The Infected Polypropylene Mesh: When Does Biofilm Form and Which Antiseptic Solution Most Effectively Removes It?

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 (PJI). 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 (SEM) to identify maturity. Immature (24 hour) and mature (72 hour) biofilm was treated with one of five commercial antiseptics for three 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 three-log reduction in colony-forming units (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 SEM 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 < 0.0083) reduced CFU counts against mature biofilms. CONCLUSION: 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.

Effects of Abaloparatide on Bone Mineral Density in Proximal Femoral Regions Corresponding to Arthroplasty Gruen Zones: A Study of Postmenopausal Women with Osteoporosis.

BACKGROUND: Low hip bone mineral density (BMD) in patients who undergo total hip arthroplasty (THA) increases the risk of periprosthetic fractures, implant instability, and other complications. Recently, emphasis has been placed on bone health optimization: treating low BMD prior to a planned orthopaedic implant procedure in an effort to normalize BMD and reduce the potential risk of future complications. Abaloparatide is a U.S. Food and Drug Administration-approved osteoanabolic agent for men and postmenopausal women with osteoporosis and a candidate drug for bone health optimization that, in addition to benefits at the spine, increases hip BMD and reduces nonvertebral fracture risk. We hypothesized that abaloparatide would improve BMD in proximal femoral regions surrounding a virtual THA stem. METHODS: This post hoc analysis obtained dual x-ray absorptiometry (DXA) hip scans from 500 randomly selected postmenopausal women with osteoporosis from the Phase-3 Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE, NCT01343004) study after 0, 6, and 18 months of abaloparatide (250 patients) or placebo (250 patients). Hip DXA scans underwent 3-dimensional (3D) modeling via 3D-Shaper, followed by virtual resection of the proximal femur and simulated placement of a tapered, flat-wedge hip stem that guided delineation of the Gruen zones that were fully (zones 1 and 7) or largely (zones 2 and 6) captured in the scanning region. Integral, cortical, and trabecular volumetric BMD, cortical thickness, and cortical surface BMD (the product of cortical volumetric BMD and cortical thickness) were determined for each zone. RESULTS: Compared with placebo, the abaloparatide group showed greater increases in integral volumetric BMD in all zones at months 6 and 18; cortical surface BMD in zones 1, 6, and 7 at month 6; cortical thickness, cortical volumetric BMD, and cortical surface BMD in all zones at month 18; and trabecular volumetric BMD in zones 1 and 7 at months 6 and 18. CONCLUSIONS: Abaloparatide increases BMD in proximal femoral regions that interact with and support femoral stems, suggesting that abaloparatide may have value for preoperative or potentially perioperative bone health optimization in patients with osteoporosis undergoing THA. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Hip joint center lateralization minimally affects the biomechanics of patient-specific flanged acetabular components: A computational model.

Patient-specific flanged acetabular components are utilized to treat failed total hip arthroplasties with large acetabular defects. Previous clinical studies from our institution showed that these implants tend to lateralize the acetabular center of rotation. However, the clinical impact of lateralization on implant survivorship is debated. Our goal was to develop a finite element model to quantify how lateralization of the native hip center affects periprosthetic strain and implant-bone micromotion distributions in a static level gait loading condition. To build the model, we computationally created a superomedial acetabular defect in a computed tomography 3D reconstruction of a native pelvis and designed a flanged acetabular implant to address this simulated bone defect. We modeled two implants, one with ~1 cm and a second with ~2 cm of hip center lateralization. We applied the maximum hip contact force and corresponding abductor force observed during level gait. The resulting strains were compared to bone fatigue strength (0.3% strain) and the micromotions were compared to the threshold for bone ingrowth (20 µm). Overall, the model demonstrated that the additional lateralization only slightly increased the area of bone at risk of failure and decreased the areas compatible with bone ingrowth. This computational study of patient-specific acetabular implants establishes the utility of our modeling approach. Further refinement will yield a model that can explore a multitude of variables and could be used to develop a biomechanically-based acetabular bone loss classification system to guide the development of patient-specific implants in the treatment of large acetabular bone defects.

A Consecutive Series of Vancouver B2 Periprosthetic Femur Fractures Treated With Contemporary Monoblock Versus Modular Revision Stems: Clinical and Radiographic Outcomes.

BACKGROUND: Tapered fluted titanium (TFT) stems are the implant design of choice for managing Vancouver B2 periprosthetic femur fractures (PFFs), producing reliable results over the past few decades. The aim of this study was to compare the radiographic and clinical outcomes of Vancouver B2 PFFs treated with contemporary monoblock versus modular TFTs. METHODS: A consecutive series of 113 patients (72 women, 64%, mean age 70 years [range, 26 to 96]) who had a B2 PFF were treated with either a monoblock (n = 42) or modular (n = 71) TFT stem between 2008 and 2021. The mean body mass index was 30 ± 7. The mean follow-up was 2.9 years. A radiographic review was performed to assess leg length and offset restoration, endosteal cortical contact length, and stem subsidence. Kaplan-Meier analyses were used to determine survivorship without revision, reoperation, or dislocation. RESULTS: There was no difference in the restoration of leg length (0.3 ± 8.0 mm) or offset (2.8 ± 8.2 mm) between the monoblock and modular cohorts (P > .05). Mean endosteal cortical contact length (47.2 ± 26.6 versus 46.7 ± 2 6.4 mm, P = .89) and stem subsidence (2.7 ± 3.5 versus 2.4 ± 3.2 mm, P = .66) did not differ. No difference in patient-reported outcome measures (Hip Disability and Osteoarthritis Outcome Score-Joint Replacement; Veterans RAND 12 Item Health Survey Physical and Mental; visual analog score; and Lower Extremity Activity Scale) between the groups was observed. Survivorship at 2 years free from reoperation, revision, and dislocation was 90.4, 90.3, and 97.6%, respectively, for the monoblock cohort; and 84.0, 86.9, and 90.0%, respectively, for the modular cohort. CONCLUSIONS: No significant differences in radiographic or clinical outcomes were observed between patients treated with monoblock or modular TFTs in this large series of B2 PFFs.

Arthritis Foundation/HSS Workshop on Hip Osteoarthritis, Part 1: Epidemiology, Early Development, and Cohorts From Around the World.

Far more publications are available for osteoarthritis of the knee than of the hip. Recognizing this research gap, the Arthritis Foundation, in partnership with the Hospital for Special Surgery, convened an in-person meeting of thought leaders to review the state of the science of and clinical approaches to hip osteoarthritis. This article summarizes the recommendations and clinical research gaps gleaned from 5 presentations given in the "how hip osteoarthritis begins" session of the 2023 Hip Osteoarthritis Clinical Studies Conference, which took place on February 17 and 18, 2023, in New York City.

Arthritis Foundation/HSS Workshop on Hip Osteoarthritis, Part 4: Nonoperative Options, Machine Learning in Predicting Total Hip Arthroplasty, Robotics, and Phenotyping to Guide Precision Rehabilitation.

Far more publications are available for osteoarthritis of the knee than of the hip. Recognizing this research gap, the Arthritis Foundation (AF), in partnership with the Hospital for Special Surgery (HSS), convened an in-person meeting of thought leaders to review the state of the science of and clinical approaches to hip osteoarthritis. This article summarizes the recommendations gleaned from presentations given in the "late-stage osteoarthritis" session of the 2023 Hip Osteoarthritis Clinical Studies Conference, which took place on February 17 and 18, 2023, in New York City. It covers conservative treatment, decision-making in end-stage hip osteoarthritis, advancements in robotics, and the role of phenotyping in precision rehabilitation post-total hip arthroplasty (THA).

Arthritis Foundation/HSS Workshop on Hip Osteoarthritis, Part 2: Detecting Hips at Risk: Early Biomechanical and Structural Mechanisms.

Far more publications are available for osteoarthritis of the knee than of the hip. Recognizing this research gap, the Arthritis Foundation (AF), in partnership with the Hospital for Special Surgery (HSS), convened an in-person meeting of thought leaders to review the state of the science of and clinical approaches to hip osteoarthritis. This article summarizes the recommendations gleaned from 5 presentations given in the "early hip osteoarthritis" session of the 2023 Hip Osteoarthritis Clinical Studies Conference, which took place on February 17 and 18, 2023, in New York City. It also summarizes the workgroup recommendations from a small-group discussion on clinical research gaps.

Arthritis Foundation/HSS Workshop on Hip Osteoarthritis, Part 3: Rehabilitation and Exercise.

Far more publications are available for osteoarthritis of the knee than of the hip. Recognizing this research gap, the Arthritis Foundation (AF), in partnership with the Hospital for Special Surgery (HSS), convened an in-person meeting of thought leaders to review the state of the science of and clinical approaches to hip osteoarthritis. This article summarizes the recommendations gleaned from 5 presentations given on hip-related rehabilitation at the 2023 Hip Osteoarthritis Clinical Studies Conference, which took place on February 17 and 18, 2023, in New York City.

Changes in leg length and hip offset in navigated imageless vs. conventional total hip arthroplasty.

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.

A vertebral skeletal stem cell lineage driving metastasis.

Vertebral bone is subject to a distinct set of disease processes from long bones, including a much higher rate of solid tumour metastases1-4. 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.

Genetic Risk Factors for End-Stage Hip Osteoarthritis Treated With Total Hip Arthroplasty: A Genome-wide Association Study.

BACKGROUND: Although a genetic component to hip osteoarthritis (OA) has been described, focused evaluation of the genetic components of end-stage disease is limited. We present a genomewide association study for patients undergoing total hip arthroplasty (THA) to characterize the genetic risk factors associated with end-stage hip osteoarthritis (ESHO), defined as utilization of the procedure. METHODS: Patients who underwent primary THA for hip OA were identified in a national patient data repository using administrative codes. Fifteen thousand three hundred and fifty-five patients with ESHO and 374,193 control patients were identified. Whole genome regression of genotypic data for patients who underwent primary THA for hip OA corrected for age, sex, and body mass index (BMI) was performed. Multivariate logistic regression models were used to evaluate the composite genetic risk from the identified genetic variants. RESULTS: There were 13 significant genes identified. Composite genetic factors resulted in an odds ratio 1.04 for ESHO (P < .001). The effect of genetics was lower than that of age (Odds Ratio (OR): 2.38; P < .001) and BMI (1.81; P < .001). CONCLUSION: Multiple genetic variants, including 5 novel loci, were associated with end-stage hip OA treated with primary THA. Age and BMI were associated with greater odds of developing end-stage disease when compared to genetic factors.

Does Acetabular Bone Loss Severity Associate With Patient-Reported Outcome Measures and Reoperation Rate in Revision Total Hip Arthroplasty?

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.

PTH Treatment Increases Cortical Bone Mass More in Response to Compression than Tension in Mice.

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).

Characterization of Genetic Risk of End-Stage Knee Osteoarthritis Treated with Total Knee Arthroplasty: A Genome-Wide Association Study.

BACKGROUND: End-stage knee osteoarthritis (OA) is a highly debilitating disease for which total knee arthroplasty (TKA) serves as an effective treatment option. Although a genetic component to OA in general has been described, evaluation of the genetic contribution to end-stage OA of the knee is limited. To this end, we present a genome-wide association study involving patients undergoing TKA for primary knee OA to characterize the genetic features of severe disease on a population level. METHODS: Individuals with the diagnosis of knee OA who underwent primary TKA were identified in the U.K. Biobank using administrative codes. The U.K. Biobank is a data repository containing prospectively collected clinical and genomic data for >500,000 patients. A genome-wide association analysis was performed using the REGENIE software package. Logistic regression was also used to compare the total genetic risk between subgroups stratified by age and body mass index (BMI). RESULTS: A total of 16,032 patients with end-stage knee OA who underwent primary TKA were identified. Seven genetic loci were found to be significantly associated with end-stage knee OA. The odds ratio (OR) for developing end-stage knee OA attributable to genetics was 1.12 (95% confidence interval [CI], 1.10 to 1.14), which was lower than the OR associated with BMI (OR = 1.81; 95% CI, 1.78 to 1.83) and age (OR = 2.38; 95% CI, 2.32 to 2.45). The magnitude of the OR for developing end-stage knee OA attributable to genetics was greater in patients <60 years old than in patients ≥60 years old (p = 0.002). CONCLUSIONS: This population-level genome-wide association study of end-stage knee OA treated with primary TKA was notable for identifying multiple significant genetic variants. These loci involve genes responsible for cartilage development, cartilage homeostasis, cell signaling, and metabolism. Age and BMI appear to have a greater impact on the risk of developing end-stage disease compared with genetic factors. The genetic contribution to the development of severe disease is greater in younger patients. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Intermittent parathyroid hormone increases stability and improves osseointegration of initially unstable implants.

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.

Femoral Component Undersizing and Alignment are Risk Factors for Early Periprosthetic Femur Fracture.

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.

Effects of teriparatide and loading modality on modeling-based and remodeling-based bone formation in the human femoral neck.

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.

Identifying alternative antibiotics that elute from calcium sulfate beads for treatment of orthopedic infections.

There has been increasing interest in the use of a synthetic absorbable calcium sulfate (CaSO4 ) for local antibiotic delivery in orthopaedic infections. The purpose of this study was to quantify elution kinetics of six antibiotics (amikacin, meropenem, fosfomycin, minocycline, cefazolin, and dalbavancin) from a clinically relevant CaSO4 bead model and compare elution and antimicrobial activity to the current clinical gold standards: vancomycin and tobramycin. Antibiotic-loaded synthetic CaSO4 beads were immersed in phosphate buffered saline and incubated at 37°C. Eluent was harvested at eight time points over 28 days. Antibiotic concentrations were measured by high performance liquid chromatography to quantify elution rates. CaSO4 beads demonstrated burst release kinetics. Dalbavancin, cefazolin, and minocycline all demonstrated similar elution profiles to vancomycin. Amikacin and meropenem demonstrated favorable elution profiles and durations of above-minimum inhibitory concentration when compared to tobramycin. Clinical Significance: This study provides important novel data regarding the utility of amikacin, meropenem and dalbavancin as alternative choices to place in CaSO4 carriers when treating orthopaedic infections.

Immune Response to Persistent Staphyloccocus Aureus Periprosthetic Joint Infection in a Mouse Tibial Implant Model.

Staphyloccocus aureus is one of the major pathogens in orthopedic periprosthetic joint infection (PJI), a devastating complication of total joint arthroplasty that often results in chronic and persistent infections that are refractory to antibiotics and require surgical interventions. Biofilm formation has been extensively investigated as a reason for persistent infection. The cellular composition, activation status, cytokine profile, and role of the immune response during persistent S. aureus PJI are incompletely understood. In this study, we used histology, multiparametric flow cytometry, and gene expression analysis to characterize the immune response in a clinically relevant orthopedic PJI model. We tested the hypothesis that persistent S. aureus infection induces feedback mechanisms that suppress immune cell activation, thereby affecting the course of infection. Surprisingly, persistent infection was characterized by strikingly high cytokine gene expression indicative of robust activation of multiple components of innate and adaptive immunity, along with ongoing severe neutrophil-dominated inflammation, in infected joint and bone tissues. Activation and expansion of draining lymph nodes and a bone marrow stress granulopoiesis reaction were also maintained during late phase infection. In parallel, feedback mechanisms involving T-cell inhibitory receptors and exhaustion markers, suppressive cytokines, and regulatory T cells were activated and associated with decreased T-cell proliferation and tissue infiltration during the persistent phase of infection. These results identify the cellular and molecular components of the mouse immune response to persistent S. aureus PJI and indicate that neutrophil infiltration, inflammatory cytokine responses, and ongoing lymph node and bone marrow reactions are insufficient to clear infection and that immune effector mechanisms are suppressed by feedback inhibitory pathways. These immune-suppressive mechanisms are associated with diminished T-cell proliferation and tissue infiltration and can be targeted as part of adjuvant immunotherapeutic strategies in combination with debridement of biofilm, antibiotics, and other therapeutic modalities to promote eradication of infection. © 2021 American Society for Bone and Mineral Research (ASBMR).

A Comparison of Risks and Benefits Regarding Hip Arthroplasty Fixation.

Since the field-changing invention of noncemented hip arthroplasty fixation in the 1980s, noncemented fixation has been progressively replacing cemented fixation. However, analyses of fixation frequencies reveal new patterns in cement versus noncemented preferences. Although cementation is again gaining ground in the United States, noncemented models remain the dominant fixation mode, seen in more than 90% of all hip arthroplasties. This stark preference is likely driven by concerns regarding implant durability and patient safety. Although advances in surgical techniques, intensive perioperative care, and improved instrument have evolved in both methods, data from large arthroplasty registries reveal shifting risks in contemporary hip arthroplasty, calling the use of noncemented fixation into question. Varying risk profiles regarding sex, age, or health comorbidities and morphological and functional differences necessitate personalized risk assessments. Furthermore, certain patient populations, based on the literature and data from large registries, have superior outcomes from cemented hip arthroplasty techniques. Therefore, we wanted to critically evaluate the method of arthroplasty fixation in primary hip arthroplasties for unique patient populations.