Effects of antiseptic irrigation solutions on osseointegration in a cementless tibial implantation mouse model.

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 (H2O2) 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% H2O2, 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.

A translational murine model of aseptic loosening with osseointegration failure.

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.

Staphyloccocus aureus biofilm, in absence of planktonic bacteria, produces factors that activate counterbalancing inflammatory and immune-suppressive genes in human monocytes.

Staphyloccocus aureus (S. aureus) is a major bacterial pathogen in orthopedic periprosthetic joint infection (PJI). S. aureus forms biofilms that promote persistent infection by shielding bacteria from immune cells and inducing an antibiotic-tolerant metabolic state. We developed an in vitro system to study S. aureus biofilm interactions with primary human monocytes in the absence of planktonic bacteria. In line with previous in vivo data, S. aureus biofilm induced expression of inflammatory genes such as TNF and IL1B, and their anti-inflammatory counter-regulator IL10. S. aureus biofilm also activated expression of PD-1 ligands, and IL-1RA, molecules that have the potential to suppress T cell function or differentiation of protective Th17 cells. Gene induction did not require monocyte:biofilm contact and was mediated by a soluble factor(s) produced by biofilm-encased bacteria that was heat resistant and >3 kD in size. Activation of suppressive genes by biofilm was sensitive to suppression by Jak kinase inhibition. These results support an evolving paradigm that biofilm plays an active role in modulating immune responses, and suggest this occurs via production of a soluble vita-pathogen-associated molecular pattern, a molecule that signals microbial viability. Induction of T cell suppressive genes by S. aureus biofilm provides insights into mechanisms that can suppress T cell immunity in PJI.

Dispersion interaction between thin conducting cylinders.

The ground state and excited state resonance dipole-dipole interaction energy between two elongated conducting molecules is explored in this study. We review the current status for ground state interactions. This interaction is found to be of a much longer range than in the case when the molecules are pointlike and nonconducting. These are well known results found earlier by Davies, Ninham, and Richmond, and later, using a different formalism, by Rubio and co-workers. We show how the theory can be extended to excited state interactions. A characteristic property observed from our calculation is that the interaction energy dependence on separation (R) follows f(R)/R2 for both resonance and van der Waals cases in the long-range limit. Under some limits, f(R) has a logarithmic dependency, while under others, it has constant values. We predict an unusual slow decay rate for the energy transfer between conducting molecules.

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. 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.

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.

Dalbavancin is thermally stable at clinically relevant temperatures against methicillin-sensitive Staphylococcus Aureus.

Introduction: While the rate of orthopaedic infections has remained constant over the years, the burden on healthcare systems continues to rise with an aging population. Local antibiotic delivery via polymethyl methacrylate bone cement is a common adjunct in treating bone and joint infections. Dalbavancin is a novel lipoglycopeptide antibiotic in the same class as vancomycin that has shown efficacy against Gram-positive organisms when used systemically but has not been investigated as a local antibiotic. This study aims to identify whether dalbavancin is thermally stable at the temperatures expected during the polymerization of polymethyl methacrylate cement. Methods: Stock solutions of dalbavancin were prepared and heated using a polymerase chain reaction machine based upon previously defined models of curing temperatures in two clinically relevant models: a 10 mm polymethyl methacrylate bead and a polymethyl methacrylate articulating knee spacer model. Aliquots of heated dalbavancin were then transferred to be incubated at core body temperature (37 ∘C) and analyzed at various time points up to 28 d. The minimum inhibitory concentration at which 90 % of colonies were inhibited (MIC90) for each heated sample was determined against methicillin-sensitive Staphylococcus aureus (American Type Culture Collection, ATCC, 0173K) using a standard microbroth dilution assay. Results: The average MIC90 of dalbavancin was 1.63 µgmL-1 ±0.49 against 0173K S. aureus. There were no significant differences in the relative MIC90 values after heating dalbavancin in either model compared to unheated control dalbavancin. Conclusions: Dalbavancin is thermally stable at the curing temperatures of polymethyl methacrylate cement and at human core body temperature over 28 d. Future in vitro and in vivo studies are warranted to further investigate the role of dalbavancin as a local antibiotic prior to its clinical use.

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.

Origin of anomalously stabilizing ice layers on methane gas hydrates near rock surface.

Gas hydrates (GHs) in water close to freezing temperatures can be stabilised via the formation of ice layers. In a recent work [Boström et al., Astron. Astrophys., A54, 650, 2021], it was found that a surface region with partial gas dilution could be essential for obtaining nano- to micron-sized anomalously stabilizing ice layers. In this paper, it is demonstrated that the Casimir-Lifshitz free energy in multi-layer systems could induce thinner, but more stable, ice layers in cavities than those found for gas hydrates in a large reservoir of cold water. The thickness and stability of such ice layers in a pore filled with cold water could influence the leakage of gas molecules. Additional contributions, e.g. from salt-induced stresses, can also be of importance, and are briefly discussed.

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.