Abstract

Establishing disease biomarkers has been a long-sought after goal to improve Osteoarthritis (OA) diagnosis, prognosis, clinical and pharmaceutical interventions. Given the role of the synovium in contributing to OA, a meta-analysis was performed to determine significant synovial biomarkers in human OA tissue, compared to non-OA patients. Outcomes will direct future research on marker panels for OA disease modelling in vitro/in vivo, aiding clinical research into OA disease targets.

A PRISMA compliant search of databases was performed to identify potential biomarker studies analysing human, OA, synovial samples compared to non-OA/healthy participants. The Risk of Bias In Non-Randomised Studies of Interventions (ROBINS-I) tool assessed methodological quality, with outcome analysed by Grading of Recommendations Assessment, Development and Evaluation (GRADE). Meta-analyses were conducted for individual biomarkers using fixed or random effect models, as appropriate. Where three or more studies included a specific biomarker, Forest Plot comparisons were generated.

3230 studies were screened, resulting in 34 studies encompassing 25 potential biomarkers (1581 OA patients and 695 controls). Significant outcomes were identified for thirteen comparisons. Eleven favoured OA (IL-6, IL-10, IL-13, IP-10, IL-8, CCL4, CCL5, PIICP, TIMP1, Leptin and VEGF), two favoured non-OA controls (BMP-2 and HA). Notably, PIICP showed the largest effect (SMD 6.11 [3.50, 8.72], p <0.00001, I² 99%), and TIMP1 resulted critically important (0.95 [0.65, 1.25], p <0.00001, I² 82%). Leptin and CCL4 showed lower effects (SMD 0.81 [0.33, 1.28], p =0.0009; 0.59 [0.32, 0.86], p <0.0001, respectively).

Thirteen significant synovial biomarkers showed links with OA bioprocesses including collagen turnover, inflammatory mediators and ECM components. Limitations arose due to bias risk from incomplete or missing data, publication bias of inconclusive results, and confounding factors from patient criteria. These findings suggest markers of potential clinical viability for OA diagnosis and prognosis that could be correlated with specific disease stages.

The aim of the study was to report the survival of open reduction and internal fixation (ORIF) of Vancouver B fractures associated with the Exeter Stem (ES) at a minimum of 5 years.

This retrospective cohort study assessed 129 consecutive patients with Vancouver B type fractures treated with ORIF from 2008-2016 at a minimum of 5 years. Patient records were examined, and the following recorded: details of primary prosthesis, details of injury, Vancouver classification, details of operative management, complications, and requirement for reoperation. Data was analysed using SPSS. Survival analysis was undertaken using the endpoint ‘reoperation for any reason’.

Mean age at fracture was 78.2 (SD10.6, 46-96) and 54 (43%) were female. Vancouver subclassifications were: 24% B1, 70.5% B2 and 5.5% B3. For all Vancouver B fractures, Kaplan Meier analysis demonstrated a 5 year survival free from reoperation of 88.8% (82.0-94.7 95%CI). Fourteen patients required reoperation, most commonly within the first year for non-union and plate fracture (5.4%). Five-year survival for any reoperation differed significantly according to fracture type (p=0.016) and was worst in B1s: B1 76.6% (61.3-91.9); B2 92.6% 986.9-98.3); and 100% of B3. Univariate analysis identified B1 type (p=0.008) and a transverse fracture pattern (p=0.003) to be significantly associated with the need for reoperation.

Adopting a strategy of fixation of all Vancouver B fractures involving the ES where the fracture was anatomically reducible and the bone cement interface was well-fixed was associated with a 5 year survival, free from reoperation of 88.8%.

Abstract

Abstract

This study aims to determine the lifetime risk of revision surgery after primary knee arthroplasty (KA).

The Scottish Arthroplasty Project dataset was utilised to identify all patients undergoing primary KA during the period 1998–2019. The cumulative incidence function for revision and death was calculated and adjusted analyses utilised cause-specific Cox regression modelling to determine the influence of patient-factors. The lifetime risk was calculated for patients aged between 45–99 years using multiple decrement lifetable methodology.

The lifetime risk of revision ranged between 32.7% (95% Confidence Interval (CI) 22.62–47.31) for patients aged 45–49 years and 0.63% (95%CI 0.1–4.5) for patients aged over 90 years. Adjusted analyses demonstrated the converse effect of age on revision (Hazard Ratio (HR) 0.5, 95%CI 0.5–0.6) and death (HR 3.5, 95%CI 3.4–3.7). Male sex was associated with increased risks of revision (HR 1.1, 95%CI 1.1–1.2) and death (HR 1.4, 95%CI 1.3–1.4). Patients with inflammatory arthropathy had a higher risk of death (HR 1.7, 95%CI 1.7–1.8), but were less likely to be revised (HR 0.85, 95%CI 0.74–0.98) than those treated for osteoarthritis. Patients with greater number of comorbidities and greater levels of socio-economic deprivation were at increased risk of death, but neither increased the risk of revision.

The lifetime risk of revision knee arthroplasty varies depending on patient sex, age at surgery and underlying diagnosis. Patients aged between 45 and 49 years have a one in three probability of revision surgery within their lifetime. Conversely, patients aged 90 years or over were very unlikely to experience revision.

This study aims to determine satisfaction rates after hip and knee arthroplasty in patients who did not initially respond to PROMs, characteristics of non-responders, and contact preferences to maximise response rates. We performed a prospective cohort study of 709 patients undergoing THA and 737 patients undergoing TKA in a single centre in 2018. EQ-5D health related quality of life score and Oxford Hip/knee scores (OHS/OKS) were completed preoperatively and at 1year postoperatively via post when satisfaction was also assessed. Univariate, multivariate and receiver operator curve analysis were performed.

151/709 (21.2%) hip patients were non-responders, 83 (55.0%) of whom were contactable. 108/737 (14.6%) knee patients were non-responders, 91 (84.3%) of whom were contactable. There was no difference in satisfaction after arthroplasty between initial non-responders and responders for hips (74/81 vs 476/516, p=0.847) or knees (81/93 vs 470/561, p=0.480). Initial and persistent non-response was associated with younger age, higher BMIs and significantly worse preoperative PROMS for both hip and knee patients (p=0.05). Multivariate analysis demonstrated that younger age, higher BMI and poorer pre-operative OHS were independently associated with persistent non-response to hip PROMs (p<0.05). For the entire cohort (n=1352) patients <67 years were less likely to respond to postal PROMs with OR 0.63 (0.558 to 0.711). Using a threshold of >66.4 years predicted a preference for contact by post with 65.4% sensitivity and 68.1% specificity (AUC 0.723 (0.647-0.799 95%CI, p<0.001)).

Most initial non-responders were ultimately contactable with effort. Satisfaction rates were not inferior in patients who did not initially respond to PROMs.

Cemented total hip replacement (THR) provides excellent outcomes and is cost-effective. Polished taper-slip (PTS) stems demonstrate successful results and have overtaken traditional composite-beam (CB) stems. Recent reports indicate they are associated with a higher risk of postoperative periprosthetic femoral fracture (PFF) compared to CB stems. This study evaluates risk factors influencing fracture characteristics around PTS and CB cemented stems.

Data were collected for 584 PFF patients admitted to eight UK centres from 25/05/2006-01/03/2020. Radiographs were assessed for Unified Classification System (UCS) grade and Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA) type. Statistical comparisons investigated relationships by age, gender, and stem fixation philosophy (PTS versus CB). The effect of multiple variables was estimated using multinomial logistic regression to estimate odds ratios (OR) with 95% confidence intervals (CI).

Median (IQR) age was 79.1 (72.0–86.0) years, 312 (53.6%) patients were female, and 495 (85.1%) stems were PTS. The commonest UCS grade was type B1 (278, 47.6%). The commonest AO/OTA type was spiral (352, 60.3%). Metaphyseal-split fractures occurred only with PTS stems with an incidence of 10.1%. Male gender was associated with a five-fold reduction in odds of a type C fracture (OR 0.22, 95% CI 0.12 to 0.41, p<0.001) compared to a type B fracture. CB stems were associated with significantly increased odds of transverse fracture (OR 9.51, 95% CI 3.72 to 24.34, p <0.001) and wedge fracture (OR 3.72, 95% CI 1.16 to 11.95, p <0.05) compared to PTS stems.

This is the largest study investigating PFF characteristics around cemented stems. The commonest fracture types are B1 and spiral fractures. PTS stems are exclusively associated with metaphyseal-split fractures, but their incidence is low. Males have lower odds of UCS grade C fractures compared to females. CB stems had higher odds of bending type fractures (transverse and wedge) compared to PTS stems. Biomechanical testing is needed for validation and investigation of modifiable factors which may reduce the risk of unstable fracture patterns requiring complex revision surgery over internal fixation.

The aim of this study is to determine whether fixation, as opposed to revision arthroplasty, can be safely used to treat reducible Vancouver B type fractures in association with a cemented collarless polished tapered femoral stem (the Exeter).

This is a retrospective cohort study of 152 operatively managed consecutive unilateral Vancouver B fractures involving Exeter stems. 130 were managed with open reduction and internal fixation (ORIF) and 22 with revision arthroplasty. Radiographs were assessed and classified by 3 observers. The primary outcome measure was revision of ≥1 component. Kaplan Meier survival analysis was performed. Logistic regression was used to identify risk factors for revision following ORIF. Secondary outcomes included any reoperation, complications, blood transfusion, length of hospital stay and mortality.

Fractures (B1 n=74 (49%); B2 n=50 (33%); and B3 n=28 (18%)) occurred at mean 6.7±10.4 years after primary THA (n=143) or hemiarthroplasty (n=15). Mean follow up was 6.5 ±2.6 years (3.2 to 12.1). Rates of revision and reoperation were significantly higher following revision arthroplasty compared to ORIF for B2 (p=0.001) fractures and B3 fractures (p=0.05). Five-year survival was significantly better following ORIF: 92% (86.4 to 97.4 95%CI) Vs 63% (41.7 to 83.3), p<0.001. No independent predictors of revision following ORIF were identified: fixation of B2 or B3 fractures was not associated with an increased risk of revision. Dislocation was the commonest mode of failure after revision arthroplasty. ORIF was associated with reduced blood transfusion requirement and reoperations, but there were no differences in medical complications, hospital stay or mortality between surgical groups.

When the bone-cement interface was intact and the fracture was anatomically reducible, Vancouver B2 fractures around Exeter stems can be treated with fixation as opposed to revision arthroplasty. Fixation of Vancouver B3 fractures can be performed in frail elderly patients without increasing revision risk.

Aims

Metaphyseal tritanium cones can be used to manage the tibial bone loss commonly encountered at revision total knee arthroplasty (rTKA). Tibial stems provide additional fixation and are generally used in combination with cones. The aim of this study was to examine the role of the stems in the overall stability of tibial implants when metaphyseal cones are used for rTKA.

Though knee osteoarthritis (OA) is diagnosed and monitored radiographically, full thickness cartilage loss (FTCL) has rarely been correlated with radiographic classification. This study aims to analyse which classification system correlates best with FTCL and assessing their reliability.

Prospective study of 300 consecutive patients undergoing total knee arthroplasty (TKA) for OA. Two blinded examiners independently graded preoperative radiographs using 5 systems: Kellgren-Lawrence (KL); International Knee Documentation Committee (IKDC); Fairbank; Brandt; and Ahlback. Interobserver agreement was assessed using the intraclass correlation coefficient. Intraoperatively, anterior cruciate ligament (ACL) status and FTCL in 16 regions of interest were recorded. Radiographic classification and FTCL were correlated using the Spearman correlation coefficient.

On average, each knee had 6.8±3.1 regions of FTCL, most common medially. The commonest patterns of FTCL were medial with patellofemoral (48%) and tricompartmental (30%). ACL status was associated with pattern of FTCL (p=0.02). All classification systems demonstrated moderate ICC, but this was highest for IKDC: whole knee 0.68 (95%CI 0.60–0.74); medial compartment 0.84 (0.80–0.87); and lateral compartment 0.79 (0.73–0.83). Correlation with FTCL was strongest for Ahlback (Spearman rho 0.27–0.39) and KL (0.30–0.33), though all systems demonstrated medium correlation. The Ahlback was the most discriminating in severe OA. Osteophyte presence in the medial compartment had high positive predictive value for FTCL, but not in the lateral compartment.

The Ahlback and KL systems had the highest correlation with confirmed cartilage loss. However, the IKDC system displayed best interobserver reliability, with favourable correlation with FTCL in medial and lateral compartments, though less discriminating in severe disease.

Successful return to work (RTW) is a crucial outcome after primary total knee arthroplasty (TKA) in patients under 65 years old. We aimed to determine whether TKA facilitated RTW in patients <65 years, whose intention was to return preoperatively.

We prospectively assessed 106 TKA patients under 65 years over a 1 year period both preoperatively and at 1 year following surgery. Patient demographics were collected including Oxford knee score, Oxford-APQ, VAS pain/health scores and EQ-5D. A novel questionnaire was distributed to delineate pre-operative employment status and post-operative intentions. This included questions on nature of pre and post-operative occupation, whether joint disease affected their ability to work and details of retirement plans and how this was affected by their knee.

69 patients intended to return to work following their TKA. Following arthroplasty, 57/69 patients (82.6%) returned to work at a mean of 16.4 weeks (SD 16.6). Univariate analysis showed significant factors facilitating RTW included, pre-operative oxford knee score, pre-operative Oxford-APQ score and pre-operative EQ-5D score. These were not predictive on multivariate analysis.

This study finds that TKA facilitates return to work in 83% of those who intend to return to work following their surgery. This could have significant positive and health and financial cost implications for the individual, health system and society.

Anterior knee pain (AKP) is the commonest complication of total knee arthroplasty (TKA). This study aims to assess whether sagittal femoral component position is an independent predictor of AKP after cruciate retaining single radius TKA without primary patellofemoral resurfacing.

From a prospective cohort of 297 consecutive TKAs, 73 (25%) patients reported AKP and 89 (30%) reported no pain at 10 years. Patients were assessed pre-operatively and at 1, 5 and 10 years using the short form 12 and Oxford Knee Score (OKS). Variables assessed included demographic data, indication, reoperation, patella resurfacing, and radiographic criteria.

Patients with AKP (mean age 67.0 (38–82), 48 (66%) female) had mean Visual Analogue Scale (VAS) Pain scores of 34.3 (range 5–100). VAS scores were 0 in patients with no pain (mean age 66.5 (41–82), 60 (67%) female). Femoral component flexion (FCF), anterior femoral offset ratio, and medial proximal tibial angle all differed significantly between patients with AKP and no pain (p<0.001), p=0.007, p=0.009, respectively). All PROMs were worse in the AKP group at 10 years (p<0.05). OKSs were worse from 1 year (p<0.05). Multivariate analysis confirmed FCF and Insall ratio <0.8 as independent predictors of AKP (R² = 0.263). Extension of ≥0.5° predicted AKP with 87% sensitivity.

AKP affects 25% of patients following single radius cruciate retaining TKA, resulting in inferior patient-reported outcome measures at 10 years. Sagittal plane positioning and alignment of the femoral component are important determinants of long-term AKP with femoral component extension being a major risk factor.

To investigate predictors of periprosthetic fracture level (around stem (Vancouver B) or distal to stem (Vancouver C/D) in cemented polished tapered femoral stems.

Retrospective cohort study of 188 patients (mean age 79 (range 30–91); 99 (53%) male) with unilateral periprosthetic femoral fractures associated with CPT stems. Medical notes were reviewed and the following recorded: patient demographics, past medical history, drug history, date of prosthesis insertion, and date of injury. Radiographs analysis included Vancouver classification, cement restrictor type, cement mantle to implant tip distance, cortical thickness, femoral diameter and DORR classification. Univariate, multivariate and ROC curve analysis was performed.

Fractures occurred at mean 7.5 years following primary procedure: 152 (83%) were B fractures; and 36 (19%) C/D. On univariate analysis female gender, lower BMI, osteoporosis, NSAID use, Bisphosphonate therapy, cortical thickness, distal cement mantle length and distal cement mantle length:femoral diameter ratio were significantly associated with C level fractures (p<0.05). Distal cement mantle lengths of >19.6mm (AUC 0.688, p<0.001) were associate with C level fractures. Multivariate analysis demonstrated female gender and distal cement mantle length:femoral diameter ratio to be independent predictors of C level periprosthetic fractures.

Though female sex is the largest independent predictor of periprosthetic fractures distal to a CPT femoral stem, the relationship between cortical thickness and distal cement mantle length appears significant. As fractures distal to the stem are invariably managed by ORIF, whereas fractures around the stem frequently require revision arthroplasty, this has relevance at primary surgery in osteoporotic females to reduce the need for complex revisions.

Risk of revision following total knee replacement is relatively high in patients under 55 years of age, but little is reported regarding non-revision outcomes. This study aims to identify predictors of dissatisfaction following TKR in patients younger than 55 years of age.

We assessed 177 TKRs (157 consecutive patients) from 2008 to 2013. Data was collected on age, sex, implant, indication, BMI, social deprivation, range of motion, and prior knee surgery in addition to Oxford Knee Score (OKS) and SF-12 score. Postoperative data included knee range of motion, complications, and OKS, SF-12 score and satisfaction measures at one year.

Overall, 24.9% of patients (44/177) were unsure or dissatisfied with their TKR. Significant predictors of dissatisfaction on univariable analysis (p<0.05) included: Kellgren-Lawrence grade 1/2 osteoarthritis; indication; poor preoperative OKS; postoperative complications; and poor improvements in OKS and pain component score (PCS) of the SF-12. Odds ratios for dissatisfaction by indication compared to primary OA: OA with previous meniscectomy 2.86; OA in multiply operated knee 2.94; OA with other knee surgery 1.7; OA with BMI>40kgm-2 2; OA post-fracture 3.3; and inflammatory arthropathy 0.23. Multivariable analysis showed poor preoperative OKS, poor improvement in OKS and postoperative stiffness, particularly flexion of <90°, independently predicted dissatisfaction (p<0.005).

Patients coming to TKR when under 55 years of age differ from the ‘average’ arthroplasty population, often having complex knee histories and indications for surgery, and an elevated risk of dissatisfaction.

25–40% of unicompartmental knee replacement (UKR) revisions are performed for unexplained pain possibly secondary to elevated proximal tibial bone strain. This study investigates the effect of tibial component metal backing and polyethylene thickness on cancellous bone strain in a finite element model (FEM) of a cemented fixed bearing medial UKR, validated using previously published acoustic emission data (AE).

FEMs of composite tibiae implanted with an all-polyethylene tibial component (AP) and a metal backed one (MB) were created. Polyethylene of thickness 6–10mm in 2mm increments was loaded to a medial load of 2500N. The volume of cancellous bone exposed to <−3000 (pathological overloading) and <−7000 (failure limit) minimum principal (compressive) microstrain (µ∊) and >3000 and >7000 maximum principal (tensile) microstrain was measured.

Linear regression analysis showed good correlation between measured AE hits and volume of cancellous bone elements with compressive strain <−3000µ∊: correlation coefficients (R= 0.947, R2 = 0.847), standard error of the estimate (12.6 AE hits) and percentage error (12.5%) (p<0.001). AP implants displayed greater cancellous bone strains than MB implants for all strain variables at all loads. Patterns of strain differed between implants: MB concentrations at the lateral edge; AP concentrations at the keel, peg and at the region of load application. AP implants had 2.2 (10mm) to 3.2 (6mm) times the volume of cancellous bone compressively strained <−7000µ∊ than the MB implants. Altering MB polyethylene insert thickness had no effect. We advocate using caution with all-polyethylene UKR implants especially in large or active patients where loads are higher.

Joint registries report that 25–40% of UKR revisions are performed for pain. Proximal tibial strain and microdamage are possible causes of this “unexplained” pain. The aim of this study was to examine the effect of UKR implant design and material on proximal tibial cortical strain and cancellous microdamage.

Composite Sawbone tibias were implanted with cemented UKR components: 5 fixed bearing all-polyethylene (FB-AP), 5 fixed bearing metal backed (FB-MB), and 5 mobile bearing metal backed implants (MB-MB). Five intact tibias were used as controls. Tibias were loaded in 500N increments to 2500N. Cortical surface strain was measured using digital image correlation (DIC). Cancellous microdamage was measured using acoustic emission (AE), a technique which detects elastic waves produced by the rapid release of energy during microdamage events.

DIC showed significant differences in anteromedial cortical strain between implants at 1500N and 2500N in the proximal 10mm only (p<0.001) with strain shielding in metal backed implants. AE showed significant differences in cancellous microdamage (AE hits), between implants at all loads (p=0.001). FB-AP implants displayed significantly more hits at all loads than both controls and metal backed implants (p<0.001). FB-AP implants also differed significantly by displaying AE hits on unloading (p=0.01), reflecting a lack of implant stiffness. Compared to controls, the FB-AP implant displayed 15x the total AE hits, the FB-MB 6x and the MB-MB 2.7x. All-polyethylene medial UKR implants are associated with greater cancellous bone microdamage than metal backed implants even at low loads.

Patient expectations and their fulfilment are an important factor in determining patient-reported outcome and satisfaction of hip (THR) and knee replacement (TKR). The aim of this prospective cohort study was to examine the expectations of patients undergoing THR and TKR, and to identify differences in expectations, predictors of high expectations and the relationship between the fulfilment of expectations and patient-reported outcome measures. During the study period, patients who underwent 346 THRs and 323 TKRs completed an expectation questionnaire, Oxford score and Short-Form 12 (SF-12) score pre-operatively. At one year post-operatively, the Oxford score, SF-12, patient satisfaction and expectation fulfilment were assessed. Univariable and multivariable analysis were performed. Improvements in mobility and daytime pain were the most important expectations in both groups. Expectation level did not differ between THR and TKR. Poor Oxford score, younger age and male gender significantly predicted high pre-operative expectations (p < 0.001). The level of pre-operative expectation was not significantly associated with the fulfilment of expectations or outcome. THR better met the expectations identified as important by patients. TKR failed to meet expectations of kneeling, squatting and stair climbing. High fulfilment of expectation in both THR and TKR was significantly predicted by young age, greater improvements in Oxford score and high pre-operative mental health scores. The fulfilment of expectations was highly correlated with satisfaction.

Unicompartmental knee replacements (UKRs) have inconsistent and variable survivorships reported in the literature. It has been suggested that many are revised for ongoing pain with no other mode of failure identified. Using a medial UKR with an all-polyethylene non-congruent tibial component from 2004–7, we noted a revision rate of 9/98 cases (9.2%) at a mean of 39 months. Subchondral sclerosis was noted under the tibial component in 3/9 revisions with well fixed implants, and the aim of this study was to investigate this as a mode of failure. 89 UKRs in 77 patients were investigated radiographically (at mean 50 months) and with SF-12 and Oxford Knee scores at mean follow up 55 months. Subjectively 23/89 cases (25%) had sclerosis under the tibial component. We describe a method of quantifying this sclerosis as a greyscale ratio (GSR), which was significantly correlated with presence/absence of sclerosis (p<0.001). Significant predictors of elevated GSR (increasing sclerosis) were female sex (p<0.001) and elevated BMI (P=0.010) on both univariate and multivariate analysis. In turn, elevated GSR was significantly associated with poorer improvement in OKS (p<0.05) at the time of final follow up. We hypothesise that this sclerosis results from repetitive microfracture and adaptive remodelling in the proximal tibia due to increased strain. Finite element analysis is required to investigate this further, but we suggest caution should be employed when considering all polyethylene UKR implants in older women and in those with BMI >35.

Purpose

The aim of the present study was to look at survivorship and patient satisfaction of a fixed bearing unicompartmental knee arthroplasty with an all-polyethylene tibial component.