PLOD2 gene expression in infrapatellar fat pad is correlated with fat mass in obese patients with end-stage knee osteoarthritis.

Objective: To investigate associations between obesity-linked systemic factors and gene expression indicative for the inflammatory and fibrotic processes in the infrapatellar fat pad (IFP), in a population of obese patients with end-stage knee osteoarthritis (KOA). Methods: We collected human IFPs from 48 patients with a mean body mass index (BMI) of 35.44 â€‹kg/m2 during total knee replacement procedures. These patients were part of a randomized controlled trial and met the criteria of having OA and a BMI of ≥30 â€‹kg/m2. Blood samples were collected to assess serum levels of glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, and leptin. Total body composition was measured using dual-energy X-ray absorptiometry. Gene expressions of IL6, TNFA, COL1A1, IL1B, ASMA, PLOD2 in the IFP were analyzed. Results: Univariate analysis resulted in a positive correlation between BMI and procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2) expression (r2 â€‹= â€‹0.13). In univariate analyses of obesity-linked systemic factors and PLOD2, significant correlations were found for lean mass (r2 â€‹= â€‹0.20), fat mass (r2 â€‹= â€‹0.20), serum cholesterol (r2 â€‹= â€‹0.17), serum triglycerides (r2 â€‹= â€‹0.19) and serum leptin (r2 â€‹= â€‹0.10). A multiple linear regression model indicated fat mass to be a strong predictor of PLOD2 production in the IFP (r2 â€‹= â€‹0.22, P â€‹= â€‹0.003). Conclusion: Our study demonstrates the positive association between fat mass and PLOD2 expression in the IFP of obese end-stage knee OA patients. This may indicate that within this patient population the fibrotic process in the IFP is influenced by systemic adipose tissue, next to local inflammatory processes.

Patterns of knee osteoarthritis management in general practice: a retrospective cohort study using electronic health records.

OBJECTIVE: This study determined patterns of knee osteoarthritis (OA) management by general practitioners (GPs) using routine healthcare data from Dutch general practices from 2011 to 2019. DESIGN: A retrospective cohort study was conducted using the Integrated Primary Care Information database between 2011 and 2019. Electronic health records (EHRs) of n = 750 randomly selected knee OA patients (with either codified or narrative diagnosis) were reviewed against eligibility criteria and n = 503 patients were included. Recorded information was extracted on GPs' management from six months before to three years after diagnosis and patterns of management were analysed. RESULTS: An X-ray referral was the most widely recorded management modality (63.2%). The next most widely recorded management modalities were a referral to secondary care (56.1%) and medication prescription or advice (48.3%). Records of recommendation of/referral to other primary care practitioners (e.g. physiotherapists) were found in only one third of the patients. Advice to lose weight was least common (1.2%). Records of medication prescriptions or recommendation of/referral to other primary care practitioners were found more frequently in patients with an X-ray referral compared to patients without, while records of secondary care referrals were found less frequently. Records of an X-ray referral were often found in narratively diagnosed knee OA patients before GPs recorded a code for knee OA in their EHR. CONCLUSION: These findings emphasize the importance of better implementing non-surgical management of knee OA in general practice and on initiatives for reducing the overuse of X-rays for diagnosing knee OA in general practice.

Is radiographic osteoarthritis associated with pain and disability of the ankle?

Objective: Ankle osteoarthritis (OA) is relatively understudied. It often affects younger people compared to OA in other joints. Evidence on the association between radiographic OA and ankle symptoms remains contradicting. We therefore examined the association of degree of radiographic talocrural, subtalar and talonavicular OA with severity of ankle pain, disability and predominant symptoms. Method: A cross-sectional study was conducted in a radiology department serving primary and secondary care. From the total study population (adults referred for ankle radiography), patients with chronic ankle complaints were selected (N â€‹= â€‹231). Before radiography, participants completed a questionnaire on severity of ankle pain and disability using the Ankle Osteoarthritis Scale (AOS), and on their predominant symptoms, i.e. pain, functional loss, stiffness and/or instability. To assess the associations of the Kellgren-Lawrence scores (0, 1 or ≥2) with the primary outcomes (AOS), linear regression, and with the secondary outcomes predominant symptoms, logistic regression analyses were applied. Results: Radiographic OA was not associated with AOS-pain and -disability. Radiographic talocrural OA was associated with functional loss (OR 3.26, 95% CI: 1.31; 8.11). A positive trend was seen between radiographic talonavicular OA and stiffness (OR 2.63, 95% CI: 0.97; 7.15). Conclusion: The presence of radiographic OA is not associated with severity of ankle pain and disability in patients with chronic ankle complaints referred for ankle radiography. However, radiographic talocrural OA is associated with functional loss and radiographic talonavicular OA with stiffness as predominant symptom. These findings may contribute to better recognition of ankle OA in clinical practice.

Acetabular dysplasia and the risk of developing hip osteoarthritis at 2,5,8, and 10 years follow-up in a prospective nationwide cohort study (CHECK).

OBJECTIVE: To assess the relationship between acetabular dysplasia (AD) and the risk of incident and end-stage radiographic hip osteoarthritis (RHOA) over 2,5,8 and 10 years. DESIGN: Individuals (n = 1002) aged between 45 and 65 from the prospective Cohort Hip and Cohort Knee (CHECK) were studied. Anteroposterior pelvic radiographs were obtained at baseline and 2,5,8, and 10-years follow-up. False profile radiographs were obtained at baseline. AD was defined as a lateral center edge angle, an anterior center edge angle, or both <25° at baseline. The risk of developing RHOA was determined at each follow-up moment. Incident RHOA was defined by Kellgren & Lawrence (KL) grade ≥2 or total hip replacement (THR), end-stage RHOA by a KL grade ≥3 or THR. Associations were expressed in odds ratios (OR) using logistic regression with generalized estimating equations. RESULTS: AD was associated with the development of incident RHOA at 2 years follow-up (OR 2.46, 95% CI 1.00-6.04), 5 years follow-up (OR 2.28, 95% CI 1.20-4.31), and 8 years follow-up (OR 1.86, 95%CI 1.22-2.83). AD was only associated with end-stage RHOA at 5 years follow-up (OR 3.75, 95% CI 1.02-13.77). No statistically significant associations were observed between AD and RHOA at 10-years follow-up. CONCLUSION: Baseline AD in individuals between 45 and 65 years is associated with an increased risk of developing RHOA within 2- and 5 years. However, this association seems to weaken after 8 years and disappears after 10 years.

Metabolic syndrome and the progression of knee osteoarthritis on MRI.

OBJECTIVE: Metabolic osteoarthritis (OA) is one of the proposed clinical phenotypes defined by the existence of metabolic syndrome (MetS). This study aimed to (1) investigate whether MetS and its components are associated with progression of knee OA magnetic resonance imaging (MRI) features, and (2) to evaluate the interaction of MetS with menopause and progression of MRI features. METHOD: 682 women from the Rotterdam Study who participated in a sub-study with knee MRI data available and 5-year follow-up were included. Tibiofemoral (TF) and patellofemoral (PF) OA features were assessed with the MRI Osteoarthritis Knee Score. MetS was quantified by the MetS severity Z-score. Generalized estimating equations were used to evaluate associations between MetS and menopausal transition and progression of MRI features. RESULTS: MetS severity at baseline was associated with progression of osteophytes in all compartments, bone marrow lesions (BMLs) in the PF compartment, and cartilage defects in the medial TF compartment. Waist circumference was associated with progression of osteophytes in all compartments and cartilage defects in the medial TF compartment. High-density lipoprotein (HDL)-cholesterol levels were associated with progression of osteophytes in the medial and lateral TF compartment and glucose levels with osteophytes in the PF and medial TF compartment. No interactions were found between MetS with menopausal transition and MRI features. CONCLUSION: Women with higher MetS severity at baseline showed progression of osteophytes, BMLs, and cartilage defects, indicating more structural knee OA progression after 5 years. Further studies are required to understand whether targeting MetS components may prevent the progression of structural knee OA in women.

Does pain medication influence outcomes in elderly people seeking care for back pain? BACE cohort study.

BACKGROUND: Back pain is common among older adults resulting in the high societal and economic burden of persistent pain and disability. Pain medications are frequently prescribed for back pain, especially among older patients, but the efficacy of analgesics on back pain in this patient population remains under debate. In the present study, we investigated the outcomes (i.e. pain intensity and disability) of pain medication use in older people with back pain participating in a prospective cohort study. METHODS: A total of 669 patients aged >55 years consulting a general practitioner for a new episode of back complaints were included in this study. The association between pain medication use and outcomes (pain intensity and disability) was assessed at 3-month follow-up. RESULTS: Pain medication users were observed to experience more pain and disability at baseline compared with non-users. At 3-month follow-up, patients from all subgroups (e.g. pain medication users versus non-users) improved over time. Yet medication users had higher pain intensity and poorer disability scores compared with non-users. Patients who de-escalated or stopped pain medication had lower pain and disability than non-users. When comparing different types of medications (i.e. paracetamol, non-steroidal anti-inflammatory drugs, opioids), none of the groups showed better scores regarding pain and disability in users compared with non-users. Opioid users displayed the highest levels of pain and disability. CONCLUSIONS: In the present study, although patients who de-escalated or stopped analgesics had less pain and disability, pain medication overall does not result in better outcomes in older people with back pain. SIGNIFICANCE: Older patients taking pain medication did not report better outcomes than the ones who did not, except for those who de-escalated or stopped pain medication. Caution should be taken in prescribing pain medication for older patients with back pain in primary care.

Potential surrogate outcomes in individuals at high risk for incident knee osteoarthritis.

OBJECTIVE: To study potential surrogate outcomes for osteoarthritis (OA) incidence by evaluating the association of short-term changes in clinical and imaging biomarkers with long-term clinical knee OA incidence. DESIGN: Middle-aged women with overweight/obesity, but free of knee symptoms were recruited through their general practitioners. At baseline, after 2.5 years, and after 6.5 years, questionnaires, physical examination, radiographs, and Magnetic resonance imaging (MRI) scans were obtained. The percentage of knees with a minimal clinically important difference for knee pain severity, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain/stiffness/function, and joint space narrowing, and of those with progression/regression of medial knee alignment, chronic knee pain, radiographic osteophytes, and cartilage defects, bone marrow lesions, osteophytes, and effusion/synovitis on MRI were determined. For each of these potential surrogate outcomes with ≥10% improvement or progression in the population over 2.5 years, the association with incident clinical knee OA, defined using the combined ACR-criteria, after 6.5 years was determined. RESULTS: Most pre-defined potential surrogate outcomes showed ≥10% change in the population over 2.5 years, but only worsening of TF cartilage defects, worsening of TF osteophytes on MRI, and an increase in pain severity were significantly associated with greater clinical knee OA incidence after 6.5 years. These potential surrogate outcomes had high specificity and negative predictive value (89-91%) and low sensitivity and positive predictive value (20-28%) CONCLUSIONS: Worsening of TF cartilage defects and TF osteophytes on MRI, and increased pain severity could be seen as surrogate outcomes for long-term OA incidence. However, higher positive predictive values seem warranted for the applicability of these factors in future preventive trials.

3D patellar shape is associated with radiological and clinical signs of patellofemoral osteoarthritis.

OBJECTIVE: To examine the association between 3D patellar shape and 1) isolated magnetic resonance imaging (MRI)-based patellofemoral osteoarthritis (PFOA), 2) the morphological features of PFOA, and 3) the clinical symptoms of PFOA. DESIGN: MRI data from 66 women with isolated MRI-based PFOA and 66 age- and BMI-matched healthy women were selected from a cohort study. The patellae were manually segmented from MRI scans and used to create a 3D statistical shape model (SSM) of the patella. Structural abnormalities were semi-standardized scored on MRI using MRI osteoarthritis knee score (MOAKS). Regression analyses were applied to determine the associations between the shape parameters retrieved from the SSM, group status, clinical symptoms, and structural abnormalities. RESULTS: Four shape variants showed a statistically significant (<0.05) association with the group status. The mode responsible for most of the shape variations showed participants with PFOA possess a relatively thicker dorsal bump on the articular part of the patella, compared to patellae of control participants. Three of these variants showed an association with the presence of osteophytes and cartilage loss on the patella. Multiple associations were found between patellar shape and the clinical symptoms of PFOA. CONCLUSIONS: Patellar shape is associated with the prevalence of MRI-based PFOA in women. Some shape variants were also associated with clinical symptoms. Interestingly, one particular shape variant associated with the presence of MRI-based PFOA was earlier shown to be associated with structural abnormalities associated with OA in a population aged under 40. This may suggest that patellar shape may be an early detectable risk factor for PFOA.

Smaller intercondylar notch size and smaller ACL volume increase posterior cruciate ligament rupture risk.

PURPOSE: Little is known about risk factors for sustaining a posterior cruciate ligament (PCL) rupture. Identifying risk factors is the first step in preventing a PCL rupture from occurring. The morphology of the knee in patients who ruptured their PCL may differ from that of control patients. The hypothesis was that the intercondylar notch dimensions, 3-D volumes of the intercondylar notch and, the 3-D volumes of both the ACL and the PCL were correlated to the presence of a PCL rupture. METHODS: The magnetic resonance imaging (MRI) scans of 30 patients with a proven PCL rupture were compared to 30 matched control patients with proven intact ACL and PCL. Control patients were selected from patients with knee trauma during sports but without cruciate ligament injury. Patients have been matched for age, height, weight, BMI, and sex. The volumes of the intercondylar notch and both the ACL and PCL were measured on 3D reconstructions. Second, the bicondylar width, the notch width, and the notch width index were measured of all subjects. The relationship between our measurements and the presence of a PCL rupture was analysed. RESULTS: The results show a significant difference in the volumes of the intercondylar notch and the ACL between patients with a ruptured PCL and control patients. Patients with a PCL rupture have smaller intercondylar notch volumes and smaller ACL volumes. There were no significant differences in the bicondylar width, notch width, and notch width index. In the control patients, a significant correlation between the volume of the PCL and the volume of the ACL was found (0.673, p < 0.001). CONCLUSION: Patients with a PCL rupture have smaller intercondylar volumes and smaller ACL volumes when compared to control patients. Second, patients with smaller ACL volumes have smaller PCL volumes. This study shows, for the first time, that there are significant size and volume differences in the shape of the knee between patients with a PCL rupture and control patients. LEVEL OF EVIDENCE: IV.

Occurrence of comorbidity following osteoarthritis diagnosis: a cohort study in the Netherlands.

OBJECTIVE: To determine the risk of comorbidity following diagnosis of knee or hip osteoarthritis (OA). DESIGN: A cohort study was conducted using the Integrated Primary Care Information database, containing electronic health records of 2.5 million patients from the Netherlands. Adults at risk for OA were included. Diagnosis of knee or hip OA (=exposure) and 58 long-term comorbidities (=outcome) were defined by diagnostic codes following the International Classification of Primary Care coding system. Time between the start of follow-up and incident diagnosis of OA was defined as unexposed, and between diagnosis of OA and the end of follow-up as exposed. Age and sex adjusted hazard ratios (HRs) comparing comorbidity rates in exposed and unexposed patient time were estimated with 99.9% confidence intervals (CI). RESULTS: The study population consisted of 1,890,712 patients. For 30 of the 58 studied comorbidities, exposure to knee OA showed a HR larger than 1. Largest positive associations (HR with (99.9% CIs)) were found for obesity 2.55 (2.29-2.84) and fibromyalgia 2.06 (1.53-2.77). For two conditions a HR < 1 was found, other comorbidities showed no association with exposure to knee OA. For 26 comorbidities, exposure to hip OA showed a HR larger than 1. The largest were found for polymyalgia rheumatica 1.81 (1.41-2.32) and fibromyalgia 1.70 (1.10-2.63). All other comorbidities showed no associations with hip OA. CONCLUSION: This study showed that many comorbidities were diagnosed more often in patients with knee or hip OA. This suggests that the management of OA should consider the risk of other long-term-conditions.

Prevalence of radiographic ankle osteoarthritis in different subgroups of patients referred for ankle radiography.

BACKGROUND: Ankle osteoarthritis(OA) has detrimental effects on physical health and has a relatively early disease onset compared to OA in other joints. However, the prevalence of radiographic ankle OA in different subgroups of patients referred for ankle radiography remains unknown. Therefore, we aimed to determine the prevalence of radiographic talocrural, subtalar and talonavicular OA(Kellgren-Lawrence scale ≥2) in a population referred for ankle radiography. Moreover, we aimed to identify differences in prevalence between specific subgroups of patients i.e. Body Mass Index (BMI), sex, age and reason for referral. METHODS: A cross-sectional study was conducted at a radiology department serving primary and secondary care. Patients completed a questionnaire before radiography. Features of radiographic ankle OA were assessed for subgroups of patients, including; BMI, sex, age and reason for referral (chronic vs (sub)acute complaints). To examine the difference in (features of) radiographic OA for subgroups, multinomial and logistic regression were used to calculate Odds Ratios (ORs), with adjustment for age, sex and BMI. RESULTS: Data from 893 patients that visited the radiology department across 16 months in 2017 or 2018 were included for analysis. Prevalence of radiographic ankle OA was 9.2%, 0.4% and 7.0%, for the talocrural, subtalar and talonavicular joint, respectively. Obesity was associated with radiographic talonavicular OA (adjusted OR 2.16, 95%CI:1.09; 5.26). Radiographic talocrural and talonavicular OA were both positively associated with male sex [(adjusted OR 4.64, 95%CI:276; 7.81) and (adjusted OR 1.95, 95%CI:1.13; 3.35), respectively]. CONCLUSION: Radiographic ankle OA was more common in men and obese patients that were referred to radiology.

Associations between biomarkers of matrix metabolism and inflammation with pain and fatigue in participants suspected of early hip and or knee osteoarthritis: data from the CHECK study.

OBJECTIVES: To assess the associations of biomarkers in serum [highsensitivity C-reactive protein (hs-CRP), serum cartilage oligomeric protein (sCOMP), serum propeptide of type I procollagen (sPINP) and serum osteocalcin (sOC)] and urine [urinary type II collagen telopeptide (uCTX-2)] with the extent and progression of nocturnal pain, pain while walking, and fatigue in participants with hip and/or knee pain suspected to be early stage osteoarthritis (OA). METHODS: hs-CRP, uCTX-2, sCOMP, sPINP and sOC were measured at baseline in 1,002 participants of the Cohort Hip and Cohort Knee (CHECK). Nocturnal pain, pain while walking and fatigue were assessed by self-reported questionnaires at baseline and 2-year follow-up. Associations between these biomarkers and symptoms were examined using logistic and linear regression analyses. RESULTS: hs-CRP was significantly associated with mild nocturnal pain (OR 1.18 95% CI 1.01-1.37), with mild and moderate pain while walking (OR 1.17 95% CI 1.01-1.35 and OR 1.56 95% CI 1.29-1.90, respectively) and with progression of nocturnal pain (OR 1.25 95% CI 1.07-1.46). uCTX-2 was associated with mild nocturnal pain (OR 1.40 95% CI 1.05-1.85) and with mild and severe-extreme pain while walking (OR 1.35 95% CI 1.04-1.75 and OR 2.55 95% CI 1.03-6.34, respectively). sPINP was associated with severe-extreme nocturnal pain (OR 0.45 95% CI 0.25-0.82). No significant associations were found for sCOMP and sOC, nor for any of the biomarkers and fatigue. CONCLUSION: This study of biomarkers in a large cohort of participants with hip and/or knee pain suspected to reflect early stage hip and/or knee OA suggests that inflammation and cartilage matrix degeneration play a role in pain, but not in fatigue.

The responsiveness of muscle strength tests in adults with intellectual disabilities.

BACKGROUND: Muscle strength is both a strong predictor for future negative health outcomes and a prerequisite for physical fitness and daily functioning of adults with ID. Therefore, it is important to be able to monitor the muscle strength of adults with ID over time. The aim of this study is to assess the responsiveness of five field tests that measure muscle strength and endurance (grip strength, hand-held dynamometry of leg extension and arm flexion, 10RM-test of the seated squat and the biceps curl, 30-s chair stand and the 5-times Chair stand) in adults with ID after a 24-week resistance-exercise training (RT) programme. METHOD: The responsiveness of the five muscle strength and endurance tests was assessed by correlating the change scores of the five tests with the slope of the training progression of specific exercises within the RT-programme, namely, the step up, seated squat, biceps curl and triceps curl. RESULTS: The 10RM-test of the seated squat was significantly correlated with the step up (R = 0.53, P = 0.02) and the seated squat (R = 0.70 P = 0.00). None of change scores on the other tests was significantly correlated with the training progression of the exercises. CONCLUSION: The 10RM test of the seated squat could potentially be used to evaluate the effects of an RT-programme in adults with ID. Responsiveness of the grip strength, hand held dynamometry, 10RM-test of the biceps curl, 30-s chair stand and the 5-times chair stand could not yet be confirmed.

Estimating incidence and prevalence of hip osteoarthritis using electronic health records: a population-based cohort study.

OBJECTIVE: To determine the incidence and prevalence of hip osteoarthritis (OA) in electronic health records (EHRs) of Dutch general practices by using narrative and codified data. METHOD: A retrospective cohort study was conducted using the Integrated Primary Care Information database. An algorithm was developed to identify patients with narratively diagnosed hip OA in addition to patients with codified hip OA. Incidence and prevalence estimates among people aged ≥30 were assessed from 2008 to 2019. The association of comorbidities with codified hip OA diagnosis was analysed using multivariable logistic regression. RESULTS: Using the hip OA narrative data algorithm (positive predicted value = 72%) in addition to codified hip OA showed a prevalence of 1.76-1.95 times higher and increased from 4.03% in 2008 to 7.34% in 2019. The incidence was 1.83-2.41 times higher and increased from 6.83 to 7.78 per 1000 person-years from 2008 to 2019. Among codified hip OA patients, 39.4% had a previous record of narratively diagnosed hip OA, on average approximately 1.93 years earlier. Hip OA patients with a previous record of spinal OA, knee OA, hypertension, and hyperlipidaemia were more likely to be recorded with a hip OA code. CONCLUSION: This study using Dutch EHRs showed that epidemiological estimates of hip OA are likely to be an underestimation. Using our algorithm, narrative data can be added to codified data for more realistic epidemiological estimates based on routine healthcare data. However, developing a valid algorithm remains a challenge, possibly due to the diagnostic complexity of hip pain in general practice.

Clustering of comorbidities and associated outcomes in people with osteoarthritis - A UK Clinical Practice Research Datalink study.

OBJECTIVE: To examine the clusters of chronic conditions present in people with osteoarthritis and the associated risk factors and health outcomes. METHODS: Clinical Practice Research Datalink (CPRD) GOLD was used to identify people diagnosed with incident osteoarthritis (n = 221,807) between 1997 and 2017 and age (±2 years), gender, and practice matched controls (no osteoarthritis, n = 221,807) from UK primary care. Clustering of people was examined for 49 conditions using latent class analysis. The associations between cluster membership and covariates were quantified by odds ratios (OR) using multinomial logistic regression. General practice (GP) consultations, hospitalisations, and all-cause mortality rates were compared across the clusters identified at the time of first diagnosis of osteoarthritis (index date). RESULTS: In both groups, conditions largely grouped around five clusters: relatively healthy; cardiovascular (CV), musculoskeletal-mental health (MSK-MH), CV-musculoskeletal (CV-MSK) and metabolic (MB). In the osteoarthritis group, compared to the relatively healthy cluster, strong associations were seen for 1) age with all clusters; 2) women with the MB cluster (OR 5.55: 5.14-5.99); 3) obesity with the CV-MSK (OR 2.11: 2.03-2.20) and CV clusters (OR 2.03: 1.97-2.09). The CV-MSK cluster in the osteoarthritis group had the highest number of GP consultations and hospitalisations, and the mortality risk was 2.45 (2.33-2.58) times higher compared to the relatively healthy cluster. CONCLUSIONS: Of the five identified clusters, CV-MSK, CV, and MSK-MH are more common in OA and CV-MSK cluster had higher health utilisation. Further research is warranted to better understand the mechanistic pathways and clinical implications.

Can we predict which patients with plantar heel pain are more likely to benefit from insoles? A secondary exploratory analysis of a randomized controlled trial.

BACKGROUND: Plantar heel pain (PHP) is a common cause of foot complaints, for which treatment with custom-made insoles is frequently applied. So far few studies have investigated patient characteristics that predict response to these treatments. The aim of this secondary exploratory analysis was twofold; firstly, to identify patient characteristics that predict prognosis in patients with PHP treated with insoles, and secondly to identify characteristics that might interact with treatment with insoles. METHODS: Data from a randomized trial in which participants received either custom insoles (N = 70) or sham insoles (N = 69) were used. At baseline, information was collected on demographics, foot symptoms, foot and ankle range of motion, navicular drop, presence of neuropathic pain, physical activity and other illnesses in the last 12 months. The primary outcome of this study was the Foot Function Index score (FFI) at 26 weeks. Multivariable linear regression models were generated to identify patients characteristics that predict the outcome for each type of intervention (i.e. insoles and GP-led usual care). RESULTS: We found two variables associated with a better function score at 26 weeks in patients treated with insoles, female sex (ß - 9.59 95%CI -17.87; - 1.31) and a lower FFI score at baseline (ß 0.56 95%CI 0.30; 0.82). Explorative analyses in patients treated with insoles showed no significant interaction effects between the type of insole (custom-made versus sham) and any of the potential predictive factors. CONCLUSION: When communicating about the effect of insoles for PHP clinicians should take sex and the amount of pain and disability at first presentation into account. Women and people with better foot function scores at baseline (according to FFI) might respond better to treatment with insoles in terms of foot function. TRIAL REGISTRATION: Trial registration: NTR5346 .

Genicular artery embolization as a novel treatment for mild to moderate knee osteoarthritis: protocol design of a randomized sham-controlled clinical trial.

INTRODUCTION: Knee osteoarthritis is a common disease with pain as the most prevalent symptom. Previous cohort studies have shown genicular artery embolization to reduce pain symptoms in patients with mild to moderate knee osteoarthritis. Patients resistant to conservative therapy but not eligible yet for surgical treatment due to young age or comorbidities may profit from an effective and sustained pain reduction treatment. This study is a randomized sham-controlled trial to evaluate the efficacy of genicular artery embolization in patients with knee osteoarthritis. METHODS AND ANALYSIS: Fifty-eight patients with mild-to-moderate knee osteoarthritis will be recruited and randomly allocated to the treatment or control group in a 1:1 ratio. Participants in the treatment group will undergo genicular artery embolization. Patients in the control group will undergo sham treatment. Outcome measurements will be assessed at baseline and after 1, 4, 8, and 12 months with questionnaires, pressure pain threshold testing, and MR imaging. The MR imaging protocol is designed to (semi)quantitatively assess osteoarthritis in the knee joint. The primary outcome is the change from baseline of the Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale after 4 months. Secondary outcomes include change in osteoarthritis-related questionnaires, pressure pain threshold, and OA-related MRI features, particularly synovitis and bone marrow lesions. ETHICS AND DISSEMINATION: This trial will determine the efficacy of genicular artery embolization compared to a sham treatment. This is of importance to assess before proceeding to larger-scale efficiency studies and, ultimately, implementing this treatment into day to day clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT03884049. Registered on 21 March 2019.

Bone Union Assessment with Computed Tomography (CT) and Statistical Associations with Mechanical or Histological Testing: A Systematic Review of Animal Studies.

Objective and accurate assessment of bone union after a fracture, arthrodesis, or osteotomy is relevant for scientific and clinical purposes. Bone union is most accurately imaged with computed tomography (CT), but no consensus exists about objective assessment of bone union from CT images. It is unclear which CT-generated parameters are most suitable for bone union assessment. The aim of this review of animal studies is to find which CT-generated parameters are associated most strongly with actual bone union. Scientific databases were systematically searched. Eligible studies were studies that (1) were animal studies, (2) created a fracture, (3) assessed bone union with CT, (4) performed mechanical or histological testing as measure of actual bone union, and (5) associated CT-generated outcomes to mechanical or histological testing results. Two authors selected eligible studies and performed risk of bias assessment with QUADAS-2 tool. From 2567 studies that were screened, thirteen studies were included. Most common CT parameters that were investigated were bone mineral density, bone volume, and total callus volume. Studies showed conflicting results concerning the associations of these parameters with actual bone union. CT-assessed torsional rigidity (assessed by three studies) and callus density (assessed by two studies) showed best results. The studies investigating these two parameters reported moderate to strong associations with actual bone union. CT-assessed torsional rigidity and callus density seem the most promising parameters to represent actual bone union after a fracture, arthrodesis, or osteotomy.Prospero trial registration number: CRD42020164733.

The prevalence of radiographic thumb base osteoarthritis: a meta-analysis.

INTRODUCTION: Osteoarthritis (OA) affects millions of people worldwide. In hand OA, the thumb base is the most affected single joint. The reported radiographic prevalence ranges from 0 to 100%, making the true radiographic prevalence unclear. Hence, we conducted a meta-analysis on the age and sex-specific prevalence of radiographic thumb base OA. METHODS: We performed a search in Embase, Medline Ovid, Web of Science Core Collection, Cochrane Central Register of Trials, and Google Scholar. We included studies of the general population that reported thumb base OA for males and females separately based on a hand radiograph and reported the age of these groups. Using meta-regression, we estimated the odds ratio (OR) of having radiographic thumb base OA for age and sex, while adjusting for within-study correlation. RESULTS: The initial search yielded 4,278 articles; we finally included 16 studies that reported the age- and sex-stratified prevalence. Taken together, there were 104 age and gender specific-prevalence rates that could be derived from the 16 studies. The prevalence of radiographic OA for the 50-year-old male and female participants was 5.8% and 7.3%, respectively, while the respective prevalence for 80-year-old male and female participants was 33.1% and 39.0%. We found an OR for having radiographic OA of 1.06 (95%CI [1.055-1.065], p < 0.001) per increasing year of age, and 1.30 (95%CI: 1.05-1.61], p = 0.014) for females. CONCLUSION: In the general population, radiographic thumb base OA is more prevalent in females and is strongly associated with age.

Statistical shape modeling of the hip and the association with hip osteoarthritis: a systematic review.

OBJECTIVE: To summarize available evidence on the association between hip shape as quantified by statistical shape modeling (SSM) and the incidence or progression of hip osteoarthritis. DESIGN: We conducted a systematic search of five electronic databases, based on a registered protocol (available: PROSPERO CRD42020145411). Articles presenting original data on the longitudinal relationship between radiographic hip shape (quantified by SSM) and hip OA were eligible. Quantitative meta-analysis was precluded because of the use of different SSM models across studies. We used the Newcastle-Ottawa Scale (NOS) for risk of bias assessment. RESULTS: Nine studies (6,483 hips analyzed with SSM) were included in this review. The SSM models used to describe hip shape ranged from 16 points on the femoral head to 85 points on the proximal femur and hemipelvis. Multiple hip shape features and combinations thereof were associated with incident or progressive hip OA. Shape variants that seemed to be consistently associated with hip OA across studies were acetabular dysplasia, cam morphology, and deviations in acetabular version (either excessive anteversion or retroversion). CONCLUSIONS: Various radiographic, SSM-defined hip shape features are associated with hip OA. Some hip shape features only seem to increase the risk for hip OA when combined together. The heterogeneity of the used SSM models across studies precludes the estimation of pooled effect sizes. Further studies using the same SSM model and definition of hip OA are needed to allow for the comparison of outcomes across studies, and to validate the found associations.