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Classically, particle-induced periprosthetic osteolysis at the implant-bone interface has explained the aseptic loosening of joint replacement. This response is preceded by triggering both the innate and acquired immune response with subsequent activation of osteoclasts, the bone-resorbing cells. Although particle-induced periprosthetic osteolysis has been considered a foreign body chronic inflammation mediated by myelomonocytic-derived cells, current reports describe wide heterogeneous inflammatory cells infiltrating the periprosthetic tissues. This review aims to discuss the role of those non-myelomonocytic cells in periprosthetic tissues exposed to wear particles by showing original data. Specifically, we discuss the role of T cells (CD3+, CD4+, and CD8+) and B cells (CD20+) coexisting with CD68+/TRAP- multinucleated giant cells associated with both polyethylene and metallic particles infiltrating retrieved periprosthetic membranes. This review contributes valuable insight to support the complex cell and molecular mechanisms behind the aseptic loosening theories of orthopedic implants.

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Introduction: Aseptic and septic loosening by mechanical failure is one of the main causes of proximal femur endoprosthesis failure with different clinical consequences such as pain, inflammation, progressive loosening of muscular volume, and strength with functional limitation. We present a case series of four patients with aseptic and septic loosening of femur endoprosthesis that was treated with a novel technique that combines different methods to achieve primary stability. Case Report: Four patients with an average age of 49.5 years (35-70 years), two women and two men, were referred to the Orthopedic Surgery Department of the San Ignacio University Hospital of Bogota. Two of them with a history of oncological disease, ruling out a tumor relapse through local images and extension examinations; another patient with a history of firearm injury to the left thigh with multiple secondary complications, which required various reconstructive procedures; and the oldest patient with a history of total hip replacement. The main complaint of the four patients was thigh pain not caused by trauma and initial assessment radiographs of all of them showed signs of loosening of the prosthetic material, with septic etiology in two of the patients and aseptic etiology in the other two. Therefore, they were scheduled for revision surgery of prosthetic components. These patients recover functional status and resolved pain in the early post-operative period and during long-term follow-up. Only one of the patients, time after the surgical procedure, required removal of the osteosynthesis material due to persistent bone infectious process. Conclusion: Septic and aseptic loosening is one of the most common complications of proximal femur endoprosthesis, resulting in significant pain and functional decline in patients. We present a novel surgical technique that allows primary stabilization of the construct that allows early rehabilitation, improvement of functionality, and no signs of new loosening.

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BACKGROUND: Aspirin has been shown to be a safe and cost-effective thromboprophylaxis agent with equivalent preventive efficacy to warfarin and fewer side-effects. However, animal studies have suggested delayed bone healing with aspirin and other inhibitors of prostaglandin synthesis. The impact of aspirin on aseptic loosening following cementless total hip arthroplasty (THA) has yet to be explored. Our aim was to determine if patients receiving aspirin for thromboprophylaxis had higher rates of aseptic loosening vs patients receiving warfarin after THA. METHODS: We identified 11,262 consecutive primary uncemented THA performed between 2006 and 2017. Postoperatively, either warfarin (target international normalized ratio 1.5-2.0) or aspirin chemoprophylaxis were prescribed for 4 weeks. We recorded demographics, length of stay, body mass index, preoperative nonsteroidal antiinflammatory drug use, and Elixhauser comorbidity index. All revisions because of aseptic loosening within 1 year of the index procedure were identified radiographically, confirmed intraoperatively, and did not fulfill Musculoskeletal Infection Society criteria for periprosthetic infection. Multivariate logistic regression analysis was performed. RESULTS: There was no difference (P = .14) in the rates of revision for aseptic loosening between patients in the aspirin cohort (14/4530; 0.31%; P = .14) and the warfarin cohort (36/6682; 0.54%). After accounting for confounding variables, no significant difference was noted in aseptic loosening rates between patients treated with aspirin vs those treated with warfarin (adjusted odds ratio 0.51; P = .11). Perioperative nonsteroidal antiinflammatory drug was not significantly associated with aseptic loosening (adjusted odds ratio 1.20; P = .67). CONCLUSION: While multiple agents are available for venous thromboprophylaxis, there is increasing evidence in favor of the use of aspirin. This study allays the notion that aspirin increases the rates of aseptic loosening following uncemented hip arthroplasty.

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BACKGROUND: In an era of innovation in surgical approaches for total hip arthroplasty (THA), there is concern for increasing trends of early failure. The purpose of this study is to evaluate the incidence of early failure of primary THA stratified by surgical approach. METHODS: A retrospective review was performed on consecutive primary THAs completed from 2007 to 2014 at a high-volume center. THAs were stratified by surgical approach. Only the direct anterior (DAA) and posterior approaches (PA) were included. The primary outcome measure was early revision (<5 years). Descriptive statistics were performed using SAS software. RESULTS: In total, 6894 primary THAs performed between 2007 and 2014 were included. Across 2431 DAA THAs and 4463 PA THAs, there were 103 revisions overall. There was no difference in the overall revision rate for DAA THAs (1.69%) compared to PA THAs (1.39%) (P = .33). The DAA had a higher rate of early revisions for femoral component loosening compared to the PA (P = .0003). About 35.7% of DAA THAs were revised for femoral loosening compared to 8% for the PA (P = .0003). Early failure by femoral loosening occurred more often via the DAA in Dorr A bone (P = .03). The PA had a higher incidence of revision for instability (P = .04). There was no difference in modes of failure with regards to time to failure, acetabular loosening, early periprosthetic fracture, or infection. CONCLUSION: The DAA had a higher incidence of femoral loosening while PA had a higher mode of failure due to instability. Overall revision rates were not statistically different between approaches.

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The imbalance between bone formation and osteolysis plays a key role in the pathogenesis of aseptic loosening. Strontium ranelate (SR) can promote bone formation and inhibit osteolysis. The aim of this study was to explore the role and mechanism of SR in aseptic loosening induced by wear particles. Twenty wild-type (WT) female C57BL/6j mice and 20 sclerostin-/- female C57BL/6j mice were used in this study. Mice were randomly divided into four groups: WT control group, WT SR group, knockout (KO) control group, and KO SR group. We found that SR enhanced the secretion of osteocalcin (0.72±0.007 in WT control group, 0.98±0.010 in WT SR group, P=0.000), Runx2 (0.34±0.005 in WT control group, 0.47±0.010 in WT SR group, P=0.000), β-catenin (1.04±0.05 in WT control group, 1.22±0.02 in WT SR group, P=0.000), and osteoprotegerin (OPG) (0.59±0.03 in WT control group, 0.90±0.02 in WT SR group, P=0.000). SR significantly decreased the level of receptor activator for nuclear factor-κB ligand (RANKL) (1.78±0.08 in WT control group, 1.37±0.06 in WT SR group, P=0.000) and improved the protein ratio of OPG/RANKL, but these effects were not observed in sclerostin-/- mice. Our findings demonstrated that SR enhanced bone formation and inhibited bone resorption in a wear particle-mediated osteolysis model in wild-type mice, and this effect relied mainly on the down-regulation of sclerostin levels to ameliorate the inhibition of the canonical Wnt pathway.

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AIMS: The Corail stem has good long-term results. After four years of using this stem, we have detected a small group of patients who have presented with symptomatic metaphyseal debonding. The aim of this study was to quantify the incidence of this complication, to delineate the characteristics of patients presenting with this complication and to compare these patients with asymptomatic controls to determine any important predisposing factors. PATIENTS AND METHODS: Of 855 Corail collarless cementless stems implanted for osteoarthritis, 18 presented with symptomatic metaphyseal debonding. A control group of 74 randomly selected patients was assembled. Clinical and radiological parameters were measured and a logistic regression model was created to evaluate factors associated with metaphyseal debonding. RESULTS: The prevalence of this complication was 2.1% in our series. In the multivariable model, the presence of a Dorr B-type proximal femur was associated with metaphyseal debonding (odds ratio (OR) 10.73, 95% confidence interval (CI) 2.31 to 49.97, p = 0.002), as was a body mass index > 25 kg/m2 (OR 6.85, 95% CI 1.06 to 44.28, p = 0.04). Smaller stems and the use of a polyethylene acetabular liner appeared to be protective when compared with metal and ceramic setting hard-on-hard bearings. CONCLUSION: We have described an uncommon but important mode of failure of the Corail stem. Surgeons should be aware of this phenomenon; overweight patients with Dorr B-type femurs and in whom hard bearings are used appear to be particularly at risk. Cite this article: Bone Joint J 2017;99-B:1435-41.

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The aseptic loosening rate of the Mayo hip prosthesis femoral stem was determined in a 44 patient (52 hips) series, by comparing preoperative and postoperative clinical and radiographic parameters, over a minimal 5-year postoperative period. Loosening was obvious before five years in four hips (7.6%), while the stem was considered stable in the remaining 48 hips over a mean 6.1 year period, therefore accounting for a 92.3% Kaplan-Meier survival rate. We conclude that the aseptic loosening rate is too high for the Mayo hip prosthesis femoral stem, as compared to literature data concerning the non-conservative stems.

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AIMS: The biological reaction to wear debris is critical to the osteolysis underlying aseptic loosening of joint prosthetic implants. In an attempt to reduce aseptic loosening, ceramics have been introduced. This study was designed to evaluate, compare and correlate the expression of Toll-like receptors (TLRs), their intracellular adaptors and proinflammatory cytokines in cultured macrophages challenged with titanium or zirconia particles, as well as particle-induced osteolysis in calvaria and hyperalgesia and edema in hind paw. MAIN METHODS: TLRs and their adaptors were evaluated at the mRNA level by RT-PCR, and cytokine expression was evaluated at the mRNA and protein levels. Osteolysis and hyperalgesia and edema were evaluated in vivo, in calvaria and hind paw, respectively. KEY FINDINGS: Cultured macrophages challenged with zirconia or titanium particles expressed increased mRNA for TLRs 2, 3, 4 and 9, and their adaptors MyD88, TRIF and NF-κB and cytokines TNF-α, IL-1ß and IL-6, which were also increased at protein level. Quantitative differences are evident and, in general, zirconia particle-induced pro-inflammatory gene expression was lower than that induced by titanium particles. In in vivo experiments, exposition to titanium or zirconia particles induced osteolysis in calvaria and hyperalgesia and edema in hind paw; however those induced by zirconia particles were significantly lower. There is a strong and positive correlation between the expressions of mRNA for TLR4, NF-κB, TNF-α, IL-1ß and IL-6. SIGNIFICANCE: Collectively, our data suggest that zirconia ceramic particles are less bioactive than titanium particles.

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