Aims. The aim of this study was to estimate time to arthroplasty among patients with hip and knee osteoarthritis (OA), and to identify factors at enrolment to first-line intervention that are prognostic for progression to surgery. Methods. In this longitudinal register-based observational study, we identified 72,069 patients with hip and knee OA in the Better Management of Patients with Osteoarthritis Register (BOA), who were referred for first-line OA intervention, between May 2008 and December 2016. Patients were followed until the first primary arthroplasty surgery before 31 December 2016, stratified into a hip and a knee OA cohort. Data were analyzed with Kaplan-Meier and multivariable-adjusted Cox regression. Results. At five years, Kaplan-Meier estimates showed that 46% (95% confidence interval (CI) 44.6 to 46.9) of those with hip OA, and 20% (95% CI 19.7 to 21.0) of those with knee OA, had progressed to arthroplasty. The strongest prognostic factors were desire for surgery (hazard ratio (HR) hip 3.12 (95% CI 2.95 to 3.31), HR knee 2.72 (95% CI 2.55 to 2.90)), walking difficulties (HR hip 2.20 (95% CI 1.97 to 2.46), HR knee 1.95 (95% CI 1.73 to 2.20)), and frequent pain (HR hip 1.56 (95% CI 1.40 to 1.73), HR knee 1.77 (95% CI 1.58 to 2.00)). In hip OA, the probability of progression to surgery was lower among those with comorbidities (e.g. ≥ four conditions; HR 0.64 (95% CI 0.59 to 0.69)), with no detectable effects in the knee OA cohort. Instead, being overweight or obese increased the probability of OA progress in the knee cohort (HR 1.25 (95% CI 1.15 to 1.37)), but not among those with hip OA. Conclusion. Patients with hip OA progressed faster and to a greater extent to arthroplasty than patients with knee OA. Progression was strongly influenced by patients’ desire for surgery and by factors related to severity of OA symptoms, but factors not directly related to OA symptoms are also of importance. However, a large proportion of patients with OA do not seem to require surgery within five years, especially among those with knee OA. Cite this article: Bone Joint J 2022;104-B(7):792–800

Introduction. The mortality and serious side effects risk of both medical and surgical management of hip and knee osteoarthritis (OA) has been widely published. To date however, there are no studies comparing safety between the two treatment modalities. We aimed to systematically review the published evidence on the mortality and serious complications risk of the various treatments for hip and knee OA. Methods. We searched for studies investigating the safety of arthroplasty, arthroscopy, opioids, non-steroidal anti-inflammatory drugs (NSAIDS), and paracetamol using PubMed, Score, Cochrane, PEDRO, and Google Scholar. The phrase “osteoarthritis treatment” was searched and then combined using Boolean connectors (“OR and “AND) with “serious complications” or “serious adverse events” or “mortality”. The quality of included studies was assessed based on the approach used by the AAOS in judging the quality of treatment studies. Results. 19 studies were included in the review. Mortality risk was highest for Naproxen HR = 3 (1.9; 4.6) and lowest for total hip replacement RR = 0.7 (0.7; 0.7). Highest serious gastrointestinal complication risk was reported for diclofenac OR = 4.77 (3.94; 5.76) and lowest for total knee replacement HR = 0.6 (0.49; 0.75). Ibuprofen had the highest renal complications risk OR=2.32 (1.45; 3.71) whereas celecoxib had the lowest RR = 0.61 (0.4; 0.94). Celecoxib users had the highest cardiovascular (CV) complication risk OR=2.26 (1; 5.1) and the lowest was for tramadol RR = 1.1 (0.87; 1.4). Discussion. Long term medical management of hip and knee OA particularly with NSAIDS may carry a higher mortality risk compared to surgery. Conclusion. The practitioner and patient should carefully consider the risks of medications as well as surgery prior to commencing treatment. Treatment choice should also be tailored to the patient taking into account known GI, CVS, and renal co-morbidities

To identify the differences in inflammatory profiles between hip OA, knee OA and non-OA control cohorts and investigate the association between cytokine expression and clinical outcome measurements, specifically pain. A total of 250 individuals were recruited in three cohorts (100 knee OA, 50 hip OA, 100 control). Serum was collected and inflammatory profiles analysed using the Multiplex Human Cytokine Panel (Millipore) on the Luminex 100 platform (Luminex Corp., Austin, TX). The pain, physical function and activity limitations of hip OA cohort were scored using the WOMAC, SF-36, HHS and UCLA scores. All cytokine levels were compared between cohorts individually using Mann–Whitney–Wilcoxon (MWW) test with Bonferroni multiple comparison correction. Within hip OA cohorts, the effect of hip alignment (impingement and dysplasia) and radiographic grade (Kellgren and Lawrence grade, K/L grade) on cytokine levels were accessed by MWW test. Spearman's rank correlation test used to assess the association between cytokines and pain levels. The three cohorts showed distinct inflammatory profiles. Specifically, EGF, FGF-2, MCP-3, MIP-1a, IL-8 were significant different between knee and hip OA; FGF-2, GRO, IL-8, MCP-1, VEGF were significant different between hip OA and control; Eotaxin, GRO, MCP-1, MIP-1b, VEGF were significant different between knee OA and control (p-value < 0.0012). For hip OA cohorts, cytokines do not differ between K/L grade three and K/L grade four or between patients that displayed either impingement or dysplasia. Three cytokines were significant associated with pain: IL-6 (p-value = 0.045), MDC (p-value = 0.032) and IP-10 (p-value = 0.038). We have demonstrated that differences in serum inflammatory profiles exist between hip and knee OA patients. These differences suggest that OA may include different inflammatory subtypes according to affected joints. We also identified that the cytokine IL-6, MDC and IP-10 are associated with pain level in hip OA patients. These cytokines might help explain the inconsistent of presentation of pain with radiographical severity of OA joints. Future studies are needed to validate our findings and then to understand the following questions: (1) how differently affected joints are reflected in systematic biomarkers; (2) how these cytokines are biologically involved in the OA pain pathway

Objectives: To explore the potential clinical benefits of PRGF injections for the treatment of OA in a retrospective observational study and to characterize the PRGF treatment in OA patients. Methods: A total of 62 patients with symptomatic OA (Knee OA, 41 patients; hip OA, 21 patients) were treated with a series of three weekly intra-articular injections of PRGF and studied retrospectively. ELISA assays were used to determine the levels of VEGF-A, HGF, PDGF, TGF-β1 and IGF-I in PRGF. The patients completed the WOMAC questionnaires prior to PRGF treatment at two and six months after its instauration. The primary efficacy criteria were mean change from baseline through two and six months in the WOMAC index pain and physical function scores. Change scores for the Harris hip scores were calculated for 6 months post-treatment. Age and BMI were included in the models. results The mean age and BMI of the participants with hip and knee OA were 59 and 60 years and 27.8 and 28.5 kg/m2 respectively. In knee OA the differences between pain scores at baseline and two or six months were highly significant (−1.766, 95% CI: −1.073 to −2.458, p=0.000, and −2.320, CI: −3.838 to −0.803, p=0.011) The observed success rates for the pain sub-scale reached 37% by two months and 31.7% by six months. After two months, WOMAC physical function scores decreased significantly (−4.772, 95% CI: −6.864 to −2.681, p=0.000). The changes at six months were not statistically significant (n=41). The success rates for the physical function subscale were 31.4% by two months and 31.7% by six months (n=41). In hip OA the differences between WOMAC pain and Harris hip core scores at baseline and six months were significant. The success rate for the pain subscale and Harris hip score reached 58% and 85% by six months. PRGF resulted in a moderate enrichment in platelet number, 2.0 ± 0.5-fold increase compared to peripheral blood. The levels of the main platelet secretory growth factors were 27.28 ± 10.90 ng/cc for TGF-β1 and 15.66 ± 8.02 ng/cc for PDGF. VEGF was also secreted from platelets but was less abundant, 437± 446 pg/cc. Other GFs present in PRGF refiect mainly plasma levels; among these growth factors are IGF-I (55.53 ± 20.87 ng/cc) and the less concentrated HGF (472 ± 221 pg/cc). Discussion: Due to the localized nature of OA, the possibility of intra-articular administration of PRGF, along with its biocompatibility and non-immunogenicity, may make this unique molecular mixture an attractive treatment for OA. PRGF may have therapeutic effects in OA joints via multiple biologic mechanisms. The results of this study will give a first impression of potential effectiveness of PRGF for the local treatment of hip and knee OA

Background: Falls are a major concern in the elderly population both from a clinical perspective and that of health resource provision. This study evaluates the incidence of falls in patients awaiting hip or knee replacement and the impact of joint replacement surgery 2 years later. Method: Patients aged 65-80 years listed for primary hip or knee arthroplasty for osteoarthritis (OA) were invited to participate. Patients completed a questionnaire including Western Ontario and McMaster University OA Index (WOMAC) scores 0-100, 100 best, history of falls and fractures. Function was measured using Timed Up and Go (TUG) walk test. All tests were repeated at two years. Results: One hundred and ninety-nine patients (84 hips, 115 knees) were recruited with a mean age of 72 years (standard deviation 4.0) and predominantly female (57 %). At two years 144 patients were reviewed of whom 128 had undergone arthroplasty. After surgery, 29/128 (23%) reported falling compared to 55 of these 128 (43%) falling at baseline; only 13/128 (11%) had fallen more than once. Fifteen patients sustained minor injuries and one patient reported a fractured wrist. Of the patients who had undergone joint replacement and fell at baseline 36/55 (66%) patients reported no falls at follow-up, whilst there were 11 new fallers. Patients reporting falls had significantly lower WOMAC pain and function scores, and slower TUG scores at both baseline and two-year review. Conclusion: Patients with severe hip and knee OA awaiting arthroplasty reported a higher incidence of falls compared to the normal population but reported fewer falls after surgery. However, almost one in four patients were still reporting falling at the two-year review. Injury including periprosthetic fractures can have serious clinical and economic consequences. This study highlights the need to evaluate a falls prevention programme in arthroplasty management

Objective: The clinical significance of biochemical bone markers in the diagnosis and severity of Osteoarthritis remains still unknown. The relationship between biochemical bone turnover markers and commonly recognizable radiographic features of knee and hip osteoarthritis remains unclear. Purpose: We evaluated the serum levels of Receptor Activator of Nuclear Factor-κB Ligand (RANKL), Bone-specific Alkaline Phosphatase (b-ALP), Osteocalcin and Osteoprotegerin in two groups of patients suffering from osteoarthritis of the Knee or Hip respectively, aiming to correlate these results with the radiographically assessed severity of the disease and the patients’ age. The results between the two groups were also compared. Patients-Methods: Between March 2007 and February 2009, a total of 175 patients suffering from Knee or Hip Osteoarthritis were enrolled in the study. Following proper radiographic evaluation, the osteoarthritic changes of patients were graded by 3 orthopaedic surgeons according to the system of Kellgren and Lawrence; at the same time the serum levels of biochemical markers were determined. Results: Osteoprotegerin was found to be positively correlated with age in both the Knee (r=0.376, p=0.000) and Hip (r=0.425, p=0.001) group, whether Osteocalcin was significantly correlated with the age in the group of Knee Osteoarthritis(r=0.218, p=0.02). No other significant correlation was noted between the serum level of markers and age of patients in both groups. There was not significant difference in the mean serum level of biochemical markers among patients belonging to each of the four different levels of severity of hip and knee OA. There was no significant impact of the type of Osteoarthritis, to the serum level of all biochemical markers. Conclusions: Based on our results, it seems that none of the serum biochemical markers studied can be used (either independently or in combination with the others) as surrogates for radiographic imaging in Hip and Knee osteoarthritis

Introduction & aims: Quadriceps muscle wasting is common in patients with osteoarthritis (OA) of the hip and knee. Previous studies,using ultrasound and performing biopsies, have demonstrated quadriceps muscle fibre atrophy. Thigh girth measurements are quoted in textbooks as a means of quantitatively assessing muscle bulk. This study has looked at these measurements in patients with hip and knee OA to see if these measurements are useful. Method: 87 patients (mean age 62, range 36–87) with a diagnosis of OA were seen in the pre-assessment clinic. 47 were awaiting total hip replacement (THR) and 40 were awaiting total knee replacement (TKR).All were awaiting primary arthroplasty and had not had previous joint surgery. Thigh girth measurements were taken at 2 points corresponding with one-third and two-thirds of the length between the anterior superior iliac spine and the tibial tuberosity. These measurements were taken for both thighs. The observed differences were analysed with normal probability plots and paired Student’s t-tests. Results: No significant difference in thigh girth could be detected in patients awaiting total knee replacement. Girth was significantly reduced in the thigh on the side of planned THR. This difference was apparent when measured both proximally and distally. Conclusion: Measurements of thigh girth were not useful indicators of quadriceps wasting in patients awaiting TKR. Patients awaiting THR should have thigh girth measured, those with reduced thigh girth on the side of planned arthroplasty may have quadriceps atrophy and can then be referred for physiotherapy prior to surgery

This study aimed to determine the prevalence of osteoporosis in patients awaiting hip and knee replacement for osteoarthritis and to review them two years later to determine the changes in bone density following joint replacement. Patients aged between 65 and 80 years awaiting total hip or knee replacement were invited to participate. Lumbar spine, bilateral femoral and forearm bone mineral density (BMD) measurements were obtained using dual energy x-ray absorptiometry. BMD values were standardised using previously published T-scores and Z-scores. To assess clinical status, patients completed a questionnaire including the Western Ontario and McMaster University OA Index (WOMAC). All measurements were repeated at two-years. Participants included 199 patients (84 hips and 115 knees) with a mean age of 72 years (SD 4.0) and were predominantly female (hips 67%, knees 50%). At baseline 46/199 (23%) patients (39 females) had evidence of osteoporosis (WHO definition) at one or more sites with the highest prevalence at the forearm (14%). At two-years 144 patients attended for review with 128 having undergone hip (56) or knee (72) replacement. At this review 39/144 (27%) patients (33 females) had evidence of osteoporosis at one or more sites with the highest prevalence at the forearm (22%). The greatest bone loss occurred at the forearm with median BMD change of minus 4% for females (25th percentile minus 7.3%, 75th percentile minus 1.9%) and minus 2.9% for males (25th percentile minus 4.6%, 75th percentile minus 1.1%). There was a significant difference in WOMAC Pain scores at follow-up between the osteo-porotic and non-osteoporotic knee patients (67 versus 81, p=0.002) indicating that osteoporotic patients had greater knee pain. We have identified the forearm as not only the site with the highest prevalence of osteoporosis but also the greatest bone loss at follow-up. Further evaluation of forearm bone density measurements in the preopera-tive assessment and follow-up of patients awaiting joint replacement for hip and knee OA is required. Larger studies are needed to confirm our finding that the presence of osteoporosis is predictive of worse patient-reported outcomes of knee replacement

To design osteoarthritis (OA) care based on prognosis, we need to identify individuals who are most likely of disease progression. We estimated survival time of the native hip and knee joint and evaluated what patient-related and OA disease-related factors associated with progression to joint replacement surgery.

We included 72,069 patients referred to first-line OA intervention (patient education and exercise) during 2008 and 2016 and registered in the Swedish quality register Better Management of Patients with Osteoarthritis (BOA). Kaplan–Meier survival analyses were used to estimate joint survival time. Hazard ratios (HR) with 95% confidence interval [CI] were calculated using multiple Cox regression.

The 5-year survival time of the native joint was 56% for hip OA and 80% for knee OA. Disease-related factors were more strongly associated with progression to joint replacement (e.g. willingness for surgery HR; hip 2.9 [95% CI, 2.7–3.1], knee 2.7 [2.6–2.9] and walking difficulties (HR; hip 2.2 [2.0–2.5], knee 1.9 [1.7–2.2]), than patient-related factors such socioeconomic factors (e.g. highest income quartile HR; hip 1.3 [1.2–1.3], knee 1.3 [1.2–1.4]) and comorbidities (e.g. ≥6 conditions HR; hip: 0.7 [0.6–0.7], knee; 1.1 [1.0–1.2]).

Patients with hip OA were more likely to undergo surgery and at an earlier time compared with those with knee OA. Progression was strongly influenced by factors associated with the OA disease, but other patient-related factors are important. However, a large proportion of patients with OA do not seem to require surgery, especially among those with knee OA.

The primary objective of this study was to determine if surgical treatment for spinal stenosis is comparable to total hip and knee arthroplasty in improving patients’ self-reported quality of life. An age, sex and time of surgery matched cohort of patients who had undergone elective primary one-two level spinal decompression (n=90) with (n=26 /90) or without fusion for spinal stenosis (n=40 with degenerative spondylolisthesis) and elective primary total hip (n=90) and knee (n = 90) arthroplasty for osteoarthritis were compared. The primary outcome measure was the preoperative and two year postoperative Medical Outcomes Study Short Form-36 (SF-36) questionnaire.

There was no significant difference in the mean pre-operative Physical Component Summary (PCS) / Mental Component Summary between groups [Spine −32/43; Hip − 30/45; Knee 31/46 (p > 0.5)]. With the exception of the knee MCS (p=0.2), postoperative scores were significantly improved for all groups [Spine −40/53; Hip − 43/51; Knee 39/48 (p < 0.001)]. Overall the hip surgery had the great impact on PCS and the spine surgery on MCS.

Studies have shown the significant impact on overall patient quality of life and cost-effectiveness of primary total joint arthroplasty. The results of this unique study show that surgical intervention for spinal stenosis has a similar positive effect at two year follow up. This study provides data that supports the need advocacy regarding waiting time initiatives and surgical resources for the treatment of patients with symptomatic spinal stenosis with a similar demographic to those with primary OA of the hip or knee.

As there is currently no evidenced-based and systematic way of prioritising people requiring JRS we aimed to develop a clinically relevant system to improve prioritisation of people who may require JRS. An important challenge in this area is to accurately assign a queue position and improve list management. To identify priority criteria areas eight workshops were held with surgeons and patients. Domains derived were pain, activity limitations, psychosocial wellbeing, economic impact and deterioration. Draft questions were developed and refined through structured interviews with patients and consultation with consultants. 38 items survived critical appraisal and were mailed to 600 patients. Eleven items survived clinimetric and statistical item reduction.

Validation then included co-administration with standardised questionnaires (960 patients), verification of patient MAPT scores through clinical interview, examination of concordance with surgeon global ratings and test-retest.

Ninety-six Victorian surgeons weighted items using Discrete Choice Experiments (DCEs). The DCE scaling generated a scale, which clearly ranked patients across the disease continuum. The MAPT differentiated people on or not on waiting lists (p<0.001), and was highly correlated with other questionnaires, e.g., unweighted-MAPT vs WOMAC (r=0.78), Oxford Hip/Knee (r=0.86/0.75), Quality of Life (r=0.78), Depression (r=0.64), Anxiety (r=0.60), p<0.001 for all. Test-retest was excellent (ICC=0.89, n=90). Cronbachs reliability was also high 0.85. The MAPT is now routinely administered across all Victorian hospitals undertaking arthroplasty where the response rate is generally above 90%. In the hands of clinicians the MAPT has been used to facilitate fast-tracking of patients with the greatest need, monitoring for deterioration in those waiting for surgery or having a trial of non-operative treatment and deferment of surgery for those that may benefit from further non-operative treatments.

The MAPT is short, easy to complete and clinically relevant. It is a specific measure of severity of hip/knee arthritis and assigns priority for surgery. It has excellent psychometric and clinimetric properties evidenced by concordance with standard disease-specific and generic scales and widespread use and endorsement across health services.

Wearable inertial sensors can detect abnormal gait associated with knee or hip osteoarthritis (OA). However, few studies have compared sensor-derived gait parameters between patients with hip and knee OA or evaluated the efficacy of sensors suitable for remote monitoring in distinguishing between the two. Hence, our study seeks to examine the differences in accelerations captured by low-frequency wearable sensors in patients with knee and hip OA and classify their gait patterns. We included patients with unilateral hip and knee OA. Gait analysis was conducted using an accelerometer ipsilateral with the affected joint on the lateral distal thighs. Statistical parametric mapping (SPM) was used to compare acceleration signals. The k-Nearest Neighbor (k-NN) algorithm was trained on 80% of the signals' Fourier coefficients and validated on the remaining 20% using 10-fold cross-validation to classify the gait patterns into hip and knee OA. We included 42 hip OA patients (19 females, age 70 [63–78], BMI of 28.3 [24.8–30.9]) and 59 knee OA patients (31 females, age 68 [62–74], BMI of 29.7 [26.3–32.6]). The SPM results indicated that one cluster (12–20%) along the vertical axis had accelerations exceeding the critical threshold of 2.956 (p=0.024). For the anteroposterior axis, three clusters were observed exceeding the threshold of 3.031 at 5–19% (p = 0.0001), 39–54% (p=0.00005), and 88–96% (p = 0.01). Regarding the mediolateral axis, four clusters were identified exceeding the threshold of 2.875 at 0–9% (p = 0.02), 14–20% (p=0.04), 28–68% (p < 0.00001), and 84–100% (p = 0.004). The k-NN model achieved an AUC of 0.79, an accuracy of 80%, and a precision of 85%. In conclusion, the Fourier coefficients of the signals recorded by wearable sensors can effectively discriminate the gait patterns of knee and hip OA. In addition, the most remarkable differences in the time domain were observed along the mediolateral axis

The April 2023 Knee Roundup. 360. looks at: Does bariatric surgery reduce complications after total knee arthroplasty?; Mid-flexion stability in total knee arthroplasties implanted with kinematic alignment: posterior-stabilized versus medial-stabilized implants; Inflammatory response in robotic-arm-assisted versus conventional jig-based total knee arthroplasty; Journey II bicruciate stabilized (JII-BCS) and GENESIS II total knee arthroplasty: the CAPAbility, blinded, randomized controlled trial; Lifetime risk of revision and patient factors; Platelet-rich plasma use for hip and knee osteoarthritis in the USA; Where have the knee revisions gone?; Tibial component rotation in total knee arthroplasty: CT-based study of 1,351 tibiae

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

Aims. Osteoarthritis (OA) is the most prevalent joint disease. However, the specific and definitive genetic mechanisms of OA are still unclear. Methods. Tissue-related transcriptome-wide association studies (TWAS) of hip OA and knee OA were performed utilizing the genome-wide association study (GWAS) data of hip OA and knee OA (including 2,396 hospital-diagnosed hip OA patients versus 9,593 controls, and 4,462 hospital-diagnosed knee OA patients versus 17,885 controls) and gene expression reference to skeletal muscle and blood. The OA-associated genes identified by TWAS were further compared with the differentially expressed genes detected by the messenger RNA (mRNA) expression profiles of hip OA and knee OA. Functional enrichment and annotation analysis of identified genes was performed by the DAVID and FUMAGWAS tools. Results. We detected 33 common genes, eight common gene ontology (GO) terms, and one common pathway for hip OA, such as calcium and integrin-binding protein 1 (CIB1) (PTWAS = 0.025, FCmRNA = -1.575 for skeletal muscle), adrenomedullin (ADM) (PTWAS = 0.022, FCmRNA = -4.644 for blood), Golgi apparatus (PTWAS <0.001, PmRNA = 0.012 for blood), and phosphatidylinositol 3' -kinase-protein kinase B (PI3K-Akt) signalling pathway (PTWAS = 0.033, PmRNA = 0.005 for blood). For knee OA, we detected 24 common genes, eight common GO terms, and two common pathways, such as histocompatibility complex, class II, DR beta 1 (HLA-DRB1) (PTWAS = 0.040, FCmRNA = 4.062 for skeletal muscle), Follistatin-like 1 (FSTL1) (PTWAS = 0.048, FCmRNA = 3.000 for blood), cytoplasm (PTWAS < 0.001, PmRNA = 0.005 for blood), and complement and coagulation cascades (PTWAS = 0.017, PmRNA = 0.001 for skeletal muscle). Conclusion. We identified a group of OA-associated genes and pathways, providing novel clues for understanding the genetic mechanism of OA. Cite this article:Bone Joint Res. 2020;9(3):130–138

Aims. The aetiologies of common degenerative spine, hip, and knee pathologies are still not completely understood. Mechanical theories have suggested that those diseases are related to sagittal pelvic morphology and spinopelvic-femoral dynamics. The link between the most widely used parameter for sagittal pelvic morphology, pelvic incidence (PI), and the onset of degenerative lumbar, hip, and knee pathologies has not been studied in a large-scale setting. Methods. A total of 421 patients from the Cohort Hip and Cohort Knee (CHECK) database, a population-based observational cohort, with hip and knee complaints < 6 months, aged between 45 and 65 years old, and with lateral lumbar, hip, and knee radiographs available, were included. Sagittal spinopelvic parameters and pathologies (spondylolisthesis and degenerative disc disease (DDD)) were measured at eight-year follow-up and characteristics of hip and knee osteoarthritis (OA) at baseline and eight-year follow-up. Epidemiology of the degenerative disorders and clinical outcome scores (hip and knee pain and Western Ontario and McMaster Universities Osteoarthritis Index) were compared between low PI (< 50°), normal PI (50° to 60°), and high PI (> 60°) using generalized estimating equations. Results. Demographic details were not different between the different PI groups. L4 to L5 and L5 to S1 spondylolisthesis were more frequently present in subjects with high PI compared to low PI (L4 to L5, OR 3.717; p = 0.024 vs L5 to S1 OR 7.751; p = 0.001). L5 to S1 DDD occurred more in patients with low PI compared to high PI (OR 1.889; p = 0.010), whereas there were no differences in L4 to L5 DDD among individuals with a different PI. The incidence of hip OA was higher in participants with low PI compared to normal (OR 1.262; p = 0.414) or high PI (OR 1.337; p = 0.274), but not statistically different. The incidence of knee OA was higher in individuals with a high PI compared to low PI (OR 1.620; p = 0.034). Conclusion. High PI is a risk factor for development of spondylolisthesis and knee OA. Low pelvic incidence is related to DDD, and may be linked to OA of the hip. Level of Evidence: 1b. Cite this article: Bone Joint J 2020;102-B(9):1261–1267

Aims. To assess how the cost-effectiveness of total hip arthroplasty (THA) and total knee arthroplasty (TKA) varies with age, sex, and preoperative Oxford Hip or Knee Score (OHS/OKS); and to identify the patient groups for whom THA/TKA is cost-effective. Methods. We conducted a cost-effectiveness analysis using a Markov model from a United Kingdom NHS perspective, informed by published analyses of patient-level data. We assessed the cost-effectiveness of THA and TKA in adults with hip or knee osteoarthritis compared with having no arthroplasty surgery during the ten-year time horizon. Results. THA and TKA cost < £7,000 per quality-adjusted life-year (QALY) gained at all preoperative scores below the absolute referral thresholds calculated previously (40 for OHS and 41 for OKS). Furthermore, THA cost < £20,000/QALY for patients with OHS of ≤ 45, while TKA was cost-effective for patients with OKS of ≤ 43, since the small improvements in quality of life outweighed the cost of surgery and any subsequent revisions. Probabilistic and one-way sensitivity analyses demonstrated that there is little uncertainty around the conclusions. Conclusion. If society is willing to pay £20,000 per QALY gained, THA and TKA are cost-effective for nearly all patients who currently undergo surgery, including all patients at and above our calculated absolute referral thresholds. Cite this article: Bone Joint J 2020;102-B(7):950–958

Introduction and Objective. An important subset of patients is dissatisfied after total joint arthroplasty (TJA) due to residual functional impairment. This study investigated the assessment of objectively measured step-up performance following TJA, to identify patients with poor functional improvement after surgery, and to predict residual functional impairment during early postoperative rehabilitation. Secondary, longitudinal changes of block step-up (BS) transfers were compared with functional changes of subjective patient reported outcome measures (PROMs) following TJA. Materials and Methods. Patients with end stage hip or knee osteoarthritis (n = 76, m/f = 44/32; mean age = 64.4 standard deviation 9.4 years) were measured preoperatively and 3 and 12 months postoperatively. PROMs were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function subscore. BS transfers were assessed by wearable-derived measures of time. In our cohort, subgroups were formed based on either 1) WOMAC function score or 2) BS performance, isolating the worst performing quartile (impaired) of each measure from the better performing others (non-impaired). Subgroup comparisons were performed with the Man-Whitney-U test and Wilcoxon Signed rank test resp. Responsiveness was calculated by the effect size, correlations with Pearson's correlation coefficient. A regression analysis was conducted to investigate predictors of poor functional outcome. Results. WOMAC function scores were strongly correlated to WOMAC pain scores (Pearson's r=0.67–0.84) and moderately correlated to BS performance (Pearson's r = 0.31–0.54). Prior to surgery, no significant differences for WOMAC function scores and BS performance were found between the impaired and non-impaired subgroups. One year after TJA, our cohort performed significantly better at WOMAC and BS with largest effect size for the non-impaired subgroups (0.62 and 0.43 resp.) At 12 months postop, 56% of patients allocated to the impaired subgroup defined by WOMAC, represented the impaired subgroup defined by BS. Allocation to the impaired subgroup at 3 months postop, raised the odds for belonging to the impaired subgroup at 12 months for WOMAC with an odds ratio=19.14 (67%) and for BS with an odds ratio=4.41 (42%). Conclusions. Assessment of BS performance following TJA reveals residual functional impairment that is not captured by pain-dominated PROMs. Its additional use may help to early identify those patients at risk for a poor outcome

There is an evolving body of evidence that demonstrates the role of epigenetic mechanisms, such as DNA-methylation in the pathogenesis of OA. This systematic review aims to summarize the current evidence of DNA methylation and its influence on the pathogenesis of OA. A pre-defined protocol in alignment with the PRISMA guidelines was employed to systematically review eight bibliographic databases, to identify associations between DNA-methylation of articular chondrocytes and osteoarthritis. A search of Medline (Ovid), Embase, Web-of-Science, Scopus, PubMed, Cinahl (EBSCOhost), Cochrane Central and Google Scholar was performed between 1st January 2015 to 31st January 2021. Data extraction was performed by two independent reviewers. During the observation period, we identified 15 gene specific studies and 24 genome wide methylation analyses. The gene specific studies mostly focused on the expression of pro-inflammatory markers, such as IL8 and MMP13 which are overexpressed in OA chondrocytes. DNA hypomethylation in the promoter region resulted in overexpression, whereas hypermethylation was seen in non-OA chondrocytes. Others reported on the association between OA risk genes and the DNA methylation pattern close to RUNX2, which is an important OA signal. The genome wide methylation studies reported mostly on differentially methylated regions comparing OA chondrocytes and non-OA chondrocytes. Clustering of the regions identified genes that are involved in skeletal morphogenesis and development. Differentially methylated regions were seen in hip OA and knee OA chondrocytes, and even within different regions of an OA affected knee joint, differentially methylated regions were identified depending on the disease stage. This systematic review demonstrates the growing evidence of epigenetic mechanisms, such as DNA methylation, in the pathogenesis of OA. In recent years, there has been a focus on the interplay between OA risk genes and DNA methylation changes which revealed a reactivation of genes responsible for endochondral ossification during development. These are important findings and may help to identify eventual future therapeutic targets. However, the current body of literature is mostly showing the differences in DNA methylation of OA chondrocytes and non-OA chondrocytes, but a true longitudinal analysis demonstrating the DNA methylation changes actually happening is still not available

The relationship between pain catastrophizing and emotional disorders including anxiety and depression in patients with hip or knee osteoarthritis undergoing total joint replacement (TJR) is an emerging area of study. The purpose of this study was to examine the association between catastrophizing, anxiety, depression and postoperative pain and functional outcomes following primary TJR. A prospective cohort study of preoperative TJR patients at one academic arthroplasty centre over a one-year period was conducted. Pain catastrophizing was assessed using the Pain Catastrophizing Scale (PCS), and anxiety/depression using the Hospital Anxiety and Depression Scale (HADS-A, HADS-D) at preoperative assessment. Postoperative outcomes at one-year included patient perceived level of hip/knee pain using a visual analogue scale (VAS), subjective perception of function using the Oxford Hip/Knee Scores, and objective function using the Knee Society Score (KSS) and Harris Hip scores (HHS). Median regression was used to assess pattern of relationship between preoperative PCS clinically relevant catastrophizing (CRC), abnormal HADS-A, abnormal HADS-D and postoperative outcomes at one-year. Median difference and 95% confidence interval (CI) were reported. T-tests were performed to determine mean differences in postoperative outcomes among patients with PCS CRC, abnormal HADS-A, and abnormal HADS-D scores versus those with normal scores at preoperative assessment. P-values less than 0.05 were considered statistically significant. The sample included 463 TJR patients (178 hips, 285 knees). Both the PCS-rumination CRC sub-domain (median difference 1, 95% CI 0.31–1.69, p=0.005) and abnormal HADS-A (median difference 1, 95% CI 0.36–1.64, p=0.002) were identified as significant predictors of one-year VAS pain. PCS-magnification CRC sub-domain was also identified as a significant predictor of KSS/HHS at one-year (median difference 1.3, 95% CI −5.23–0.11, p=0.041). Preoperative VAS pain, Oxford and HHS/KSS scores were significantly inferior in patients who had CRC PCS, abnormal HADS-A, and abnormal HADS-D scores compared to patients with normal scores. At one-year, PCS CRC patients also had significantly inferior VAS pain (p=0.001), Oxford (p < 0 .0001) and KSS/HHS (p=0.025). Abnormal HADS-A and HADS-D patients experienced significantly inferior postoperative VAS pain (HADS-A p=0.025, HADS-D p=0.030), Oxford (HADS-A p=0.001, HADS-D p=0.030), but no difference in KSS/HHS (HADS-A = 0.069, HADS-D = 0.071) compared to patients with normal PCS/HADS scores. However, patients with CRC PCS experienced significantly greater improvement in preoperative to postoperative VAS pain (p < 0 .0001), Oxford (p=0.003) and HHS/KSS (p < 0 .0001). Similarly, patients with abnormal HADS scores showed significant improvement in preoperative to one-year postoperative change scores, as compared to normal patients in VAS pain (HADS-A p=0.011, HADS-D p=0.024), KSS/HHS (HADS-A p=0.017, HADS-D p=0.031), but not Oxford (HADS-A p=0.299, HADS-D p=0.558). Patients who are anxious, depressed or who pain catastrophize have worse preoperative function and pain. Postoperatively, pain and functional outcomes are also inferior in such patients, however they do experience a significantly greater improvement in outcomes. Furthermore, it appears that rumination and anxiety traits predict pain levels postoperatively. Although these patients report higher levels of pain postoperatively, as compared to preoperative, great improvement can be expected following hip and knee TJR