Effects of neuromuscular control and strengthening exercises on MRI-measured thigh tissue composition and muscle properties in people with knee osteoarthritis - an exploratory secondary analysis from a randomized controlled trial.

OBJECTIVE: To investigate the effects of adding strength training to neuromuscular control exercises on thigh tissue composition and muscle properties in people with radiographic-symptomatic knee osteoarthritis (KOA). METHODS: In this exploratory secondary analysis of a randomized controlled trial, using a complete-case approach, participants performed 12 weeks of twice-weekly neuromuscular control exercise and patient education (NEMEX, n = 34) or NEMEX plus quadriceps strength training (NEMEX+ST, n = 29). Outcomes were MRI-measured inter- and intramuscular adipose tissue (InterMAT, IntraMAT), quadriceps muscle cross-sectional area (CSA), knee-extensor strength, specific strength (strength/lean CSA) and 30 s chair-stands. Between-group effects were compared using a mixed model analysis of variance. RESULTS: At 12 weeks, responses to NEMEX+ST overlapped with NEMEX for all outcomes. Both groups reduced InterMAT (NEMEX+ST=25 %, NEMEX=21 %); between-group difference: 0.8cm2 (95 % CI: -0.1, 1.7). NEMEX+ST decreased IntraMAT (2 %) and NEMEX increased IntraMAT (4 %); between-group difference 0.1 %-points (-0.3, 0.5). Both groups increased quadriceps CSA and lean CSA (CSA minus IntraMAT), improved knee-extensor strength and specific strength, and improved chair-stand performance with a trend towards greater effects in NEMEX+ST. CONCLUSION: Adding strength training to 12 weeks of neuromuscular control exercises provided largely similar effects to neuromuscular control exercises alone in decreasing InterMAT and IntraMAT, in improving knee-extensor strength, CSA and in improving performance-based function in KOA persons, with a trend towards greater effects with additional strength training. Notably, both groups substantially reduced InterMAT and improved specific strength (an index of muscle quality). Our hypothesis-generating work warrants exploration of the roles played by InterMAT and IntraMAT in exercise effects in KOA.

Associations of dexamethasone's effect on morphine consumption after total knee arthroplasty-Subgroup analyses.

The DEXamethasone twice for pain treatment after Total Knee Arthroplasty (DEX-2-TKA) trial showed that adding one and two doses of 24 mg intravenous dexamethasone to paracetamol, ibuprofen and local infiltration analgesia, reduced morphine consumption (primary outcome) within 48 h after TKA. We aimed to explore the differences in the effect of dexamethasone on morphine consumption in different subgroups. Quantile regression adjusted for site was used to test for significant interaction between the predefined dichotomised subgroups and treatment group. The subgroups were defined based on baseline data: sex (male/female), age (≤65 years/>65 years), American Society of Anaesthesiologists (ASA)-score (ASA I + II/III), visual analogue score of preoperative pain at rest (≤30 mm/>30 mm), pain during mobilisation (≤30 mm/>30 mm), type of anaesthesia (spinal anaesthesia/general anaesthesia and spinal converted to general anaesthesia), and prior daily use of analgesics (either paracetamol and/or NSAID/neither). These analyses were supplemented with post hoc multivariate linear regression analyses. Test of interaction comparing sex in the pairwise comparison between DX2 (dexamethasone [24 mg] + dexamethasone [24 mg]) versus placebo (p = .02), showed a larger effect of dexamethasone on morphine consumption in male patients compared to females. Test of interaction comparing age in the pairwise comparison between DX1 (dexamethasone [24 mg] + placebo) versus placebo (p = .04), showed a larger effect of dexamethasone on morphine consumption in younger patients (≤65 years) compared to older. All remaining subgroup analyses showed no evidence of a difference. The supplemental multivariate analyses did not support any significant interaction for sex (p = .256) or age (p = .730) but supported a significant interaction with the type of anaesthesia (p < .001). Our results from the quantile regression analyses indicate that the male sex and younger age (≤65 years) may be associated with a larger analgesic effect of dexamethasone than the effects in other types of patients. However, this is not supported by post-hoc multivariate linear regression analyses. The two types of analyses both supported a possible interaction with the type of anaesthesia.

Usage of guideline-adherent core treatments for knee osteoarthritis before and after consulting an orthopaedic surgeon: A prospective cohort study.

Objective: To describe 1) the proportion of patients with knee osteoarthritis (OA) undergoing guideline-adherent core treatments until six months after primary referral to an orthopaedic surgeon, 2) which specific treatment pathways these patients undertake and 3) the characteristics of patients choosing different treatment pathways. Design: This prospective cohort study consecutively invited patients referred to an orthopaedic surgeon due to knee OA at two Danish hospitals from October 2018 to December 2020. Before and six months after consulting the surgeon, patients answered a questionnaire reporting which treatments they had received for knee OA. The proportion receiving the combination of guideline-adherent treatments (i.e., exercise, education, and dietary weight management if needed) was determined. We evaluated the specific treatment usage before and until six months after the consultation and investigated characteristics of patients undertaking different pathways. Results: Out of 5251 eligible patients, 2574 (49%) had complete data and were included in analyses. 23% received guideline-adherent treatments, 10% had no treatment. Patients underwent 1143 unique treatment pathways, 62% including treatments not recommended/recommended against. Those who underwent guideline-adherent pathways had similar characteristics to those who did not but tended to be females, retired, had longer-lasting knee problems, have comorbidities, and higher education levels. Conclusions: Only one in four patients with knee OA received treatment adhering to clinical guidelines before and six months after consulting the surgeon. Patients used many different treatment pathways. There is a need for a structured effort to increase the use of guideline-adherent core treatments. Trial Identifiers: Registration: NCT03746184, Protocol: PMID: 34233992.

Impact of Nordic Arthroplasty Register Association (NARA) collaboration on demographics, methods and revision rates in knee arthroplasty: a register-based study from NARA 2000-2017.

BACKGROUND AND PURPOSE: We have previously observed differences in treatment and outcome of knee arthroplasties in the Nordic countries. To evaluate the impact of Nordic collaboration in the last 15 years we aimed to compare patient demographics, methods, and revision rates in primary knee arthroplasties among the 4 Nordic countries. PATIENTS AND METHODS: We included 535,051 primary knee arthroplasties reported 2000-2017 from the Nordic Arthroplasty Register Association (NARA) database. Kaplan-Meier analysis (KM) and restricted mean survival time (RMST) analysis were used to evaluate the cumulative revision rate (CRR) and RMST estimates with 95% confidence intervals (CI) and to compare countries in relation to risk of revision for any reason. RESULTS: After 2010, the increase in incidence of knee arthroplasty plateaued in Sweden and Denmark but continued to increase in Finland and Norway. In 2017 the incidence was highest in Finland with 226 per 105 person-years, while it was less than 150 per 105 in the 3 other Nordic countries. In total knee arthroplasties performed for osteoarthritis (OA), overall CRR at 15 years for revision due to any reason was higher in Denmark (CRR 9.6%, 95% CI 9.2-10), Norway (CRR 9.1%, CI 8.7-9.5), and Finland (CRR 7.0%, CI 6.8-7.3) compared with Sweden (CRR 6.6%, CI 6.4-6.8). There were differences among the countries in use of implant brand and type, fixation, patellar component, and use of unicompartmental knee arthroplasty. INTERPRETATION: We evinced a slowing growth of incidence of knee arthroplasties in the Nordic countries after 2010 with Finland having the highest incidence. We also noted substantial differences among the 4 Nordic countries, with Sweden having a lower risk of revision than the other countries. No impact of NARA could be demonstrated and CRR did not improve over time.

Opioid and Analgesic Use Before and After Revision Knee Arthroplasty for the Indications "Pain Without Loosening" Versus "Aseptic Loosening" - A Danish Nationwide Study.

BACKGROUND: It is uncertain if patients undergoing revision knee arthroplasty for "pain without loosening" are relieved of pain. This study aimed to compare pre- and postoperative analgesic consumption by patients undergoing revision for "pain without loosening" versus "aseptic loosening" and to determine predictors for postoperative long-term opioid use. METHODS: A retrospective nationwide study of 1,037 revisions for "pain without loosening" and 2,317 revisions for "aseptic loosening" during 1997-2018 from the Danish Knee Arthroplasty Register was carried out. Analgesic use was defined by prescription reimbursement, and long-term opioid use by prescription reimbursement in 4 consecutive quarters. RESULTS: In the preoperative year, 37% and 29% of patients revised for "pain without loosening" and "aseptic loosening" were opioid users compared to 32% and 30% in the postoperative year. Non-steroidal anti-inflammatory drug (NSAID) use was significantly lower postoperatively for both indications (35% versus 28% for "pain without loosening" and 33% versus 25% for "aseptic loosening"). Use of other analgesics was unchanged. Long-term opioid use increased postoperatively by 4% for patients with "pain without loosening" (P = .029) and by 3% for "aseptic loosening" (P = .003). New long-term opioid users (without preoperative long-term use) were 9% for "pain without loosening" and 8% for "aseptic loosening". Predictors of new long-term opioid use were other opioid-requiring diagnoses or procedures within the first postoperative year, Charlson Comorbidity Index (CCI) ≥3, and preoperative long-term NSAID use. CONCLUSION: The consumption of opioids decreased slightly after knee arthroplasty revision for the indication "pain without loosening", but not for "aseptic loosening". The amount of new long-term opioid users increased for both indications.

Prosthesis survival after revision knee arthroplasty for "pain without loosening" versus "aseptic loosening": a Danish nationwide study.

Background and purpose - Patients having a knee arthroplasty revision for the indication "pain without loosening" may have a higher risk of re-revisions than patients revised for other indications. The primary aim of this study was to compare the survival of knee arthroplasties revised for "pain without loosening" compared with "aseptic loosening." The second was to investigate the prosthesis survival rates in 3 surgical subgroups (total knee arthroplasty (TKA)-TKA; partial revision (revision of tibial or femoral component); unicompartmental knee arthroplasty-TKA) and to compare the prosthesis survival rates for 1997-2009 and 2010-2018. Patients and methods - 4,299 revisions were identified in the period 1997-2018 from the Danish Knee Arthroplasty Register. Of these, 1,111 (26%) were performed due to "pain without loosening" without any other indications, 674 (16%) due to "pain without loosening" combined with other indications, and 2,514 (59%) due to "aseptic loosening". Survival analysis was performed by a Cox multivariate analysis and Kaplan-Meier curves were presented. Results - The cumulated proportions of re-revision after 2, 5, and 20 years were 12% (95% CI 10-14), 18% (CI 16-20), and 23% (CI 20-25) for "pain without loosening" versus 11% (CI 9.3-12), 16% (CI 14-17), and 19% (CI 18-21) for "aseptic loosening." There were no statistically significant differences between the 2 indications in repeated analyses for each of the surgical subgroups. The hazard ratio for re-revision comparing "pain without loosening" with "aseptic loosening" was 1.03 (CI 0.87-1.2). The 8-year risk of re-revision for "pain without loosening" was 22% (CI 19-26) versus 22% (CI 20-25) for "aseptic loosening" in the period from 1997-2009, and 18% (CI 15-22) versus 14% (CI 13-16) in the period from 2010-2018. Interpretation - The risk of re-revision was similar for patients having a knee arthroplasty revision for the indication "pain without loosening" compared with "aseptic loosening." However, we observed a slight improvement of prosthesis survival rates after revisions for both indications from 1997-2009 to 2010-2018. We cannot recommend for or against revision in cases with "pain without loosening" based on these data alone.

Disentangling treatment pathways for knee osteoarthritis: a study protocol for the TREATright study including a prospective cohort study, a qualitative study and a cost-effectiveness study.

INTRODUCTION: Knee osteoarthritis (OA) is associated with chronic knee pain and functional disability that negatively affect the ability to carry out normal daily activities. Patients are offered a large variety of non-surgical treatments, often not in accordance with clinical guidelines. This observational study will provide a comprehensive overview of treatment pathways for knee OA during the first 2 years after consulting an orthopaedic surgeon, including timing and order of treatment modalities, predictors of treatment outcomes, cost-effectiveness of treatment pathways and patients' views on different treatment pathways. METHODS AND ANALYSIS: Patients with primary referrals to an orthopaedic surgeon due to knee OA are consecutively invited to participate and fill out a questionnaire prior to their consultation with an orthopaedic surgeon. Follow-up questionnaires will be obtained at 6 and 24 months after inclusion. Based on a prospective cohort study design, including questionnaires and register data, we will (1) describe treatment pathways for knee OA during the first 2 years after consulting an orthopaedic surgeon; (2) describe the characteristics of patients choosing different treatment pathways; (3) develop predictive models for patient-self-determined classifications of good and poor treatment outcomes; (4) evaluate the cost-effectiveness of treatment pathways that live up to clinical guidelines versus pathways that do not; based on a qualitative study design using semistructured individual interviews, we will (5) describe the patients' perspectives on treatment pathways for knee OA. ETHICS AND DISSEMINATION: The study is approved by the Danish regional ethical committee (journal number H-17017295) and the Danish Data Protection Agency (journal number AHH-2017-072). Data will be anonymised and handled in line with the General Data Protection Regulation and the Danish Data Protection Act. The study results will be submitted to international open-access peer-reviewed journals and disseminated at conferences. TRIAL REGISTRATION NUMBER: NCT03746184, pre-results.

Strength training in addition to neuromuscular exercise and education in individuals with knee osteoarthritis-the effects on pain and sensitization.

BACKGROUND: There is a lack of evidence of the relative effects of different exercise modes on pain sensitization and pain intensity in individuals with knee osteoarthritis (KOA). METHODS: Ninety individuals with radiographic and symptomatic KOA, ineligible for knee replacement surgery, were randomized to 12 weeks of twice-weekly strength training in addition to neuromuscular exercise and education (ST+NEMEX-EDU) or neuromuscular exercise and education alone (NEMEX-EDU). Outcomes were bilateral, lower-leg, cuff pressure pain- and tolerance thresholds (PPT, PTT), temporal summation (TS), conditioned pain modulation (CPM), self-reported knee pain intensity and number of painful body sites. RESULTS: After 12 weeks of exercise, we found significant differences in increases in PPT (-5.01 kPa (-8.29 to -1.73, p = .0028)) and PTT (-8.02 kPa (-12.22 to -3.82, p = .0002)) in the KOA leg in favour of ST+NEMEX-EDU. We found no difference in effects between groups on TS, CPM or number of painful body sites. In contrast, there were significantly greater pain-relieving effects on VAS mean knee pain during the last week (-8.4 mm (-16.2 to -0.5, p = .0364) and during function (-16.0 mm (-24.8 to -7.3, p = .0004)) in favour of NEMEX-EDU after 12 weeks of exercise. CONCLUSION: Additional strength training reduced pain sensitization compared to neuromuscular exercise and education alone, but also attenuated the reduction in pain intensity compared to neuromuscular exercise and education alone. The study provides the first dose- and type-specific insight into the effects of a sustained exercise period on pain sensitization in KOA. Future studies are needed to elucidate the role of different exercise modes. SIGNIFICANCE: This study is an important step towards better understanding the effects of exercise in pain management of chronic musculoskeletal conditions. We found that strength training in addition to neuromuscular exercise and education compared with neuromuscular exercise and education only had a differential impact on pain sensitization and pain intensity, but also that regardless of the exercise mode, the positive effects on pain sensitization and pain intensity were comparable to the effects of other therapeutic interventions for individuals with knee osteoarthritis.

Association between fixation type and revision risk in total knee arthroplasty patients aged 65 years and older: a cohort study of 265,877 patients from the Nordic Arthroplasty Register Association 2000-2016.

Background and purpose - The population of the Nordic countries is aging and the number of elderly patients undergoing total knee arthroplasty (TKA) is also expected to increase. Reliable fixation methods are essential to avoid revisions. We compared the survival of different TKA fixation concepts with cemented fixation as the gold standard.Patients and methods - We used data from the Nordic Arthroplasty Register Association (NARA) database of 265,877 unconstrained TKAs performed for patients aged ≥ 65 years with primary knee osteoarthritis between 2000 and 2016. Kaplan-Meier (KM) survival analysis with 95% confidence intervals (CI) and the Cox multiple-regression model were used to compare the revision risk of the fixation methods.Results - Cemented fixation was used in 243,166 cases, uncemented in 8,000, hybrid (uncemented femur with cemented tibia) in 14,248, and inverse hybrid (cemented femur with uncemented tibia) fixation in 463 cases. The 10-year KM survivorship (95% CI) of cemented TKAs was 96% (96 - 97), uncemented 94% (94 - 95), hybrid 96% (96 - 96), and inverse hybrid 96% (94 - 99), respectively. Uncemented TKA was associated with increased risk of revision compared with the cemented TKA; the adjusted hazard ratio was 1.3 (95% CI 1.1 - 1.4).Interpretation - Cemented, hybrid, and inverse hybrid TKAs showed 10-year survival rates exceeding 95%. Uncemented fixation was associated with an increased risk of revision in comparison with cemented fixation. As both hybrid and inverse hybrid fixation were used in only a limited number of TKAs, indicating possibility of selection bias in their favor, cemented TKA still remains the gold standard, as it works reliably in the hands of many.

DEX-2-TKA - DEXamethasone twice for pain treatment after Total Knee Arthroplasty: Detailed statistical analysis plan for a randomized, blinded, three-group multicentre clinical trial.

BACKGROUND: Optimization of post-operative pain treatment is of upmost importance. Multimodal analgesia is the main post-operative pain treatment principle, but the evidence on optimal analgesic combinations is unclear. With the "DEXamethasone twice for pain treatment after TKA" trial, we aim to investigate the role of one or two doses of glucocorticoid for post-operative pain treatment after total knee arthroplasty. To ensure transparency and minimization of bias, we present this article with a detailed statistical analysis plan, to be published before the last participant is enrolled. METHODS: "DEXamethasone twice for pain treatment after TKA" (DEX-2-TKA) is a randomized, blinded, three-group multicentre clinical trial. Participants will be randomized to one of three intervention groups: single dose of iv dexamethasone 24 mg, two consecutive doses of iv dexamethasone 24 mg or matching iv placebo. All three intervention groups will receive paracetamol, NSAID (ibuprofen) and local infiltration analgesia. Participants, treatment providers, outcome assessors, data managers, statisticians and conclusion drawers will be blinded to the allocated intervention. The primary outcome is total opioid consumption (iv morphine milligram equivalents) 0-48 hours post-operatively. Secondary outcomes are (1) visual analogue scale pain levels: (a) during active 45 degrees flexion of the knee at 24 and 48 hours post-operatively, (b) at rest at 24 and 48 hours post-operatively, and (c) during 0-24 hours (highest score) and 24-48 hours post-operatively (highest score); and (2) the proportion of participants with one or more adverse events within 48 hours post-operatively. DISCUSSION: The DEX-2-TKA trial will provide high quality data regarding benefits and harms of adding one or two high-doses of dexamethasone to a multimodal analgesic regimen. TRIAL REGISTRATION: EudraCT: 2018-001099-39 (08/06-18); ClinicalTrials.gov: NCT03506789 (24/04-2019).

The effect of fixation type on the survivorship of contemporary total knee arthroplasty in patients younger than 65 years of age: a register-based study of 115,177 knees in the Nordic Arthroplasty Register Association (NARA) 2000-2016.

Background and purpose - Cemented fixation is regarded as the gold standard in total knee arthroplasty (TKA). Among working-age patients, there has been controversy regarding the optimal fixation method in TKA. To address this issue, we conducted a register-based study to assess the survivorship of cemented, uncemented, hybrid, and inverse hybrid TKAs in patients aged < 65 years.Patients and methods - We used the Nordic Arthroplasty Register Association data of 115,177 unconstrained TKAs performed for patients aged < 65 years with primary knee osteoarthritis over 2000-2016. Kaplan-Meier (KM) survival analysis with 95% confidence intervals (CI) and Cox multiple-regression model with adjustment for age, sex, and nation were used to compare fixation methods in relation to revision for any reason.Results - The 10-year KM survivorship of cemented TKAs was 93.6% (95% CI 93.4-93.8), uncemented 91.2% (CI 90.1-92.2), hybrid 93.0% (Cl 92.2-93.8), and inverse hybrid 96.0% (CI 94.1-98.1). In the Cox model, hybrid TKA showed decreased risk of revision after 6 years' follow-up compared with the reference group (cemented) (hazard ratio [HR] 0.5 [CI 0.4-0.8]), while uncemented TKAs showed increased risk of revision both < 1 year (HR 1.4 [1.1-1.7]) and > 6 years' (HR 1.3 [1.0-1.7]) follow-up compared to the reference.Interpretation - Both cemented and hybrid TKAs had 10-year survival rates exceeding 92->93% in patients aged < 65 years. Cemented TKA, however, was used in the vast majority (89%) of the operations in the current study. As it performs reliably in the hands of many, it still deserves the status of gold standard for TKA in working-age patients.

DEX-2-TKA-DEXamethasone twice for pain treatment after Total Knee Arthroplasty: A protocol for a randomized, blinded, three-group multicentre clinical trial.

BACKGROUND: Multimodal analgesia is considered the leading principle for post-operative pain treatment, but no gold standard after total knee arthroplasty (TKA) exists. AIM: To investigate the beneficial and harmful effects of one or two doses of 24 mg intravenous dexamethasone (DXM) as part of a multimodal analgesic regimen (paracetamol, NSAID and perioperative local infiltration analgesia) after TKA. We hypothesize that addition of DXM will reduce post-operative opioid consumption. METHODS: DEXamethasone twice for pain treatment after TKA is a randomized, blinded, three-group multicentre clinical trial. Participants will be randomized to one of three groups: placebo, single dose of DXM or two consecutive doses of DXM. Participants, treatment providers and investigators will be blinded to the allocated intervention. The primary outcome is total opioid consumption (units of morphine equivalents) 0-48 hours post-operatively. INCLUSION CRITERIA: unilateral, primary TKA; age ≥18 years; American Society of Anesthesiologists-Score 1-3; Body Mass Index ≥18 and ≤40; for women-not pregnant; and written informed consent. EXCLUSION CRITERIA: allergy or contraindications against trial medication; daily use of high dose opioid and/or use of methadone/transdermal opioids; daily use of systemic glucocorticoids; dysregulated diabetes; and patients suffering from alcohol and/or drug abuse. Four-hundred-and-eighty-six eligible participants are needed to detect or discard a difference of 10 mg morphine equivalents 0-48 hours post-operatively maintaining a familywise error rate of 0.05 and a power of 90% for the three possible pairwise comparisons. DISCUSSION: Recruiting is planned to commence September 2018 and expected to finish March 2020. TRIAL REGISTRATION: EudraCT: 2018-001099-39 (08/06-18); ClinicalTrials.gov: NCT03506789 (24/04-2019). Editorial Comment This is the protocol for the largest randomized clinical trial investigating the effect of one or two doses of dexamethasones on pain treatment after total knee arthroplasty. Due to the pragmatic and rigerous design this study will deliver results of high quality and external validity.

The benefits of collaboration: the Nordic Arthroplasty Register Association.

The Nordic Arthroplasty Register Association (NARA) was established in 2007 by arthroplasty register representatives from Sweden, Norway and Denmark with the overall aim to improve the quality of research and thereby enhance the possibility for quality improvement with arthroplasty surgery. Finland joined the NARA collaboration in 2010.NARA minimal hip, knee and shoulder datasets were created with variables that all countries can deliver. They are dynamic datasets, currently with 25 variables for hip arthroplasty, 20 for knee arthroplasty and 20 for shoulder arthroplasty.NARA has published statistical guidelines for the analysis of arthroplasty register data. The association is continuously working on the improvement of statistical methods and the application of new ones.There are 31 published peer-reviewed papers based on the NARA databases and 20 ongoing projects in different phases. Several NARA publications have significantly affected clinical practice. For example, metal-on-metal total hip arthroplasty and resurfacing arthroplasty have been abandoned due to increased revision risk based on i.a. NARA reports. Further, the use of uncemented total hip arthroplasty in elderly patients has decreased significantly, especially in Finland, based on the NARA data.The NARA collaboration has been successful because the countries were able to agree on a common dataset and variable definitions. The collaboration was also successful because the group was able to initiate a number of research projects and provide answers to clinically relevant questions. A number of specific goals, set up in 2007, have been achieved and new one has emerged in the process. Cite this article: EFORT Open Rev 2019;4 DOI: 10.1302/2058-5241.4.180058.

Bone remodeling of the proximal tibia after uncemented total knee arthroplasty: secondary endpoints analyzed from a randomized trial comparing monoblock and modular tibia trays-2 year follow-up of 53 cases.

Background and purpose - Bone remodeling as a response to bone trauma, postoperative immobilization, and device-related bone reactions can lead to loss of bone stock and increase the risk of periprosthetic fracture and aseptic loosening. This study investigates the adaptive bone remodeling of the proximal tibia after uncemented total knee arthroplasty (TKA). Patients and methods - We performed a 2-year follow up of 53 patients (mean age 62 (38-70) years, 27 of whom were men, who received an uncemented TKA in a randomized controlled trial with bone mineral density (BMD) as secondary endpoint. Patients were randomized to 2 groups of either monoblock (A) or modular (B) polyethylene design. The TKAs were performed using the uncemented Zimmer Nexgen trabecular metal. Measurements of BMD were done postoperatively and after 3, 6, 12, and 24 months. BMD was measured in 3 regions of interest (ROI). Results and interpretation - In group A statistically significant changes in BMD were seen after 24 months in both the medial and lateral ROI. BMD decreased medially by 15% (p = 0.004) and laterally by 13% (p = 0.01). In group B the BMD changes were limited and after 24 months returned to the preoperative values. The differences in BMD change between groups were statistically significant in both the medial (p = 0.03) and lateral (p = 0.02) ROI. In the distal ROI we found no significant change in BMD in either group. A significantly different bone remodeling pattern of the proximal tibia was seen in the 2 groups with a higher degree of bone loss in the knees that received the monoblock polyethylene design, indicating that the flexible monoblock implant design, previously shown to improve fixation, does not decrease the bone loss of the proximal tibia.

Effect of Combination of Paracetamol (Acetaminophen) and Ibuprofen vs Either Alone on Patient-Controlled Morphine Consumption in the First 24 Hours After Total Hip Arthroplasty: The PANSAID Randomized Clinical Trial.

Importance: Multimodal postoperative analgesia is widely used but lacks evidence of benefit. Objective: Investigate beneficial and harmful effects of 4 nonopioid analgesics regimens. Design, Setting, and Participants: Randomized, blinded, placebo-controlled, 4-group trial in 6 Danish hospitals with 90-day follow-up that included 556 patients undergoing total hip arthroplasty (THA) from December 2015 to October 2017. Final date of follow-up was January 1, 2018. Interventions: Participants were randomized to receive paracetamol (acetaminophen) 1000 mg plus ibuprofen 400 mg (n = 136; PCM + IBU), paracetamol 1000 mg plus matched placebo (n = 142; PCM), ibuprofen 400 mg plus matched placebo (n = 141; IBU), or half-strength paracetamol 500 mg plus ibuprofen 200 mg (n = 140; HS-PCM + IBU) orally every 6 hours for 24 hours postoperatively, starting 1 hour before surgery. Main Outcomes and Measures: Two co-primary outcomes: 24-hour morphine consumption using patient-controlled analgesia in pairwise comparisons between the 4 groups (multiplicity-adjusted thresholds for statistical significance, P < .0042; minimal clinically important difference, 10 mg), and proportion of patients with 1 or more serious adverse events (SAEs) within 90 days (multiplicity-adjusted thresholds for statistical significance, P < .025). Results: Among 559 randomized participants (mean age, 67 years; 277 [50%] women), 556 (99.5%) completed the trial and were included in the analysis. Median 24-hour morphine consumption was 20 mg (99.6% CI, 0-148) in the PCM + IBU group, 36 mg (99.6% CI, 0-166) for PCM alone, 26 mg (99.6% CI, 2-139) for IBU alone, and 28 mg (99.6% CI, 2-145) for HS-PCM + IBU. The median difference in morphine consumption between the PCM + IBU group vs PCM alone was 16 mg (99.6% CI, 6.5 to 24; P < .001); for the PCM-alone group vs HS-PCM + IBU, 8 mg (99.6% CI, -1 to 14; P = .001); and for the PCM + IBU group vs IBU alone, 6 mg (99.6% CI, -2 to 16; P = .002). The difference in morphine consumption was not statistically significant for the PCM + IBU group vs HS-PCM + IBU (8 mg [99.6% CI, -2 to 16]; P = .005) or for the PCM-alone group vs IBU alone (10 mg [99.6% CI, -2 to 16]; P = .004) after adjustment for multiple comparisons and 2 co-primary outcomes. There was no significant difference between the IBU-alone group vs HS-PCM + IBU (2 mg [99.6% CI, -10 to 7]; P = .81). The proportion of patients with SAEs in groups receiving IBU was 15%, and in the PCM-alone group, was 11%. The relative risk of SAE was 1.44 (97.5% CI, 0.79 to 2.64; P = .18). Conclusions and Relevance: Among patients undergoing THA, paracetamol plus ibuprofen significantly reduced morphine consumption compared with paracetamol alone in the first 24 hours after surgery; there was no statistically significant increase in SAEs in the pooled groups receiving ibuprofen alone vs with paracetamol alone. However, the combination did not result in a clinically important improvement over ibuprofen alone, suggesting that ibuprofen alone may be a reasonable option for early postoperative oral analgesia. Trial Registration: ClinicalTrials.gov Identifier: NCT02571361.

Bone Remodeling of the Distal Femur After Uncemented Total Knee Arthroplasty-A 2-Year Prospective DXA Study.

Loss of bone stock as a response to the bone trauma, immobilization, and stress shielding related to joint replacement surgery increases the risk of fracture of the distal femur after total knee arthroplasty. Previous studies of uncemented femoral components have reported very high levels of bone loss in the distal femur. This study investigates the adaptive bone remodeling of the distal femur after uncemented total knee arthroplasty. We performed a 2-year follow-up of 53 patients (mean age 61.5 [38-70] years, F/M = 27/26, body mass index 29.5) who because of osteoarthritis received an uncemented total knee arthroplasty. All patients received a NexGen CR-Flex Porous Femoral Component. Measurements of bone mineral density of the distal femur using dual-energy X-ray absorptiometry were performed postoperatively and after 3, 6, 12, and 24 months. Bone mineral density (g/cm2) was measured in 3 regions of interest in the periprosthetic bone of the distal femur. Repeated measures analysis of variance and Tukey post hoc test for bone mineral density changed over time (p < 0.05 were considered significant). In the distal femur, significant changes in bone mineral density were seen after 24 months of follow-up, and bone mineral density decreased by 23.6% in the anterior region behind the anterior flange of the prosthesis (p < 0.001), 10.1% in the posterior region (p < 0.001), and 5.5% in the most proximal region (p < 0.001). We found highly significant bone mineral change in the distal femur after uncemented total knee arthroplasty, most pronounced in the anterior region, where a decrease in bone mineral density of almost 25%, was seen. Taking the expected age-related decay in bone mineral density in this age group into consideration, the decrease was substantial and must be considered to predispose to periprosthetic fractures.

Hospital volume and the risk of revision in Oxford unicompartmental knee arthroplasty in the Nordic countries -an observational study of 14,496 cases.

BACKGROUND: High procedure volume and dedication to unicompartmental knee arthroplasty (UKA) has been suggested to improve revision rates. This study aimed to quantify the annual hospital volume effect on revision risk in Oxfordu nicompartmental knee arthroplasty in the Nordic countries. METHODS: 14,496 cases of cemented medial Oxford III UKA were identified in 126 hospitals in the four countries included in the Nordic Arthroplasty Register Association (NARA) database from 2000 to 2012. Hospitals were divided by quartiles into 4 annual procedure volume groups (≤11, 12-23, 24-43 and ≥44). The outcome was revision risk after 2 and 10 years calculated using Kaplan Meier method. Multivariate Cox regression analysis was used to assess the Hazard Ratio (HR) of any revision due to specific reasons with 95% confidence intervals (CI). RESULTS: The implant survival was 80% at 10 years in the volume group ≤11 procedures per year compared to 83% in other volume groups. The HR adjusted for age category, sex, year of surgery and nation was 0.87 (95% CI: 0.76-0.99, p = 0.036) for the group 12-23 procedures per year, 0.78 (95% CI: 0.68-0.91, p = 0.002) for the group 24-43 procedures per year and 0.82 (95% CI: 0.70-0.94, p = 0.006) for the group ≥44 procedures per year compared to the low volume group. Log-rank test was p = 0.003. The risk of revision for unexplained pain was 40-50% higher in the low compared with other volume groups. CONCLUSION: Low volume hospitals performing ≤11 Oxford III UKAs per year were associated with an increased risk of revision compared to higher volume hospitals, and unexplained pain as revision cause was more common in low volume hospitals.

Microbiological diagnosis in revision of infected knee arthroplasties in Denmark.

BACKGROUND: Revision of infected knee arthroplasties is associated with high failure rates (30-40%). An understanding of the microbiology is important to optimize treatment and outcome. We describe microbiological diagnostic practice and diagnosis in revision of infected knee arthroplasties. METHODS: One hundred and two partial revisions (open debridement and exchange of tibial insert) and 213 two-stage procedures performed due to infection in 275 patients from 1 July 2011 to 30 June 2013 were included and analysed by linkage to data from a nationwide registry on microbiological test results. RESULTS: 78 (24.8%) revisions were culture negative, 192 (60.9%) showed monomicrobial growth and 43 (14.3%) polymicrobial growth. Staphylococcus aureus was the most frequent isolate in mono-culture in 70 (22.2%) revisions and in polymicrobial culture in 15 revisions with a total frequency of 27.0%. Only one case (1.4%) of methicillin-resistance was registered. Coagulase-negative staphylococci (CoNS) were frequent, sole pathogen in 65 revisions and in polymicrobial cultures in 28 revisions with a total frequency of 29.5%. A pre-operative knee aspiration was performed in 50% and preoperative blood cultures were performed in 22% of cases. In 73% of the preoperative knee-aspirations bacteriological findings were fully or partially in accordance with intraoperative cultures. In 54% of the later re-revisions due to infection (treatment-failures) the cultured species differed from or was not detected at index revision surgery. CONCLUSIONS: The 25% culture negative cases in combination with only 50% preoperative knee aspirations and prevailing high failure rates confirm the need for improvement of diagnostic practice and treatment of infected knee arthroplasties.

Low Preoperative BMD Is Related to High Migration of Tibia Components in Uncemented TKA-92 Patients in a Combined DEXA and RSA Study With 2-Year Follow-Up.

BACKGROUND: The fixation of uncemented tibia components in total knee arthroplasty may rely on the bone quality of the tibia; however, no previous studies have shown convincing objective proof of this. Component migration is relevant as it has been shown to predict aseptic loosening. METHODS: We performed 2-year follow-up of 92 patients who underwent total knee arthroplasty surgery with an uncemented tibia component. Bone mineral density (BMD; g/cm2) of the tibia host bone was measured preoperatively using dual energy X-ray absorptiometry. The proximal tibia was divided into 2 regions of interest (ROI) in the part of the tibia bone where the components were implanted. Radiostereometric analysis was performed postoperatively and after 3, 6, 12, and 24 months. The primary outcome was maximum total point motion (MTPM; mm). Regression analysis was performed to evaluate the relation between preoperative BMD and MTPM. RESULTS: We found low preoperative BMD in ROI1 to be significantly related to high MTPM at all follow-ups: after 3 months (R2 = 20%, PBMD = 0.017), 6 months (R2 = 29%, PBMD = 0.003), 12 months (R2 = 33%, PBMD = 0.001), and 24 months (R2 = 27%, PBMD = 0.001). We also found a significant relation for low BMD in ROI2 and high MTPM: 3 months (R2 = 19%, PBMD = 0.042), 6 months (R2 = 28%, PBMD = 0.04), 12 months (R2 = 32%, PBMD = 0.004), and 24 months (R2 = 24%, PBMD = 0.005). CONCLUSION: Low preoperative BMD in the tibia is related to high MTPM. Thus, high migration of uncemented tibia components is to be expected in patients with poor bone quality.

Different incidences of knee arthroplasty in the Nordic countries.

Background and purpose - The annual number of total knee arthroplasties (TKAs) has increased worldwide in recent years. To make projections regarding future needs for primaries and revisions, additional knowledge is important. We analyzed and compared the incidences among 4 Nordic countries Patients and methods - Using Nordic Arthroplasty Register Association (NARA) data from 4 countries, we analyzed differences between age and sex groups. We included patients over 30 years of age who were operated with TKA or unicompartmental knee arthroplasty (UKA) during the period 1997-2012. The negative binomial regression model was used to analyze changes in general trends and in sex and age groups. Results - The average annual increase in the incidence of TKA was statistically significant in all countries. The incidence of TKA was higher in women than in men in all 4 countries. It was highest in Finland in patients aged 65 years or more. At the end of the study period in 2012, Finland's total incidence was double that of Norway, 1.3 times that of Sweden and 1.4 times that of Denmark. The incidence was lowest in the youngest age groups (< 65 years) in all 4 countries. The proportional increase in incidence was highest in patients who were younger than 65 years. Interpretation - The incidence of knee arthroplasty steadily increased in the 4 countries over the study period. The differences between the countries were considerable, with the highest incidence in Finland. Patients aged 65 years or more contributed to most of the total incidence of knee arthroplasty.