Objectives. Salubrinal is a synthetic agent that elevates phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α) and alleviates stress to the endoplasmic reticulum. Previously, we reported that in chondrocytes, Salubrinal attenuates expression and activity of matrix metalloproteinase 13 (MMP13) through downregulating nuclear factor kappa B (NFκB) signalling. We herein examine whether Salubrinal prevents the degradation of articular cartilage in a mouse model of osteoarthritis (OA). Methods. OA was surgically induced in the left knee of female mice. Animal groups included age-matched sham control, OA placebo, and OA treated with Salubrinal or Guanabenz. Three weeks after the induction of OA, immunoblotting was performed for NFκB p65 and p-NFκB p65. At three and six weeks, the femora and tibiae were isolated and the sagittal sections were stained with Safranin O. Results. Salubrinal suppressed the progression of OA by downregulating p-NFκB p65 and MMP13. Although Guanabenz elevates the phosphorylation level of eIF2α, it did not suppress the progression of OA. Conclusions. Administration of Salubrinal has chondroprotective effects in arthritic joints. Salubrinal can be considered as a potential therapeutic agent for alleviating symptoms of OA. Cite this article: Bone Joint Res 2015;4:84–92

Treatment for osteoarthritis (OA) has traditionally focused on joint replacement for end-stage disease. An increasing number of surgical and pharmaceutical strategies for disease prevention have now been proposed. However, these require the ability to identify OA at a stage when it is potentially reversible, and detect small changes in cartilage structure and function to enable treatment efficacy to be evaluated within an acceptable timeframe. This has not been possible using conventional imaging techniques but recent advances in musculoskeletal imaging have been significant. In this review we discuss the role of different imaging modalities in the diagnosis of the earliest changes of OA. The increasing number of MRI sequences that are able to non-invasively detect biochemical changes in cartilage that precede structural damage may offer a great advance in the diagnosis and treatment of this debilitating condition. Cite this article: Bone Joint J 2013;95-B:738–46

Knee arthroscopy with debridement is commonly performed to treat osteoarthritis and degenerative meniscal tears in older adults; however robust evidence does not support sustained benefit from this procedure. Current Canadian guidelines advise against its use as first line treatment. Characterizing the use of this low value procedure will facilitate efforts to maximize quality of care, minimize harm and decrease healthcare costs. We sought to understand:. 1). the volume and variations of arthroscopic knee debridement across Canada. 2). The costs associated with potentially unnecessary arthroscopy. 3). The characteristics of surgeons performing knee arthroscopy in older adults. Data were derived from National Ambulatory Care Reporting System (NACRS), the Discharge Abstract Database (DAD) and the National Physician Database for years 2011-12 to 2019-20. The study included all elective knee arthroscopies (CCI codes 1.VG.80.DA,1.VG.80.FY and 1.VG.87.DA) performed in day surgery and acute care settings in 9 provinces and 3 territories of Canada. Quebec was not included in the analysis due to different reporting methods. We set a threshold of 60 years of age at which it would be highly unlikely that a patient would undergo arthroscopy to treat anything other than osteoarthritis or degenerative meniscal tear. Trends at national and provincial levels were analyzed using regression. Costs were estimated separately using the 2020 case mix groups (CMG) and comprehensive ambulatory care classification system (CACS) methodologies. Surgeons were classified by decade of graduation from medical school (1989 and prior, 1990-99, 2000-09 and 2010+) and categorized based on the proportion of their patient population who were above (“high proportion inappropriate”) or below (“low proportion inappropriate”) the overall national proportion of ≥ 60 years of age. The number of knee arthroscopies decreased by 37% (42,785 in 2011-12 to 27,034 in 2019-20) overall and 39% (11,103 in 2011-12 to 6,772 in 2019-20) in those 60 years and older (p 25% of patients 60 years and older. Fifty four percent of surgeons who graduated prior to 1989 were considered high proportion inappropriate, whereas only 30.1% of surgeons who graduated in 2010 or later were considered high proportion inappropriate (p < 0 .0001). Knee arthroscopy continues to be a common procedure in patients over 60 despite strong evidence for lack of benefit. Lower rates in this population in some provinces are encouraging for potential opportunity for improvement. Efforts at practice change should be targeted at surgeons in practice the longest. Canada spends over $12,000,000 per year on this procedure, decreasing its use could allow these resources to be directed to other areas of orthopaedics that provide higher value care

Osteoarthritis (OA) is the most common form of arthritis and one of the ten most disabling diseases in developed countries. Total joint replacement (TJR) is considered by far as the most effective treatment for end-stage OA patients. The majority of patients achieve symptomatic improvement following TJR. However, about 22% of the TJR patients either do not improve or deteriorate after surgery. Several potential non-genetic predictors for the TJR outcome have been investigated. However, the results were either inconclusive or had very limited predictive power. The aim of this study was to identify genetic variants for the poor outcome of TJR in primary OA patients by a genome-wide association study (GWAS). Study participants were total knee or hip replacement patients due to primary OA who were recruited to the Newfoundland Osteoarthritis Study (NFOAS) before 2017. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to assess pain and functional impairment pre- and 3.99±1.38 years post-surgery. Two non-responder classification criteria were used in our study. One was defined by an absolute WOMAC change score. Participants with a change score less than 7/20 points for pain were considered as pain non-responders; and those with less than 22/68 points for function were classified as function non-responders. The second one was the Outcome Measures in Arthritis Clinical Trials and the Osteoarthritis Research Society International (OMERACT-OARSI) criteria. Blood DNA samples were genotyped using the Illumina GWAS microarrays genotyping platform. The quality control (QC) filtering was performed on GWAS data before the association of the genetic variants with non-responders to TJR was tested using the GenABEL package in R with adjustment for the relatedness of the study population and using the commonly accepted GWAS significance threshold p < 5*10. −8. to control multiple testing. In total, 316 knee and 122 hip OA patients (mean age 65.45±7.62 years, and 58% females) passed the QC check. These study participants included 368 responders and 56 non-responders to pain, and 364 responders and 68 non-responders to function based on the absolute WOMAC point score change classification. While 377 responders and 56 non-responders to pain, and 366 responders and 71 non-responders to function were identified by the OMERACT-OARSI classification criteria. Interestingly, the same results were obtained by both classification methods, and we found that the G allele of rs4797006 was significantly associated with pain non-responders with odds ratio (OR) of 5.12 (p<7.27×10. -10. ). This SNP is in intron one of the melanocortin receptor 5 (MC5R) gene on chr18. This gene plays central roles in immune response, pain sensitivity, and negative regulation of inflammatory response to antigenic stimulus. The A allele of rs200752023 was associated with function non-responders with OR of 4.41 (p<3.29×10. -8. ). The SNP is located in intron three of the RNA Binding Fox-1 Homolog 3 (RBFOX3) gene on chr17 which has been associated with numerous neurological disorders. Our data suggested that two chromosomal regions are associated with TJR poor outcomes and could be the novel targets for developing strategies to improve the outcome of the TJR

The 2021 Australian Orthopaedic Association National Joint Replacement Registry report indicated that total shoulder replacement using both mid head (TMH) length humeral components and reverse arthroplasty (RTSA) had a lower revision rate than stemmed humeral components in anatomical total shoulder arthroplasty (aTSA) - for all prosthesis types and diagnoses. The aim of this study was to assess the impact of component variables in the various primary total arthroplasty alternatives for osteoarthritis in the shoulder. Data from a large national arthroplasty registry were analysed for the period April 2004 to December 2020. The study population included all primary aTSA, RTSA, and TMH shoulder arthroplasty procedures undertaken for osteoarthritis (OA) using either cross-linked polyethylene (XLPE) or non-cross-linked polyethylene (non XLPE). Due to the previously documented and reported higher revision rate compared to other anatomical total shoulder replacement options, those using a cementless metal backed glenoid components were excluded. The rate of revision was determined by Kaplan-Meir estimates, with comparisons by Cox proportional hazard models. Reasons for revision were also assessed. For a primary diagnosis of OA, aTSA with a cemented XLPE glenoid component had the lowest revision rate with a 12-year cumulative revision rate of 4.7%, compared to aTSA with cemented non-XLPE glenoid component of 8.7%, and RTSA of 6.8%. The revision rate for TMH was lower than aTSA with cemented non-XLPE, but was similar to the other implants at the same length of follow-up. The reason for revision for cemented aTSR was most commonly component loosening, not rotator cuff deficiency. Long stem humeral components matched with XLPE in aTSA achieve a lower revision rate compared to shorter stems, long stems with conventional polyethylene, and RTSA when used to treat shoulder OA. In all these cohorts, loosening, not rotator cuff failure was the most common diagnosis for revision

The trapeziometacarpal joint (TMCJ) is the most common hand joint affected by osteoarthritis (OA), and trapezium implant arthroplasty is a potential treatment for recalcitrant OA. This meta-analysis aimed to investigate the efficacy and safety of various trapezium implants as an interventional option for TMCJ OA. Web of Science, PubMed, Scopus, Google Scholar, and Cochrane library databases were searched for relevant studies up to May 2022. Preferred Reported Items for Systematic Review and Meta-Analysis guidelines were adhered to and registered on PROSPERO. The methodological quality was assessed by National Heart, Lung, and Blood Institute tools for observational studies and the Cochrane risk of bias tool. Subgroup analyses were performed on different replacement implants, the analysis was done via Open Meta-Analyst software and P values < 0.05 were considered statistically significant. A total of 123 studies comprising 5752 patients were included. Total joint replacement (TJR) implants demonstrate greater significant improvements in visual analogue scale pain scores postoperatively. Interposition with partial trapezial resection implants was associated with the highest grip strength and highest reduction in the Disabilities of the Arm, Shoulder, and Hand score. Revision rates were highest in TJR (12.3%), and lowest in interposition with partial trapezial resection (6.2%). Total joint replacement and interposition with partial trapezial resection implants improve pain, grip strength, and DASH scores more than other implant options. Future studies should focus on high-quality randomized clinical trials comparing different implants to accumulate higher quality evidence and more reliable conclusions

Osteoarthritis (OA) is a disease of the synovial joint with synovial inflammation, capsular contracture, articular cartilage degradation, subchondral sclerosis and osteophyte formation contributing to pain and disability. Transcriptomic datasets have identified genetic loci in hip and knee OA demonstrating joint specificity. A limited number of studies have directly investigated transcriptional changes in shoulder OA. Further, gene expression patterns of periarticular tissues in OA have not been thoroughly investigated. This prospective case control series details transcriptomic expression of shoulder OA by analysing periarticular tissues in patients undergoing shoulder replacement for OA as correlated with a validated patient reported outcome measure of shoulder function, an increasing (clinically worsening) QuickDASH score. We then compared transcriptomic expression profiles in capsular tissue biopsies from the OA group (N=6) as compared to patients undergoing shoulder stabilisation for recurrent instability (the control group, N=26). Results indicated that top ranked genes associated with increasing QuickDASH score across all tissues involved inflammation and response to stress, namely interleukins, chemokines, complement components, nuclear response factors and immediate early response genes. Some of these genes were upregulated, and some downregulated, suggestive of a state of flux between inflammatory and anti-inflammatory signalling pathways. We have also described gene expression pathways in shoulder OA not previously identified in hip and knee OA, as well as novel genes involved in shoulder OA

A concern of metal on metal hip resurfacing arthroplasty is long term exposure to Cobalt (Co) and Chromium (CR) wear debris from the bearing. This study compares whole blood metal ion levels from patients drawn at one-year following Birmingham Hip Resurfacing (BHR) to levels taken at a minimum 10-year follow-up. A retrospective chart review was conducted to identify all patients who underwent a BHR for osteoarthritis with a minimum 10-year follow-up. Whole blood metal ion levels were drawn at final follow-up in June 2019. These results were compared to values from patients with one-year metal ion levels. Of the 211 patients who received a BHR, 71 patients (54 males and 17 females) had long term metal ion levels assessed (mean follow-up 12.7 +/− 1.4 years). The mean Co and Cr levels for patients with unilateral BHRs (43 males and 13 females) were 3.12 ± 6.31 ug/L and 2.62 ± 2.69 ug/L, respectively, and 2.78 ± 1.02 ug/L and 1.83 ± 0.65 ug/L for patients with bilateral BHRs (11 males and 4 females). Thirty-five patients (27 male and 8 female) had metal-ion levels tested at one-year postoperatively. The mean changes in Co and Cr levels were 2.29 ug/l (p = 0.0919) and 0.57 (p = 0.1612), respectively, at one year compared to long-term. These changes were not statistically significant. This study reveals that whole blood metal ion levels do not change significantly when comparing one-year and ten-year Co and Cr levels. These ion levels appear to reach a steady state at one year. Our results also suggest that regular metal-ion testing as per current Medicines and Healthcare products Regulatory Agency (MHRA) guidelines may be impractical for asymptomatic patients. Metal-ion levels, in and of themselves, may in fact possess little utility in determining the risk of failure and should be paired with radiographic and clinical findings to determine the need for revision

While total joint replacement (TJR) is considered as an effective intervention to relieve pain and restore joint function for end-stage osteoarthritis (OA) patients, a significant proportion of the patients are dissatisfied with their surgery outcomes. The aim of this study was to identify genetic factors that can predict patients who do or do not benefit from these surgical procedures by a genome-wide association study (GWAS). Study participants were derived from the Newfoundland Osteoarthritis Study (NFOAS) which consisted of 1086 TJR patients. Non-responders to TJR was defined as patients who did not reach the minimum clinically important difference (MCID) based on the self administered Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) in terms of pain reduction or function improvment. DNA was extracted from the blood samples of the study participants and genotyped by Illumina GWAS genotyping platform. Over two million single nucleotide polymorphisms (SNPs) across the genome were genotyped and tested for assocition with non-responders. 39 non-responders and 44 age, sex, and BMI matched responders were included in this study. Four chromosome regions on chromosomes 5, 7, 8, and 12 were suggested to be associated with non-responders with p < 1 0–5. The most promising one was on chromosome 5 with the lead SNP rs17118094 (p=1.7×10–6) which can classify 72% of non-responders accurately. The discriminatory power of this SNP alone is very promising as indicated by an area under the curve (AUC) of 0.72 with 95% confidence interval of 0.63 to 0.81, which is much better than any previously studied predictors mentioned above. All the patients who carry two copies of the G allele (minor allele) of rs17118094 were non-responders and 75% of those who carry one copy of the G allele were non-responders. The discriminatory ability of the lead SNPs on chromosomes 7 and 12 were comparable to the one on chromosome 5 with an AUC of 0.74, and 88% of patients who carry two copies of the A allele of rs10244798 on chromosome 7 were non-responders. Similarly, 88% of patients who carry two copies of the C allele of rs10773476 on chromosome 12 were non-responders. While the discriminatory ability of rs9643244 on chromosome 8 was poor with an AUC of 0.26, its strong association with non-responders warrants a further investigation in the region. The study identified four genomic regions harboring genetic factors for non-responders to TJR. The lead SNPs in those regions have great discriminatory ability to predict non-responders and could be used to create a genetic prediction model for clinical unitilty and application

Multiple studies have shown that the symptomatology of knee osteoarthritis weakly correlate to radiographic severity of disease. Current literature however does not have much in the way of comparing functional outcomes of those with OA knees with radiographic severity. Our objective was to compare radiographic measurements of OA knees with self-reported functional outcomes and determine if radiographic severity of OA knees correlated with loss of functional ability. A retrospective review of prospectively collected registry data of 305 patients with osteoarthritis of the knee was collected. The patient's x-rays were reviewed, and radiographic measurements were taken to include medial, lateral and patellofemoral joint space distance measured in millimetres. The Kellgren and Lawrence, and Ahlback classifications of radiographic knee OA were computed. These were correlated with severity of functional limitations was measured using the SF36, Knee society score (KSS) and Oxford knee scores. Statistical analysis were conducted with SPSS V22.0 statistical software. Demographic characteristics and functional assessments were analysed using one way ANOVA test. Post-hoc test using Tukey HSD and effect size (partial-eta squared η. 2. ) was performed if one-way ANOVA was found to be statistically significant. A p-value of 0.05 or less was considered statistically significant. Pre-operative patient demographics are shown in table 1. Patients in with Grade 2 osteoarthritis were significantly younger than Grade 4 patients (post-hoc p=0.003). There were no statistically significant differences in age between the other Grades, and there were no differences in BMI or gender or operative site between all grades. There were significant differences in KSS Function scores between Grade 2 and Grade 3 patients (post-hoc p=0.017) and Grade 2 and 4 patients (post-hoc p < 0 .001). Statistically significant differences were also found between Grade 1 and Grade 4 patients for the KSS Knee score (post-hoc p=0.016). There were significant differences in Oxford knee score (post-hoc p=0.026) and SF- Physical Function (post-hoc p < 0 .001) between Grade 2 and Grade 4 patients too. The effect size η. 2. for KSS Function, KSS Knee and Oxford knee score was 0.05, 0.06 and 0.33 respectively. When comparing the loss of joint space with the functional scores, there were no statistically significant correlations. Our study show that the radiological severity of knee osteoarthritis based on the two scoring methods was able to correlate with worsening functional scores. Most notably, the differences in KSS function scores correlated strongly between Grade 2 and Grade 3 patients. Of note, there was no correlation between the loss of joint space and the severity of functional limitations across any of the scoring systems. Our study showed that although both the Kellgren and Lawrence and Ahlback radiological grading of Osteoarthritis were able to correlate with worsening functional scores, this was not due to loss of joint space alone and further studies need to be conducted on the other contributors to the scoring system such as osteophytes and subchondral sclerosis. Our study show that the radiological severity of knee osteoarthritis based on the two scoring methods was able to correlate with worsening functional scores. Most notably, the differences in KSS function scores correlated strongly between Grade 2 and Grade 3 patients. Of note, there was no correlation between the loss of joint space and the severity of functional limitations across any of the scoring systems. Our study showed that although both the Kellgren and Lawrence and Ahlback radiological grading of Osteoarthritis were able to correlate with worsening functional scores, this was not due to loss of joint space alone and further studies need to be conducted on the other contributors to the scoring system such as osteophytes and subchondral sclerosis. For any figures or tables, please contact authors directly

Osteoarthritis (OA) is a chronic degenerative joint disease with cartilage degeneration, subchondral bone sclerosis, synovial inflammation and osteophyte formation. Sensory nerves play an important role in bone metabolism and in the progression of inflammation. This study explored the effects of capsaicin-induced sensory nerve denervation on OA progression in mice. This study was approved by the Institutional Animal Care and Use Committee. OA was induced via destabilization of the medial meniscus (DMM). Sensory denervation was induced by subcutaneous injection of capsaicin (90mg/kg) one week prior to DMM. One week after capsaicin injection, sensory denervation in the tibia was confirmed by immunofluorescent staining with calcitonin gene-related peptide (CGRP)-specific antibodies. Four weeks after DMM, micro-CT scans, histological analysis and RT-PCR tests were performed to evaluate OA progression. Statistical analysis was performed using SPSS 13. P values of less than 0.05 were considered statistically significant. Subcutaneous injection of capsaicin successfully induced tibial sensory denervation (n=3), which aggravated OA by increasing subchondral bone resorption. The Osteoarthritis Research Society International (OARSI) score of the capsaicin+DMM group (n=8) (11.81±2.92) was significantly higher (P=0.003) than the score of the vehicle+DMM group (n=8) (8.31±1.80). The BV/TV of the tibial subchondral bone in the capsaicin+DMM group (n=8) was 55.67%±3.08, which was significantly lower (P < 0 .001) than in the vehicle+DMM group (n=8) (86.22%±1.92). In addition, the level of expression of somatostatin in the capsaicin+DMM group (n=8) was lower than in the vehicle+DMM group (n=8) (P=0.007). Capsaicin-induced sensory denervation increased tibial subchondral bone resorption, reduced the expression of somatostatin and eventually exacerbated the existing cartilage degeneration in mice. Despite capsaicin is often used clinically to relieve OA pain, its safety is still controversial according to the OARSI guidelines for the non-surgical management of knee osteoarthritis. The findings of our study suggest that application of capsaicin, although effective in relieving pain, may accelerate the progression of existing OA

Rapidly progressive osteoarthritis of the hip (RPOH) is an unusual subset of osteoarthritis. It is characterized by rapid joint space loss, chondroly­sis, and sometimes marked femoral head and acetabular destruction as a late finding. The exact pathogenetic mechanism is unknown. Potential causes of RPOH include subchondral insufficiency fracture resulting from osteoporosis, increasing posterior pelvic tilt as a mechanical factor, and high serum levels of matrix metalloproteinase (MMP)-3 as biological factors. This study was aimed to identify some markers that associate with the destructive process of RPOH by analyzing the proposed pathological factors of the disease, MMP-3, pelvic tilt, and osteoporosis. Of female patients who visited our hospital with hip pain from 2012 through 2018, this study enrolled female patients with sufficient clinical records including the onset of hip pain, age and body mass index (BMI) at the onset, a series of radiographs during the period of >12 months from the onset of hip pain, and hematological data of MMP-3 and C-reactive protein (CRP). We found the hip joints of 31 patients meet the diagnostic criteria of RPOH, chondrolysis >two mm in one year, or 50% joint space narrowing in one year. Those patients were classified into two groups, 17 and 14 patients with and without subsequent femoral head destruction in one year shown by computed tomography, respectively. Serum MMP-3 and CRP were measured with blood samples within one year after the hip pain onset. The cortical thickness index (CTI) as an indicator of osteoporosis and pelvic tilt parameters were evaluated on the initial anteroposterior radiograph of the hip. These factors were statistically compared between the two groups. This study excluded male patients because RPOH occurs mainly in elderly females and the reference intervals of MMP-3 are different between males and females. There was no difference in age at onset or bone mass index between the RPOH patients with and without subsequent femoral head destruction. Serum levels of MMP-3 were significantly higher in the RPOH patients with the destruction (152.1 ± 108.9 ng/ml) than those without the destruction (66.8 ± 27.9 ng/ml) (P = 0.005 by Mann-Whitney test). We also found increased CRP in the patients with femoral head destruction (0.725 ± 1.44 mg/dl) compared with those without the destruction (0.178 ± 0.187 mg/dl) (P = 0.032 by Mann-Whitney test). No difference in the duration between the hip pain onset and the blood examination was found between the two groups. There was no significant difference in CTI or pelvic tilt between the two groups. The pathological condition that may increase serum MMP-3 and CRP could be involved in femoral head destruction after chondrolysis of the hip in patients with RPOH

Introduction. Although surgical remedies tend to be the long-term solutions for patients with osteoarthritis (OA), many alternatives exist that offer the potential to slow progression, alleviate pain, and/or restore function. One such option is the unloader OA knee brace. The objective of this study was to assess the in vivo medial joint space narrowing with and without the brace during weight-bearing portion of gait. Methods. Twenty subjects were evaluated after being clinically assessed by a single surgeon to be bone-on-bone on the medial side. In vivo gait kinematics were collected using a validated 3D-to-2D fluoroscopic registration technique (Figure 1). Subjects were asked to first walk on a treadmill without a brace (Figure 2), and then, after a qualified technician fit a properly sized brace to each subject, they were asked to walk again (Figure 3). In vivo fluoroscopic images were captured and registered at heel-strike (HS) and mid stance (MS) for both scenarios. CT scans were used to acquire the patient-specific bone models that were used in the registration process. Results. All twenty subjects experienced a positive increase in medial joint space and verbally stated their knee pain lessened while wearing the brace. The average medial joint space change was 1.7±0.8 mm (3.1 max, 0.3 min) at HS and 1.6±0.8 mm (3.7 max, 0.4 min) at MS (Figure 4). Five patients experienced more than 2.5 mm of medial joint space change when wearing the unloader brace, indicating substantial effectiveness of the brace. Conclusion. While previous unloader brace studies have focused on outcome scores and patient satisfaction to analyze brace effectiveness, this study quantifiably demonstrated improvement in joint space narrowing due to the unloader brace. These results suggest that unloader braces may provide benefit in the interim when symptoms of OA are present prior to need for surgical intervention. For any figures or tables, please contact the authors directly

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

The superficial zone (SFZ) of articular cartilage has unique structural and biomechanical features, and is important for joint long-term function. Previous studies have shown that TGF-β/Alk5 signaling upregulating PRG4 expression maintains articular cartilage homeostasis. However, the exact role and molecular mechanism of TGF-β signaling in SFZ of articular cartilage homeostasis are still lacking. In this study, a combination of in vitro and in vivo approaches were used to elucidate the role of Alk5 signaling in maintaining the SFZ of articular cartilage and preventing osteoarthritis initiation. Mice with inducible cartilage SFZ-specific deletion of Alk5 were generated to assess the role of Alk5 in OA development. Alterations in cartilage structure were evaluated histologically. The chondrocyte apoptosis and cell cycle were detected by TUNEL and Edu staining, respectively. Isolation, culture and treatment of SFZ cells, the expressions of genes associated with articular cartilage homeostasis and TGF-β signaling were analyzed by qRT-PCR. The effects of TGF-β/Alk5 signaling on proliferation and differentiation of SFZ cells were explored by cells count and alcian blue staining. In addition, SFZ cells isolated from C57 mice were cultured in presence of TGF-β1 or SB505124 for 7 days and transplanted subcutaneously in athymic mice. Postnatal cartilage SFZ-specific deletion of Alk5 induced an OA-like phenotype with degradation of articular cartilage, synovial hyperplasia as well as enhanced chondrocyte apoptosis, overproduction of catabolic factors, and decreased expressions of anabolic factors in chondrocytes. qRT-PCR and IHC results confirmed that Alk5 gene was effectively deleted in articular cartilage SFZ cells. Next, the PRG4-positive cells in articular cartilage SFZ were significantly decreased in Alk5 cKO mice compared with those in Cre-negative control mice. The mRNA expression of Aggrecan and Col2 were decreased, meanwhile, expression of Mmp13 and Adamts5 were significantly increased in articular cartilage SFZ cells of Alk5 cKO mice. In addition, Edu and TUNEL staining results revealed that slow-cell cycle cell number and increase the apoptosis positive cell in articular cartilage SFZ of Alk5 cKO mice compared with Cre-negative mice, respectively. Furthermore, all groups of SFZ cells formed ectopic solid tissue masses 1 week after transplantation. Histological examination revealed that the TGF-β1-pretreated tissues was composed of small and round cells and was positive for alcian blue staining, while the SB505124-pretreated tissue contained more hypertrophic cells though it did stain with alcian blue. TGF-β/alk5 signaling is an essential regulator of the superficial layer of articular cartilage by maintaining chondrocyte number, its differentiation properties, and lubrication function. Furthermore, it plays a critical role in protecting cartilage from OA initiation

Introduction. Robotic-assisted hip arthroplasty helps acetabular preparation and implantation with the assistance of a robotic arm. A computed tomography (CT)-based navigation system is also helpful for acetabular preparation and implantation, however, there is no report to compare these methods. The purpose of this study is to compare the acetabular cup position between the assistance of the robotic arm and the CT-based navigation system in total hip arthroplasty for patients with osteoarthritis secondary to developmental dysplasia of the hip. Methods. We studied 31 hips of 28 patients who underwent the robotic-assisted hip arthroplasty (MAKO group) between August 2018 and March 2019 and 119 hips of 112 patients who received THA under CT-based navigation (CT-navi group) between September 2015 and November 2018. The preoperative diagnosis of all patients was osteoarthritis secondary to developmental dysplasia of the hip. They received the same cementless cup (Trident, Stryker). Robotic-assisted hip arthroplasty were performed by four surgeons while THA under CT-based navigation were performed by single senior surgeon. Target angle was 40 degree of radiological cup inclination (RI) and 15 degree of radiological cup anteversion (RA) in all patients. Propensity score matching was used to match the patients by gender, age, weight, height, BMI, and surgical approach in the two groups and 30 patients in each group were included in this study. Postoperative cup position was assessed using postoperative anterior-posterior pelvic radiograph by the Lewinnek's methods. The differences between target and postoperative cup position were investigated. Results. The acetabular cup position of all cases in both Mako and CT-navi group within Lewinnek's safe zone (RI: 40±10 degree; RA: 15±10 degree) in group were within this zone. Three was no significant difference of RI between Mako and CT-navi group (40.0 ± 2.1 degree vs 39.7± 3.6 degree). RA was 15.0 ± 1.2 degree and 17.0 ± 1.9 degree in MAKO group and in CT-navi group, respectively, with significant difference (p<0.001). The differences of RA between target and postoperative angle were smaller in MAKO group than CT-navi group (0.60± 1.05 degree vs 2.34± 1.40 degree, p<0.001). The difference or RI in MAKO group was smaller than in CT-navi, however, there was no significance between them (1.67± 1.27 degree vs 2.39± 2.68 degree, p=0.197). Conclusions. Both the assistance of the robotic arm and the CT-based navigation system were helpful to achieve the acetabular cup implantation, however, MAKO system achieved more accurate acetabular cup implantation than CT-based navigation system in total hip arthroplasty for the patients with OA secondary to DDH. Longer follow-up is necessary to investigate the clinical outcome

Patient satisfaction is an important measure of patient-centered outcomes and physician performance. Given the continued growth of the population undergoing surgical intervention for osteoarthritis (OA), and the concomitant growth in the associated direct costs, understanding what factors drive satisfaction in this population is critical. A potentially important driver not previously considered is satisfaction with pre-surgical consultation. We investigated the influence of pre-surgical consultation satisfaction on overall satisfaction following surgery for OA. Study data are from 1263 patients who underwent surgery for hip (n=480), knee (n=597), and spine (n=186) OA at a large teaching hospital in Toronto, Canada. Before surgery, patient-reported satisfaction with information received and degree of input in decision-making during the pre-surgical consultation was assessed, along with expectations of surgery (regarding pain, activity limitation, expected time to full recovery and likelihood of complete success). Pre- and post-surgery (6 weeks, and 3, 6, and 12 months) patients reported their average pain level in the past week (0–10, 10 is worst). At each follow-up time-point, two pain variables were defined, pain improvement (minimal clinically important difference from baseline ≥2 points) and ‘acceptable’ pain (pain score ≤ 3). Patients also completed a question on satisfaction with the results of the surgery (very dissatisfied/dissatisfied/somewhat satisfied/very satisfied) at each follow-up time point. We used multilevel ordinal logistic regression to examine the influence of pre-surgery satisfaction with consultation on the trajectory of satisfaction over the year of recovery controlling for expectations of surgery, pain improvement, acceptable pain, socio-demographic factors (age, sex, and education), body mass index, comorbidity, and depressive symptoms (Hospital Anxiety and Depression Scale). Mean age of the sample was 65.5 years, and over half (54.3%) were women. Overall, 74% and 78.9% of patients were satisfied with the information received and with the decision-making in the pre-surgical consultation, respectively, no significant differences were found by surgical joint (p=0.22). Post-surgery, levels of satisfaction varied very little over time (6 weeks: 92.5% were satisfied and 66.4% were very satisfied, 1 year: 91.1% were satisfied and 65.6% were very satisfied). Results from a model including time, surgical joint, satisfaction with consultation and control factors indicated that being satisfied with the information received in the pre-surgical consultation was associated with higher odds of being more satisfied after surgery (OR: 1.2, 95% CI: 1–1.4). Additionally, spine and knee patients were more likely to be dissatisfied than hip patients (OR: 3.2, 95% CI: 2.1–4.9 and OR: 2.5, 95% CI: 1.8–3.4 for spine and knee patients respectively). Achieving pain improvement (OR: 1.7, 95% CI: 1.3–2.4) and acceptable pain (OR: 2.5, 95% CI: 1.6–3.9) were both significantly associated with greater satisfaction. Pre-operative expectations were not significantly associated with post-surgery satisfaction. Findings highlight the important role of pre-surgery physician-patient communication and information on post-surgery satisfaction. This points to the need to ensure organizational provisions that foster supportive and interactive relationships between surgeons and their patients to improve patients' satisfaction. Findings also highlight that early post-recovery period (i.e. <= 3 months) as a key driver of longer-term satisfaction

Introduction. Fracture around the knee can lead to posttraumatic osteoarthritis (PTOA) of the knee. Malunion, malalignment, intra-articular osseous defects, retained internal fixation devices, and compromised soft tissues may affect the outcome of total knee replacement (TKR). On average, the posttraumatic patient subsets were 10.4 years younger than those for primary knee OA. Recently, there were several studies reporting the outcome of THA for posttraumatic OA hip. However, no current literature defines the comparative functional outcome between PTOA and primary OA knee. The purpose of our study was to compare the midterm outcomes of patients undergoing TKR following periarticular knee fractures/ligamentous injuries versus primary osteoarthritis (PO) of the knee. Materials and methods. Retrospective chart reviews of patients underwent TKR between 2008 and 2013 were identified. 136 patients underwent open reduction and internal fixation with plate and screws or ligament reconstruction while 716 patients were primary OA. Mean follow up time was comparable in both groups. Demographic data, medical comorbidities, WOMAC, visual analogue scale, and complications were recorded. Results. There were significantly different in age (56.5 vs 63.8 years, p<0.0001), gender (48.5% vs 63.1% of female, p=0.0014), and obese (62.3% vs 76.0%, p=0.025) between PTOA and PO groups, respectively. The PO group had higher comorbidities than PTOA group including anticoagulant usage (51% vs 30.9%, p=0.0002), number of disease ≥ 4 (69.6% vs 45.3%, p<0.0001), ASA class ≥3 (38.8% vs 21.6%, p<0.0001), and Charlson Comorbidity Index (3.6 vs 2.8, p<0.0001). The PTOA group had longer operative time (110.9 vs 100.1 minutes, p<0.0001) than PO group. Preoperatively anatomical axis of the knee was approximately valgus in PTOA but varus alignment in PO group (p<0.0001). However, postoperatively anatomical and mechanical axis was comparable in both groups. Postoperative VAS (1.8 vs 1.2, p=0.002) at 1 year follow up and pain component of WOMAC (77.8 vs 85.7, p=0.013) in PTOA group was worse than PO group, respectively. On the contrary, there was no difference in postoperative complication and readmission rate between groups. Conclusion. Total knee replacement for Post-traumatic OA was associated with poorer functional outcome compared to those for primary osteoarthritis in midterm follow up

The advent of modern anatomic shoulder arthroplasty occurred in the 1990's with the revelation that the humeral head dimensions had a fixed ratio between the head diameter and height. As surgeons moved from the concept of balancing soft tissue tension by using variable neck lengths for a given humeral head diameter, a flawed concept based on lower extremity reconstruction, improvements in range of motion and function were immediately observed. Long term outcome has validated this guiding principle for anatomic shoulder replacement with improved longevity of implants, improved patient and surgeon expectations and satisfaction with results. Once the ideal humeral head prosthesis is identified, and its position prepared, the surgeon must use a method to fix the position of the head that is correct in three dimensions and has the security to withstand patient activities and provide maximal longevity. Based again on lower extremity concepts, long stems were the standard of care, initially with cement, and now, almost universally without cement for a primary shoulder replacement. The incredibly low revision rates for humeral stem aseptic loosening shifted much of the attempted innovation to the challenges on the glenoid side of the reconstruction. However, glenoid problems including revision surgery, infections, periprosthetic fractures, and other complications often required the removal of the humeral stem. And, in many cases, the overall results of the procedure and the patient's long-term outcome was affected by the difficulty in removing the stem, leading surgeons to compromise the revision procedure, avoid revision surgery, or add to the overall morbidity with humeral fractures and substantial bone loss. With improved technology, including bone ingrowth methods, better matching of the proximal stem geometry to the humerus, and an understanding that the center of rotation (torque) on the humeral component is at the level of the humeral osteotomy, shorter stems and stemless humeral components were developed, now more than 10 years ago, primarily in Europe. With more than a decade of experience, our European colleagues have shown us that stemless humeral component replacement with a device that has both cortical and cancellous fixation is as effective as a stemmed device, easier to implant as well as revise when needed. The short-term results of the cancellous fixation stemless devices are acceptable, but longer follow-up is needed. Currently, the most widely used humeral components in the USA are short stem components, although the recent FDA approval of numerous stemless devices has initiated a shift from short stems to stemless devices. The truth is, short stem devices have a firm position in the USA surgeons' armamentarium today due to regulatory restrictions. A decade ago, without a predicate on the market, it was not conceivable that a stemless device that was already gaining popularity in Europe would be able to get 510K approval, and therefore would require a lengthy and expensive FDA IDE process. However, shorter stems had already been approved in the USA, as long as the stem length was 7 centimeters, matching the market predicate. Now, in 2018, based on evidence and outcomes, stemless humeral components should be the first choice when treating primary osteoarthritis of the glenohumeral joint. Short stem or longer stem devices should be reserved for those cases where stemless fixation is not possible, which is less than 10% of patients with primary OA of the shoulder

Background. Despite the excellent clinical success of total knee arthroplasty (TAK), controversy remains concerning whether or not to resurface the patella. This has led to a number of randomized controlled trials. Randomized controlled trials constitute the most reliable source of evidence for the evaluation of the efficacy of a potential intervention. But most of these studies include all degree of osteoarthritis of the patellofemoral joint. So we did this prospective study to compare clinical and radiological outcomes after TKA with or without patellar resurfacing in patients with grade IV osteoarthritis on patellofemoral joint. Materials and Methods. 123 cases (93 patients) with Kellgren-Lawrence grade IV osteoarthritis on patellofemoral joint were enrolled for this study. At the operating room, they were randomly assigned to undergo patella resurfacing (62 cases) or patella retention (61 cases). Among them, 114 cases that could be followed for more than 2 years were included in this study (resurfacing group; 59 cases, retention group; 55 cases). When patellar retention was performed, osteophytes of the patella were removed and marginal electrocauterization was carried out. Preoperative and postoperative clinical outcomes were evaluated and compared regarding the Hospital for Special Surgery Patellar (HSSP) score (total 100 point; anterior knee pain, functional limitation, tenderness, crepitus, Q-strength). We also compared Hospital for Special Surgery (HSS) and WOMAC scores, and range of motion (ROM). We also compared radiological outcomes at the final follow up, with regards to mechanical axis of the lower limb, patella tilt and patella congruence angle between two groups. Results. Average HSSP score was 85 in resurfacing group, 83 in retention group, which were showing no significant differences between groups (p=.75). Anterior knee pain subscale also showed no significant differences between groups (40 in resurfacing group, 36 in retention group, p= 0.52). HSS score improved to 94 points in resurfacing group and 95 points in retention group showing no significant difference (p=.92). While WOMAC score and range of motion was 32 point and 128°±10.5° in resurfacing group, respectively, they were 29 point and 126°±11.5° in retention group, without significant inter-group difference (p>.05). There were no differences between two groups in mechanical axis of the lower limb and patella tilt, patella congruence (p>0.05). Conclusion. Clinical and radiological outcomes were ‘good’ after TKA with or without patellar resurfacing in patients with high grade osteoarthritis of the patellofemoral joint without significant differences. Thus, this study suggested that TKA without patellar resurfacing is a good treatment option in patients with high grade osteoarthritis of the patellofemoral joint