Kaempferol attenuates particle-induced osteogenic impairment by regulating ER stress via the IRE1α-XBP1s pathway.

Periprosthetic osteolysis and subsequent aseptic loosening are the primary causes of failure following total joint arthroplasty. Wear particle-induced osteogenic impairment is recognized as an important contributing factor in the development of osteolysis, with endoplasmic reticulum (ER) stress emerging as a pivotal underlying mechanism. Hence, searching for potential therapeutic targets and agents capable of modulating ER stress in osteoblasts is crucial for preventing aseptic loosening. Kaempferol (KAE), a natural flavonol compound, has shown promising osteoprotective effects and anti-ER stress properties in diverse diseases. However, the influence of KAE on ER stress-mediated osteogenic impairment induced by wear particles remains unclear. In this study, we observed that KAE effectively relieved TiAl6V4 particles-induced osteolysis by improving osteogenesis in a mouse calvarial model. Furthermore, we demonstrated that KAE could attenuate ER stress-mediated apoptosis in osteoblasts exposed to TiAl6V4 particles, both in vitro and in vivo. Mechanistically, our results revealed that KAE mitigated ER stress-mediated apoptosis by upregulating the IRE1α-XBP1s pathway while concurrently partially inhibiting the IRE1α-regulated RIDD and JNK activation. Collectively, our findings suggest that KAE is a prospective therapeutic agent for treating wear particle-induced osteolysis and highlight the IRE1α-XBP1s pathway as a potential therapeutic target for preventing aseptic loosening.

Mechanical loading intensities affect the release of extracellular vesicles from mouse bone marrow-derived hematopoietic progenitor cells and change their osteoclast-modulating effect.

Low-intensity loading maintains or increases bone mass, whereas lack of mechanical loading and high-intensity loading decreases bone mass, possibly via the release of extracellular vesicles by mechanosensitive bone cells. How different loading intensities alter the biological effect of these vesicles is not fully understood. Dynamic fluid shear stress at low intensity (0.7 ± 0.3 Pa, 5 Hz) or high intensity (2.9 ± 0.2 Pa, 1 Hz) was used on mouse hematopoietic progenitor cells for 2 min in the presence or absence of chemical compounds that inhibit release or biogenesis of extracellular vesicles. We used a Receptor activator of nuclear factor kappa-Β ligand-induced osteoclastogenesis assay to evaluate the biological effect of different fractions of extracellular vesicles obtained through centrifugation of medium from hematopoietic stem cells. Osteoclast formation was reduced by microvesicles (10 000× g) obtained after low-intensity loading and induced by exosomes (100 000× g) obtained after high-intensity loading. These osteoclast-modulating effects could be diminished or eliminated by depletion of extracellular vesicles from the conditioned medium, inhibition of general extracellular vesicle release, inhibition of microvesicle biogenesis (low intensity), inhibition of ESCRT-independent exosome biogenesis (high intensity), as well as by inhibition of dynamin-dependent vesicle uptake in osteoclast progenitor cells. Taken together, the intensity of mechanical loading affects the release of extracellular vesicles and change their osteoclast-modulating effect.

Enhanced Osteolysis Targeted Therapy through Fusion of Exosomes Derived from M2 Macrophages and Bone Marrow Mesenchymal Stem Cells: Modulating Macrophage Polarization.

Aseptic loosening of prostheses is a highly researched topic, and wear particle-induced macrophage polarization is a significant cause of peri-prosthetic osteolysis. Exosomes derived from bone marrow mesenchymal stem cells (BMSCs-Exos) promote M2 polarization and inhibit M1 polarization of macrophages. However, clinical application problems such as easy clearance and lack of targeting exist. Exosomes derived from M2 macrophages (M2-Exos) have good biocompatibility, immune escape ability, and natural inflammatory targeting ability. M2-Exos and BMSCs-Exos fused exosomes (M2-BMSCs-Exos) are constructed, which targeted the osteolysis site and exerted the therapeutic effect of both exosomes. M2-BMSCs-Exos achieved targeted osteolysis after intravenous administration inhibiting M1 polarization and promoting M2 polarization to a greater extent at the targeted site, ultimately playing a key role in the prevention and treatment of aseptic loosening of prostheses. In conclusion, M2-BMSCs-Exos can be used as a precise and reliable molecular drug for peri-prosthetic osteolysis. Fused exosomes M2-BMSCs-Exos  were originally proposed and successfully prepared, and exosome fusion technology provides a new theoretical basis and solution for the clinical application of therapeutic exosomes.

The influence of biological DMARDs on aseptic arthroplasty loosening: a retrospective cohort study.

OBJECTIVE: To investigate whether biological DMARDs affect the risk of aseptic loosening after total hip/knee arthroplasty (THA/TKA) in patients with RA. METHODS: We retrospectively identified all patients suffering from RA who underwent THA/TKA at our academic centre between 2002 and 2015 and linked them with an existing prospective observational RA database at our institution. The risk of aseptic loosening was estimated using radiological signs of component loosening (RCL). A time-dependent Cox regression analysis was used to compare the risk of implant loosening between patients treated with traditional DMARDS and biological DMARDs, or alternately both over time. RESULTS: A total of 155 consecutive total joint arthroplasties (TJAs) (103 TKA vs 52 THA) was retrospectively included in the study. Mean age at implantation was 59 ± 13 years. Mean follow-up time was 69 ± 43 months. Overall, 48 (31%) TJAs showed signs of RCL, with 28 (27.2%) RCLs occurring after TKA compared with 20 after THA (38.5%). A significant difference regarding the incidence of RCL between the traditional DMARDs group (39 cases of RCL, 35%) and the biological DMARDs group (nine cases of RCL, 21%) (P = 0.026) was observed using the log-rank test. This was also true when using a time-dependent Cox regression with therapy as well as arthroplasty location (hip vs knee) as variables (P = 0.0447). CONCLUSION: Biological DMARDs may reduce the incidence of aseptic loosening after TJA in patients with RA compared with traditional DMARDs. This effect seems to be more pronounced after TKA than THA.

Larger stem to bone diameter ratio predicts lower cemented endoprosthesis failure.

BACKGROUND AND OBJECTIVES: With continued advances in treatment options, patients with endoprosthetic reconstruction are living longer and consequently relying upon their devices for a longer duration. Major causes of endoprosthesis failure include aseptic loosening and mechanical failure. In the setting of tumor resection, loss of bone stock and use of radiation therapy increase the risk for these complications. As such, considerations of remaining native bone and stem length and diameter may be increasingly important. We asked the following questions: (1) What was the overall rate of endoprosthesis failure at a minimum of 5-year follow-up? (2) Does resection length increase implant failure rates? (3) Does implant size and its ratio to cortical width of bone alter implant failure rates? METHODS: We retrospectively analyzed patient outcomes at a single institution between the years of 1999-2022 who underwent cemented endoprosthetic reconstruction at the hip or knee and identified 150 patients. Of these 150, 55 had a follow-up of greater than 5 years and were used for analysis. Radiographs of these patients at time of surgery were assessed and measured for resection length, bone diameter, stem diameter, and remaining bone length. Resection percentage, and stem to bone diameter ratios were then calculated and their relationship to endoprosthesis failure were analyzed. RESULTS: Patients in this cohort had a mean age of 55.8, and mean follow-up of 59.96 months. There were 78 distal femoral replacements (52%), 16 proximal femoral replacements (10.7%), and 56 proximal tibial replacements (37.3%). There were five patients who experienced aseptic loosening and six patients who experienced mechanical failure. Patients with implant failure had a smaller mean stem to bone diameter (36% vs. 44%; p = 0.002). A stem to bone diameter of 40% appeared to be a breaking point between success and failure in this series, with 90% of patients with implant failure having a stem: bone ratio less than 40%. Stem to bone ratio less than 40% increased risk for failure versus stems that were at least 40% the diameter of bone (6/19 [31.6%] vs. 0/36 [0%]; odds ratio 0.68; p < 0.001). Resection length did not appear to have an impact on the rates of aseptic loosening and mechanical failure in this series. CONCLUSIONS: Data from this series suggests a benefit to using stems with a larger diameter when implanting cemented endoprostheses at the hip or knee. Stems which were less than 40% the diameter of bone were substantially more likely to undergo implant failure.

16S rRNA sequencing reveals microbiota differences in orthopedic implants between aseptic loosening and prosthetic joint infection cases.

Prosthetic joint infection (PJI) and aseptic loosening (AL) are common complications of total joint arthroplasty. An accumulation of evidence indicates the presence of microbial communities on prosthetic implants, but the overall microbial profile is unclear. In this study, we aimed to investigate the differences in the microbial composition of prosthetic implants obtained from PJI and AL patients using the 16S rRNA sequencing method. Patients who underwent revision hip, knee, or shoulder arthroplasty caused by PJI (n = 20) or AL (n = 10) were enrolled in the study. 16S rRNA sequencing targeting the V3-V4 region was performed on the microbial specimens collected from synovial fluid, periprosthetic deep-tissue, and biofilm during the revision surgery. The sequenced raw data were analysed for microbial composition and ecological and differential abundance analyses using bioinformatics tools. The AL group had relatively balanced and higher diversity, with Staphylococcus, Streptococcus, and Veillonella being prominent. In the PJI group, Staphylococcus and Pseudomonas were predominant, especially in deep-tissue samples and biofilm samples, respectively. The differential abundance analysis identified 15 and 2 distinctive taxa in the AL and PJI groups, respectively. Our findings provided preliminary insights supporting the existence of periprosthetic microbiota in orthopedic implants and explaining the differences in microbial composition between the AL and PJI groups.

Weight-bearing pain and implant migration, progressive radiolucencies, radiolucency more than 2 mm and subsidence on radiographs and CT are generally accepted criteria for knee arthroplasty loosening: An international Delphi consensus study.

PURPOSE: Establishing the diagnosis of loosening in total or unicondylar knee arthroplasty remains a challenge with different clinical and radiological signs evaluated in study designs with high risk of bias, where few or incomplete criteria are formulated for establishing the diagnosis of implant loosening. This study aimed at evaluating the variability between different clinical and radiological criteria and establish a consensus regarding clinical and radiological criteria for the diagnosis of knee arthroplasty loosening. METHODS: Highly specialized knee surgeons focusing on revision arthroplasty were invited to take part in an international panel for a Delphi consensus study. In the first round, the participants were asked to state their most important clinical and radiological criteria for implant loosening. In a second round, the panel's agreement with the collected criteria was rated on a 5-point Likert scale (1-5). High variability was defined by receiving at least one score each indicating complete disagreement and complete agreement. Consensus was established when over 70% of participants rated a criterion as 'fully agree' (5) or 'mostly agree' (4). RESULTS: High variability was observed in 56% of clinical criteria and 38% of radiological criteria. A consensus was reached on one clinical (weight-bearing pain [82%]) and four radiological criteria, that is, implant migration, progressive radiolucencies, subsidence and radiolucencies >2 mm on X-ray or computed tomography (CT) (84%-100%). CONCLUSION: Amongst specialized knee revision surgeons, there is high variability in clinical and radiological criteria that are seen as important contributing factors to diagnosis of knee implant loosening. A consensus was reached on weight-bearing pain as clinical criterion and on implant migration, progressive radiolucencies, subsidence and radiolucencies of more than 2 mm on X-ray or CT as radiological criteria. The variability rates observed, along with the criteria that reached consensus, offer important insights for the standardization of diagnostic protocols. LEVEL OF EVIDENCE: Level V.

Non-invasive quantitative assessment of induced component displacement can safely and accurately diagnose tibial component loosening in patients: A prospective diagnostic study.

PURPOSE: Aseptic loosening often requires major, expensive and invasive revision surgery. Current diagnostic modalities merely show indirect signs of loosening. A recent proof of concept study proposed a non-invasive technique for the quantitative and visual assessment of implant movement as a diagnostic aid for tibial component loosening. The primary research question addressed is whether this novel diagnostic modality can safely and effectively aid the diagnosis of aseptic loosening. METHODS: This clinical study included patients suspected of aseptic total knee arthroplasty (TKA) loosening listed for revision surgery and asymptomatic patients. Safety was evaluated using a numerical rating scale (NRS) for discomfort and by registration of adverse events. Feasibility was assessed by recording the duration and ease of the procedure. Intra- and interrater reliability were evaluated. In symptomatic patients, diagnostic accuracy metrics were evaluated with intra-operative assessment as a reference test. RESULTS: In total, 34 symptomatic and 38 asymptomatic knees with a TKA were analysed. The median NRS for discomfort during loading was 6 (interquartile range [IQR]: 3.75-7.00) in symptomatic patients and 2 (IQR: 1.00-3.00) in asymptomatic patients. No adverse events were reported. The majority of users found the use of the loading device easy. The median time spent in the computed tomography room was 9 min (IQR: 8.00-11.00). Excellent to good intra- and interrater reliabilities were achieved. Diagnostic accuracy analysis resulted in a sensitivity of 0.91 (95% confidence interval [CI]: 0.72-0.97) and a specificity of 0.72 (95% CI: 0.43-0.90). CONCLUSIONS: The proposed diagnostic method is safe, feasible, reliable and accurate in aiding the diagnosis of aseptic tibial component loosening. LEVEL OF EVIDENCE: Level II.

MRI and SPECT/CT demonstrate, with low certainty of evidence, the highest diagnostic accuracy for aseptic knee arthroplasty loosening: A systematic comparative diagnostic test review and meta-analysis.

PURPOSE: The purpose of this study was to evaluate and compare the diagnostic accuracy of modalities used to aid the diagnosis of aseptic knee arthroplasty loosening. METHODS: A comparative diagnostic test accuracy systematic review and meta-analysis was conducted following the Cochrane and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. PubMed, EMBASE and Cochrane databases were searched for original articles evaluating diagnostic modalities up to March 2024. Included studies compared the modality (index test) to the intraoperative finding as reference test. The QUADAS-C (Quality Assessment of Diagnostic Accuracy Studies-Comparative) tool was used to assess the quality of the included studies. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to evaluate the certainty of evidence. Level of evidence was evaluated using the Oxford Levels of Evidence tool. The primary outcome was the summary of diagnostic accuracy metrics for each modality as demonstrated by a summary receiver-operating characteristic (SROC) curve. RESULTS: The search yielded 467 articles. Of these, 14 articles were included. These 14 articles evaluated a total of five different diagnostic modalities: bone scintigraphy (three studies, 146 cases), 18-fluorodeoxyglucose positron emission tomography (two studies, 50 cases), single-photon emission computed tomography combined with computed tomography (SPECT/CT) (seven studies, 371 cases), radionuclide arthrogram (three studies, 196 cases) and magnetic resonance imaging (MRI) (one study, 116 cases). Nine studies exhibited a high risk of bias in patient selection, and all studies showed a high risk of bias related to the reference test. The majority of the included studies were classified as Level III evidence, leading to an overall low level of certainty in the evidence. The most accurate tests, as demonstrated by the SROC analysis, were MRI and SPECT/CT, with sensitivities ranging from 0.00 to 1.00 and 0.33 to 1.00 and specificities between 0.31-1.00 and 0.00-1.00, respectively. CONCLUSIONS: This review and meta-analysis evaluated available diagnostic modalities to aid the diagnosis of knee arthroplasty loosening and based on a low certainty of evidence suggests that MRI and SPECT/CT are currently the most accurate modalities available to aid the diagnosis of aseptic loosening of knee arthroplasty components. LEVEL OF EVIDENCE: Level III.

Visible fluid motion on manipulation as the new threshold for intraoperatively determined knee arthroplasty component loosening: A Delphi study.

PURPOSE: There is a lack of a clear, uniform definition for intraoperatively assessed component loosening of a knee arthroplasty component, complicating the interpretation and interchangeability of results of diagnostic studies using an intraoperative observation as the reference test. The purpose of this study was to establish a consensus among specialised knee revision surgeons regarding the definition of intraoperatively determined loosening of total or unicondylar knee arthroplasty components. METHODS: Utilising the Delphi consensus method, an international panel of highly specialised knee revision surgeons was invited to participate in a three-round process. The initiation of the first round involved the exploration of possible criteria for intraoperatively determined loosening with open questions. The second round focused on rating these criteria importance on a five-point Likert scale. For the third round, criteria that reached consensus were summarised in consecutive definitions for intraoperatively determined loosening and proposed to the panel. Consensus was established when over 70% of participants agreed with a definition for intraoperatively determined loosening. RESULTS: The 34 responding panel members described in total 60 different criteria in the first round of which 34 criteria received consensus in the second round. Summarising these criteria resulted in four different definitions as minimal requirements for intraoperatively determined loosening. Eighty-eight percent of the panel members agreed on defining a component as loose if there is visible fluid motion at the interface observed during specific movements or when gently applying direct force. CONCLUSION: This study successfully established a consensus using a Delphi method among knee revision surgeons on the definition of intraoperatively determined component loosening. By agreeing on the visibility of fluid motion as new definition, this study provides a standardised reference for future diagnostic research. This definition will enhance the interpretability and interchangeability of future diagnostic studies evaluating knee arthroplasty component loosening. LEVEL OF EVIDENCE: Level V.

Risk of tibial baseplate loosening is low in patients following unrestricted kinematic alignment total knee arthroplasty using a cruciate-retaining medial conforming insert: A study using radiostereometric analysis at 2 years.

PURPOSE: Assessing the risk of tibial baseplate loosening in patients after unrestricted kinematically aligned (unKA) total knee arthroplasty (TKA) using a medially conforming insert is important because baseplates generally are aligned in varus which has been linked to an increased incidence of aseptic loosening following mechanically aligned TKA. Two limits that indicate long-term stability in patients are a change in maximum total point motion between 1 and 2 years (ΔMTPM) < 0.2 mm and anterior tilt at 2 years < 0.8°. The purposes were to determine: (1) the number of patients with ΔMTPM > 0.2 mm, (2) the number of patients with anterior tilt > 0.8° and (3) whether increased varus baseplate and limb alignment were associated with increased migration. METHODS: Thirty-five patients underwent cemented, caliper-verified, unKA TKA using a medially conforming tibial insert with posterior cruciate ligament (PCL) retention. Biplanar radiographs acquired on the day of surgery and at 1.5, 3, 6, 12 and 24 months were processed with model-based radiostereometric analysis (RSA) software to determine migration and the number of patients with migration above the two stability limits. Medial proximal tibial angle (MPTA), hip-knee-ankle angle (HKAA) and posterior slope angle (PSA) were analyzed for an association with migration in six degrees of freedom and in MTPM. RESULTS: Thirty-two of 35 patients were available for analysis at 2 years. One patient exhibited ΔMTPM > 0.2 mm. The same patient exhibited anterior tilt > 0.8°. Varus rotation (p = 0.048, r ≤ 0.34) and medial translation (p = 0.0273, r ≤ 0.29) increased with increased varus baseplate alignment. CONCLUSION: The results indicate low risk of long-term baseplate loosening in patients. Although varus rotation and medial translation increased with increased varus baseplate alignment, the magnitudes of the migrations were minimal and did not increase ΔMTPM and anterior tilt. LEVEL OF EVIDENCE: Level II, therapeutic prospective cohort study.

Comparison Of Early And Late Aseptic Baseplate Failure In Primary Reverse Shoulder Arthroplasty With And Without Structural Glenoid Autograft.

INTRODUCTION: Early reverse total shoulder arthroplasty (RTSA) designs demonstrated high glenoid baseplate complication and revision rates. While contemporary designs have reduced the incidence of glenoid baseplate failures, there are reports of elevated failure risks in RTSA with glenoid bone grafting within the first 2 years. This study aims to evaluate the incidence and etiology of aseptic glenoid baseplate failure with a contemporary central screw baseplate. The null hypothesis is that majority of the baseplate failure occurs within the first 2 years and use of glenoid bone grafting does not lead to higher risk of baseplate failure. METHODS: In 2014 - 2019, 753 consecutive patients who underwent primary RSA using the same inlay press-fit humeral stem and monoblock central screw baseplate were retrospectively reviewed. Fracture and septic arthropathy cases were excluded. All patients underwent preoperative radiographic and computed tomography evaluation. If there was significant glenoid erosion (Walch A2, B2, B3, C1, C2, E2, E3, and/or E4 variants), patient-specific structural glenoid bone grafting was performed. All patients underwent standardized radiographic follow-up and failure was strictly defined as any hardware breakage and/or shift in glenoid baseplate position. Failures were defined as "early" if occurring within 2 years and "late" if occurring greater than 2 years after surgery. Comparative analysis was performed to evaluate demographics, glenoid graft use, and graft union rates between the cohorts. RESULTS: There were 23 patients with baseplate failures (23/753, 3.0%) at mean of 23 months. Twenty-two failures (96%) occurred in patients who received structural glenoid bone grafting. Only 1 failure (0.2%) occurred when bone grafting was not indicated (p<0.001). The most common failure pattern was associated with B2 glenoid (16/23, 70%). There were 5 (22%) early failures and 18 (78%) late failures. There were no differences in any patient demographic characteristics between cohorts. All 5 early failures had graft nonunion and 4/5 occurred without trauma. In the 18 late failures , 9/18 (50%) occurred without trauma (p=0.135). Seventeen of these patients had glenoid grafting, of which 9/17 (53%) had graft nonunion. CONCLUSIONS: Contemporary RTSA glenoid baseplate designs have an acceptably low incidence of failure. However, the addition of structural bone graft to correct glenoid wear leads to higher aseptic baseplate failure rate. The majority of these patients suffer failure after the 2-year postoperative mark, highlighting the necessity of longer follow-up. Further analysis is necessary to quantify glenoid characteristics (severity of glenoid erosion, critical size of graft) associated with failure.

Humeral stem loosening is not always prosthetic joint infection.

BACKGROUND: Aseptic humeral stem loosening is an uncommon complication of shoulder arthroplasty, and its presence has been considered a highly specific predictor of prosthetic joint infection (PJI). Literature on aseptic humeral stem loosening is sparse. The primary purpose of this study was to determine the rate of aseptic humeral loosening in revision shoulder arthroplasty. Secondarily, we sought to identify predictors of septic and aseptic humeral loosening. METHODS: Our institutional revision shoulder arthroplasty database was reviewed. Inclusion criteria were patients with humeral stem loosening as indicated in the operative report. Patient demographics, index surgery and indication, revision surgery and indication, and operative data were recorded. Charts were manually reviewed, and PJI scores were calculated using the International Consensus Meeting scoring criteria. International Consensus Meeting classifications of PJI "unlikely" and "possible" were considered aseptic, and PJI "probable" and "definite" were considered septic. Statistical analysis was performed to determine associations between the abovementioned variables and aseptic humeral loosening. RESULTS: Forty-six patients with 48 shoulders were included in our analysis. Ten cases (21%) were classified as definite PJI, 13 cases (27%) were classified as probable PJI, 4 cases (8%) were classified as possible PJI, and 21 cases (44%) were classified as PJI unlikely. On analysis of stem design, there were no statistically significant associations with aseptic loosening; although, a lack of proximal porous ingrowth surface trended toward higher rates of aseptic loosening in all patients and in anatomic total shoulder arthroplasty (ATSA) and reverse total shoulder arthroplasty (RTSA) subgroup analyses. In the index RTSA subgroup, aseptic loosening was associated with female sex (P = .005). Seventeen of 39 shoulders (44%) that underwent either index ATSA or RTSA demonstrated concomitant glenoid loosening. The absence of glenoid loosening was associated with aseptic humeral loosening in index ATSA and RTSA (P < .001). CONCLUSION: Fifty-two % of revision shoulder arthroplasty cases with humeral loosening performed at our institution were aseptic. There appear to be distinct demographic and radiographic factors that are more commonly associated with aseptic as opposed to septic humeral loosening. Our data demonstrate that demographic predictors of aseptic loosening of RTSA include female sex. The absence of glenoid component loosening is associated with aseptic humeral loosening and concomitant glenoid loosening is associated with septic humeral loosening. Understanding of these factors can guide the preoperative index of suspicion for PJI in the setting of humeral stem loosening.

Zirconium as a Promising Synovial Biomarker for Loose Cemented Knee Prosthesis.

BACKGROUND: Aseptic loosening is the most common mode of failure after total knee arthroplasty. Despite this, the diagnosis often remains challenging and mainly relies on imaging modalities. Until today, no biomarker exists to aid in diagnosing loosening of the implants. As zirconium (Zr) is often found in bone cement, where it serves as radiopacifier, this study aimed to establish Zr as a synovial biomarker for loosened cemented knee prostheses. METHODS: A total of 31 patients scheduled for revision of a cemented knee prostheses were included. In all patients, the initial used cement contained Zr. After arthrotomy, specimens of synovial fluid were taken and levels of Zr were measured by inductively coupled plasma mass spectrometry. Depending on the necessary amount of force for explantation, the implants were graded "loose" or "well-fixed". Preoperative radiographs were evaluated by 2 independent physicians. RESULTS: The concentration of Zr in the synovial fluid differed significantly (P < .001) between the "loose" (mean 170.9 µg/L, range 0 to 1941 µg/L) and the "well-fixed" (mean 0.6 µg/L, range 0 to 6 µg/L) implants. The receiver operating characteristic analysis revealed 0.25 µg/l as an optimal cutoff value leading to a sensitivity of 0.84, a specificity of 0.92, a positive predictive value of 0.94, and a negative predictive value of 0.79. There was no significant difference in the diagnostic performance compared to radiographs (P = .66). CONCLUSIONS: Zirconium proved to be a reliable novel synovial biomarker for diagnosing aseptic loosening of knee prothesis fixed with cement containing Zr. This biomarker should not be interpreted in isolation, but in combination with existing diagnostic tools.

Osteoporosis and Total Knee Arthroplasty: Higher 5-Year Implant-Related Complications.

BACKGROUND: The risk of revision surgery in patients who have osteoporosis after total knee arthroplasty (TKA) is understudied. Our aim was to compare the 5-year cumulative risk of revision surgery after TKA in patients who have preoperative osteoporosis. METHODS: A national administrative claims database was queried for patients undergoing primary TKA from 2010 to 2021. There were 418,054 patients included, and 41,760 (10%) had osteoporosis. The 5-year incidence of revision surgery was examined for all-causes, periprosthetic fracture (PPF), aseptic loosening, and periprosthetic joint infection (PJI). A multivariable analysis was conducted using Cox proportional hazards models. Hazards ratios (HRs) were reported with 95% confidence intervals (CIs). RESULTS: The 5-year rate of all-cause revision surgery was higher for patients who had osteoporosis (HR 1.1, 95% CI: 1.0 to 1.2), however, the highest risk of revision surgery was seen for PPF (HR 1.8, 95% CI: 1.6 to 2.1). Patients who had osteoporosis also had elevated risk of revision surgery for PJI (HR 1.2, 95% CI: 1.1 to 1.3) and aseptic loosening (HR 1.2, 95% CI: 1.1 to 1.3). Osteoporosis was independently associated with PJI and aseptic loosening at a higher rate in obese patients. CONCLUSIONS: In unadjusted survival analysis, those who had osteoporosis have a marginally lower risk of all-cause revision surgery. However, after controlling for age, sex and comorbidities, patients who had osteoporosis have a nearly 2-fold increased risk of 5-year revision for PPF after TKA, and mildly increased risk of revision for all causes, aseptic loosening, and PJI. Obesity may also modulate this association. Future studies should determine the extent to which treatment of osteoporosis modifies these postoperative outcomes.

Sex-Specific Implant Fixation Can Reduce Revision Rates in Total Hip Arthroplasty: Evidence From the Swiss National Joint Registry.

BACKGROUND: Patient's sex is considered a risk factor for revision following primary total hip arthroplasty (THA), but sex-specific treatment guidelines are lacking. The purpose was to assess sex-specificity of risk factors for periprosthetic femoral fractures (PFFs) and aseptic stem loosening (ASL) in a nationwide register study. METHODS: All uncemented and hybrid THAs for hip osteoarthritis registered in the Swiss National Joint Registry were considered. 86,423 THAs were analyzed. Comparable THA subsets for both sexes were obtained through propensity score matching (1:1). A sex-specific analysis of risk factors for early PFF or ASL was performed using recursive partitioning analyses. RESULTS: In women, PFFs were most significantly associated with uncemented THA fixation (P < .0001) and age (P < .01, threshold: 70.5 years). The ASLs were solely associated with patient age of <65 years (P = .023). In men, PFFs were associated exclusively with an American Society of Anesthesiologists (ASA) score >2 (P = .026). The ASLs were not correlated to any of the potential risk factors analyzed. A mathematical simulation indicated that avoiding uncemented THA fixation in women ≥70.5 years of age decreased the number of revisions within the observational period by 21% in this subset and by 4.9% in the entire patient population. CONCLUSION: Uncemented THA should be avoided in women >70.5 years due to the increased risk of early PFF, while the mode of stem fixation did not influence revision risk in men. A sex-specific regimen for THA fixation has the potential to markedly reduce early THA revision rates.

Total Hip Arthroplasty Following Operative Fixation of Acetabular Fracture: A Contemporary Series.

BACKGROUND: Total hip arthroplasty (THA) is the operation of choice for salvage of post-traumatic arthritis following acetabular fracture. While high failure rates have been reported for these procedures, existing literature reports mainly on historical implant designs and techniques. We aimed to describe implant survivorships, complications, radiographic results, and clinical outcomes of contemporary THA following prior open reduction internal fixation (ORIF) of an acetabular fracture. METHODS: We identified 104 patients undergoing THA following prior ORIF of an acetabular fracture from 2000 to 2015 via our institutional total joint registry. Mean age at THA was 50 years (range, 18 to 79 years), 71% were men, and mean body mass index was 27 (range, 18 to 52). All patients were implanted with uncemented acetabular components, and 89% had uncemented stems. Some hardware from prior fixation was retained in 94% of cases. Mean follow-up was 10 years (range, 2 to 21 years). RESULTS: The 10-year survivorships free of any revision and any reoperation were 98% and 97%, respectively. There were 4 revisions: 1 each for psoas tendonitis, dislocation, acetabular aseptic loosening, and periprosthetic joint infection. There were 9 complications that did not lead to reoperation: 5 dislocations, 2 periprosthetic femur fractures, 1 sciatic nerve palsy, and 1 case of symptomatic heterotopic ossification. All unrevised components appeared radiographically well-fixed. Mean Harris Hip Score improved from mean 50 preoperatively to mean 82 at 5 years (P < .001). CONCLUSIONS: In this series of contemporary THAs following prior acetabular fracture ORIF, revision-free survivorship was excellent with only a single case of acetabular aseptic loosening. These results are encouraging and suggest that contemporary implants and techniques have notably improved on historic results. LEVEL OF EVIDENCE: Therapeutic, Level IV.

The Use of Erythromycin and Colistin Cement in Total Knee Arthroplasty Does Not Reduce the Incidence of Infection: A Randomized Study in 2,893 Knees With a 9-year Average Follow-Up.

BACKGROUND: One of the most severe complications of primary total knee arthroplasty (TKA) is prosthetic joint infection. Currently, the use of antibiotic-loaded cement for the prevention of infection is still controversial. The aim of the present study was to evaluate if the use of antibiotic-loaded cement reduces the infection rate in primary TKA in long-term follow-up (more than 5 years average follow-up). METHODS: This study is the follow-up extension of a prospective randomized study, with 2,893 cemented TKA performed between 2005 and 2010 at our institution. There were 2 different cohorts depending on which bone cement was used: without antibiotics (control group) or those loaded with erythromycin and colistin (study group). All patients received the same systemic prophylactic antibiotics. The patients were followed for a minimum of twelve months. The diagnosis of prosthetic joint infection was done according to Zimmerli criteria. RESULTS: In 1,452 patients, the prosthetic components were fixed using bone cement without antibiotics, whereas in 1,441 patients, bone cement was loaded with erythromycin and colistin. Both groups were comparable in terms of all the possible risk factors studied. We found a total of 53 deep infections, with a mean rate of 1.8%. There were no differences between the groups as to whether bone cement with or without antibiotics had been used (P = .58). The average duration of follow-up was 8.7 years. In terms of prosthetic revision due to aseptic loosening, there were no differences between groups (P = .32), with 33 revision arthroplasties in the control group and 37 in the study group. Moreover, we analyzed the erythromycin resistance rate, with no differences between both groups (P = .6). CONCLUSIONS: The use of erythromycin and colistin-loaded bone cement in TKA did not lead to a decrease in the rate of infection in long-term follow-up, a finding that suggests that its use would not be indicated in the general population.

Femoral Component Debonding Frequently Missed on Advanced Imaging Prior to Revision of a Recalled Total Knee Arthroplasty.

BACKGROUND: Identification of femoral component debonding in the work-up of painful total knee arthroplasty (TKA) often poses a diagnostic challenge. The purpose of this study was to compare the sensitivity and specificity of radiographs, computed tomography (CT), and magnetic resonance imaging (MRI) for identifying femoral component loosening with debonding at the time of revision of a primary TKA with a recalled polyethylene insert. METHODS: Using an institutional database, we identified all cases of revision TKA performed for this specific implant recall following a primary TKA between 2014 and 2022. Patients who had a preoperative radiograph, CT, and MRI were included (n = 77). Sensitivity, specificity, and positive and negative likelihood ratio (LR) for predicting loosening were compared among the imaging modalities, using the intraoperative evidence of implant loosening as the gold standard. RESULTS: At the time of revision surgery, the femoral component was noted to have aseptic loosening with debonding in 46 of the 77 (60%) of the TKAs. There were no significant differences in demographics in the cohort with femoral debonding compared to those with well-fixed implants. The CT demonstrated a sensitivity of 28% and a specificity of 97%, while the MRI demonstrated a sensitivity of 37% and a specificity of 94% for detecting femoral loosening due to debonding. Both CT and MRI demonstrated poor negative LRs for femoral loosening (LR 0.7). CONCLUSIONS: In this series of revision TKAs for a specific recalled component, neither CT nor MRI accurately diagnosed femoral component debonding. For patients who have this implant, it is imperative to interrogate the implant-cement interface intraoperatively and prepare for full revision surgery as well as marked bone loss secondary to osteolysis.

High Rates of Early Septic Failure, But Low Rates of Aseptic Loosening after Revision Total Knee Arthroplasty with Contemporary Rotating-Hinge Prostheses.

BACKGROUND: The purpose of this study was to determine implant survivorship and functional outcomes for revision total knee arthroplasty (rTKA) with contemporary rotating-hinge knee implants. METHODS: A retrospective review identified 115 rTKAs using contemporary rotating-hinge implants from 2014 to 2018 for the treatment of instability (34, 30%), reimplantation after periprosthetic joint infection (PJI) (33, 29%), aseptic loosening (25, 22%), arthrofibrosis (14, 12%), periprosthetic fracture (4, 3%), osteolysis (4, 3%), and femoral component fracture (1, 1%). There were 70 women (61%), and the mean age was 67 years (range, 27 to 94). The mean follow-up was 3 years (range, 2 to 6). Kaplan-Meier analysis and Cox proportional hazard models estimated survivorship. RESULTS: The re-revision rate was 20% (23 of 115) at an average of 18 months postoperatively. Re-revision indications included PJI (n = 14), aseptic loosening (n = 4), arthrofibrosis (n = 2), instability/malalignment (n = 1), femoral stem fracture (n = 1), and hinge mechanism disruption (n = 1). At 2 and 5 years, survivorship free from all-cause re-revision was 86% and 64%, and survivorship free from re-revision for aseptic loosening was 100% and 87%, respectively. Use of a rotating-hinge implant in reimplantation after PJI was a risk factor for subsequent re-revision (hazard ratio = 2.4, P = 0.046). On a radiographic review of unrevised rotating-hinges, there were major radiolucent lines around 2 femoral and 5 tibial components. The mean Knee Osteoarthritis Outcomes Score for Joint Replacement (KOOS JR) increased from 43 preoperatively to 60 at 1 year (P < 0.001). CONCLUSION: In patients treated with a rotating-hinge implant for rTKA, there were relatively poor 2-year (86%) and 5-year (64%) survivorship free from all-cause re-revision, most commonly due to PJI. Mid-term survivorship free from re-revision for aseptic loosening was modest (87%). There should be a goal to mitigate complications in complex rTKAs with rotating-hinge implants, namely PJI.