Aims

To evaluate inducing osteoarthritis (OA) by surgical destabilization of the medial meniscus (DMM) in mice with and without a stereomicroscope.

Introduction Sacroiliac joint pain is resistant to diagnosis by clinical methods. CT guided diagnostic blocks are the gold standard in diagnosing SI joint pathology (Maigne J.Y. et al, Spine 1996). The current blocks have various pit falls. We have devised a new functional diagnostic block which is a modification of the currently available blocks for diagnosing sacroiliac joint pain. Methods The patient suspected of having sacroiliac joint pain undergoes a CT-guided sacroiliac joint catheterisation. The patient is subsequently admitted to the hospital for two full days. On admission patient is charted for an injection of either a local anaesthetic or normal saline (placebo) through the catheter into the joint 2–3mls every 3–4 hourly. Only one drug is administered on any given day. On day one, the nurse in charge of the patient by the flip of a coin will decide to give one of the drugs for the day, the patient or the treating doctor not aware of the drug injected. The first injection starts at 0600hrs and the last injection at 2200 hrs. The injection details and pain score are documented on a standardised form. The patient is then taken through a range of physical activity which usually provokes the sacroiliac joint pain. The next day, the patient receives the alternate drug and undergoes the same protocol. On the third morning the patient is discharged with an appropriate follow-up. The injection given, average pain score and the level of comfort with physical activity are summarised into a form. Discussion Our modified block has the following advantages, it is a double blinded assessment, the effect of a placebo can be tested, and it is also a functional assessment which is recorded over two days and not just a one-off response. The conclusion of the block is determined by the patient’s response and not examiner depended

Introduction Zygapophysial joint pain can be treated by RF neurotomy of the medial branch of the dorsal primary rami of the adjacent spinal nerves. The provision of radiofrequency (RF) neurotomy for spinal joint pain has been highlighted as an emerging trend in Australia, Europe and North America. However, there is controversy regarding the efficacy of this procedure. RF neurotomy for spinal pain has been investigated in several experimental and observational studies but these have reported conflicting results. The purpose of this project was to provide a systematic review of the literature on RF neurotomy for the treatment of spinal pain of zygapophysial joint origin. Method Electronic database searches, screening of reference lists, hand searching and consultation with experts in the field was undertaken to identify relevant studies. Publications were selected based on predetermined inclusion criteria and the methodological quality of each was rated. Qualitative analysis was performed using the Cochrane Collaboration Back Review Group (CCBRG) levels of evidence (RCTs only) and those used by the National Health and Medical Research Council (NHMRC) (RCTs, observational studies, systematic reviews and guidelines). Results The search strategy identified 382 potential publications. Of these, 80 studies were selected for review, including 7 RCTs, 52 observational studies, 11 systematic reviews and 10 guidelines. There is conflicting (CCBRG) evidence regarding the efficacy of RF neurotomy for lumbar zygapophysial joint pain. The conclusions of systematic reviews and observational studies are conflicting regarding the efficacy of this procedure for the lumbar spine. In contrast, there is limited (CCBRG) evidence that RF neurotomy is efficacious for neck pain of zygapophysial joint origin in the short term. However, this was reported in one very small RCT which reported only one composite outcome. Discussion This systematic review found that there is no consistent evidence from either multiple (large) RCTs or systematic reviews that RF neurotomy is efficacious in the treatment of spinal joint pain RCTs need to be conducted with larger sample sizes, (patient) relevant outcomes and adequate assessment of side-effects, which can be serious

Purpose and background:. Sacroiliitis identified by MRI is considered as a keystone in the diagnosis of spondyloarthritis. To reduce the number of unnecessary MRI scans it would be ideal if sacroiliac (SI) joint pain provocation tests could be used to identify patients at risk of having sacroiliitis. The aim of the current study was to investigate the diagnostic value of three pain provocation SI-joint tests for sacroiliitis identified by MRI. Methods:. Patients (n=454, mean age 32 years, 54% women) without clinical signs of nerve root compression were selected from a cohort consisting of patients with persistent low back pain referred to an outpatient spine clinic. Data from the Gaenslen's Test, Thigh Thrust Test and Long Dorsal Sacroiliac Ligaments Test and sacroiliitis identified by MRI were analysed. Results:. The prevalence of SI-joints with sacroiliitis was 5%. In the whole study group, only the Thigh Trust Test was associated with sacroiliitis, ROC area 0.58 (95% CI 0.51–0.65), sensitivity 31% (18–47) and specificity 85% (82–87). In men, sacroiliitis was associated with all three SI joint tests and multitest regimens, with the greatest ROC area found for ≥ 1 positive out of 3 tests, (0.68 (0.56–0.80)), sensitivity 56% (31–79) and specificity 81% (77–85). In women, no significant associations were observed between the assessed SI joint tests and sacroiliitis. Conclusions:. Only in men were the performed SI-joint tests found to be associated with sacroiliitis identified by MRI. Although, the diagnostic value was limited, the results indicate that the use of SI joint tests for sacroiliitis may be optimised by gender-separated analyses

The AMPA/kainate glutamate receptor (GluR) antagonist NBQX reduced bone destruction when injected intra-articularly, in rat antigen induced arthritis (AIA) and is similarly protective in rodent models of osteoarthritis. NBQX reduced bone turnover in vivo and reduced mineralization in human primary osteoblasts (HOBs) in vitro. We are developing sustained release GluR antagonist delivery methods, to improve therapeutic effect. DNQX loaded Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were synthesized via double emulsion. DNQX loaded thermosetting hydrogels were synthesised by dissolving Pluronic-F127 (22% w/v) and Carbopol 934 (0.5% w/v) in dH₂O, homogenising with DNQX/NBQX and set in dialysis cassettes at 37˚C. Supernatants from nanoparticles and hydrogels suspended in PBS (37˚C) were analysed using high performance liquid chromatography to determine drug release. Y201 MSCs were differentiated to osteoblasts (DMEM+10% FBS, Dexamethasone, β-Glycerophosphate and Ascorbic acid-2-phosphate) in sustained presence/absence of NBQX (200µM) or DNQX (200 and 400µM). Alizarin red staining quantified mineralisation at 14 days. Nanoparticles encapsulated 2.5mM DNQX (encapsulation efficiency=22%) and released encapsulated drug over 4 weeks. Hydrogels released 2.5mM DNQX load over 24 hours in 37˚C PBS. Y201 alizarin red staining was significantly reduced by both DNQX (p<0.01) and NBQX (p<0.05), compared to untreated controls. PLGA nanoparticles and hydrogels revealed different sustained release profiles. Sustained treatment with GluR antagonists reduced mineralisation in Y201 derived osteoblasts, consistent with effects of NBQX in HOBs. Sustained release of NBQX and DNQX in nanoparticles and hydrogels may improve efficacy of AMPA/kainate GluR antagonists in reducing bone remodelling and enhancing their bone protective potential in the treatment of joint disease.

Anterior cruciate ligament (ACL) injuries have been increasing, especially amongst adolescents. These injuries can increase the risk for early-onset knee osteoarthritis (OA). The consequences of late-stage knee OA include structural joint change, functional limitations and persistent pain. Interleukin-6 (IL-6) is a pro-inflammatory biomarker reflecting knee joint healing, and increasing evidence suggests that IL-6 may play a critical role in the development of pathological pain. The purpose of this study was to determine the relationship between subjective knee joint pain and function, and synovial fluid concentrations of the pro-inflammatory cytokine IL-6, in adolescents undergoing anterior cruciate ligament reconstruction surgery. Seven youth (12-17 yrs.) undergoing anterior cruciate ligament (ACL) reconstruction surgery participated in this study. They completed the Pedi International Knee Documentation Committee (Pedi-IKDC) questionnaire on knee joint pain and function. At the time of their ACL reconstruction surgery, synovial fluid samples were collected through aspiration to dryness with a syringe without saline flushing. IL-6 levels in synovial fluid (sf) were measured using enzyme linked immunosorbent assay. Spearman's rho correlation coefficient was used to determine the correlation between IL-6 levels and scores from the Pedi-IKDC questionnaire. There was a statistically significant correlation between sfIL-6 levels and the Pedi-IKDC Symptoms score (-.929, p=0.003). The correlations between sfIL-6 and Pedi-IKDC activity score (.546, p = .234) and between sfIL-6 and total Pedi-IKDC score (-.536, p = .215) were not statistically significant. This is the first study to evaluate IL-6 as a biomarker of knee joint healing in an adolescent population, reported a very strong correlation (-.929, p=0.003) between IL-6 in knee joint synovial fluid and a subjective questionnaire on knee joint pain. These findings provide preliminary scientific evidence regarding the relationship between knee joint pain, as determined by a validated questionnaire and the inflammatory and healing status of the patient's knee. This study provides a basis and justification for future longitudinal research on biomarkers of knee joint healing in patients throughout their recovery and rehabilitation process. Incorporating physiological and psychosocial variables to current return-to-activity (RTA) criteria has the potential to improve decision making for adolescents following ACL reconstruction to reduce premature RTA thereby reducing the risk of re-injury and risk of early-onset knee OA in adolescents

Varus malalignment increases the susceptibility of cartilage to mechanical overloading, which stimulates catabolic metabolism to break down the extracellular matrix and lead to osteoarthritis (OA). The altered mechanical axis from the hip, knee to ankle leads to knee joint pain and ensuing cartilage wear and deterioration, which impact millions of the aged population. Stabilization of the remaining damaged cartilage, and prevention of further deterioration, could provide immense clinical utility and prolong joint function. Our previous work showed that high tibial osteotomy (HTO) could shift the mechanical stress from an imbalanced status to a neutral alignment. However, the underlying mechanisms of endogenous cartilage stabilization after HTO remain unclear. We hypothesize that cartilage-resident mesenchymal stem cells (MSCs) dampen damaged cartilage injury and promote endogenous repair in a varus malaligned knee. The goal of this study is to further examine whether HTO-mediated off-loading would affect human cartilage-resident MSCs' anabolic and catabolic metabolism. This study was approved by IACUC at Xi'an Jiaotong University. Patients with medial compartment OA (52.75±6.85 yrs, left knee 18, right knee 20) underwent open-wedge HTO by the same surgeons at one single academic sports medicine center. Clinical data was documented by the Epic HIS between the dates of April 2019 and April 2022 and radiographic images were collected with a minimum of 12 months of follow-up. Medial compartment OA with/without medial meniscus injury patients with unilateral Kellgren /Lawrence grade 3–4 was confirmed by X-ray. All incisions of the lower extremity healed well after the HTO operation without incision infection. Joint space width (JSW) was measured by uploading to ImageJ software. The Knee injury and Osteoarthritis Outcome Score (KOOS) toolkit was applied to assess the pain level. Outerbridge scores were obtained from a second-look arthroscopic examination. RNA was extracted to quantify catabolic targets and pro-inflammatory genes (QiaGen). Student's t test for two group comparisons and ANOVA analysis for differences between more than 2 groups were utilized. To understand the role of mechanical loading-induced cartilage repair, we measured the serial changes of joint space width (JSW) after HTO for assessing the state of the cartilage stabilization. Our data showed that HTO increased the JSW, decreased the VAS score and improved the KOOS score significantly. We further scored cartilage lesion severity using the Outerbridge classification under a second-look arthroscopic examination while removing the HTO plate. It showed the cartilage lesion area decreased significantly, the full thickness of cartilage increased and mechanical strength was better compared to the pre-HTO baseline. HTO dampened medial tibiofemoral cartilage degeneration and accelerate cartilage repair from Outerbridge grade 2 to 3 to Outerbridge 0 to 1 compared to untreated varus OA. It suggested that physical loading was involved in HTO-induced cartilage regeneration. Given that HTO surgery increases joint space width and creates a physical loading environment, we hypothesize that HTO could increase cartilage composition and collagen accumulation. Consistent with our observation, a group of cartilage-resident MSCs was identified. Our data further showed decreased expression of RUNX2, COL10 and increased SOX9 in MSCs at the RNA level, indicating that catabolic activities were halted during mechanical off-loading. To understand the role of cartilage-resident MSCs in cartilage repair in a biophysical environment, we investigated the differentiation potential of MSCs under 3-dimensional mechanical loading conditions. The physical loading inhibited catabolic markers (IL-1 and IL-6) and increased anabolic markers (SOX9, COL2). Knee-preserved HTO intervention alleviates varus malalignment-related knee joint pain, improves daily and recreation function, and repairs degenerated cartilage of medial compartment OA. The off-loading effect of HTO may allow the mechanoregulation of cartilage repair through the differentiation of endogenous cartilage-derived MSCs

Osteoarthritis (OA) is a highly prevalent degenerative joint disorder characterized by joint pain and physical disability. Aberrant subchondral bone induces pathological changes and is a major source of pain in OA. In the subchondral bone, which is highly innervated, nerves have dual roles in pain sensation and bone homeostasis regulation. The interaction between peripheral nerves and target cells in the subchondral bone, and the interplay between the sensory and sympathetic nervous systems, allow peripheral nerves to regulate subchondral bone homeostasis. Alterations in peripheral innervation and local transmitters are closely related to changes in nociception and subchondral bone homeostasis, and affect the progression of OA. Recent literature has substantially expanded our understanding of the physiological and pathological distribution and function of specific subtypes of neurones in bone. This review summarizes the types and distribution of nerves detected in the tibial subchondral bone, their cellular and molecular interactions with bone cells that regulate subchondral bone homeostasis, and their role in OA pain. A comprehensive understanding and further investigation of the functions of peripheral innervation in the subchondral bone will help to develop novel therapeutic approaches to effectively prevent OA, and alleviate OA pain. Cite this article: Bone Joint Res 2022;11(7):439–452

Aims. Intra-articular (IA) injection may be used when treating hip osteoarthritis (OA). Common injections include steroids, hyaluronic acid (HA), local anaesthetic, and platelet-rich plasma (PRP). Network meta-analysis allows for comparisons between two or more treatment groups and uses direct and indirect comparisons between interventions. This network meta-analysis aims to compare the efficacy of various IA injections used in the management of hip OA with a follow-up of up to six months. Methods. This systematic review and network meta-analysis used a Bayesian random-effects model to evaluate the direct and indirect comparisons among all treatment options. PubMed, Web of Science, Clinicaltrial.gov, EMBASE, MEDLINE, and the Cochrane Library were searched from inception to February 2023. Randomized controlled trials (RCTs) which evaluate the efficacy of HA, PRP, local anaesthetic, steroid, steroid+anaesthetic, HA+PRP, and physiological saline injection as a placebo, for patients with hip OA were included. Results. In this meta-analysis of 16 RCTs with a total of 1,735 participants, steroid injection was found to be significantly more effective than placebo injection on reported pain at three months, but no significant difference was observed at six months. Furthermore, steroid injection was considerably more effective than placebo injection for functional outcomes at three months, while the combination of HA+PRP injection was substantially more effective at six months. Conclusion. Evidence suggests that steroid injection is more effective than saline injection for the treatment of hip joint pain, and restoration of functional outcomes. Cite this article: Bone Joint J 2024;106-B(6):532–539

It is not unusual for patients prior to their total hip arthroplasty (THA) to indicate that their symptoms worsen with certain meteorological conditions. However, the prevalence and evolution of weather-related pain (WRP) following THA remain poorly understood. The aim of this study was to investigate the prevalence of WRP both before and after primary THA, to assess the impact of THA on pre-existing WRP, and to identify potential risk factors associated with WRP. An in-person survey was conducted on 442 primary THAs, in 327 consecutive patients at the time of their postoperative follow-up. Each patient was assessed using a questionnaire specifically designed to address weather-related joint pain before and after their THA. The clinical evaluation included patient-reported outcome scores (PROMS). Preoperatively, 17% of THA hips experienced WRP, with 71% achieving complete resolution postoperatively (p < 0.001). In patients with WRP in multiple joints and their hip, the THA failed to alleviate the WRP in 31% of the cases. In addition, 8% of the THA patients developed de-novo WRP after surgery. Although the overall prevalence of WRP in hips post-THA was 12%, the prevalence was 29% in hips with WRP preoperatively and 31% in the hips of patients with WRP in multiple joints as well as their hip. WRP in other joints, the initial diagnosis, body mass index (BMI), and age were correlated with WRP following THA. WRP is not uncommon prior to and after THA. Although THA can effectively alleviate WRP in specific patient populations, it does not universally eliminate preoperative WRP or prevent the emergence of new WRP after surgery

For all the research into arthroplasty, provision of total knee arthroplasty (TKR) services based on gender in the Australian context is yet to be explored. International literature points toward a heavily gender biased provision of TKA services, skewed away from female patients. This research has aimed to assess the current experience of Australian female patients and to explore better assessment techniques that could provide more equitable services. A retrospective cohort analysis has been conducted using pre-op PROMs data, where available, from the Australian National Joint Replacement Registry (AOANJRR), between 7 August 2018 and 31 December 2021, including: EQ VAS Health; Oxford Knee Score; joint pain; and KOOS-12. Data was adjusted for age, ASA score, BMI, primary diagnosis, public vs private hospital, surgeon gender and years of practice (as estimated from years of registry data available). Of 1,001,231 procedures performed, 27,431 were able to be analysed (12,300 male and 15,131 female). Gender-based bias against female patients reached statistical significance across all PROM scores, according to the Kruskal-Wallis test of difference (p-value <0.0001). Males were more likely to undergo TKR than females, with odds ratios remaining statistically significant when adjusted for age, ASA score, BMI, primary diagnosis, and hospital type. Numbers were further analysed for surgeon years of recorded practice and surgeon gender with mixed results. This study found that women were less likely to undergo TKR despite worse scores on every pre-op PROM available, thus we demonstrate a statistically significant gender-based bias against female patients. More effort needs to be made to identify the base of this bias and find new ways to assess patients that can provide more equitable provision of healthcare

Knee osteoarthritis (KOA) diagnosis is based on symptoms, assessed through questionnaires such as the WOMAC. However, the inconsistency of pain recording and the discrepancy between joint phenotype and symptoms highlight the need for objective biomarkers in KOA diagnosis. To this end, we study relationships among clinical and molecular data in a cohort of women (n=51) with Kellgren-Lawrence grade 2–3 KOA through Support Vector Machine (SVM) and a regulation network model (RNM). Clinical descriptors (i.e., pain catastrophism (CA); depression (DE); functionality (FU); joint pain (JP); rigidity (RI); sensitization (SE); synovitis (SY)) are used to classify patients. A Youden's test is performed for each classifier to determine optimal binarization thresholds for the descriptors. Thresholds are tested against patient stratification according to baseline WOMAC data from the Osteoarthritis Initiative, and the mean accuracy is 0.97. For our cohort, the data used as SVM inputs are KOA descriptors, synovial fluid (SL) proteomic measurements (n=25), and transcription factors (TF) activation obtained from RNM [2] stimulated with the SL measurements. The relative weights after classification reflect input importance. The performance of each classifier is evaluated through AUC-ROC analysis. The best classifier with clinical data is CA (AUC = 0.9), highly influenced by FU and SE, suggesting that kinesophobia is involved in pain perception. With SL input, leptin strongly influences every classifier, suggesting the importance of low-grade inflammation. When TF are used, the mean AUC is limited to 0.608, which can be related to the pleomorphic behaviour of osteoarthritic chondrocytes. Nevertheless, FU has an AUC of 0.7 with strong importance of FOXO downregulation. Though larger and longitudinal cohorts are needed, this unique combination of SVM and RNM shall help to map objectively KOA descriptors. Acknowledgements: Catalan & Spanish governments 2020FI_b00680; STRATO-PID2021126469ob-C21-2, European Commission (MSCA-TN-ETN-2020-Disc4All-955735, ERC-2021-CoG-O-Health-101044828). ICREA Academia

Background. Procedural sedation (PS) requires two suitably qualified clinicians and a dedicated monitored bed space. We present the results of intra-articular haematoma blocks (IAHB), using local anaesthetic, for the manipulation of closed ankle fracture dislocations and compared resource use with PS. Methods. Patients received intra-articular ankle haematoma blocks for displaced ankle fractures requiring manipulation between October 2020 to April 2021. The technique used 10ml of 1% lignocaine injected anteromedially into the tibiotalar joint. Pain scores (VAS), time from first x-ray to reduction, and acceptability of reduction were recorded. A comparison was made by retrospective analysis of patients who had undergone PS for manipulation of an ankle fracture over the six month period March – August 2020. Results. During the periods assessed, 25 patients received an IAHB and 28 received PS for ankle fractures requiring manipulation (mean age 57.8yr vs 55.1yr). Time from first x-ray to manipulation was 65.9 min (IAHB) vs 82.9 min (PS) (p = 0.087). In the IAHB group mean pain scores pre, during and post manipulation were 6.1, 4.7 and 2.0 respectively (‘pre’ to ‘during’ p < 0.05; ‘pre’ to ‘post’ p < 0.01). In the IAHB group, 23 (92%) had a satisfactory reduction without need of PS or general anaesthetic. In the PS group 23 (82%) had a satisfactory reduction. There was no significant difference in the number of unsatisfactory first attempt reductions between the groups. There were no cases of deep infection post operatively in either group. Conclusion. Intra-articular haematoma block of the ankle appears to be an efficacious, safe and inexpensive means of providing analgesia for manipulation of displaced ankle fractures. Advantages of this method include avoiding the risks of procedural sedation, removing the requirement of designated clinical space and need for qualified clinicians to give sedation, and the ability to re-manipulate under the same block

Introduction. Transtibial osseointegration (TFOI) for amputees has limited but clear literature identifying superior quality of life and mobility versus a socketed prosthesis. Some amputees have knee arthritis that would be relieved by a total knee replacement (TKR). No other group has reported performing a TKR in association with TTOI (TKR+TTOI). We report the outcomes of nine patients who had TKR+TTOI, followed for an average 6.5 years. Materials & Methods. Our osseointegration registry was retrospectively reviewed to identify all patients who had TTOI and who also had TKR, performed at least two years prior. Four patients had TKR first the TTOI, four patients had simultaneous TKR+TTOI, and one patient had 1 OI first then TKR. All constructs were in continuity from hinged TKR to the prosthetic limb. Outcomes were: complications prompting surgical intervention, and changes in daily prosthesis wear hours, Questionnaire for Persons with a Transfemoral Amputation (QTFA), and Short Form 36 (SF36). All patients had clinical follow-up, but two patients did not have complete survey and mobility tests at both time periods. Results. Six (67%) were male, average age 51.2±14.7 years. All primary amputations were performed to manage traumatic injury or its sequelae. No patients died. Five patients (56%) developed infection leading to eventual transfemoral amputation 36.0±15.3 months later, and 1 patient had a single debridement six years after TTOI with no additional surgery in the subsequent two years. All patients who had transfemoral amputation elected for and received transfemoral osseointegration, and no infections occurred, although one patient sustained a periprosthetic fracture which was managed with internal fixation and implant retention and walks independently. The proportion of patients who wore their prosthesis at least 8 hours daily was 5/9=56%, versus 7/9=78% (p=.620). Even after proximal level amputation, the QTFA scores improved versus prior to TKR+TTOI, although not significantly: Global (45.2±20.3 vs 66.7±27.6, p=.179), Problem (39.8±19.8 vs 21.5±16.8, p=.205), Mobility (54.8±28.1 vs 67.7±25.0, p=.356). SF36 changes were also non-significant: Mental (58.6±7.0 vs 46.1±11.0, p=.068), Physical (34.3±6.1 vs 35.2±13.7, p=.904). Conclusions. TKR+TTOI presents a high risk for eventual infection prompting subsequent transfemoral amputation. Although none of these patients died, in general, TKR infection can lead to patient mortality. Given the exceptional benefit to preserving the knee joint to preserve amputee mobility and quality of life, it would be devastating to flatly force transtibial amputees with severe degenerative knee joint pain and unable to use a socket prosthesis to choose between TTOI but a painful knee, or preemptive transfemoral amputation for transfemoral osseointegration. Therefore, TTOI for patients who also request TKR must be considered cautiously. Given that this frequency of infection does not occur in patients who have total hip replacement in association with transfemoral osseointegration, the underlying issue may not be that linked joint replacement with osseointegrated limb replacement is incompatible, but may require further consideration of biological barriers to ascending infection and/or significant changes to implant design, surgical technique, or other yet-uncertain factors

Aims. Adenosine, lidocaine, and Mg. 2+. (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery. Methods. Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed. Results. Despite comparable knee function, ALM-treated males had reduced systemic inflammation, synovial fluid angiogenic and pro-inflammatory mediators, synovitis, and fat pad fibrotic changes, compared to controls. Within the ACL graft, ALM-treated males had increased expression of tissue repair markers, decreased inflammation, increased collagen organization, and improved graft-bone healing. In contrast to males, females had no evidence of persistent systemic inflammation. Compared to controls, ALM-treated females had improved knee extension, gait biomechanics, and elevated synovial macrophage inflammatory protein-1 alpha (MIP-1α). Within the ACL graft, ALM-treated females had decreased inflammation, increased collagen organization, and improved graft-bone healing. In articular cartilage of ALM-treated animals, matrix metalloproteinase (MMP)-13 expression was blunted in males, while in females repair markers were increased. Conclusion. At 28 days, ALM therapy reduces inflammation, augments tissue repair patterns, and improves joint function in a sex-specific manner. The study supports transition to human safety trials. Cite this article: Bone Joint Res 2024;13(6):279–293

Total joint replacement (TJR) is by far the most effective therapy for end-stage OA patients. Most of patients achieve joint pain reduction and function improvement following to TJR, however up to 22% of them either do not improve or deteriorate after surgery. The aim of this study was to identify genetic variants to be associated with poor outcome of TJR in primary OA patients by a genome-wide association approach (GWAS). Study participants were primary OA patients from the Newfoundland Osteoarthritis Study (NFOAS) that comprised total knee or hip replacement and recruited before 2016 in St. John's, NL. DNA samples were extracted from patients' blood. Study participants completed their pre-operation and 3.99±1.38 years post-surgery outcome assessment using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). DNA samples were genotyped using the genome-wide Illumina HumanOmni2.58 genotyping microarray containing 2.4 million SNPs. Pre-association quality control filtering was conducted for the raw genotyping data using PLINK 1.7 program, and genotype imputation was performed using the IMPUTE2 algorithm with multiple population reference data from 1000 Genome Project. The imputed data with ∼3.1 million variants was used to test the association with non-responders to TJR using the additive genetic model. Eighty three primary OA patients (44 responders and 39 non-responders) were included in the analysis. Association analysis detected three chromosomal regions on chr5, 7, and 8 to be significantly associated with non-responding to pain. The top SNPs at these loci are intergenic variants that include SNP (rs17118094, p=4.4×10-5) on chr5. This SNP is adjacent to SGCD gene that plays an important role in muscular strength and maintenance. Another associated SNP (rs71572810, p=4.7×10-5) is nearby IMMP2L gene on chr7. This gene is reported to be associated with behavioral abnormalities. Finally, SNP (rs6992938, p=5.8×10-5) on chr8 is located downstream of TRPA1 gene that is known to have a central role in the pain response to endogenous inflammatory mediators. Three loci were also found to be significantly associated with non-responding to function. The lead variant in the locus on chr1 is an intergenic SNP (rs9729377, p=1.7×10-5) falling between CTBS and MCOLN2 genes. CTBS gene is associated with TNF-α, a cytokine that stimulate the inflammation acute phase reaction, and MCOLN2 gene plays a role in the chemokine secretion and macrophage migration in the innate immune response. Other top SNPs in loci on chr2 and 10 harbor CCDC93, INSIG2, and KLF6 genes that are associated with heel bone mineral density, hypercholesterolemia, obesity and BMI. To our knowledge, this project is the first study that investigated the association between genetic factors and TJR non-responders. Our results demonstrated that genes related to muscle strength, behavioral trait, pain response, and inflammation play a significant role in poor outcome of TJR, warranting further investigation

Aims

The primary aim was to assess whether preoperative health-related quality of life (HRQoL) was associated with postoperative mortality following total hip arthroplasty (THA) and knee arthroplasty (KA). Secondary aims were to assess whether patient demographics/comorbidities and/or joint-specific function were associated with postoperative mortality.

Introduction and Objective. TKA have shown both excellent long-term survival rate and symptoms and knee function improvement. Despite the good results, the literature reports dissatisfaction rates around 20%. This rate of dissatisfaction could be due to the overstuff that mechanically aligned prostheses could produce during the range of motion. Either size discrepancy between bone resection and prosthetic component and constitutional mechanical tibiofemoral alignment (MTFA) alteration might increase soft tissue tension within the joint, inducing pain and functional limitation. Materials and Methods. Total knee arthroplasties performed between July 2019 and September 2020 were examined and then divided into two groups based on the presence (Group A) or absence (Group B) of patellofemoral overstuff, defined as a thickness difference of more than 2 mm between chosen component and bone resection performed, taking into account at least one of the following: femoral medial and lateral condyle, medial or lateral trochlea and patella. Based on pre and post-operative MTFA measurements, Group A was further divided into two subgroups whether the considered alignment was modified or not. Patients were assessed pre-operatively and at 6 months post-op using the Knee Society Score (KSS), Oxford Knee Score (OKS), Forgotten Joint Score (FJS), Visual Analogue Scale (VAS) and Range of Motion (ROM). Results. One hundred total knee arthroplasties were included in the present study, 69 in Group A and 31 in group B. Mean age and BMI of patients was respectively 71 and 29.2. The greatest percentage of Patellofemoral Overstuff was found at the distal lateral femoral condyle. OKS, KSS functional score, and FJS were statistically significant higher in patients without Patellofemoral Overstuff. Therefore, Group A patients with a non-modified MTFA demonstrated statistically significant better KSS, ROM and FJS. Conclusions. Patellofemoral Overstuff decrease post-operative clinical scores in patients treated with TKA. The conventional mechanically aligned positioning of TKA components might be the primary cause of prosthetic overstuffing leading to worsened clinical results. Level of evidence: III; Prospective Cohort Observational study;

Aims

Dislocation of the hip remains a major complication after periacetabular tumour resection and endoprosthetic reconstruction. The position of the acetabular component is an important modifiable factor for surgeons in determining the risk of postoperative dislocation. We investigated the significance of horizontal, vertical, and sagittal displacement of the hip centre of rotation (COR) on postoperative dislocation using a CT-based 3D model, as well as other potential risk factors for dislocation.

Aims

Children with spinal dysraphism can develop various musculoskeletal deformities, necessitating a range of orthopaedic interventions, causing significant morbidity, and making considerable demands on resources. This systematic review aimed to identify what outcome measures have been reported in the literature for children with spinal dysraphism who undergo orthopaedic interventions involving the lower limbs.

Aims

Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA).

The October 2023 Research Roundup³⁶⁰ looks at: Gut microbiota in high-risk individuals for rheumatoid arthritis associated with disturbed metabolome and initiates arthritis by triggering mucosal immunity imbalance; International Consensus on Anaemia Management in Surgical Patients (ICCAMS); Sleep disturbance trends in the short-term postoperative period for patients undergoing total joint replacement; Achilles tendon tissue turnover before and immediately after an acute rupture; Quadriceps or hip exercises for patellofemoral pain? A randomized controlled equivalence trial; Total-body MRI for screening in patients with multiple osteochondromas.

Aims

The primary aim of this prospective, multicentre study is to describe the rates of returning to golf following hip, knee, ankle, and shoulder arthroplasty in an active golfing population. Secondary aims will include determining the timing of return to golf, changes in ability, handicap, and mobility, and assessing joint-specific and health-related outcomes following surgery.

The August 2024 Trauma Roundup³⁶⁰ looks at: Does topical vancomycin prevent fracture-related infections in closed fractures undergoing open reduction and internal fixation? A randomized controlled trial; Is postoperative splinting advantageous after upper limb fracture surgery?; Does suprapatellar nailing resolve knee pain?; Locking versus non-locking plate fixation in comminuted talar neck fractures: a biomechanical study using cadaveric specimens; Revolutionizing recovery metrics: PROMIS versus SMFA in orthopaedic trauma care; Dorsal hook plating of patella fractures: reliable fixation and satisfactory outcomes; The impact of obesity on subtrochanteric femur fracture outcomes; Low-dose NSAIDs (ketorolac) and cytokine modulation in orthopaedic polytrauma: a detailed analysis.

Aims

Osteoarthritis (OA) is a common degenerative joint disease worldwide, which is characterized by articular cartilage lesions. With more understanding of the disease, OA is considered to be a disorder of the whole joint. However, molecular communication within and between tissues during the disease process is still unclear. In this study, we used transcriptome data to reveal crosstalk between different tissues in OA.

Osteoarthritis (OA) is mainly caused by ageing, strain, trauma, and congenital joint abnormalities, resulting in articular cartilage degeneration. During the pathogenesis of OA, the changes in subchondral bone (SB) are not only secondary manifestations of OA, but also an active part of the disease, and are closely associated with the severity of OA. In different stages of OA, there were microstructural changes in SB. Osteocytes, osteoblasts, and osteoclasts in SB are important in the pathogenesis of OA. The signal transduction mechanism in SB is necessary to maintain the balance of a stable phenotype, extracellular matrix (ECM) synthesis, and bone remodelling between articular cartilage and SB. An imbalance in signal transduction can lead to reduced cartilage quality and SB thickening, which leads to the progression of OA. By understanding changes in SB in OA, researchers are exploring drugs that can regulate these changes, which will help to provide new ideas for the treatment of OA.

Cite this article: Bone Joint Res 2023;12(9):536–545.

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Knee osteoarthritis (OA) involves a variety of tissues in the joint. Gene expression profiles in different tissues are of great importance in order to understand OA.

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A higher failure rate has been reported in haematogenous periprosthetic joint infection (PJI) compared to non-haematogenous PJI. The reason for this difference is unknown. We investigated the outcome of haematogenous and non-haematogenous PJI to analyze the risk factors for failure in both groups of patients.

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After a few passages of in vitro culture, primary human articular chondrocytes undergo senescence and loss of their phenotype. Most of the available chondrocyte cell lines have been obtained from cartilage tissues different from diarthrodial joints, and their utility for osteoarthritis (OA) research is reduced. Thus, the goal of this research was the development of immortalized chondrocyte cell lines proceeded from the articular cartilage of patients with and without OA.

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The present study aimed to investigate whether patients with inflammatory bowel disease (IBD) undergoing joint arthroplasty have a higher incidence of adverse outcomes than those without IBD.

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The aims were to assess whether preoperative joint-specific function (JSF) and health-related quality of life (HRQoL) were associated with level of clinical frailty in patients waiting for a primary total hip arthroplasty (THA) or knee arthroplasty (KA).

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This study examined whether systemic administration of melatonin would have different effects on osseointegration in ovariectomized (OVX) rats, depending on whether this was administered during the day or night.

Joint replacement is a life-enhancing, cost-effective surgical intervention widely used to treat disabling joint pain mainly caused by osteoarthritis. Hip and knee joint replacements are common, highly successful operations bringing many patients relief from pain, and improve mobility. Prosthetic joint infections (PJI) are often difficult to diagnose; diagnosis often relying on a combination of clinical findings, microbiological data and histological evaluation of periprosthetic tissue. The majority of recent studies demonstrate a higher sensitivity for the culture of sonication fluid (62–94%) than periprosthetic tissue (55–88%). The Royal Devon & Exeter NHS Foundation Trust provided a specialist multidisciplinary team. We evaluated the use of sonication for identifying pathogens during revision hip and knee replacement in our unit with the intention of applying for further grants to study this technology in more detail; it was a diagnostic feasibility study. The target recruitment was 50 patients; 25 consecutive patients undergoing revision hip arthroplasty for any reason, and 25 undergoing revision knee arthroplasty for any reason. The majority of patients were identified in outpatient clinics. Our results show that tissue culture remains more sensitive than sonication. The sensitivity for direct sonication was 75% compared with 80% for tissue culture; sensitivity of enriched sonication was 80 %, compared to the unit results for tissue culture of 83%. The combined sensitivity of tissue culture was better as a higher number of tissue specimens were obtained. The different methodology might explain reported differences between this and other studies; however, our study does not support the use of sonication as the only tool in the diagnosis of PJI

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To analyze the short-term outcome of two types of total wrist arthroplasty (TWA) in terms of wrist function, migration, and periprosthetic bone behaviour.

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The aim of this study was to determine the effectiveness of home-based prehabilitation on pre- and postoperative outcomes in participants awaiting total knee (TKA) and hip arthroplasty (THA).

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This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA.

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This study aimed to compare the outcomes of two different postoperative management approaches following surgical fixation of ankle fractures: traditional cast immobilization versus the Early Motion and Directed Exercise (EMADE) programme.

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The mean age of patients undergoing total knee arthroplasty (TKA) has reduced with time. Younger patients have increased expectations following TKA. Aseptic loosening of the tibial component is the most common cause of failure of TKA in the UK. Interest in cementless TKA has re-emerged due to its encouraging results in the younger patient population. We review a large series of tantalum trabecular metal cementless implants in patients who are at the highest risk of revision surgery.

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Psychological status may be an important predictor of outcome after periacetabular osteotomy (PAO). The aim of this study was to investigate the influence of psychological distress on postoperative health-related quality of life, joint function, self-assessed pain, and sports ability in patients undergoing PAO.

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We aimed to evaluate the utility of ⁶⁸Ga-citrate positron emission tomography (PET)/CT in the differentiation of periprosthetic joint infection (PJI) and aseptic loosening (AL), and compare it with ^99mTc-methylene bisphosphonates (^99mTc-MDP) bone scan.

Introduction. Patient-reported outcome (PRO) data are variably collected before and after total hip/knee arthroplasty (THA/TKA). We assessed the generalizability of incentivized, prospectively collected PRO data for THA/TKA patient-reported outcome performance measure (PRO-PM) development. Methods. The Centers for Medicare & Medicaid Services (CMS) received PRO data voluntarily submitted by hospitals in a bundled payment model for THA/TKA procedures. Participating hospitals who collected and successfully submitted these data received an increase in their overall quality score, possibly resulting in a positive impact on model reconciliation payments. PRO data were collected from Medicare Fee-For-Service beneficiaries >= 65 years undergoing elective primary THA/TKA procedures from July 1 to August 31, 2016 at hospitals participating in the model. Pre-operative PRO and risk variable data were collected 0 – 90 days prior to surgery, while post-operative PRO data were collected 270 – 365 days following elective THA/TKA. PRO pre-op and post-op data were matched to Medicare claims data for determination of clinically eligible procedures and clinical comorbidities. We compared the characteristics of patients submitting PRO data to other elective primary THA/TKA recipients in the US. Results. Four patient characteristics were associated with HOOS Jr. mean change scores (sex, narcotic use in past 90 days, other joint pain, and back pain) and four with KOOS Jr. mean change scores (sex, Hispanic ethnicity, other joint pain, and back pain). The frequency of simultaneous bilateral procedures, dementia, trauma, and dialysis were statistically significantly lower in patients submitting PRO data compared to other US Medicare beneficiaries undergoing elective primary THA/TKA, but no difference was greater than 1.5% absolute percentage points between groups. Conclusions. Offering financial incentives in alternative payment models to encourage PRO data collection and submission can produce generalizable data for PRO measure development. The possibility of non-respondent biases will need to be specifically considered in measure development

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The purpose of this study was to explore a simple and effective method of preparing human acellular amniotic membrane (HAAM) scaffolds, and explore the effect of HAAM scaffolds with juvenile cartilage fragments (JCFs) on osteochondral defects.

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Return to sport following undergoing total (TKA) and unicompartmental knee arthroplasty (UKA) has been researched with meta-analyses and systematic reviews of varying quality. The aim of this study is to create an umbrella review to consolidate the data into consensus guidelines for returning to sports following TKA and UKA.

Background and purpose of the study. Axial Spondyloarthritis (axSpA) is commonly mistaken as chronic mechanical back pain. Delayed diagnosis averages 5- 8 years with impacts on effective and timely management, outcomes and quality of life. NICE Guidance (2017) highlights the importance of the recognition and referral of suspected axial spondyloarthritis. This study investigated the occurrence of physiotherapy care prior to diagnosis of axSpA within physiotherapy outpatient settings. Methods and results. A retrospective review was performed of all patients diagnosed with axSpA who had received physiotherapy care prior to their diagnosis from 1990–2016. Three or more episodes of care prior to diagnosis was taken as unrecognised axSpA. Information was obtained on diagnostic codes, number of episodes of care and contacts per episode from nine outpatient physiotherapy services. Analysis showed that 263 people (17–69 years) diagnosed with axSpAs had received physiotherapy care prior to diagnosis. Within this population, 103 (44%) had received ≥3 episodes of care. Number of contacts within each episode ranged from 3 (47 people) to 58 (1 person) [median=11 contacts-10 people]. Average time from initial physiotherapy episode to date of diagnosis was 6.4 years (range=0.3–12.8 years, median=8.8 years). The most common assigned diagnostic code was back pain (49.6%), followed by shoulder (11.1%), knee (8.5%), neck (7.7%), ankle/foot (4.3%), tendonitis (4.2%), joint pain (3.4%), osteoarthritis (3.4%) and sacroiliac joint (2%). Conclusion. Findings illustrate the extent of unrecognised axial spondyloarthritis referred to and missed in musculoskeletal physiotherapy practice. It is essential to improve screening and recognition of inflammatory back pain and possible axSpA in musculoskeletal assessments, supported by rheumatology referral guidance. No conflicts of interest. No funding obtained

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Circular RNA (circRNA) S-phase cyclin A-associated protein in the endoplasmic reticulum (ER) (circSCAPER, ID: hsa_circ_0104595) has been found to be highly expressed in osteoarthritis (OA) patients and has been associated with the severity of OA. Hence, the role and mechanisms underlying circSCAPER in OA were investigated in this study.

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The aim of this prospective study was to assess the long-term clinical, radiological, functional, and quality of life (QoL)-related outcome of patients treated with the synthetic Ligament Advanced Reinforcement System (LARS) device for anterior cruciate ligament (ACL) rupture.

Objectives. In this study, we compared the pain behaviour and osteoarthritis (OA) progression between anterior cruciate ligament transection (ACLT) and osteochondral injury in surgically-induced OA rat models. Methods. OA was induced in the knee joints of male Wistar rats using transection of the ACL or induction of osteochondral injury. Changes in the percentage of high limb weight distribution (%HLWD) on the operated hind limb were used to determine the pain behaviour in these models. The development of OA was assessed and compared using a histological evaluation based on the Osteoarthritis Research Society International (OARSI) cartilage OA histopathology score. Results. Both models showed an increase in joint pain as indicated by a significant (p < 0.05) decrease in the values of %HLWD at one week post-surgery. In the osteochondral injury model, the %HLWD returned to normal within three weeks, while in the ACLT model, a significant decrease in the %HLWD was persistent over an eight-week period. In addition, OA progression was more advanced in the ACLT model than in the osteochondral injury model. Furthermore, the ACLT model exhibited a higher mean OA score than that of the osteochondral injury model at 12 weeks. Conclusion. The development of pain patterns in the ACLT and osteochondral injury models is different in that the OA progression was significant in the ACLT model. Although both can be used as models for a post-traumatic injury of the knee, the selection of appropriate models for OA in preclinical studies should be specified and relevant to the clinical scenario. Cite this article: T. Tawonsawatruk, O. Sriwatananukulkit, W. Himakhun, W. Hemstapat. Comparison of pain behaviour and osteoarthritis progression between anterior cruciate ligament transection and osteochondral injury in rat models. Bone Joint Res 2018;7:244–251. DOI: 10.1302/2046-3758.73.BJR-2017-0121.R2