synthesis (1.8-fold increase vs IC or other two combinations; p<0.05). Combo1 & 2 were less effective. Discussion. Current study reports two important findings: 1) the same combination of agents, but administered at various treatment regimens, can induce different effects. Prolonged administration of anti-TNF-α and BMP-7 (Combo1) had a strong effect on cell survival and matrix preservation, but was less effective in inducing chondrocyte synthetic activity suggesting that overstimulation/overdosing can have a detrimental effect on chondrocyte anabolism; 2) a window of opportunity exists to arrest cell death and delay/prevent cartilage degeneration


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.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 70 - 70
2 Jan 2024
Ely E Collins K Lenz K Paradi S Liedtke W Chen Y Guilak F
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Osteoarthritis (OA) is the leading cause of pain and disability worldwide and is characterized by the degenerative changes of articular cartilage. Joint loading is required for cartilage maintenance; however, hyper-physiologic loading is a risk factor for OA. Mechanosensitive ion channels Piezo1 and Piezo2 synergistically transduce hyper-physiologic compression of chondrocytes, leading to chondrocyte death and onset of OA. This injury response is inhibited by Piezo channel loss of function, however the mechanistic role of Piezo channels in vivo is unknown. We examined the hypothesis that deletion of Piezo in chondrocytes will protect mice from joint damage and pain-related behaviors following a surgical destabilization of the medial meniscus (DMM), investigating a key mechanistic and mechanobiological role of these channels in the pathogenesis of OA.

Aggrecan-Cre Piezo1 and Piezo1/2 knockout mice ((Agc)1-CREERT2;Piezo1fl/flPiezo2fl/fl) were generated and given a 5-day Tamoxifen regimen at 12-weeks of age (n=6–12/group/sex). Cre-negative mice served as controls. At 16-weeks, mice received DMM surgery on the left knee. 12-weeks following DMM prior to sacrifice, activity and hyperalgesia were measured using spontaneous running wheels and a small animal algometer. Structural changes in bone, cartilage, and synovium were characterized using microCT, histology, and Modified Mankin Score criteria.

Knockout of Piezo1/2 channels was chondroprotective in both sexes following DMM surgery as demonstrated by reduced Modified Mankin Score compared to control animals. Piezo1 KO was chondroprotective in only female mice, indicating a sexually dimorphic response. Piezo1 and Piezo1/2 KO was protective against pain in male mice, while females displayed no differences compared to controls. No changes were observed in bone morphology.

Chondrocyte-specific Piezo1/2 knockout protects the knee joint from structural damage, hyperalgesia and functional deficits in a surgical model of PTOA in male and female mice, illustrating the importance of Piezo channels in response to injury in vivo. Future work aims to interrogate potential sexually dimorphic responses to cartilage damage and investigating Piezo2 KO mice.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_13 | Pages 26 - 26
1 Nov 2021
Amado I Hodgkinson T Murphy C Kennedy O
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Introduction and Objective

Traditionally, osteoarthritis (OA) has been associated mostly with degradation of cartilage only. More recently, it has been established that other joint tissues, in particular bone, are also centrally involved. However, the link between these two tissues remains unclear. This relationship is particularly evident in post-traumatic OA (PTOA), where bone marrow lesions (BMLs), as well as fluctuating levels of inflammation, are present long before cartilage degradation begins. The process of bone-cartilage crosstalk has been challenging to study due to its multi-tissue complexity. Thus, the use of explant model systems have been crucial in advancing our knowledge. Thus, we developed a novel patellar explant model, to study bone cartilage crosstalk, in particular related to subchondral bone damage, as an alternative to traditional femoral head explants or cylindrical core specimens. The commonly used osteochondral explant models are limited, for our application, since they involve bone damage during harvest. The specifics aim of this study was to validate this novel patellar explant model by using IL-1B to stimulate the inflammatory response and mechanical stimulation to determine the subsequent developments of PTOA.

Materials and Methods

Lewis rats (n=48) were used to obtain patellar and femoral head explants which were harvested under an institutional ethical approval license. Explants were maintained in high glucose media (containing supplements), under sterile culture conditions. Initially, we characterised undamaged patellar explants and compared them with the commonly used femoral head. First, tissue viability was assessed using an assay of metabolic activity and cell damage. Second, we created chemical and mechanical damage in the form of IL-1B treatment, and mechanical stimulation, to replicate damage. Standard biochemical assays, histological assays and microstructural assays were used to evaluate responses. For chemical damage, explants were exposed to 10ng/ml of IL-1B for 24 hours at 0, 1, 3 and 7 days after harvesting. For mechanical damage, tissues were exposed to mechanical compression at 0.5 Hz, 10 % strain for 10 cycles, for 7 days. Contralateral patellae served as controls. In both groups, sGAG, ADAMTS4, and MMP-13 were measured as an assessment of representative cartilage responses while ALP, TRAP and CTSK were assessed as a representative of bone responses. In addition to this, histomorphometric, and immunohistochemical, evaluations of each explant system were also carried out.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_15 | Pages 13 - 13
1 Nov 2018
Kennedy OD
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Osteoarthritis (OA) is the most common musculoskeletal disease in the EU and is characterized by cartilage degeneration, pain and restricted movement. Post-Traumatic OA (PTOA) is a specific disease subset that occurs subsequent to traumatic injury, such as ACL rupture and makes up 12% of the overall disease burden. Our current understanding PTOA is that initial injury affects multiple tissues, and many/all contribute to overall ‘joint failure.’ MRI scans show that subchondral bone marrow lesions (BMLs) are present in 80% of ACL rupture cases in the immediate aftermath of joint injury. Their presence indicates an acute consequence in subchondral bone. It has also been suggested that BMLs overlap with, or directly represent, bone microdamage. Microdamage is known to induce osteoclast-mediated remodelling in bone. Therefore, the inhibition of subchondral bone remodelling, particularly in the early phase post-injury, may be a candidate therapeutic approach for preventing PTOA. Finally, the contiguous link between subchondral bone and articular cartilage, can allow transport of small molecules across this boundary, this suggests that bone/cartilage crosstalk is likely to be a key factor in PTOA development after injury. This presentation will summarize recent advances in our understanding these phenomena in both animal and human studies.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_II | Pages 154 - 154
1 Feb 2004
Kabbani KT
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The ankle is one of the most resisting to arthritis joints of the body, and the development of degenerative changes in it, always due to a pathologic condition or trauma. The aim of this study is to demonstrate the late post- operative results and the development of post-traumatic osteoarthritis in a series of 144 patients with malleolar fractures who have been operated with the principles and methods of AO. To judge our results, we used subjective, objective and X-Ray criteria. The main follow up was 8,6 years, final results were excellent and good in 74,3%, satisfactory in 14,6 and poor in 11,1% while post-traumatic osteoarthritis developed in 22.2% of the cases. The installation of post-traumatic osteoarthritis in malleolar fractures seems to be influenced by factors like age, sex, severity of fracture, quality of reduction and existence of posterior bone fragment bigger than 25% of the joint surface


The Bone & Joint Journal
Vol. 104-B, Issue 4 | Pages 486 - 494
4 Apr 2022
Liu W Sun Z Xiong H Liu J Lu J Cai B Wang W Fan C

Aims. The aim of this study was to develop and internally validate a prognostic nomogram to predict the probability of gaining a functional range of motion (ROM ≥ 120°) after open arthrolysis of the elbow in patients with post-traumatic stiffness of the elbow. Methods. We developed the Shanghai Prediction Model for Elbow Stiffness Surgical Outcome (SPESSO) based on a dataset of 551 patients who underwent open arthrolysis of the elbow in four institutions. Demographic and clinical characteristics were collected from medical records. The least absolute shrinkage and selection operator regression model was used to optimize the selection of relevant features. Multivariable logistic regression analysis was used to build the SPESSO. Its prediction performance was evaluated using the concordance index (C-index) and a calibration graph. Internal validation was conducted using bootstrapping validation. Results. BMI, the duration of stiffness, the preoperative ROM, the preoperative intensity of pain, and grade of post-traumatic osteoarthritis of the elbow were identified as predictors of outcome and incorporated to construct the nomogram. SPESSO displayed good discrimination with a C-index of 0.73 (95% confidence interval 0.64 to 0.81). A high C-index value of 0.70 could still be reached in the interval validation. The calibration graph showed good agreement between the nomogram prediction and the outcome. Conclusion. The newly developed SPESSO is a valid and convenient model which can be used to predict the outcome of open arthrolysis of the elbow. It could assist clinicians in counselling patients regarding the choice and expectations of treatment. Cite this article: Bone Joint J 2022;104-B(4):486–494


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_5 | Pages 11 - 11
23 Apr 2024
Lineham B Faraj A Hammet F Barron E Hadland Y Moulder E Muir R Sharma H
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Introduction. Intra articular distal tibia fractures can lead to post-traumatic osteoarthritis. Joint distraction has shown promise in elective cases. However, its application in acute fractures remains unexplored. This pilot study aims to fill this knowledge gap by investigating the benefits of joint distraction in acute fractures. Materials & Methods. We undertook a restrospective cohort study comprising patients with intra-articular distal tibia and pilon fractures treated with a circular ring fixator (CRF) at a single center. Prospective data collection included radiological assessments, Patient-Reported Outcome Measures (PROM), necessity for additional procedures, and Kellgren and Lawrence grade (KL) for osteoarthritis (OA). 137 patients were included in the study, 30 in the distraction group and 107 in the non-distraction group. There was no significant difference between the groups. Results. Mean follow-up was 3.73 years. There was no significant difference between the groups in overall complications or need for further procedures. There was no significant difference in progression of KL between the groups (1.81 vs 2.0, p=0.38) mean follow up 1.90 years. PROM data was available for 44 patients (6 distraction, 38 non-distraction) with a mean follow-up of 1.71 years. There was no significant difference in EQ5D (p=0.32) and C Olerud-H Molander scores (p=0.17). Conclusions. This pilot study suggests that joint distraction is safe in the acute setting. However, the study's impact is constrained by a relatively small patient cohort and a short-term follow-up period. Future investigations should prioritise longer-term follow-ups and involve a larger patient population to more comprehensively evaluate the potential benefits of joint distraction in acute fractures


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_6 | Pages 5 - 5
20 Mar 2023
Gupta S Sadczuk D Riddoch F Oliver W Davidson E White TO Keating JF Scott CEH
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We aimed to determine the rate of and risk factors for post-traumatic osteoarthritis (PTOA) and total knee arthroplasty (TKA) requirement after operative management of tibial plateau fractures (TPF) in older adults. We conducted a retrospective cohort study of 182 operatively managed TPFs in 180 patients ≥60 years old over a 12-year period with minimum follow up 1 year. Data including patient demographics, clinical frailty scores, mechanism of injury, management, reoperation and mortality were recorded. Radiographs were reviewed for: Schatzker classification; pre-existing knee osteoarthritis (KOA); severe joint depression >15mm; and development of PTOA. Kaplan Meier survival analysis was performed. Regression analysis was used to identify risk factors for radiographic indication for TKA and actual TKA. Forty-seven percent were Schatzker II fractures. Radiographic KOA was present at fracture in 32.6%. Fracture fixation was performed in 95.6% cases and acute TKA in 4.4%. Thirteen patients underwent late TKA (7.5%). At five-years, 11.8% (6.0-16.7 95% CI) had required TKA and 20.9% (14.4-27.4 95% CI) had a radiographic indication for TKA. Severe joint depression and pre-existing KOA were associated with worse survival for endpoints radiographic indication for TKA and actual TKA. Severe joint depression (HR 2.49(1.35-4.61 95% CI), p=0.004), pre-existing KOA (HR 2.23(1.17-4.23), p=0.015) and inflammatory arthropathy (HR 2.4(1.04-5.53), p=0.039) were independently associated with radiographic indication for TKA. In conclusion, severe joint depression and pre-existing arthritis are independent risk factors for both severe PTOA and TKA after TPFs in older adults. These features should be considered as an indication for primary management with acute TKA


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 109 - 109
11 Apr 2023
Amado I Hodgkinson T Mathavan N Murphy C Kennedy O
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Post-traumatic osteoarthritis (PTOA) is a subset of osteoarthritis, which occurs secondary to traumatic joint injury which is known to cause pathological changes to the osteochondral unit. Articular cartilage degradation is a primary hallmark of OA, and is normally associated with end-stage disease. However, subchondral bone marrow lesions are associated with joint injury, and may represent localized bone microdamage. Changes in the osteochondral unit have been traditionally studied using explant models, of which the femoral-head model is the most common. However, the bone damage caused during harvest can confound studies of microdamage. Thus, we used a novel patellar explant model to study osteochondral tissue dynamics and mechanistic changes in bone-cartilage crosstalk. Firstly, we characterized explants by comparing patella with femoral head models. Then, the patellar explants (n=269) were subjected to either mechanical or inflammatory stimulus. For mechanical stimulus 10% strain was applied at 0.5 and 1 Hz for 10 cycles. We also studied the responses of osteochondral tissues to 10ng/ml of TNF-α or IL-1β for 24hrs. In general the findings showed that patellar explant viability compared extremely well to the femoral head explant. Following IL-1β or TNF-α treatment, MMP13, significantly increased three days post exposure, furthermore we observed a decrease in sulfate glycoaminoglycan (sGAG) content. Bone morphometric analysis showed no significant changes. Contrastingly, mechanical stimulation resulted in a significant decrease sGAG particularly at 0.5Hz, where an increase in MMP13 release 24hrs post stimulation and an upregulation of bone and cartilage matrix degradation markers was observed. Furthermore, mechanical stimulus caused increases in TNF-α, MMP-8, VEGF expression. In summary, this study demonstrates that our novel patella explant model is an excellent system for studying bone-cartilage crosstalk, which responds well to both mechanical and inflammatory stimulus and is thus of great utility in the study of PTOA


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 72 - 72
14 Nov 2024
Uvebrant K Andersen C Lim HC Vonk L Åkerlund EL
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Introduction. Homogenous and consistent preparations of mesenchymal stem cells (MSCs) can be acquired by selecting them for integrin α10β1 (integrin a10-MSCs). Safety and efficacy of intra-articular injection of allogeneic integrin a10-MSCs were shown in two post-traumatic osteoarthritis horse studies. The current study investigated immunomodulatory capacities of human integrin a10-MSCs in vitro and their cell fait after intra-articular injection in rabbits. Method. The concentration of produced immunomodulatory factors was measured after licensing integrin a10-MSCs with pro-inflammatory cytokines. Suppression of T-cell proliferation was determined in co-cultures with carboxyfluorescein N-succinimidyl ester (CFSE) labelled human peripheral blood mononuclear cells (PBMCs) stimulated with anti-CD3/CD28 and measuring the CFSE intensity of CD4+ cells. Macrophage polarization was assessed in co-cultures with differentiated THP-1 cells stimulated with lipopolysaccharide and analysing the M2 macrophage cell surface markers CD163 and CD206. In vivo homing and regeneration were investigated by injecting superparamagnetic iron oxide nanoparticles conjugated with Rhodamine B-labeled human integrin a10-MSCs in rabbits with experimental osteochondral defects. MSC distribution in the joint was followed by MRI and fluorescence microscopy. Result. The production of the immunomodulatory factors indoleamine 2,3-dioxygenase and prostaglandin E2 was increased after inflammatory licensing integrin a10-MSCs. Co-cultures with integrin a10-MSCs suppressed T-cell proliferation and increased the frequency of M2 macrophages. In vivo injected integrin a10-MSCs homed to osteochondral defects and were detected in the repair tissue of the defects up to 10 days after injection, colocalized with aggrecan and type II collagen. Conclusion. This study showed that human integrin a10-MSCs have immunomodulatory capacities and in vivo can home to the site of osteochondral damage and directly participate in cartilage regeneration. This suggests that human integrin α10β1-selected MSCs may be a promising therapy for osteoarthritis with dual mechanisms of action consisting of immunomodulation and homing to damage followed by early engraftment and differentiation into chondrocyte-like cells that deposit hyaline cartilage matrix molecules


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 63 - 63
1 Dec 2022
Hoffer A Kingwell D Leith J McConkey M Ayeni OR Lodhia P
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Over half of postpartum women experience pelvic ring or hip pain, with multiple anatomic locations involved. The sacroiliac joints, pubic symphysis, lumbar spine and pelvic girdle are all well documented pain generators. However, despite the prevalence of postpartum hip pain, there is a paucity of literature regarding underlying soft tissue intra-articular etiologies. The purpose of this systematic review is to document and assess the available evidence regarding underlying intra-articular soft tissue etiologies of peri- and postpartum hip pain. Three online databases (Embase, PubMed and Ovid [MEDLINE]) were searched from database inception until April 11, 2021. The inclusion criteria were English language studies, human studies, and those regarding symptomatic labral pathology in the peri- or postpartum period. Exclusion criteria were animal studies, commentaries, book chapters, review articles and technical studies. All titles, relevant abstracts and full-text articles were screened by two reviewers independently. Descriptive characteristics including the study design, sample size, sex ratio, mean age, clinical and radiographic findings, pathology, subsequent management and outcomes were documented. The methodological quality of the included studies was assessed using the Methodological Index for Non-Randomized Studies (MINORS) instrument. The initial search identified 2472 studies. A systemic screening and assessment of eligibility identified 5 articles that satisfied the inclusion criteria. Twenty-two females were included. Twenty patients presented with labral pathology that necessitated hip arthroscopy with labral debridement or repair with or without acetabuloplasty and/or femoroplasty. One patient presented with an incidental labral tear in the context of osteitis condensans illi. One patient presented with post-traumatic osteoarthritis necessitating a hip replacement. The mean MINORS score of these 5 non-comparative studies was 2.8 (range 0-7) demonstrating a very low quality of evidence. The contribution of intra-articular soft tissue injury is a documented, albeit sparse, etiology contributing to peri- and postpartum hip pain. Further research to better delineate the prevalence, mechanism of injury, natural history and management options for women suffering from these pathologies at an already challenging time is necessary to advance the care of these patients


Although remnant-preserved ACL reconstruction (ACLR) restores knee joint stability and dampens the problem of acute ACL rupture-induced knee pain, an increasing number of patients still develop post-traumatic osteoarthritis (PTOA) after 10 to 15 years of ACLR. We previously found that remnant-preserved ACLR with concomitant medial and lateral meniscus repair may not prevent cartilage degeneration and weaken muscle strength, while the clinical features of PTOA are not clear. We hypothesized that remnant-preserved ACLR with concomitant medial and lateral meniscus tears is related to early cartilage damage, worse function recovery, patient-reported outcomes (PROs) and delayed duration to return to sports. The aim is to evaluate the remnant-preserved ACLR with complicated meniscal injuries in predicting which patients are at higher risk of osteoarthritic changes, worse function and limited activities after ACLR for 12 months. Human ethical issue was approved by a committee from Xi'an Jiaotong University. 26 young and active patients (24 male, 2 female) with ACL injuries (Sherman type I and II) with concomitant medial and lateral meniscus within 2 months were included from January 2014 to March 2022. The average age of the ACLR+ meniscus repair was 26.77±1.52 (8 right, 5 left) and isolated ACLR control was 31.92±2.61 years old (7 left, 6 right). Remnant-preserved ACLR with a 5- to 6-strand hamstring tendon graft was operated on by the same sports medicine specialists. MRI CUBE-T. 2. scanning with 48 channels was conducted by a professional radiologist. The volume of the ACL graft was created through 3 dimensional MRI model (Mimics 19, Ann Arbor). Anterior Cruciate Ligament OsteoArthritis Score (ACLOAS) was applied to score visible cartilage damage. IKDC 2000 score and VAS were assessed by two blinded researchers. Results were presented as mean± SEM of each group. The cross-sectional area and 3D volume of the ACL graft were greater in the remnant-preserved ACLR+meniscus group compared with isolated ACLR (p=0.01). It showed that ACLR+ meniscus group had early signs of joint damage and delayed meniscus healing regarding ACLOAS compared to control group (p=0.045). MRI CUBE-T. 2. prediction of radiographic cartilage degeneration was not obvious in both groups post remnant-preserved ACLR over 12 months (p>0.05). However, higher VAS scores, lower IKDC scores, and long-last joint swelling were reported in the ACLR+ meniscus repair group at the end of 12 months follow-up. Although remnant-preserved ACLR+ meniscus was able to maintain the restore the knee function, it showed delayed timing (>12 months) to return to play at the pre-injury stage, while no difference between the timing of returning to the normal daily routine of their ACLR knee compared to control (p=0.30). The cost of ACLR+ meniscus (average 10,520.76$) was higher than the control group (6,452.92$, p=0.018). Remnants-preserved ACLR with concomitant injured medial and lateral meniscus repair shows a higher risk of cartilage damage, greater cost, worse functional performance, and longer time for young male patients to return to sports after 12-month follow-up compared to isolated ACLR. Further evidence and long-term follow-up are needed to better understand the association between these results and the risk of development of PTOA in this patient cohort


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_13 | Pages 105 - 105
1 Nov 2021
Al-Rub ZA Tyas B Singisetti K
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Introduction and Objective. Evidence in literature is contradicting regarding outcomes of total knee arthroplasty (TKA) in post-traumatic osteoarthritis (PTOA) and whether they are inferior to TKA in primary osteoarthritis (OA). The aim of this review was to find out if any difference exists in the results of TKA between the two indications. Materials and Methods. The electronic databases MEDLINE, EMBASE, The Cochrane Collaboration, and PubMed were searched and screened in duplicate for relevant studies. The selected studies were further subjected to quality assessment using the modified Coleman method. The primary outcome measure was patient reported outcome, and secondary outcome measures were infection, revision, stiffness, and patella tendon rupture. Results. A total of 18 studies involved 1129 patients with a mean age of 60.6 years (range 45.7–69) and follow up of 6.3 years. The time interval from index injury to TKA was 9.1 years. Knee Society Score (KSS) in PTOA reported in 12/18 studies showed functional improvement from 42.5 to 70 post-TKA exceeding minimally clinically important difference. In TKA for primary OA vs PTOA, deep peri-prosthetic joint infection (PJI) was reported in 1.9% vs 5.4% of patients, whilst revision of prosthesis at an average of 6 years post-operatively was performed in 2.6 vs 9.7% of patients. Conclusions. TKA is a successful treatment option for PTOA. However, the risk of significant complications like PJI and implant failure requiring revision is higher than primary OA cases. Patients should be counselled about those risks. Further well-designed comparative cohort-matched studies are needed to compare outcomes between the two populations


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_III | Pages 364 - 364
1 Mar 2004
Petsatodes G Christoforides J Antonarakos P Karataglis D Pournaras J
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Aim: The results of operative treatment of acetabular fractures, as well as its role in the prevention of post-traumatic osteoarthritis are presented. Methods: From 1990 to 2000, þfty patients had an open reduction and internal þxation of an acetabular fracture. Thirty-two patients were male and eighteen were female, with an average age of 37,8 years (range: 18 to 71 years). The mechanism of injury was a motor vehicle accident in most cases (84%). 22 fractures were A-type, 24 B-type and 4 C-type according to the AO classiþcation, while according to the Letournel-Judet classiþcation 21 fractures were simple and 21 complex. Osteosynthesis was achieved with either lag screws alone or with a combination of lag screws and a buttress plate. Results: Follow-up ranged from 2–10 years (average: 5,8 years). Clinical evaluation according to the Dñ Aubigne-Postel scoring system gave 20 excellent (40%), 18 good (36%), 5 fair (10%) and 7 poor (14%) results. Early postoperative complications included 5 cases of common peroneal nerve palsy and 3 cases of wound infection. Late complications included 1 case of avascular necrosis of the femoral head, 12 cases of post-traumatic osteoarthritis (24%) and 5 cases of Brooker III heterotopic ossiþcation (10%). Conclusions: Operative treatment of ace-tabular fractures although demanding bears very good results. Post-traumatic arthritis remains a common complication, even if care is taken for the anatomic reduction of the fracture