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Background: Morbidly obese patients are an ever-growing high-risk population undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) for end-stage osteoarthritis. This study sought to identify preoperative laboratory values that may serve as predictors of periprosthetic joint infection (PJI) in morbidly obese patients undergoing THA or TKA., Methods: All morbidly obese patients with preoperative laboratory data before undergoing primary elective TKA or THA were identified using the Premier Healthcare Database. Patients who developed PJI within 90 days after surgery were compared with patients without PJI. Laboratory value thresholds were defined by clinical guidelines or primary literature. Univariate and multivariable regression analyses were utilized to assess the association between PJI and preoperative laboratory values, including total lymphocyte count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), albumin level, platelet count, albumin-globulin ratio, hemoglobin level, and hemoglobin A1c., Results: Of the 6,780 patients identified (TKA: 76.67%; THA: 23.33%), 47 (0.69%) developed PJI within 90 days after surgery. The rate of PJI was 1.69% for patients with a hemoglobin level of <12 g/dL (for females) or <13 g/dL (for males), 2.14% for those with a platelet count of <142,000/µL or >417,000/µL, 1.11% for those with an NLR of >3.31, 1.69% for those with a PLR of >182.3, and 1.05% for those with an SII of >776.2. After accounting for potential confounding factors, we observed an association between PJI and an abnormal preoperative NLR (adjusted odds ratio [aOR]: 2.38, 95% confidence interval [CI]: 1.04 to 5.44, p = 0.039), PLR (aOR: 4.86, 95% CI: 2.15 to 10.95, p < 0.001), SII (aOR: 2.44, 95% CI: 1.09 to 5.44, p = 0.029), platelet count (aOR: 3.50, 95% CI: 1.11 to 10.99, p = 0.032), and hemoglobin level (aOR: 2.62, 95% CI: 1.06 to 6.50, p = 0.038)., Conclusions: This study identified preoperative anemia, abnormal platelet count, and elevated NLR, PLR, and SII to be associated with an increased risk of PJI among patients with a body mass index of ≥40 kg/m 2 . These findings may help surgeons risk-stratify this high-risk patient population., Level of Evidence: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: No external funding was received for this work. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H979 )., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Hyperglycemia has been identified as a risk factor for periprosthetic joint infection (PJI) after total hip arthroplasty (THA). However, there is no consensus with regard to the preoperative blood glucose level (BGL) on the day of the surgical procedure associated with increased risk. We sought to identify preoperative BGL thresholds associated with an increased risk of PJI., Methods: The Premier Healthcare Database was retrospectively queried for adult patients who underwent primary, elective THA and had a measurement of the preoperative BGL recorded on the day of the surgical procedure (preoperative BGL) from January 1, 2016, to December 31, 2021. The association between preoperative BGL and 90-day PJI risk was modeled using multivariable logistic regression with restricted cubic splines. Patients with and without diabetes with a preoperative BGL associated with 1.5 times greater odds of PJI (high preoperative BGL) were then compared with patients with a normal preoperative BGL., Results: In this study, 90,830 patients who underwent THA and had a recorded preoperative BGL were identified. The preoperative BGL associated with 1.5 times greater odds of PJI was found to be 277 mg/dL in patients with diabetes and 193 mg/dL in patients without diabetes. Compared with the normal preoperative BGL cohort, those with high preoperative BGL had increased odds of PJI (adjusted odds ratio [OR], 2.60 [95% confidence interval (CI), 1.45 to 4.67] for patients with diabetes and 1.66 [95% CI, 1.10 to 2.51] for patients without diabetes) and 90-day readmissions (adjusted OR, 1.92 [95% CI, 1.45 to 2.53] for patients with diabetes and 1.66 [95% CI, 1.37 to 2.00] for patients without diabetes)., Conclusions: Increased preoperative BGL was found to be associated with an increased risk of PJI following primary THA. Surgeons should be aware of patients with diabetes and a preoperative BGL of >277 mg/dL and patients without diabetes but with a preoperative BGL of >193 mg/dL., Level of Evidence: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: No external funding was received for this work. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H815 )., (Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Tranexamic acid (TXA) is increasingly utilized during total knee arthroplasty (TKA) and total hip arthroplasty (THA) to decrease blood loss; however, there are concerns with regard to potential thromboembolic complications, particularly in high-risk patients. This study sought to define a subset of patients at elevated risk for thromboembolic complications following total joint arthroplasty (TJA) and to compare postoperative outcomes between patients who received TXA and those who did not., Methods: Patients who underwent primary, elective TJA from 2015 to 2021 were identified in the Premier Healthcare Database. Patients with a history of venous thromboembolism, defined as a history of pulmonary embolism or deep vein thrombosis, were identified and formed the high-risk cohort. Patient demographic characteristics, hospital factors, patient comorbidities, antithrombotic medication use, perioperative blood transfusion, and 90-day complications were assessed and compared between patients who received TXA and those who did not. Univariate regression and multivariable regression were performed to account for potential confounders., Results: The high-risk cohort comprised 70,759 patients who underwent TJA, of whom 46,074 (65.1%) received TXA and 24,685 (34.9%) did not. After controlling for confounding factors, patients in the TXA cohort had similar risks of pulmonary embolism (adjusted odds ratio [OR], 0.90 [95% confidence interval (CI), 0.79 to 1.02]; p = 0.097), stroke (adjusted OR, 0.97 [95% CI, 0.69 to 1.37]; p = 0.867), and myocardial infarction (adjusted OR, 0.93 [95% CI, 0.69 to 1.24]; p = 0.614) compared with patients who did not receive TXA. Patients who received TXA demonstrated decreased risks of transfusion (adjusted OR, 0.42 [95% CI, 0.38 to 0.46]; p < 0.001) and 90-day readmission (adjusted OR, 0.87 [95% CI, 0.80 to 0.94]; p < 0.001)., Conclusions: TXA utilization was not associated with an increased risk of postoperative pulmonary embolism, stroke, or myocardial infarction in patients with a history of venous thromboembolism. Furthermore, patients who received TXA had a decreased risk of transfusion and readmission. This evidence suggests that TXA may be safely utilized among select high-risk patients., Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H756 )., (Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: The relationship between anemia and the risk of venous thromboembolism (VTE) following total knee arthroplasty (TKA) and total hip arthroplasty (THA) remains unclear. Red blood cell (RBC) transfusions, which have been shown to have thrombogenic effects, may explain conflicting data. This study sought to elucidate the relationship between anemia, RBC transfusions, and VTE following total joint arthroplasty (TJA)., Methods: Using the International Classification of Diseases, Tenth Revision (ICD-10) and Current Procedural Terminology (CPT) codes, the Premier Healthcare Database was queried for all adults who underwent primary elective THA or TKA from January 2015 to December 2020. Patients were classified into 3 cohorts: those who did not have a diagnosis of anemia and did not receive an RBC transfusion (the control group), those with acute blood loss anemia who did not receive a transfusion (the anemia without transfusion group), and those with acute blood loss anemia who did receive a transfusion (the anemia with transfusion group). The primary outcomes assessed were the 90-day rate and risk of deep vein thrombosis (DVT), pulmonary embolism (PE), and aggregate VTE. Analysis of variance and pairwise comparisons were used to compare groups. Multivariable analyses were performed to account for confounding factors., Results: The 1,290,815 patients identified as having undergone TJA included 1,078,507 control patients (83.6%), 198,233 patients who had anemia without transfusion (15.4%), and 14,075 patients who had anemia and transfusion (1.1%). Age, sex, race, length of hospital stay, and hospital costs were significantly different between the 3 groups. After adjusting for confounding factors, there was no difference between the anemia without transfusion group and the control group with regard to DVT (adjusted odds ratio [OR], 0.97 [95% confidence interval (CI), 0.89 to 1.06]; p = 0.500), PE (adjusted OR, 1.04 [95% CI, 0.92 to 1.18]; p = 0.543), and VTE (adjusted OR, 0.99 [95% CI, 0.92 to 1.06]; p = 0.697). However, patients with anemia and transfusion had an increased risk of PE (adjusted OR, 1.83 [95% CI, 1.34 to 2.51]; p < 0.001) and VTE (adjusted OR, 1.39 [95% CI, 1.14 to 1.70]; p = 0.001) compared with patients in the control group., Conclusions: Patients with acute blood loss anemia who received a transfusion were at increased risk for developing VTE following TJA, whereas patients with anemia who did not receive a transfusion were not. Orthopaedic surgeons need to be aware of the risks of transfusion and individualize the use of transfusions in their patients., Level of Evidence: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H621 )., (Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Despite known surgical volume reductions in 2020 during the height of the COVID-19 pandemic, no study has fully quantified the impact of the pandemic on the number of elective inpatient total hip (THA) and total knee arthroplasty (TKA) cases. The purpose of the present study was to analyze THA and TKA case volumes in the United States during the COVID-19 pandemic., Methods: The Premier Healthcare Database was utilized to identify adults undergoing primary elective THA or TKA from January 2017 to December 2020. The National Inpatient Sample was cross-referenced to provide nationwide representative sampling weights. Patients undergoing revision total joint arthroplasty (TJA) or non-elective surgery were excluded. Two quantitative models were created from both databases to estimate TJA case volume in 2020. Descriptive statistics were utilized to report monthly changes in elective TJA utilization throughout 2020. Univariate analyses were performed to compare differences between subgroups., Results: From 2017 to 2019, it was estimated that 1,006,000 elective inpatient TJAs (64.2% TKA and 35.8% THA) were performed annually. In 2020, an estimated 526,000 to 538,000 cases (62.0% TKA and 38.0% THA) were performed, representing a 46.5% to 47.7% decrease in nationwide volume from the prior 3-year average. Moreover, the elective TJA case volume for April 2020 was 1.9% of the average for that month from 2017 through 2019. Subsequently, case volumes for May and June increased compared with the volumes for those months from 2017 through 2019. There was then a decrease in cases for July, corresponding with the "second wave" of COVID-19, followed by an additional steady monthly decline through December, corresponding with the "third wave." Finally, the elective TJA cases for December 2020 represented only 41.0% of the average case volume for that month from 2017 through 2019., Conclusions: In the midst of the 2020 COVID-19 pandemic, approximately 526,000 to 538,000 elective inpatient TJA cases were performed, representing a 46.5% to 47.7% decrease compared with the 3 previous years. The effects of the COVID-19 pandemic persisted through the end of that year, with decreased case volume through December 2020., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/G959 )., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Opioids are commonly prescribed for postoperative pain following total joint arthroplasty. Despite widespread use, few studies have examined the dose-dependent effect of perioperative opioid use on postoperative complications following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Therefore, we examined the dose-dependent relationship between opioid use and postoperative complications following primary THA and TKA., Methods: We queried the Premier Healthcare Database to identify adult patients who underwent primary elective THA or TKA from 2004 to 2014, and quantified opioid consumption within the first 3 postoperative days. Opioid consumption was standardized to morphine milligram equivalents (MMEs). Patients were divided into quintiles on the basis of MME exposure: <54, 54 to 82, 83 to 116, 117 to 172, and >172 MMEs. Primary outcomes included postoperative periprosthetic joint infection, pulmonary embolism, deep venous thrombosis, and pulmonary complications. Secondary outcomes included wound infection, wound dehiscence, and readmission within 30 and 90 days postoperatively. Univariate and multivariate analyses were performed to compare differences between groups and to account for confounders., Results: A total of 1,525,985 patients were identified. The mean age was 65.7 ± 10.8 years, 598,320 patients (39.2%) were male, and 1,174,314 patients (77.0%) were Caucasian. On multiple logistic regression analysis, increasing MME exposure was associated with a dose-dependent increased risk of postoperative complications. Compared with patients receiving <54 MMEs, exposure to >172 MMEs was associated with greater odds of periprosthetic joint infection (adjusted odds ratio [aOR], 1.37; 95% confidence interval [CI], 1.33 to 1.42), deep venous thromboembolism (aOR, 1.34; 95% CI, 1.30 to 1.38), pulmonary embolism (aOR, 1.29; 95% CI, 1.25 to 1.34), and pulmonary complications (aOR, 1.06; 95% CI, 1.05 to 1.08). Exposure to >172 MMEs was associated with increased risk of wound infection (aOR, 1.37; 95% CI, 1.33 to 1.41), wound dehiscence (aOR, 1.24; 95% CI, 1.19 to 1.31), and readmission within 30 (aOR, 1.21; 95% CI, 1.20 to 1.22) and 90 days (aOR, 1.20; 95% CI, 1.19 to 1.21)., Conclusions: Increasing opioid use within the early postoperative period following THA or TKA was associated with a dose-dependent increased risk of periprosthetic joint infection and venous thromboembolic events., Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/G524)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)

➤: The selection of an agent for prophylaxis against venous thromboembolism (VTE) is a balance between efficacy and safety. The goal is to prevent symptomatic VTE while limiting the risk of bleeding., ➤: The optimal agent for VTE prophylaxis has not been identified. The American College of Chest Physicians guidelines recommend that, after total hip or total knee arthroplasty, patients receive at least 10 to 14 days of 1 of the following prophylaxis agents: aspirin, adjusted-dose vitamin K antagonist, apixaban, dabigatran, fondaparinux, low-molecular-weight heparin, low-dose unfractionated heparin, rivaroxaban, or portable home mechanical compression., ➤: The use of aspirin for VTE prophylaxis has increased in popularity over the past decade because it is effective, and it is an oral agent that does not require monitoring. The true efficacy of aspirin needs to be determined in multicenter randomized clinical trials., ➤: Validated risk stratification protocols are essential to identify the safest and most effective regimen for VTE prophylaxis for individual patients. There is no consensus regarding the optimal method for risk stratification; the selection of a prophylaxis agent should be determined by shared decision-making with the patient to balance the risk of thrombosis versus bleeding., ➤: Patients with atrial fibrillation being treated with chronic warfarin therapy or direct oral anticoagulants should stop the agent 3 to 5 days prior to surgery. Patients do not typically require bridging therapy prior to surgery., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/G548)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Depression and poor mental health are known to be negative predictors of patient-reported outcomes after total joint arthroplasty. Although previous studies have examined these risk factors in isolation to each other, they are, in reality, closely related, and yet each represents a different aspect of one's psychological well-being. The objective of this study was to investigate the association between depression and patient-reported outcomes, taking into account patients' baseline mental health., Methods: Our prospective, institutional joint registry was queried for patients who had undergone primary elective total joint arthroplasty and had a minimum follow-up of 1 year. Baseline mental health was measured by the Short Form-12 Mental Component Summary (SF-12 MCS). Four cohorts were analyzed on the basis of the presence or absence of depression and patients' SF-12 MCS scores at the time of the surgical procedure, which were categorized as either poor or good on the basis of previously defined cutoffs. The primary outcomes were the net changes in SF-12 MCS, SF-12 Physical Component Summary (PCS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores at 4 and 12 months postoperatively. Univariate and mixed-effects model analyses were performed to control for potential confounding factors., Results: Patients with depression but good baseline mental health achieved gains in patient-reported outcomes that were comparable with those of normal controls (p > 0.05). Patients with poor baseline mental health achieved significant gains in all patient-reported outcomes, but the changes were largest for those without depression (p < 0.05). Only patients with depression and poor baseline mental health did not cross the threshold for good mental health at the time of the latest follow-up despite achieving similar gains in physical function compared with their counterparts who did not have depression., Conclusions: The effect of depression on patient-reported outcomes is more complex but less pessimistic than previously thought. Patients with depression undergoing total joint arthroplasty may have significant improvements in their patient-reported outcomes, but the net gains are modulated by their mental health at the time of the surgical procedure. Preoperative screening of patients with depression using the SF-12 MCS may help to identify those who are at risk for attaining suboptimal patient-reported outcomes and may benefit from counseling or psychiatric referral for optimization before undergoing a surgical procedure., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Health care has entered an era where value and quality have become more important than just quantity. Patient-reported outcomes are a critical aspect of the value equation. Orthopaedic surgeons will need to demonstrate that their treatment regimens actually are enhancing their patients' quality of life. In order to do this, the collection of prospective patient-reported outcome data will be critical. For most patients, this will require the use of a general health survey and a disease-specific questionnaire. Currently, most orthopaedic surgeons are not collecting this type of data. The questions are: What types of patient-generated questionnaires can provide the information needed, and how can these data be collected in a cost-effective manner? We will discuss what value means to payers and what the outcome measures are that are selected by various orthopaedic subspecialty societies to evaluate patients who undergo total hip and knee arthroplasty as well as patients with shoulder and knee problems, and we will review potential strategies to collect prospective patient-outcome data in a cost-effective manner in the office.

Background: Intra-articular corticosteroids relieve osteoarthritis pain, but rapid systemic absorption limits efficacy. FX006, a novel, microsphere-based, extended-release triamcinolone acetonide (TA) formulation, prolongs TA joint residence and reduces systemic exposure compared with standard TA crystalline suspension (TAcs). We assessed symptomatic benefits and safety of FX006 compared with saline-solution placebo and TAcs., Methods: In this Phase-3, multicenter, double-blinded, 24-week study, adults ≥40 years of age with knee osteoarthritis (Kellgren-Lawrence grade 2 or 3) and average-daily-pain (ADP)-intensity scores of ≥5 and ≤9 (0 to 10 numeric rating scale) were centrally randomized (1:1:1) to a single intra-articular injection of FX006 (32 mg), saline-solution placebo, or TAcs (40 mg). The primary end point was change from baseline to week 12 in weekly mean ADP-intensity scores for FX006 compared with saline-solution placebo. Secondary end points were area-under-effect (AUE) curves of the change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with saline-solution placebo, AUE curves of the change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with TAcs, change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with TAcs, and AUE curves of the change in weekly mean ADP-intensity scores from baseline to week 24 for FX006 compared with saline-solution placebo. Exploratory end points included week-12 changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Injury and Osteoarthritis Outcome Score Quality of Life (KOOS-QOL) subscale scores for FX006 compared with saline-solution placebo and TAcs. Adverse events were elicited at each inpatient visit., Results: The primary end point was met. Among 484 treated patients (n = 161 for FX006, n = 162 for saline-solution placebo, and n = 161 for TAcs), FX006 provided significant week-12 improvement in ADP intensity compared with that observed for saline-solution placebo (least-squares mean change from baseline: -3.12 versus -2.14; p < 0.0001) indicating ∼50% improvement. FX006 afforded improvements over saline-solution placebo for all secondary and exploratory end points (p < 0.05). Improvements in osteoarthritis pain were not significant for FX006 compared with TAcs using the ADP-based secondary measures. Exploratory analyses of WOMAC-A, B, and C and KOOS-QOL subscales favored FX006 (p ≤ 0.05). Adverse events were generally mild, occurring at similar frequencies across treatments., Conclusions: FX006 provided significant, clinically meaningful pain reduction compared with saline-solution placebo at week 12 (primary end point)., Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Background: Recombinant human bone morphogenetic protein (rhBMP)-2 is a potent osteoinductive agent; however, its clinical use has been reduced because of safety and efficacy concerns. In preclinical studies involving a critical-sized defect in a rat model, sclerostin antibody (Scl-Ab) treatment increased bone formation within the defect but did not result in reliable healing. The purpose of the current study was to evaluate bone repair of a critical-sized femoral defect in a rat model with use of local implantation of rhBMP-2 combined with systemic administration of Scl-Ab., Methods: A critical-sized femoral defect was created in rats randomized into three treatment groups: local rhBMP-2 and systemic Scl-Ab (Scl + BMP), local rhBMP-2 alone, and collagen sponge alone (operative control). The Scl + BMP group received local rhBMP-2 (10 μg) on a collagen sponge placed within the defect intraoperatively and then twice weekly injections of Scl-Ab (25 mg/kg) administered postoperatively. The femora were evaluated at twelve weeks with use of radiography, microcomputed tomography (microCT), histomorphometric analysis, and biomechanical testing., Results: At twelve weeks, all Scl + BMP and rhBMP-2 only samples were healed. No femora healed in the operative control group. Histomorphometric analysis demonstrated more bone in the Scl + BMP samples than in the samples treated with rhBMP-2 alone (p = 0.029) and the control samples (p = 0.003). MicroCT revealed that the Scl + BMP group had a 90% greater bone volume within the defect region compared with the rhBMP-2 group and a 350% greater bone volume compared with the operative control group (p < 0.001). Biomechanical testing showed that the group treated with Scl + BMP had greater torsional strength and rigidity compared with the rhBMP-2 group (p < 0.001 and p = 0.047) and the intact femoral control group (p < 0.001). Torque to failure was lower in the rhBMP-2 group compared with the intact femoral control group (p < 0.002). Mean energy to failure was higher in the Scl + BMP samples compared with the rhBMP-2 only samples (p = 0.001)., Conclusions: In a critical-sized femoral defect in a rat model, local rhBMP-2 combined with systemic administration of Scl-Ab resulted in more robust healing that was stronger and more rigid than results for rhBMP-2 alone and intact nonoperative femora., Clinical Relevance: Our study demonstrated that combining an osteoinductive agent with a systemically administered antibody that promotes bone formation can enhance bone repair and has potential as a therapeutic regimen in humans., (Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.)

➤ Although multiple theories have been proposed, no one pathophysiologic mechanism has been identified as the etiology for the development of osteonecrosis of the femoral head. However, the basic mechanism involves impaired circulation to a specific area that ultimately becomes necrotic.➤ A variety of nonoperative treatment regimens have been evaluated for the treatment of precollapse disease, with varying success. Prospective, multicenter, randomized trials are needed to evaluate the efficacy of these regimens in altering the natural history of the disease.➤ Joint-preserving procedures are indicated in the treatment of precollapse disease, with several studies showing successful outcomes at mid-term and long-term follow-up.➤ Studies of total joint arthroplasty, once femoral head collapse is present, have described excellent outcomes at greater than ten years of follow-up, which is a major advance and has led to a paradigm shift in treating these patients.➤ The results of hemiresurfacing and total resurfacing arthroplasty have been suboptimal, and these procedures have restricted indications in patients with osteonecrosis of the femoral head., (Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Little is known about the variation in complication rates among U.S. hospitals that perform elective total hip arthroplasty (THA) and total knee arthroplasty (TKA) procedures. The purpose of this study was to use National Quality Forum (NQF)-endorsed hospital-level risk-standardized complication rates to describe variations in, and disparities related to, hospital quality for elective primary THA and TKA procedures performed in U.S. hospitals., Methods: We conducted a cross-sectional analysis of national Medicare Fee-for-Service data. The study cohort included 878,098 Medicare fee-for-service beneficiaries, sixty-five years or older, who underwent elective THA or TKA from 2008 to 2010 at 3479 hospitals. Both medical and surgical complications were included in the composite measure. Hospital-specific complication rates were calculated from Medicare claims with use of hierarchical logistic regression to account for patient clustering and were risk-adjusted for age, sex, and patient comorbidities. We determined whether hospitals with higher proportions of Medicaid patients and black patients had higher risk-standardized complication rates., Results: The crude rate of measured complications was 3.6%. The most common complications were pneumonia (0.86%), pulmonary embolism (0.75%), and periprosthetic joint infection or wound infection (0.67%). The median risk-standardized complication rate was 3.6% (range, 1.8% to 9.0%). Among hospitals with at least twenty-five THA and TKA patients in the study cohort, 103 (3.6%) were better and seventy-five (2.6%) were worse than expected. Hospitals with the highest proportion of Medicaid patients had slightly higher but similar risk-standardized complication rates (median, 3.6%; range, 2.0% to 7.1%) compared with hospitals in the lowest decile (3.4%; 1.7% to 6.2%). Findings were similar for the analysis involving the proportion of black patients., Conclusions: There was more than a fourfold difference in risk-standardized complication rates across U.S. hospitals in which elective THA and TKA are performed. Although hospitals with higher proportions of Medicaid and black patients had rates similar to those of hospitals with lower proportions, there is a continued need to monitor for disparities in outcomes. These findings suggest there are opportunities for quality improvement among hospitals in which elective THA and TKA procedures are performed.

The selection of a regimen for venous thromboembolic prophylaxis after total joint arthroplasty is a balance between efficacy and safety. Bleeding may have a negative impact on clinical outcomes. Recently, both the American Academy of Orthopaedic Surgeons (AAOS) and the American College of Chest Physicians (ACCP) developed new evidence-based guidelines for venous thromboembolic prophylaxis after total joint arthroplasty. On the basis of a review of the available literature, the AAOS guideline panel was unable to make a recommendation with respect to the selection of a specific prophylaxis regimen or duration of prophylaxis following routine total joint arthroplasty. The ACCP panel recommended one of the following modalities as prophylaxis (rather than no prophylaxis at all) for a minimum of fourteen days: warfarin, low-molecular-weight heparin, fondaparinux, aspirin, rivaroxaban, dabigatran, apixaban, or portable mechanical compression. Both the AAOS and the ACCP guidelines recommended against screening with postoperative duplex ultrasonography at the time of discharge after routine total joint arthroplasty. There is renewed interest in the use of mechanical compression as prophylaxis with the advent of portable compression devices, which allow continuation of this type of prophylaxis after hospital discharge. Although the early data are promising, appropriately powered randomized trials are needed to determine the efficacy of the devices compared with other prophylaxis regimens.

Background: Systemic administration of sclerostin neutralizing antibody has led to increased bone formation in animal models of osteoporosis. The purpose of this study was to determine if systemic administration of sclerostin neutralizing antibody could increase the healing response in a critical-sized femoral defect in rats., Methods: Critical-sized femoral defects were created in Lewis rats, and the rats were randomized into four groups. The sclerostin antibody (Scl-Ab) treatment groups included the continuous Scl-Ab group (twenty-one animals), the early Scl-Ab group (fifteen animals), and the delayed Scl-Ab group (fifteen animals), which received sclerostin antibody (25 mg/kg) twice weekly for weeks 0 through 12; weeks 0 through 2; and weeks 2 through 4; respectively. Twenty-one animals in the control group received vehicle from weeks 0 through 12. In a subsequent study, bone turnover markers were measured at zero, two, six, and twelve weeks after surgery in rats receiving vehicle or sclerostin neutralizing antibody for twelve weeks (fifteen rats per group). The quality of bone formed was evaluated with radiographs, microcomputed tomography, biomechanical testing, and histologic and histomorphometric analysis., Results: In the primary study, four of fifteen defects in the continuous (zero to twelve-week) Scl-Ab group, three of fifteen defects in the early (zero to two-week) Scl-Ab group, and four of fifteen defects in the delayed (two to four-week) Scl-Ab group healed at twelve weeks, while none of the defects healed in the control group. In both studies, treatment with sclerostin antibody for twelve weeks demonstrated a significant increase in new bone formation (p < 0.05) compared with the control group. The three treatment groups did not differ significantly with respect to the healing rates and the quality of new bone formed in the defect. The serum markers of bone formation were significantly elevated in the animals in the continuous Scl-Ab group (p < 0.05) compared with the controls., Conclusions: Administration of sclerostin neutralizing antibody led to increased bone formation, resulting in complete healing of femoral defects in a small subset of rats, with a majority of the animals not healing the defect by twelve weeks.

Background: Mesenchymal stem cells are multipotent and have the ability to differentiate into bone. We conducted a preclinical trial comparing the osteogenic potential of human bone marrow aspirate with that of mesenchymal stem cell-enriched bone marrow aspirate (both mixed with demineralized bone matrix) in a critical-sized rat femoral defect model., Methods: The buffy coat was extracted from human bone marrow aspirate to obtain mesenchymal stem cell-enriched bone marrow aspirate. Fifty-nine athymic rats, each with a 6-mm femoral defect, were divided into six treatment groups: defect only (Group I), demineralized bone matrix and saline solution (Group II), demineralized bone matrix and bone marrow aspirate (Group III), demineralized bone matrix and mesenchymal stem cell-enriched bone marrow aspirate (Group IV), demineralized bone matrix and recombinant human bone morphogenetic protein-2 (rhBMP-2) (Group V [positive control]), and absorbable collagen sponge and rhBMP-2 (Group VI [positive control]). All animals were killed at twelve weeks for radiographic, micro-computed tomography, histomorphometric, and histologic analysis., Results: There was wide variability in the mesenchymal stem cell concentrations obtained from the human donors. All ten defects healed in the positive control groups (Groups V and VI). Only one defect healed in each experimental group (Groups II, III, and IV) (i.e., three of forty-four defects healed). There was no significant difference among the radiographic scores of Groups II, III, and IV (p = 0.59), and the score for each of those groups was significantly higher than that for Group I (p

Background: Mesenchymal stem cells derived from human liposuction aspirates, termed processed lipoaspirate cells, have been utilized as cellular delivery vehicles for the induction of bone formation in tissue engineering and gene therapy strategies. In this study, we sought to evaluate the efficacy of bone morphogenetic protein (BMP)-2-producing adipose-derived stem cells in inducing a posterolateral spine fusion in an athymic rat model., Methods: Single-level (L4-L5) intertransverse spinal arthrodesis was attempted with use of a type-I collagen matrix in five groups of athymic rats, with eight animals in each group. Group I was treated with 5 x 10(6) adipose-derived stem cells transduced with an adenoviral vector containing the BMP-2 gene; group II, with 5 x 10(6) adipose-derived stem cells treated with osteogenic media and 1 microg/mL of recombinant BMP-2 (rhBMP-2); group III, with 10 microg of rhBMP-2; group IV, with 1 microg of rhBMP-2; and group V, with 5 x 10(6) adipose-derived stem cells alone. The animals that showed radiographic evidence of healing were killed four weeks after cell implantation and were examined with plain radiographs, manual palpation, microcomputed tomography scanning, and histological analysis., Results: All eight animals in group I demonstrated successful spinal fusion, with a large fusion mass, four weeks postoperatively. Furthermore, group-I specimens consistently revealed spinal fusion at the cephalad level (L3 and L4), where no fusion bed had been prepared surgically. In contrast, despite substantial BMP-2 production measured in vitro, group-II animals demonstrated minimal bone formation even eight weeks after implantation. Of the groups treated with the application of rhBMP-2 alone, the one that received a relatively high dose (group III) had a higher rate of fusion (seen in all eight specimens) than the one that received the low dose (group IV, in which fusion was seen in four of the eight specimens). None of the group-V animals (treated with adipose-derived stem cells alone) demonstrated successful spine fusion eight weeks after the surgery., Conclusions: Adipose-derived stem cells show promise as gene transduction targets for inducing bone formation to enhance spinal fusion in biologically stringent environments.

Biologic therapies to promote fracture-healing such as use of bone morphogenetic proteins (BMPs) are being increasingly employed in multiple clinical scenarios. However, it has been challenging to design therapies that deliver sufficient quantities of protein over a sustained time period. A potential solution is the application of gene therapy that transfers genetic information to host cells at the fracture site, resulting in the continuous and localized production of the desired proteins. This approach has demonstrated tremendous potential in preclinical animal models of fracture-healing. This article will review the current state of gene therapy approaches to fracture-healing with an emphasis on potential clinical applications.

Background: The purpose of this study was to compare the cost-effectiveness of unicompartmental knee arthroplasty as an alternative to total knee arthroplasty in patients with degenerative arthritis limited to either the medial or lateral compartment., Methods: A decision model was created for the treatment of end-stage unicompartmental knee arthritis. A literature review was used to identify possible outcomes and their probabilities following treatment with either unicompartmental or total knee arthroplasty. Each outcome was weighted for quality of life with use of a utility factor, and effectiveness was expressed in units of quality-adjusted life years. Gross costs were estimated from Medicare reimbursement data for the relevant Current Procedural Terminology and Diagnosis-Related Group codes., Results: Sensitivity analysis demonstrated that the cost-effectiveness of unicompartmental knee arthroplasty is dependent on the assumption that its durability and functional outcomes approach those of total knee arthroplasty. Specifically, it is necessary for the survival of unicompartmental implants to be within three to four years of the assumed survival of total knee implants for unicompartmental arthroplasty to remain a cost-effective alternative. Under these assumptions, the use of unicompartmental arthroplasty is a cost-effective choice as it results in incremental gains in effectiveness at a cost of less than US dollars 50,000 (in 1998 United States dollars) per quality-adjusted life year gained., Conclusions: This study supports unicompartmental knee arthroplasty as a cost-effective alternative for the treatment of unicompartmental arthritis when the durability and function of a unicompartmental replacement are assumed to be similar to those of a primary total knee replacement. This suggests that, with appropriate patient selection, the currently available literature supports unicompartmental arthroplasty as a cost-effective alternative to total knee arthroplasty., Level of Evidence: Economic and decision analysis, Level II.

Background: The purpose of this investigation was to expand on previous studies by more fully examining the role of a variety of patient and hospital characteristics in determining adverse outcomes following total knee replacement., Methods: With use of data from all hospital admissions in California from 1991 through 2001, multiple logistic regression was performed on the information regarding patients treated with total knee replacement. Rates of mortality and readmission due to infection and pulmonary embolism during the first ninety days after discharge were regressed against a variety of independent variables, including demographic factors (age, gender, race, ethnicity, and insurance type), burden of comorbid disease (Charlson comorbidity index), and provider variables (hospital size, teaching status, and surgical volume). A separate baseline probability analysis was then performed to compare the relative importance of all predictor variables., Results: The sample size for this analysis was 222,684. A total of 1176 deaths (rate, 0.53%), 1586 infections (0.71%), and 914 pulmonary emboli (0.41%) occurred within the first ninety days after discharge. The average age of the patients at the time of surgery was sixty-nine years. Sixty-two percent of the patients were women, and 32% had a Charlson comorbidity index of >0. The significant predictors for complications (p < 0.05) included age, gender, race/ethnicity, Charlson comorbidity index, insurance type, and hospital volume. A baseline probability analysis was performed with the base case considered to be a white woman who was over the age of sixty-five years, had a Charlson comorbidity index of 0, had Medicare insurance, and was treated at a high-volume, non-teaching hospital. For a patient with the baseline case characteristics, the probability of death was 31/10,000, the probability of infection was 59/10,000, and the probability of pulmonary embolism was 41/10,000 in the first ninety days after discharge. Altering the base case by assuming that care was received at a low-volume hospital increased the expected mortality rate by a factor of 26%. Increasing the Charlson comorbidity index to 1 increased the mortality rate by 170%, whereas decreasing the age to younger than sixty-five years lowered the mortality rate by 73%. Hospital volume, comorbidity, and age had similar effects on the expected rates of readmission due to infection and pulmonary embolism., Conclusions: The effects of age and the Charlson comorbidity index on the baseline probability of adverse outcomes following total knee replacement were shown to be similar to or greater than the effect of hospital volume. This study elucidates and compares the relative importance of the effects of several different factors on outcome. This information is important when considering the conclusions and implications of this type of policy-relevant outcomes research.

Background: Warfarin, which requires coagulation monitoring, is associated with relatively high rates of thromboembolism despite providing adequate prophylaxis. This study compared an oral direct thrombin inhibitor, ximelagatran, with warfarin in order to evaluate the safety and efficacy of the medication for the prevention of venous thromboembolism in patients undergoing total knee arthroplasty., Methods: Following surgery, patients were randomly assigned to fixed-dose oral ximelagatran (36 mg twice daily) or warfarin (target international normalized ratio, 2.5), both administered for seven to twelve days in a double-blind, double-dummy design. Warfarin was initiated on the evening of the day of surgery, and ximelagatran, on the morning after surgery. The primary efficacy end point was the incidence of asymptomatic deep-vein thrombosis determined by bilateral venography, objectively confirmed symptomatic deep-vein thrombosis or pulmonary embolism, and death from all causes during treatment., Results: Adequate venograms or confirmed symptomatic events (efficacy population) were obtained for 1949 patients. Venous thromboembolism and death from all causes occurred in 22.5% (221) of 982 ximelagatran-treated patients and in 31.9% (308) of 967 warfarin-treated patients (p < 0.001). Proximal deep-vein thrombosis and pulmonary embolism were observed in 3.1% (thirty) and 0.2%, respectively, of the patients in the ximelagatran group and in 3.4% (thirty-three) and 0.4%, respectively, of the patients in the warfarin group. The six deaths from all causes included 0.3% (four) of the ximelagatran-treated patients and 0.2% (two) of the warfarin-treated patients. Major bleeding was noted in 1% (twelve) of the ximelagatran-treated patients and in 0.4% (five) of the warfarin-treated patients (p = 0.09)., Conclusions: Oral ximelagatran (36 mg twice daily), administered without coagulation monitoring or dose adjustment and started the day after total knee arthroplasty, demonstrates superior efficacy compared with warfarin prophylaxis, with no wound complications and no significant difference with respect to bleeding events, although the rate of major bleeding events was greater with ximelagatran than with warfarin., Level of Evidence: Therapeutic Level I.

Patients undergoing total hip and knee arthroplasty are at increased risk for the development of venous thromboembolic disease, and there is general agreement that these patients require prophylaxis. The selection of a prophylactic agent involves a balance between efficacy and safety and often needs to be individualized for specific patients and institutions. Despite extensive research, the ideal agent for prophylaxis against deep venous thrombosis has not been identified. The results of randomized trials indicate that low-molecular-weight heparin, warfarin, and fondaparinux are the most effective prophylactic agents after total hip arthroplasty and that low-molecular-weight heparin, warfarin, fondaparinux, and pneumatic compression boots are the most effective agents after total knee arthroplasty. The duration of prophylaxis against deep venous thrombosis after total hip and knee arthroplasty remains controversial. Prophylaxis should be continued beyond hospital discharge. In the future, the determination of the duration of prophylaxis will be based on the risk stratification of individual patients. The practice of discharging patients from the hospital without prophylaxis, even when the decision is based on negative results of procedures that screen for the presence of deep venous thrombosis, is not cost-effective.

Background: Although autogenous bone is the most widely used graft material for spinal fusion, demineralized bone matrix preparations are available as alternatives or supplements to autograft. They are prepared by acid extraction of most of the mineralized component, with retention of the collagen and noncollagenous proteins, including growth factors. Differences in allograft processing methods among suppliers might yield products with different osteoinductive activities. The purpose of this study was to compare the efficacy of three different commercially available demineralized bone matrix products for inducing spinal fusion in an athymic rat model., Methods: Sixty male athymic rats underwent spinal fusion and were divided into three groups of eighteen animals each. Group I received Grafton Putty; Group II, DBX Putty; and Group III, AlloMatrix Injectable Putty. A control group of six animals (Group IV) underwent decortication alone. Six animals from each of the three experimental groups were killed at each of three intervals (two, four, and eight weeks), and the six animals from the control group were killed at eight weeks. At each of the time-points, radiographic and histologic analysis and manual testing of the explanted spines were performed., Results: The spines in Group I demonstrated higher rates of radiographically evident fusion at eight weeks than did the spines in Group III or Group IV (p < 0.05). Manual testing of the spines at four weeks revealed variable fusion rates (five of six in Group I, two of six in Group II, and none of six in Group III). At eight weeks, all six spines in Group I, three of the six in Group II, and no spine in Group III or IV had fused. Histologic analysis of the spines in Groups I, II, and III demonstrated varying amounts of residual demineralized bone matrix and new bone formation. Group-I spines demonstrated the most new bone formation., Conclusions: This study demonstrated differences in the osteoinductive potentials of commercially available demineralized bone matrices in this animal model.

Background: Bone morphogenetic proteins (BMPs) are now being used as bone-graft substitutes to enhance spinal fusion. However, the large doses of BMP required to induce a spinal fusion in humans suggests that the delivery of these proteins should be improved. We used ex vivo adenoviral gene transfer to create BMP-2-producing bone marrow cells, and these autologous cells were found to induce a posterolateral fusion of the spine in syngeneic rats., Methods: Intertransverse spinal arthrodesis (L4 and L5) was attempted in ten groups of Lewis rats with 5 x 10 (6) BMP-2-producing rat bone marrow cells (Ad-BMP-2 cells), created through adenoviral gene transfer with guanidine hydrochloride-extracted demineralized bone matrix as a carrier (Group I); 5 x 10 (6) Ad-BMP-2 cells on a collagen sponge carrier (Group II); 10 micro g of recombinant BMP-2 (rhBMP-2) in a guanidine hydrochloride-extracted demineralized bone matrix carrier (Group III); 10 micro g of rhBMP-2 in a collagen sponge carrier (Group IV); autogenous iliac crest bone-grafting (Group V); 5 x 10 (6) beta-galactosidase-producing rat bone marrow cells, created through adenoviral gene transfer with guanidine hydrochloride-extracted demineralized bone matrix as a carrier (Group VI); decortication of the transverse processes alone (Group VII); 5 x 10 (6) uninfected rat bone marrow cells with a guanidine hydrochloride-extracted demineralized bone matrix carrier (Group VIII); guanidine hydrochloride-extracted demineralized bone matrix only (Group IX); or a collagen sponge alone (Group X). Each specimen underwent plain radiography, manual palpation, and histological analysis., Results: All spines in Groups I and II (BMP-2-producing bone marrow cells) and all spines in Groups III and IV were fused at four weeks postoperatively. In contrast, none of the spines in the other groups had fused at a minimum of eight weeks after implantation. Histological analysis of the specimens revealed that the spines that had received BMP-2-producing bone marrow cells (Groups I and II) were filled with coarse trabecular bone postoperatively, whereas those that had received rhBMP-2 (Groups III and IV) were filled with thin, lace-like trabecular bone. All of the other spines, including those that had been treated with autogenous iliac crest bone-grafting (Group V), produced little or no new bone., Conclusion: BMP-2-producing bone marrow cells, created by adenoviral gene transfer, produce sufficient BMP to induce an intertransverse fusion in the rat spine model.