Search

Background: Antiseptic solutions are commonly utilized during total joint arthroplasty (TJA) to prevent and treat periprosthetic joint infection (PJI). The purpose of this study was to investigate which antiseptic solution is most effective against methicillin-sensitive Staphylococcus aureus (MSSA) and Escherichia coli biofilms established in vitro on orthopaedic surfaces commonly utilized in total knee arthroplasty: cobalt-chromium (CC), oxidized zirconium (OxZr), and polymethylmethacrylate (PMMA)., Methods: MSSA and E. coli biofilms were grown on CC, OxZr, and PMMA discs for 24 and 72 hours. Biofilm-coated discs were treated with control or various antiseptic solutions for 3 minutes. Solutions included 10% povidone-iodine, a 1:1 mixture of 10% povidone-iodine plus 3% hydrogen peroxide, diluted povidone-iodine, 0.05% chlorhexidine gluconate, and a surfactant-based formulation of ethanol, acetic acid, sodium acetate, benzalkonium chloride, and water. Following treatment, discs were sonicated to quantify adherent bacteria or underwent imaging with scanning electron microscopy to identify biofilm. Antiseptic solutions were considered efficacious if they produced a 3-log (1,000-fold) reduction in colony-forming units compared with controls., Results: On both OxZr and CC, 10% povidone-iodine with hydrogen peroxide eradicated all MSSA, and it achieved clinical efficacy on PMMA at both 24-hour MSSA biofilm (p < 0.0002) and 72-hour MSSA biofilm (p = 0.002). On 72-hour MSSA biofilm, 10% povidone-iodine eradicated all bacteria on OxZr and CC, and it achieved clinical efficacy on PMMA (p = 0.04). On 24-hour MSSA biofilm, 10% povidone-iodine achieved efficacy on all surfaces (all p < 0.01). The surfactant-based formulation only achieved clinical efficacy on 72-hour MSSA biofilms on CC (p = 0.04) and OxZr (p = 0.07). On 72-hour E. coli biofilm, 10% povidone-iodine with or without hydrogen peroxide achieved clinical efficacy on all surfaces. No other solution achieved clinical efficacy on either MSSA or E. coli., Conclusions: Antiseptic solutions vary considerably in efficacy against bacterial biofilm. The 10% povidone-iodine solution with or without hydrogen peroxide consistently removed MSSA and E. coli biofilms on multiple orthopaedic surfaces and should be considered for clinical use., Clinical Relevance: Clinicians should be aware of the differences in the efficacy of antiseptic solutions on different orthopaedic surfaces when treating MSSA or E. coli biofilms., Competing Interests: Disclosure: The Zeiss Gemini 300 FE-SEM was provided through the National Institutes of Health S10 Shared Instrumentation Program (grant 1S10OD026989-01). Cobalt-chromium and oxidized zirconium discs were donated by Smith+Nephew. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/I289)., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Despite the success of standard antiseptic irrigation solutions in reducing periprosthetic joint infection (PJI) rates, there is still a need for more effective solutions. Synergistic use of povidone-iodine (PI) and hydrogen peroxide (H 2 O 2 ) has shown promising results; however, the optimal solution concentration balancing bactericidal activity and osseointegration remains unknown. This study aims to evaluate the impact of these antiseptic irrigation solutions on osseointegration and the bone-implant interface strength in vivo. Forty C57BL/6 mice underwent bilateral tibial implantation surgery and were randomly allocated into three groups receiving 0.3% PI, 10% PI mixed with 3% H 2 O 2 , or saline as irrigation solutions intraoperatively. Assessments were performed on postoperative Days 1 and 28, including plain radiographs, microcomputed tomography (microCT) evaluation, histological analysis, immunohistochemistry, and biomechanical pull-out testing. No wound complications were observed. MicroCT scans revealed no differences in peri-implant trabecular bone parameters. Biomechanical pull-out testing showed no differences in the bone-implant interface strength across groups. Histological analysis indicated no differences in bone and bone marrow percentage areas among treatment groups. Immunohistochemical analysis demonstrated no differences among groups in peri-implant osteocalcin, osterix, or endomucin-positive cells. In conclusion, using either antiseptic irrigation solution showed no differences in osseointegration parameters compared to the control group, demonstrating safety and the absence of toxicity. CLINICAL RELEVANCE: Dilute 0.3% povidone-iodine and a 1:1 combination of 10% povidone-iodine mixed with 3% hydrogen peroxide can be safely used during primary and revision total joint arthroplasty without compromising osseointegration or causing wound complications., (© 2024 Orthopaedic Research Society.)

An in vivo animal model of a weight-bearing intra-articular implant is crucial to the study of implant osseointegration and aseptic loosening caused by osseointegration failure. Osseointegration, defined as a direct structural and functional attachment between living bone tissue and the surface of a load-carrying implant, is essential for implant stability and considered a prerequisite for the long-term clinical success of implants in total joint arthroplasty. Compared to large animal models, murine models offer extensive genetic tools for tracing cell differentiation and proliferation. The 18- to 22-week-old C57BL/6J background mice underwent either press-fitted or loose implantation of a titanium implant, achieving osseointegration or fibrous integration. A protocol was developed for both versions of the procedure, including a description of the relevant anatomy. Samples were subjected to microcomputed tomography and underwent biomechanical testing to access osseointegration. Lastly, samples were fixed and embedded for histological evaluation. The absence of mineralized tissue and weakened maximum pull-out force in loose implantation samples indicated that these implants were less mechanically stable compared to the control at 4 weeks postoperation. Histological analysis demonstrated extensive fibrotic tissue in the peri-implant area of loose implantation samples and excellent implant osseointegration in press-fitted samples at 4 weeks. Both mechanically stable and unstable hemiarthroplasty models with either osseous ingrowth or a robust periprosthetic fibrosis were achieved in mice. We hope that this model can help address current limitations for in vivo study of aseptic loosening and lead to necessary translational benefits., (© 2024 Orthopaedic Research Society.)

The cellular and molecular mediators of peri-implant fibrosis-a most common reason for implant failure and for surgical revision after the replacement of a prosthetic joint-remain unclear. Here we show that peri-implant fibrotic tissue in mice and humans is largely composed of a specific population of skeletal cells expressing the leptin receptor (LEPR) and that these cells are necessary and sufficient to generate and maintain peri-implant fibrotic tissue. In a mouse model of tibial implantation and osseointegration that mimics partial knee arthroplasty, genetic ablation of LEPR + cells prevented peri-implant fibrosis and the implantation of LEPR + cells from peri-implant fibrotic tissue was sufficient to induce fibrosis in secondary hosts. Conditional deletion of the adhesion G-protein-coupled receptor F5 (ADGRF5) in LEPR + cells attenuated peri-implant fibrosis while augmenting peri-implant bone formation, and ADGRF5 inhibition by the intra-articular or systemic administration of neutralizing anti-ADGRF5 in the mice prevented and reversed peri-implant fibrosis. Pharmaceutical agents that inhibit the ADGRF5 pathway in LEPR + cells may be used to prevent and treat peri-implant fibrosis., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Polypropylene (PPE) mesh is commonly utilized to reconstruct catastrophic extensor mechanism disruptions in revision total knee arthroplasty. Unfortunately, these procedures are associated with a high rate of periprosthetic joint infection. The purpose of the current study was to: 1) visualize and quantify the progression of bacterial biofilm growth on PPE-mesh; and 2) determine which antiseptic solutions effectively remove viable bacteria., Methods: Knitted PPE mesh samples were cultured with either methicillin-sensitive Staphylococcus aureus (MSSA) or Escherichia coli (E. coli) for 7 days, with regular quantification of colony forming units (CFUs) and visualization using scanning electron microscopy to identify maturity. Immature (24 hour) and mature (72 hour) biofilm was treated with one of 5 commercial antiseptics for 3 minutes. A 0.05% chlorhexidine gluconate, a surfactant-based formulation of ethanol, acetic acid, sodium acetate, benzalkonium chloride, diluted povidone-iodine (0.35%), undiluted (10%) povidone-iodine, and 1:1 combination of 10% povidone-iodine and 3% hydrogen peroxide. A 3-log reduction in CFUs compared to saline was considered clinically meaningful., Results: The CFU counts plateaued, indicating maturity, at 72 hours for both MSSA and E. coli. The scanning electron microscopy confirmed confluent biofilm formation after 72 hours. The 10% povidone-iodine was clinically effective against all MSSA biofilms and immature E. coli biofilms. The 10% povidone-iodine with hydrogen peroxide was effective in all conditions. Only 10% povidone iodine formulations produced significantly (P < .0083) reduced CFU counts against mature biofilms., Conclusions: Bacteria rapidly form biofilm on PPE mesh. Mesh contamination can be catastrophic, and clinicians should consider utilizing an antiseptic solution at the conclusion of mesh implantation. Undiluted povidone-iodine with hydrogen peroxide should be considered when attempting to salvage infected PPE mesh., (Copyright © 2024 Elsevier Inc. All rights reserved.)

While previous studies on navigated total hip replacement (nTHA) focused on acetabular component positioning, we compared the results of nTHA with conventional total hip replacement (cTHA) in respect of changes in leg length and hip offset. In a single-center study results radiographic parameters of patients with unilateral THA were included. Data were retrospectively analyzed from computer navigation data and radiographs. Analysis concentrated on the discrepancy in leg length (LLD) and hip offset (OSD) between the affected and unaffected hip. The effect of the procedure was defined as the difference between postoperative and preoperative LLD and OSD values in each group. 2332 patients were analyzed. Both nTHA and cTHA were effective in restoring LLD and OSD by reducing the preoperative value significantly (p < 0.001). Regarding changes in LLD, no statistical difference between nTHA and cTHA could be found. Changes in OSD nTHA was a slightly more effective than cTHA (- 2.06 ± 6.00 mm vs. - 1.50 ± 5.35 mm; p < 0.05). Both navigated and conventional THA were successful in reconstruction of leg length and hip offset, while postoperative offset discrepancy was significantly lower in the navigated group at the cost of longer operation times. If these results are clinically relevant further investigation is needed., (© 2023. Springer Nature Limited.)

Vertebral bone is subject to a distinct set of disease processes from long bones, including a much higher rate of solid tumour metastases 1-4 . The basis for this distinct biology of vertebral bone has so far remained unknown. Here we identify a vertebral skeletal stem cell (vSSC) that co-expresses ZIC1 and PAX1 together with additional cell surface markers. vSSCs display formal evidence of stemness, including self-renewal, label retention and sitting at the apex of their differentiation hierarchy. vSSCs are physiologic mediators of vertebral bone formation, as genetic blockade of the ability of vSSCs to generate osteoblasts results in defects in the vertebral neural arch and body. Human counterparts of vSSCs can be identified in vertebral endplate specimens and display a conserved differentiation hierarchy and stemness features. Multiple lines of evidence indicate that vSSCs contribute to the high rates of vertebral metastatic tropism observed in breast cancer, owing in part to increased secretion of the novel metastatic trophic factor MFGE8. Together, our results indicate that vSSCs are distinct from other skeletal stem cells and mediate the unique physiology and pathology of vertebrae, including contributing to the high rate of vertebral metastasis., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Acetabular bone loss is a challenging clinical problem when performing revision total hip arthroplasty (rTHA). This study aimed to evaluate how acetabular bone loss severity influences (1) clinical outcomes and (2) patient-reported outcome measures (PROMs) in rTHA patients., Methods: Patients who underwent rTHA with acetabular component revision from January 2016 to February 2022 were included. Treating surgeons determined Paprosky acetabular bone loss classification intraoperatively. Patients were grouped based on numeric classification (PI, PII, or PIII) to categorize severity. Hip disability and Osteoarthritis Outcome Score for Joint Replacement (HOOS, JR.) and Lower Extremity Activity Scale (LEAS) score were collected preoperatively and 1 year postoperatively. There were 197 patients included. Paprosky classification was PI for 47 patients (23.9%), PII for 113 patients (57.4%), and PIII for 37 patients (18.8%). Mean clinical follow-up was 29 months (range, 1 to 69)., Results: Reoperation rate was 0% (0 patients), 6.2% (7 patients), and 10.8% (4 patients) for PI, PII and PIII groups respectively (P = .052). Mean preoperative HOOS, JR. and LEAS for PI, PII and PIII groups were significantly different, but 1-year postoperative HOOS, JR. and LEAS did not differ significantly. Rates of HOOS, JR. minimal clinically important difference achievement differed significantly between bone loss groups., Conclusion: In this study of rTHA patients, greater acetabular bone loss severity was associated with worse preoperative PROMs and trended toward higher reoperation rate. Postoperative PROMs for bone loss severity groups were statistically similar. Patients who had worse acetabular bone loss were more likely to achieve HOOS, JR. minimal clinically important difference postoperatively., Level of Evidence: III., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Parathyroid hormone (PTH) is an anabolic osteoporosis treatment that increases bone mass and reduces fracture risk. Clinically, the effects of PTH are site-specific, increasing bone mass more at the spine than the hip and not increasing bone mass at the radius. Differences in local loading environment between the spine, hip, and radius may help explain the variation in efficacy, as PTH and mechanical loading have been shown to synergistically increase bone mass. We hypothesized that differences in loading mode might further explain these variations. Owing to the curvature of the mouse tibia, cyclic compression of the hindlimb causes bending at the tibial midshaft, placing the anterior surface under tension and the posterior surface under compression. We investigated the combination of PTH treatment and tibial loading in an osteoblast-specific estrogen receptor-alpha knockout mouse model of low bone mass (pOC-ERαKO) and their littermate controls (LCs) and analyzed bone morphology in the tensile, compressive, and neutral regions of the tibial midshaft. We also hypothesized that pretreating wild-type C57Bl/6J (WT) mice with PTH prior to mechanical loading would enhance the synergistic anabolic effects. Compression was more anabolic than tension, and PTH enhanced the effect of loading, particularly under compression. PTH pretreatment maintained the synergistic anabolic effect for longer durations than concurrent treatment and loading alone. Together these data provide insights into more effective physical therapy and exercise regimens for patients receiving PTH treatment. © 2022 American Society for Bone and Mineral Research (ASBMR)., (© 2022 American Society for Bone and Mineral Research (ASBMR).)

Background: Known risk factors for early periprosthetic femur fracture (PFF) following total hip arthroplasty (THA) include poor bone quality and the use of cementless implants. The association between femoral component size and alignment and the risk of early PFF is not well described. We evaluated radiographic parameters of femoral component sizing and alignment as risk factors for early PFF., Methods: From 16,065 primary cementless THAs, we identified 66 cases (0.41%) of early PFFs (<90 days from index THA) at a single institution between 2016 and 2020. Sixty early PFFs were (1:2) matched to 120 controls based on the femoral component model, offset, surgical approach, age, body mass index (BMI), and gender. Radiographic assessment of preoperative bone morphology and postoperative femoral component orientation included stem alignment, metaphyseal fill, and implant congruence with medial cortical bone. A multivariable logistic regression was built to identify radiographic risk factors associated with early PFF., Results: Markers of preoperative bone quality including canal calcar ratio (P = .003), canal flare index (P < .001), anteroposterior canal bone ratio (CBR) (P < .001), and lateral CBR (P < .001) were statistically associated with PFF. Distance between the medial cortical bone and implant was greater in cases of PFF (2.5 mm vs 1.4 mm) (P < .001). A multivariate analysis demonstrated that a larger lateral metaphyseal CBR (Odds Ratio [OR] 5), valgus implant alignment (OR 5), and medial implant-bone incongruity (OR 2) increased the risk of early PFF., Conclusion: A larger lateral metaphyseal CBR, valgus component alignment, and implant incongruity with medial cortical bone posed the greatest radiographic risk for early PFF following cementless THA., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: To develop an early implant instability murine model and explore the use of intermittent parathyroid hormone (iPTH) treatment for initially unstable implants., Methods: 3D-printed titanium implants were inserted into an oversized drill-hole in the tibiae of C57Bl/6 mice (n = 54). After implantation, the mice were randomly divided into three treatment groups (phosphate buffered saline (PBS)-control, iPTH, and delayed iPTH). Radiological analysis, micro-CT (µCT), and biomechanical pull-out testing were performed to assess implant loosening, bone formation, and osseointegration. Peri-implant tissue formation and cellular composition were evaluated by histology., Results: iPTH reduced radiological signs of loosening and led to an increase in peri-implant bone formation over the course of four weeks (timepoints: one week, two weeks, and four weeks). Observational histological analysis shows that iPTH prohibits the progression of fibrosis. Delaying iPTH treatment until after onset of peri-implant fibrosis still resulted in enhanced osseointegration and implant stability. Despite initial instability, iPTH increased the mean pull-out strength of the implant from 8.41 N (SD 8.15) in the PBS-control group to 21.49 N (SD 10.45) and 23.68 N (SD 8.99) in the immediate and delayed iPTH groups, respectively. Immediate and delayed iPTH increased mean peri-implant bone volume fraction (BV/TV) to 0.46 (SD 0.07) and 0.34 (SD 0.10), respectively, compared to PBS-control mean BV/TV of 0.23 (SD 0.03) (PBS-control vs immediate iPTH, p < 0.001; PBS-control vs delayed iPTH, p = 0.048; immediate iPTH vs delayed iPTH, p = 0.111)., Conclusion: iPTH treatment mediated successful osseointegration and increased bone mechanical strength, despite initial implant instability. Clinically, this suggests that initially unstable implants may be osseointegrated with iPTH treatment. Cite this article: Bone Joint Res  2022;11(5):260-269.

Purpose: We have previously shown that a brief course of teriparatide (TPTD) stimulates bone formation in the cancellous and endocortical envelopes of the human femoral neck, and the regions of tension and compression respond differently. The purpose of the present study was to determine how much of the new bone was formed by modeling-based formation (MBF) or remodeling-based formation (RBF)., Methods: We performed a double-blind trial of TPTD vs. placebo (PBO) in patients about to undergo a total hip replacement (THR) for osteoarthritis. Participants were randomized to receive daily TPTD 20 μg or PBO for an average of 6.1 weeks (range 4.1-11.8 weeks) prior to THR. After an average of 3 weeks of study drug, double tetracycline labels were administered per standard protocol. During the THR an intact sample of the mid-femoral neck (FN) was procured; this was fixed, embedded, and sectioned transversely. Histomorphometric analysis was performed in the cancellous, endocortical, and periosteal envelopes. Additionally, separate analyses were performed in the tensile and compressive regions of the endocortical and periosteal envelopes. Sites of new bone formation were identified by the presence of tetracycline labels and designated as MBF if the underlying cement line was smooth and as RBF if it was scalloped. New bone formation on smooth cement lines adjacent to scalloped reversal lines was designated as overflow RBF (oRBF). The referent for all indices was bone surface (BS)., Results: In the cancellous and endocortical envelopes, the proportion of mineralizing surface engaged in RBF and oRBF was higher in the TPTD-treated than the PBO-treated subjects. There was also a trend toward higher MBF in TPTD vs. PBO in both envelopes. In linear mixed-effects models, TPTD was predicted to increase formation differently on the tensile and compressive surfaces depending on patient-specific anatomy, including body weight, FN angle, offset, and cortical width and porosity. Eroded surface was not different between groups in either envelope and no significant differences were observed in any parameter in the periosteal envelope., Conclusion: We conclude that the predominant early effect of TPTD in the human femoral neck is to stimulate RBF and oRBF with a trend toward an increase in MBF in the endocortical and cancellous envelopes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: The Orthopaedic In-Training Examination (OITE), produced by the American Academy of Orthopaedic Surgeons (AAOS), plays an important role in the educational mission of orthopaedic residency programs nationwide. An up-to-date understanding of this examination is critical for programs to develop an appropriate curriculum and for individuals to identify learning resources. This study presents an updated analysis of the basic science section of the OITE from 2014 to 2019., Methods: All questions from the OITE from 2014 to 2019 were reviewed. Each question from the basic science section was categorized by topic and taxonomy. The use of radiographic images or other clinical media was recorded. The reference section was analyzed for bibliometric factors. Pearson chi-square tests were used as appropriate for statistical comparison., Results: In total, 185 of 1,600 questions in the basic science section were used over the 6-year study period (11.6%). The proportion of basic science questions ranged from 10.7% to 12.0% from year to year. The most frequently tested topics were cellular and molecular biology (23.8%), physiology/pathophysiology (16.8%), and pharmacology (10.8%). There was an increase in the number of biostatistics questions from 2017 to 2019 compared with the number from 2014 to 2016 (P = 0.02). The most common taxonomic category was knowledge recall (89.7%). A total of 383 references were cited from 122 sources. The 3 most common sources accounting for 44.4% of all citations were produced by the AAOS., Discussion: The basic science section of the OITE accounts for approximately 11% of all questions, with the most common taxonomy being knowledge recall (89.7%). Recent tests have emphasized biostatistics, highlighting the importance of incorporating biostatistics into residency education. Reference materials produced by the AAOS were highly cited in this section., (Copyright © 2021 by the American Academy of Orthopaedic Surgeons.)

Anti-RANKL (receptor activator of nuclear factor kappa-B ligand) agents function by blocking the differentiation of osteoclasts, thereby proving useful in the clinical management of postmenopausal osteoporosis. The effects of such agents on osseointegration is less well understood. The purpose of the current study was to investigate whether osteoprotegerin (OPG), an osteoclast inhibitor, enhances the known anabolic effects of mechanical loading (VEH) and intermittent PTH (iPTH) using a well-established rabbit model of osseointegration. In the first set of experiments, OPG was administered either alone or combined with iPTH to study its effects on measured bone mass. The second set of experiments was conducted using a higher dosage of OPG (10 mg/kg) to explore its early impact at the cellular and molecular levels. All subjects had mechanical load applied to the implant on one extremity, and no load applied on the contralateral side. In the first set of experiments, OPG alone decreased peri-implant bone mass compared to the mechanical loading group, whereas OPG + iPTH increased peri-implant bone mass compared to the OPG group. In the second set of experiments, high-dose OPG significantly decreased osteoclast number (-74.3%) at 1 week. However, this effect was not sustained as osteoclast number returned to baseline by 2 weeks. These results suggest that systemic administration of OPG does not enhance osseointegration, but rather has a detrimental effect., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Introduction : Current methods of managing osteomyelitic voids after debridement are inadequate and result in significant morbidity to patients. Synthetic ceramic void fillers are appropriate for non-infected bone defects but serve as a nidus of re-infection in osteomyelitis after debridement. CERAMENT G (CG) is an injectable ceramic bone void filler which contains gentamicin and is currently being evaluated for use in osteomyelitic environments after debridement due to its theoretical ability to serve as a scaffold for healing while eliminating residual bacteria after debridement through the elution of antibiotics. The goal of this study was to evaluate (1) the rate of persistent infection and (2) new bone growth of a debrided osteomyelitic defect in a rat model which has been treated with either gentamicin-impregnated ceramic cement (CERAMENT G) or the same void filler without antibiotics (CERAMENT, CBVF). Methods : Osteomyelitis was generated in the proximal tibia of Sprague Dawley rats, subsequently debrided, and the defect filled with either (1) CG ( n = 20 ), (2) CBVF ( n = 20 ), or (3) nothing ( n = 20 ). Each group was euthanized after 6 weeks. Infection was detected through bacterial culture and histology. Bone growth was quantified using microCT. Results : Infection was not detected in defects treated with CG as compared with 35 % of defects ( 7 / 20 ) treated with CBVF and 50 % ( 10 / 20 ) of empty defects ( p = 0.001 ). Bone volume in the defect of CG-treated rats was greater than the CBVF (0.21 vs. 0.17, p = 0.021 ) and empty groups (0.21 vs. 0.11, p < 0.001 ) at 6 weeks after implantation. Conclusions : Ceramic void filler with gentamicin (CERAMENT G) decreased the rate of persistent infection and increased new bone growth as compared to the same void filler without antibiotics (CERAMENT) and an empty defect in a rat model of debrided osteomyelitis., Competing Interests: Aleksey Dvorzhinskiy and Mathias P. G. Bostrom have received research funding from BONESUPPORT AB, the manufacturers of CERAMENT and CERAMENT G, directly related to this study. The institution of the authors (Hospital for Special Surgery) has received funding from BONESUPPORT AB directly related to this study., (Copyright: © 2021 Aleksey Dvorzhinskiy et al.)

Aims: Due to the opioid epidemic in the USA, our service progressively decreased the number of opioid tablets prescribed at discharge after primary hip (THA) and knee (TKA) arthroplasty. The goal of this study was to analyze the effect on total morphine milligram equivalents (MMEs) prescribed and post-discharge opioid repeat prescriptions., Methods: We retrospectively reviewed 19,428 patients undergoing a primary THA or TKA between 1 February 2016 and 31 December 2019. Two reductions in the number of opioid tablets prescribed at discharge were implemented over this time; as such, we analyzed three periods (P1, P2, and P3) with different routine discharge MME (750, 520, and 320 MMEs, respectively). We investigated 90-day refill rates, refill MMEs, and whether discharge MMEs were associated with represcribing in a multivariate model., Results: A discharge prescription of < 400 MMEs was not a risk factor for opioid represcribing in the entire population (p = 0.772) or in opioid-naïve patients alone (p = 0.272). Procedure type was the most significant risk factor for narcotic represcribing, with unilateral TKA (hazard ratio (HR) = 5.62), bilateral TKA (HR = 6.32), and bilateral unicompartmental knee arthroplasty (UKA) (HR = 5.29) (all p < 0.001) being the highest risk for refills. For these three procedures, there was approximately a 5% to 6% increase in refills from P1 to P3 (p < 0.001); however, there was no significant increase in refill rates after any hip arthroplasty procedures. Total MMEs prescribed were significantly reduced from P1 to P3 (p < 0.001), leading to the equivalent of nearly 500,000 fewer oxycodone 5 mg tablets prescribed., Conclusion: Decreasing opioids prescribed at discharge led to a statistically significant reduction in total MMEs prescribed. While the represcribing rate did not increase for any hip arthroplasty procedure, the overall refill rates increased by about 5% for most knee arthroplasty procedures. As such, we are now probably prescribing an appropriate amount of opioids at discharge for knee arthroplasty procedure, but further reductions may be possible for hip arthroplasty procedures. Cite this article: Bone Joint J  2021;103-B(7 Supple B):103-110.

Aims: Aseptic loosening is a leading cause of uncemented arthroplasty failure, often accompanied by fibrotic tissue at the bone-implant interface. A biological target, neutrophil extracellular traps (NETs), was investigated as a crucial connection between the innate immune system's response to injury, fibrotic tissue development, and proper bone healing. Prevalence of NETs in peri-implant fibrotic tissue from aseptic loosening patients was assessed. A murine model of osseointegration failure was used to test the hypothesis that inhibition (through Pad4 -/- mice that display defects in peptidyl arginine deiminase 4 (PAD4), an essential protein required for NETs) or resolution (via DNase 1 treatment, an enzyme that degrades the cytotoxic DNA matrix) of NETs can prevent osseointegration failure and formation of peri-implant fibrotic tissue., Methods: Patient peri-implant fibrotic tissue was analyzed for NETs biomarkers. To enhance osseointegration in loose implant conditions, an innate immune system pathway (NETs) was either inhibited ( Pad4 -/- mice) or resolved with a pharmacological agent (DNase 1) in a murine model of osseointegration failure., Results: NETs biomarkers were identified in peri-implant fibrotic tissue collected from aseptic loosening patients and at the bone-implant interface in a murine model of osseointegration failure. Inhibition ( Pad4 -/- ) or resolution (DNase 1) of NETs improved osseointegration and reduced fibrotic tissue despite loose implant conditions in mice., Conclusion: This study identifies a biological target (NETs) for potential noninvasive treatments of aseptic loosening by discovering a novel connection between the innate immune system and post-injury bone remodelling caused by implant loosening. By inhibiting or resolving NETs in an osseointegration failure murine model, fibrotic tissue encapsulation around an implant is reduced and osseointegration is enhanced, despite loose implant conditions. Cite this article: Bone Joint J  2021;103-B(7 Supple B):135-144.

Background: A diverse array of antibacterial solutions is utilized by orthopedic surgeons in an attempt to disperse bacterial biofilm. Few studies compare these agents against biofilm grown on clinically relevant orthopedic biomaterials, such as plastic, acrylic cement, and porous titanium., Methods: MSSA biofilm was grown on plastic 48-well plates, polymethylmethacrylate cement beads and porous Ti-6Al-4V acetabular screw caps. Antibacterial solutions were tested according to manufacturer guidance and included: isotonic saline, vancomycin (1 mg/mL), polymyxin-bacitracin (500,000 U/L-50,000 U/L), povidone-iodine 0.3%, povidone-iodine 10%, a 1:1 combination of povidone-iodine 10% & 4% hydrogen peroxide, polyhexamethylene biguanide (PHMB) and betaine 0.04%, a commercial solution containing chlorhexidine gluconate (CHG) 0.05%, and a commercial solution containing benzalkonium chloride and ethanol. Twenty four and 72-hour biofilms were exposed to solutions for 3 minutes to reproduce intraoperative conditions. Solution efficacy was measured through sonication of treated surfaces followed by counting colony forming units and validated with a resazurin assay to assess cell viability. Experiments were performed in triplicate and repeated at least once. A three-fold log reduction in CFU counts versus controls was considered as a measure of solution efficacy., Results: Saline, vancomycin and polymyxin-bacitracin were ineffective compared to other solutions against planktonic MSSA. Povidone-iodine 10% and a 1:1 solution of povidone-iodine 10% and 4% hydrogen peroxide were the only effective solutions against biofilm across all three surfaces and time points., Conclusion: Commercial antibacterial solutions vary significantly in their efficacy against MSSA biofilm. Efficacy globally decreased as biofilm maturity increased. Increased solution cost did not confer increased efficacy., (Copyright © 2021. Published by Elsevier Inc.)

The US orthopaedic graduate medical education system is based on long established methods in education, but academic leaders at orthopaedic institutions now have the ability to use electronic learning innovations. Hospital for Special Surgery gathered graduate medical education leaders from orthopaedic training programs around the country and an electronic learning expert to review current orthopaedic residency and fellowship program practices. This group came to consensus with the following points: (1) current training methods do not take full advantage of available technology/innovations, (2) trainees inappropriately use electronic resources in the absence of or in an underdeveloped formal electronic training program, (3) trainees learn at different rates and in different ways requiring individualized plans for optimal content engagement, and (4) formal electronic learning programs better use time dedicated to educating trainees than informal programs. Orthopaedic graduate medical training programs that adopt these points can establish an electronic learning program to complement their traditional education program by (1) guaranteeing online content is standardized and approved, (2) reducing time spent covering standard lecture material and increasing time spent reviewing cases, and (3) engaging students of all learning backgrounds with content in both asynchronous and synchronous formats., (Copyright © 2021 by the American Academy of Orthopaedic Surgeons.)

Background: It is vital for orthopedic residents and residency programs to have a current understanding of the materials and resources utilized on the Orthopedic In-Training Examination (OITE) to tailor resident educational curricula accordingly. This study presents an updated analysis of the hip and knee section of the OITE., Methods: All OITE questions related to hip and knee reconstruction over six examinations between 2014 and 2019 were analyzed for topic, subtopic, taxonomy, imaging modalities, resident performance, and references., Results: There were 166 hip and knee reconstruction questions of 1600 OITE questions (10.4%) over a six-year period. The most commonly tested topics include mechanical properties of total knee and hip implants (10.8%), instability after THA (10.8%), periprosthetic fracture (10.2%), and prosthetic joint infection (10.2%). A total of 362 references were cited from 68 different sources. The most common sources were JOA, JBJS, JAAOS, and CORR, which were collectively responsible for 68% of all citations. There was an average publication lag of 7.1 years, with 75% of all citations falling within 10 years of the question date. Compared with a prior analysis from 2005 and 2009, there were significantly more complex multistep questions regarding treatment and fewer one-step knowledge recall questions (P = .003). Similarly, recent tests had significantly more questions involving interpretation of radiographs (55%, P < .001) and advanced imaging (9.6%, P < .001), compared with a decade ago., Conclusions: The OITE continues to evolve over time, incorporating recent literature and topics. The current analysis identifies high-yield topics and resources that can guide resident preparation for the OITE hip and knee section., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Skeletal dysplasias are a heterogeneous group of >400 genetic disorders characterized by abnormal bone growth. Many individuals experience joint pain and limitation, coming to require joint replacement much earlier than the average-statured population. In addition, prosthesis survival rate is less in the dysplastic population. The purpose of this study is to identify risk factors for surgery and provide recommendations to improve surgical outcomes., Methods: This a retrospective review of 29 individuals with a skeletal dysplasia who had 64 joint replacements between April 1985 and January 2019 at a single institution. We collected demographics, physical examination, medical history, imaging studies, surgical indication, and complications., Results: Spondyloepiphyseal dysplasia was the most common skeletal dysplasia (7), followed by pseudoachondroplasia (4) and multiple epiphyseal dysplasia (4). Average age of the cohort was 40.6 years (range 14-64). Hip arthroplasty (34) was the most commonly performed surgery. The majority of arthroplasties (75%) required custom components. Complication rate was 37.3%, most commonly pulmonary embolism (3) and pneumonia (3). Most complications (81.8%) occurred in individuals with either a pre-existing cardiopulmonary comorbidity or lumbar/sacral deformity. Body mass index did not correlate with complication severity (R = -0.042, P = .752) or rate (R = 0.006, P = .963)., Conclusion: Surgical complications are highest in patients with pre-existing cardiopulmonary conditions. Body mass index does not predict complications in this cohort. Preoperative evaluations for individuals with skeletal dysplasias should include comprehensive work-up of spine issues and extraskeletal systems that present an operative risk. Intraoperative protocol should include special consideration for placement on the table, airway maintenance, and spinal cord monitoring in select cases., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Teriparatide (TPTD) reduces risk of both vertebral and nonvertebral fracture, but increases bone mineral density (BMD) much more at the spine than the hip. TPTD and mechanical loading may have a synergistic anabolic effect on BMD, which may help explain these site-specific differences. Under normal daily activity, the femoral neck (FN) is under bending, placing one side under tension and the other under compression. We sought to further understand the relationship between mechanical loading and TPTD at the hip by investigating the effect of tensile versus compressive loading on TPTD stimulated bone formation indices in the human FN. Thirty-eight patients receiving total hip replacements for osteoarthritis were randomized to receive placebo (PBO) or TPTD for a mean treatment duration of 6 weeks prior to surgery, and double tetracycline labeling was administered to allow assessment of bone formation. The FN was harvested during surgery and analyzed for dynamic bone formation indices in the compressive and tensile regions of the endocortical and periosteal envelopes. Regression models relating outcome measures to patient characteristics including sex, age, body weight, and FN geometry were also analyzed. Overall, bone formation was higher with TPTD versus placebo on the endocortical surface, but not the periosteal surface. The level of bone formation in both TPTD and placebo groups was greater on the tensile endocortical surface and the compressive periosteal surface. There was a trend toward decreased endocortical eroded surface with TPTD in the compressive but not the tensile region. Patient age and sex explained the greatest variability in endocortical bone formation, and patient body mass and sex explained the greatest variability in periosteal bone formation. Our data represent the first dynamic comparison of teriparatide treatment under two loading modalities in human FN samples. Future work could determine whether specific hip loading intervention could amplify the benefits of teriparatide on the hip in clinical settings., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Periprosthetic joint infection (PJI) is one of the most devastating complications of total joint arthroplasty. Given the mortality and morbidity associated with PJI and the challenges in treating it, there has been increased interest in risk factors that can be modified before surgery. In this study, we used a novel mouse model to consider the role of the gut microbiome as a risk factor for PJI., Questions/purposes: (1) Does the state of the gut microbiota before surgery influence the likelihood of developing an established infection in a mouse model of PJI? (2) How does the state of the gut microbiota before surgery influence the local and systemic response to the presence of an established infection in a mouse model of PJI?, Methods: Male C57Bl/6 mice were divided into two groups: those with modified microbiome [INCREMENT]microbiome (n = 40) and untreated mice (n = 42). In [INCREMENT]microbiome mice, the gut flora were modified using oral neomycin and ampicillin from 4 weeks to 16 weeks of age. Mice received a titanium tibial implant to mimic a joint implant and a local inoculation of Staphylococcus aureus in the synovial space (10 colony forming units [CFUs]). The proportion of animals developing an established infection in each group was determined by CFU count. The local and systemic response to established infection was determined using CFU counts in surrounding joint tissues, analysis of gait, radiographs, body weight, serum markers of inflammation, and immune cell profiles and was compared with animals that received the inoculation but resisted infection., Results: A greater proportion of animals with disrupted gut microbiota had infection (29 of 40 [73%]) than did untreated animals (21 of 42 [50%]; odds ratio, 2.63, 95% CI, 1.04-6.61; p = 0.035). The immune response to established infection in mice with altered microbiota was muted; serum amyloid A, a marker of systemic infection in mice, was greater than in mice with disrupted gut microbiota with infection (689 µg/dL; range, 68-2437 µg/dL, p < 0.05); infection associated increases in monocytes and neutrophils in the spleen and local lymph node in untreated mice but not were not observed in mice with disrupted gut microbiota., Conclusions: The findings from this in vivo mouse model suggest that the gut microbiota may influence susceptibility to PJI., Clinical Relevance: These preclinical findings support the idea that the state of the gut microbiome before surgery may influence the development of PJI and justify further preclinical and clinical studies to develop appropriate microbiome-based interventions.

Background: Peri-prosthetic bone loss can result from chemical, biological, and mechanical factors. Mechanical stimulation via fluid pressure and flow at the bone-implant interface may be a significant cause. Evidence supporting mechanically induced osteolysis continues to grow, but there is no synthesis of published clinical and basic science data., Questions/purposes: We sought to review the literature on two questions: (1) What published evidence supports the concept of mechanically induced osteolysis? (2) What is the proposed mechanism of mechanically induced osteolysis, and does it differ from that of particle-induced osteolysis?, Methods: A systematic review was performed of the PubMed and Web of Science databases. Additional relevant articles were recommended by the senior authors based on their expert opinion. Abstracts were reviewed and the manuscripts pertaining to the study questions were read in full. Studies showing support of mechanically induced osteolysis were quantified and findings summarized., Results: We identified 49 articles of experimental design supporting the hypothesis that mechanical stimulation of peri-prosthetic bone from fluid pressure and flow can induce osteolysis. While the molecular mechanisms may overlap with those implicated in particle-induced osteolysis, mechanically induced osteolysis appears to be mediated by distinct and parallel pathways., Conclusions: The role of mechanical stimuli is increasingly recognized in the pathogenesis of peri-prosthetic osteolysis. Current research aims to elucidate the molecular mechanisms to better target therapeutic interventions., Competing Interests: Conflict of InterestRyan Scully, MD, F. Patrick Ross, PhD, and Anna Falghren, PhD, declare that they have no conflicts of interest. Benjamin A McArthur, MD, reports grants from Orthopedic Research and Education Foundation, during the conduct of the study. Mathias P.G. Bostrom, MD, reports being a paid consultant for Smith & Nephew, outside the submitted work., (© Hospital for Special Surgery 2018.)

Objective: Local antibiotic delivery systems with differing chemical and mechanical properties have been developed to assist in the management of osteomyelitis. We investigated the bone conductive and resorptive capabilities of a calcium phosphate-calcium sulfate (CaP/CaS) composite compared with commercially available polymethylmethacrylate (PMMA). In addition, we compared the in vivo preventative and treatment efficacies of both biomaterials in a proven osteomyelitis model., Methods: Sixty-four, male Sprague-Dawley rats were inoculated with 10 μl of 1.5 x 108 CFU/ml of Staphylococcus aureus in a surgically drilled defect in the right proximal tibia. Infected animals were randomly allocated into prevention and treatment groups with 32 rats each. In the prevention group, the defect was filled with a plug containing either PMMA or CaP/CaS immediately after the inoculation. In the treatment group, the infected defects were irrigated, debrided, and filled with either a PMMA or CaP/CaS plug. Both CaP/CaS and PMMA were impregnated with 10% weight of vancomycin. Rats were sacrificed 6 weeks after cement insertion. Infection was detected by bacterial culture and histological analysis. Bone formation in the defect was assessed with micro-computed tomography and histology., Results: No bacteria were detected in any group. Both the prevention and treatment groups using CaP/CaS had significantly more bone volume fraction, bone area, and cartilage area than the PMMA groups., Conclusions: When loaded with 10% of vancomycin, CaP/CaS and PMMA have the same efficacy for treatment and prevention of osteomyelitis. CaP/CaS enhances bone defect healing through improved bone remodeling in our osteomyelitis rat model., Competing Interests: The authors disclose receiving materials from BoneSupport, but no financial support. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Aims: It is increasingly appreciated that coordinated regulation of angiogenesis and osteogenesis is needed for bone formation. How this regulation is achieved during peri-implant bone healing, such as osseointegration, is largely unclear. This study examined the relationship between angiogenesis and osteogenesis in a unique model of osseointegration of a mouse tibial implant by pharmacologically blocking the vascular endothelial growth factor (VEGF) pathway., Materials and Methods: An implant was inserted into the right tibia of 16-week-old female C57BL/6 mice (n = 38). Mice received anti-VEGF receptor-1 (VEGFR-1) antibody (25 mg/kg) and VEGF receptor-2 (VEGFR-2) antibody (25 mg/kg; n = 19) or an isotype control antibody (n = 19). Flow cytometric (n = 4/group) and immunofluorescent (n = 3/group) analyses were performed at two weeks post-implantation to detect the distribution and density of CD31 hi EMCN hi endothelium. RNA sequencing analysis was performed using sorted CD31 hi EMCN hi endothelial cells (n = 2/group). Osteoblast lineage cells expressing osterix (OSX) and osteopontin (OPN) were also detected with immunofluorescence. Mechanical pull-out testing (n = 12/group) was used at four weeks post-implantation to determine the strength of the bone-implant interface. After pull-out testing, the tissue attached to the implant surface was harvested. Whole mount immunofluorescent staining of OSX and OPN was performed to determine the amount of osteoblast lineage cells., Results: Flow cytometry revealed that anti-VEGFR treatment decreased CD31 hi EMCN hi vascular endothelium in the peri-implant bone versus controls at two weeks post-implantation. This was confirmed by the decrease of CD31 and endomucin (EMCN) double-positive cells detected with immunofluorescence. In addition, treated mice had more OPN-positive cells in both peri-implant bone and tissue on the implant surface at two weeks and four weeks, respectively. More OSX-positive cells were present in peri-implant bone at two weeks. More importantly, anti-VEGFR treatment decreased the maximum load of pull-out testing compared with the control., Conclusion: VEGF pathway controls the coupling of angiogenesis and osteogenesis in orthopaedic implant osseointegration by affecting the formation of CD31 hi EMCN hi endothelium. Cite this article: Bone Joint J 2019;101-B(7 Supple C):108-114.

Aims: Custom flange acetabular components (CFACs) are a patient-specific option for addressing large acetabular defects at revision total hip arthroplasty (THA), but patient and implant characteristics that affect survivorship remain unknown. This study aimed to identify patient and design factors related to survivorship., Patients and Methods: A retrospective review of 91 patients who underwent revision THA using 96 CFACs was undertaken, comparing features between radiologically failed and successful cases. Patient characteristics (demographic, clinical, and radiological) and implant features (design characteristics and intraoperative features) were collected. There were 74 women and 22 men; their mean age was 62 years (31 to 85). The mean follow-up was 24.9 months (sd 27.6; 0 to 116). Two sets of statistical analyses were performed: 1) univariate analyses (Pearson's chi-squared and independent-samples Student's t -tests) for each feature; and 2) bivariable logistic regressions using features identified from a random forest analysis., Results: Radiological failure and revision rates were 23% and 12.5%, respectively. Revisions were undertaken at a mean of 25.1 months (sd 26.4) postoperatively. Patients with radiological failure were younger at the time of the initial procedure, were less likely to have a diagnosis of primary osteoarthritis (OA), were more likely to have had ischial screws in previous surgery, had fewer ischial screw holes in their CFAC design, and had more proximal ischial fixation. Random forest analysis identified the age of the patient and the number of locking and non-locking screws used for inclusion in subsequent bivariable logistic regression, but only age (odds ratio 0.93 per year) was found to be significant., Conclusion: We identified both patient and design features predictive of CFAC survivorship. We found a higher rate of failure in younger patients, those whose primary diagnosis was not OA, and those with more proximal ischial fixation or fewer ischial fixation options. Cite this article: Bone Joint J 2019;101-B(6 Supple B):68-76.

Aims: The aim of this study was to evaluate fretting and corrosion in retrieved oxidized zirconium (OxZr; OXINIUM, Smith & Nephew, Memphis, Tennessee) femoral heads and compare the results with those from a matched cohort of cobalt-chromium (CoCr) femoral heads., Patients and Methods: A total of 28 OxZr femoral heads were retrieved during revision total hip arthroplasty (THA) and matched to 28 retrieved CoCr heads according to patient demographics. The mean age at index was 56 years (46 to 83) in the OxZr group and 70 years (46 to 92) in the CoCr group. Fretting and corrosion scores of the female taper of the heads were measured according to the modified Goldberg scoring method., Results: The OxZr-retrieved femoral heads showed significantly lower mean corrosion scores than the CoCr heads (1.3 (1 to 2.75) vs 2.1 (1 to 4); p < 0.01). Mean fretting scores were also significantly lower in the OxZr cohort when compared with the CoCr cohort (1.3 (1 to 2) vs 1.5 (1 to 2.25); p = 0.02). OxZr heads had more damage in the proximal region compared with the distal region of the head. Location had no impact on damage of CoCr heads. A trend towards increased corrosion in large heads was seen only in the CoCr heads, although this was not statistically significant., Conclusion: Retrieval analysis of OxZr femoral heads showed a decreased amount of fretting and corrosion compared with CoCr femoral heads. OxZr seems to be effective at reducing taper damage. Cite this article: Bone Joint J 2019;101-B:386-389.

The application of tranexamic acid (TXA) in total joint arthroplasty has dramatically improved peri-operative blood management. In light of these benefits, a study by Huang et al., "Intravenous and Topical Tranexamic Acid Alone Are Superior to Tourniquet Use for Primary Total Knee Arthroplasty," evaluates the need for continued use of the intra-operative tourniquet, which remains a routine practice with documented benefits and adverse effects. This review evaluates the study's design and critically interprets its findings for clinical practice. Through a prospective, randomized trial, Huang et al. demonstrated that among selected patients undergoing primary total knee arthroplasty, the use of a tourniquet results in no reduction in blood loss beyond that provided by TXA alone. Moreover, the use of TXA without a tourniquet led to improved early clinical outcomes such as reduced post-operative swelling, improved knee range of motion at discharge, and enhanced patient satisfaction. As medicine is practiced in an increasingly value-driven environment, this study provides a useful method for evaluating the utility of commonly used interventions. Its findings highlight the need for future investigations into the optimal administration of TXA in total knee arthroplasty., Competing Interests: Christopher M. Brusalis, MD, and Shawn S. Richardson, MD, declare that they have no conflicts of interest. Mathias P.G. Bostrom, MD, reports being a paid consultant for Smith and Nephew, outside the submitted work.N/AN/ADisclosure forms provided by the authors are available with the online version of this article.The submitted manuscript is a review article that does not involve research participants, patient data, or any other information other than a review of published literature. Therefore, no IRB approval was obtained.

Background: Periprosthetic joint infection (PJI) remains a devastating complication following total joint arthroplasty. Current animal models of PJI do not effectively recreate the clinical condition and thus provide limited help in understanding why treatments fail. We developed a mouse model of the first-stage surgery of a 2-stage revision for PJI involving a 3-dimensionally printed Ti-6Al-4V implant and a mouse-sized cement spacer that elutes vancomycin., Methods: Vancomycin was mixed with polymethylmethacrylate (PMMA) cement and inserted into custom-made mouse-sized spacer molds. Twenty C57BL/6 mice received a proximal tibial implant and an intra-articular injection of 3 × 10 colony-forming units of Staphylococcus aureus Xen36. At 2 weeks, 9 mice underwent irrigation and debridement of the leg with revision of the implant to an articulating vancomycin-loaded PMMA spacer. Postoperatively, mice underwent radiography and serum inflammatory-marker measurements. Following euthanasia of the mice at 6 weeks, bone and soft tissues were homogenized to quantify bacteria within periprosthetic tissues. Implants and articulating spacers were either sonicated to quantify adherent bacteria or examined under scanning electron microscopy (SEM) to characterize the biofilm., Results: Vancomycin-loaded PMMA spacers eluted vancomycin for ≤144 hours and retained antimicrobial activity. Control mice had elevated levels of inflammatory markers, radiographic evidence of septic loosening of the implant, and osseous destruction. Mice treated with a vancomycin-loaded PMMA spacer had significantly lower levels of inflammatory markers (p < 0.01), preserved tibial bone, and no intra-articular purulence. Retrieved vancomycin-loaded spacers exhibited significantly lower bacterial counts compared with implants (p < 0.001). However, bacterial counts in periprosthetic tissue did not significantly differ between the groups. SEM identified S. aureus encased within biofilm on control implants, while vancomycin-loaded spacers contained no bacteria., Conclusions: This animal model is a clinically representative model of PJI treatment. The results suggest that the antimicrobial effects of PMMA spacers are tightly confined to the articular space and must be utilized in conjunction with thorough tissue debridement and systemic antibiotics., Clinical Relevance: These data provide what we believe to be the first insight into the effect of antibiotic-loaded cement spacers in a clinically relevant animal model and justify the adjunctive use of intravenous antibiotics when performing a 2-stage revision for PJI.

Background: Antibiotic use in polymethylmethacrylate (PMMA) spacers has historically been limited to those which are "heat-stable" and thus retain their antimicrobial properties after exposure to the high temperatures which occur during PMMA curing., Methods: This study examines the requirement of "heat stability" by measuring temperatures of Palacos and Simplex PMMA as they cure inside commercial silicone molds of the distal femur and proximal tibia. Temperature probes attached to thermocouples were placed at various depths inside the molds and temperatures were recorded for 20 minutes after PMMA introduced and a temperature curve for each PMMA product was determined. A "heat-stable" antibiotic, vancomycin, and a "heat-sensitive" antibiotic, ceftazidime, were placed in a programmable thermocycler and exposed to the same profile of PMMA curing temperatures. Antimicrobial activity against Staphylococcus aureus was compared for heat-treated antibiotics vs room temperature controls., Results: Peak PMMA temperatures were significantly higher in tibial (115.2°C) vs femoral (85.1°C; P < .001) spacers. In the hottest spacers, temperatures exceeded 100°C for 3 minutes. Simplex PMMA produced significantly higher temperatures (P < .05) compared with Palacos. Vancomycin bioactivity did not change against S aureus with heat exposure. Ceftazidime bioactivity did not change when exposed to femoral temperature profiles and was reduced only 2-fold with tibial profiles., Conclusion: The curing temperatures of PMMA in knee spacers are not high enough or maintained long enough to significantly affect the antimicrobial efficacy of ceftazidime, a known "heat-sensitive" antibiotic. Future studies should investigate if more "heat-sensitive" antibiotics could be used clinically in PMMA spacers., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to quantify grit, conscientiousness, and self-control in orthopaedic residency applicants and current orthopaedic surgery residents. As part of a continual reassessment of the selection process, this study will help to improve this process by assessing the introduction of these non-cognitive assessments. This is the first study to both evaluate and compare the applicants' scores to those of current residents. This introduction will allow selection of not only the current top performers but those who have the wherewithal (read grit) to sustain their efforts throughout their residency., Design: A cross-sectional study composed of a confidential electronic survey consisting of a 17-item Grit scale, 10-item Self-control scale, and 9-item Conscientiousness scale was completed by medical school applicants and orthopaedic residents., Setting: Department of Orthopaedic Surgery, Hospital for Special Surgery., Participants: Fifty-six (100%) medical student applicants (mean age = 27) were invited to participate in our study following a full day of interviews. Forty-five residents (mean age = 31) were asked and 32 (72%) completed the same surveys 4 months later., Results: There was a significant difference in grit for medical students (M = 4.19, SD = 0.34) and residents (M =3.86, SD = 0.48); t(86) = 3.76, p = 0.000. All grit subscales were also significantly different for medical students versus residents. Medical students (conscientiousness M = 4.60, SD = 0.41; self-control M = 3.51, SD = 0.30) and residents (conscientiousness M = 4.42, SD = 0.53; self-control M = 3.31, SD = 0.73) scored similarly in the conscientiousness t(86) = 1.75, p = 0.084 and self-control scales t(86) = 1.74, p = 0.086. Academic performance indicators such as the USMLE scores and residency ranking were also compared among medical student applicants., Conclusions: The similar and above average levels of conscientiousness and self-control demonstrate the persevering nature of the individual who elects to pursue an orthopaedic residency program. Although the grit levels were different between medical school student and residents, they were above average for both groups, again demonstrating the type of individual willing to pursue an orthopaedic residency program. This study was the first to demonstrate varying degrees of grit for high-performing students versus residents in a competitive program, which seems to suggest that grit can vary over time. Future studies will investigate the validity of these non-cognitive variables in predicting achievement prospectively in a residency program., (Copyright © 2017 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Bone marrow lesions (BMLs) are radiologic abnormalities in magnetic resonance images of subchondral bone that are correlated with osteoarthritis. Little is known about the physiologic processes within a BML, although BMLs are associated with mechanical stress, bone tissue microdamage and increased bone remodeling. Here we establish a rabbit model to study the pathophysiology of BMLs. We hypothesized that in vivo loads that generate microdamage in cancellous bone would also create BMLs and increase bone remodeling. In vivo cyclic loading (0.2-2.0 MPa in compression for 10,000 cycles at 2 Hz) was applied to epiphyseal cancellous bone in the distal femurs of New Zealand white rabbits (n=3, right limb loaded, left limb controls experienced surgery but no loading). Magnetic resonance images were collected using short tau inversion recovery (STIR) and T1 weighted sequences at 1 and 2 weeks after surgery/loading and histological analysis of the BML was performed after euthanasia to examine tissue microdamage and remodeling. Loaded limbs displayed BMLs while control limbs showed only a small BML-like signal caused by surgery. Histological analysis of the BML at 2 weeks after loading showed increased tissue microdamage (p=0.03) and bone resorption (p=0.01) as compared to controls. The model described here displays the hallmarks of load-induced BMLs, supporting the use of the model to examine changes in bone during the development, progression and treatment of BMLs., (Copyright © 2017 Elsevier Ltd. All rights reserved.)