Abstract
Background
To evaluate the effect of statin use on osteoarthritis (OA) incidence/progression using magnetic resonance imaging (MRI) in a population-based cohort with predominantly ...pre-radiographic knee OA.
Methods
A cohort aged 40–79 years with knee pain was recruited using random population sampling and followed for 7 years. Baseline exclusions were inflammatory arthritis, recent knee surgery/injury, and inability to undergo MRI. At baseline, current statin use was ascertained. Baseline and follow-up MRIs were read semi-quantitatively for cartilage damage (grade 0–4, 0/1 collapsed, 6 regions), osteophytes (grade 0–3, 8 regions), bone marrow lesions (BML) (grade 0–3, 6 regions) and effusion (grade 0–3). The primary outcome was cartilage damage incidence/progression, while secondary outcomes were incidence/progression of osteophytes, BML, and effusion, each defined as an increase by ≥1 grade at any region. To ensure population representative samples, sample weights were used. Logistic regression was used to assess the association of statin use at baseline with incidence/progression of MRI outcomes. Analyses were adjusted for sex, age, BMI, and multiple comorbidities requiring statin therapy.
Results
Of 255 participants evaluated at baseline, 122 completed the 7-year follow-up. Statin use was not significantly associated with progression of cartilage damage (OR 0.82; 95% CI 0.17, 4.06), osteophytes (OR 3.48; 95% CI 0.40, 30.31), BML (OR 0.61; 95% CI 0.12, 3.02), or effusion (OR 2.38; 95% CI 0.42, 13.63), after adjusting for confounders.
Conclusion
In this population-based cohort of predominantly pre-radiographic knee OA, statins did not affect MRI incidence/progression of cartilage damage, BML, osteophytes or effusion. Therefore, statin use does not appear to affect people with pre-radiographic stages of knee OA.
The use of tramadol among osteoarthritis (OA) patients has been increasing rapidly around the world, but population-based studies on its safety profile among OA patients are scarce. We sought to ...determine if tramadol use in OA patients is associated with increased risks of all-cause mortality, cardiovascular diseases (CVD), venous thromboembolism (VTE), and hip fractures compared with commonly prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) or codeine.
Using administrative health datasets from British Columbia, Canada, we conducted a sequential propensity score-matched cohort study among all OA patients between 2005 and 2013. The tramadol cohort (i.e., tramadol initiation) was matched with four comparator cohorts (i.e., initiation of naproxen, diclofenac, cyclooxygenase-2 Cox-2 inhibitors, or codeine). Outcomes are all-cause mortality, first-ever CVD, VTE, and hip fractures within the year after the treatment initiation. Patients were followed until they either experienced an event, left the province, or the 1-year follow-up period ended, whichever occurred first. Cox proportional hazard models were used to estimate hazard ratios after adjusting for competing risk of death.
Overall, 100,358 OA patients were included (mean age: 68 years, 63% females). All-cause mortality was higher for tramadol compared to NSAIDs with rate differences (RDs/1000 person-years, 95% CI) ranging from 3.3 (0.0-6.7) to 8.1 (4.9-11.4) and hazard ratios (HRs, 95% CI) ranging from 1.2 (1.0-1.4) to 1.5 (1.3-1.8). For CVD, no differences were observed between tramadol and NSAIDs. Tramadol had a higher risk of VTE compared to diclofenac, with RD/1000 person-years (95% CI) of 2.2 (0.7-3.7) and HR (95% CI) of 1.7 (1.3-2.2). Tramadol also had a higher risk of hip fractures compared to diclofenac and Cox-2 inhibitors with RDs/1000 person-years (95% CI) of 1.9 (0.4-3.4) and 1.7 (0.2-3.3), respectively, and HRs (95% CI) of 1.6 (1.2-2.0) and 1.4 (1.1-1.9), respectively. No differences were observed between tramadol and NSAIDs for all events.
OA patients initiating tramadol have an increased risk of mortality, VTE, and hip fractures within 1 year compared with commonly prescribed NSAIDs, but not with codeine.
To develop a whole-joint, unidimensional, irreversible, and fine-grained MRI knee osteoarthritis (OA) severity score, based on cartilage, osteophytes and meniscus (OA-COM), and to predict progression ...across different severity states using OA-COM as outcome and clinical variables as predictors. Optimal OA-COM thresholds were 12, 18, 24 and 30, for KL grades 1 to 4. Significant predictors of progression (depending on threshold) included physical exam effusion, malalignment and female sex, with other selected predictors age, BMI and crepitus. OA-COM (0-54 range) is a whole-joint, unidimensional, irreversible, and fine-grained MRI OA severity score reflecting cartilage, osteophytes and menisci. OA-COM scores 12, 18, 24 and 30 are equivalent to KL grades 1 to 4, while offering fine-grained differentiation of states between KL grades, and within pre-radiographic disease (KL = 0) or late-stage disease (KL = 4). In modeling, several clinical variables predicted progression across different states over 7 years.
The purpose of this study was to compare three strategies for reducing population health burden of osteoarthritis (OA): improved pharmacological treatment of OA-related pain, improved access to joint ...replacement surgery, and prevention of OA by reducing obesity and overweight.
We applied a validated computer microsimulation model of OA in Canada. The model simulated a Canadian-representative open population aged 20 years and older. Variables in the model included demographics, body mass index, OA diagnosis, OA treatment, mortality, and health-related quality of life. Model parameters were derived from analyses of national surveys, population-based administrative data, a hospital-based cohort study, and the literature. We compared 8 what-if intervention scenarios in terms of disability-adjusted life years (DALYs) relative to base-case, over a wide range of time horizons.
Reductions in DALYs depended on the type of intervention, magnitude of the intervention, and the time horizon. Medical interventions (a targeted increase in the use of painkillers) tended to produce effects quickly and were, therefore, most effective over a short time horizon (a decade). Surgical interventions (increased access to joint replacement) were most effective over a medium time horizon (two decades or longer). Preventive interventions required a substantial change in BMI to generate a significant impact, but produced more reduction in DALYs than treatment strategies over a very long time horizon (several decades).
In this population-based modeling study we assessed the potential impact of three different burden reduction strategies in OA. Data generated by our model may help inform the implementation of strategies to reduce the burden of OA in Canada and elsewhere.
To determine associations between features of osteoarthritis (OA) on MRI and knee pain severity and knee pain progression.
Baseline, 3.3- and 7.5-year assessments were performed for 122 subjects with ...baseline knee pain (age 40-79), sample-weighted for population (with knee pain) representativeness. MRIs were scored for: osteophytes (0:absent to 3:large); cartilage (0:normal to 4:full thickness defect; 0/1 collapsed); subchondral sclerosis (0:none to 3:>50% of site), subchondral cyst (0:absent to 3:severe), bone marrow lesions (0:none to 3:≥50% of site); and meniscus (0:normal to 3:maceration/resection), in 6-8 regions each. Per feature, scores were averaged across regions. Effusion/synovitis (0:absent to 3:severe) was analyzed as ≥2 vs. <2. Linear models predicted WOMAC knee pain severity (0-100), and binary models predicted 10+ (minimum perceptible clinical improvement MPCI) and 20+ (minimum clinically important difference MCID) increases. Models were adjusted for age, sex, BMI (and follow-up time for longitudinal models).
Pain severity was associated with osteophytes (7.17 per unit average; 95% CI = 3.19, 11.15) and subchondral sclerosis (11.03; 0.68, 21.39). MPCI-based pain increase was associated with osteophytes (odds ratio per unit average 3.20; 1.36, 7.55), subchondral sclerosis (5.69; 1.06, 30.44), meniscal damage (1.68; 1.08, 2.61) and effusion/synovitis ≥2 (2.25; 1.07, 4.71). MCID-based pain increase was associated with osteophytes (3.79; 1.41, 10.20) and cartilage defects (2.42; 1.24, 4.74).
Of the features investigated, only osteophytes were consistently associated with pain cross-sectionally and longitudinally in all models. This suggests an important role of bone in early knee osteoarthritis.
Cam and/or pincer morphologies (CPM) are potential precursors to hip osteoarthritis (OA) and important contributors to non-arthritic hip pain. However, only some CPM hips develop OA and/or pain, and ...it is not clear why. Anterior impingement between the femoral head/neck contour and acetabular rim during motion is a proposed pathomechanism. Understanding how activity and deformity combine to produce impingement may shed light on the causes of hip degeneration/pain. The objective of this study was to determine the accuracy of a subject-specific hip model driven by subject-specific motion data in predicting anterior impingement.
We recruited 22 participants with CPM (both with and without pain) and 11 controls. We collected subject-specific 3D kinematics during squatting and sitting flexion, adduction, and internal rotation (FADIR) (an active and a passive maneuver, respectively, proposed to provoke impingement). We then developed 3D subject-specific hip models from supine 3T hip MRI scans that predicted the beta angle (a measure of anterior femoroacetabular clearance) for each frame of acquired kinematics. To assess the accuracy of these predictions, we measured the beta angle directly in the final position of squatting and sitting FADIR using open MRI scans. We selected the frame of motion data matching the static imaged posture using the least-squares error in hip angles. Model accuracy for each subject was calculated as the absolute error between the open MRI measure of beta and the model prediction of beta at the matched time frame. To make the final model accuracy independent of goodness of match between open MRI position and motion data, a threshold was set for least-squares error in hip angles, and only participants that were below this threshold were considered in the final model accuracy calculation, yielding results from 10 participants for squatting and 7 participants for sitting FADIR.
For squatting and sitting FADIR, we found an accuracy of 1.1°(0.8°) and 1.3°(mean (SD), and root mean squared error, respectively) and 0.5°(0.3°) and 0.6°, respectively.
This subject-specific hip model predicts anterior femoroacetabular clearance with an accuracy of about 1°, making it useful to predict anterior impingement during activities measured with motion analysis.
Abstract
Objective
To identify magnetic resonance imaging (MRI) predictors (cartilage C, osteophytes O and meniscus M scores) of prevalent and 3-year incident medial tibiofemoral (MTF) and lateral ...tibiofemoral (LTF) knee joint tenderness and patellofemoral (PF) grind.
Methods
Population-based knee pain cohort aged 40–79 was assessed at baseline (
N
= 255), 3- and 7-year follow-up (
N
= 108 × 2 = 216). COM scores were measured at 6/8/6 subregions respectively. Age-sex-BMI adjusted logistic models predicted prevalence versus relevant COM predictors (medial, lateral or patellar / trochlear groove scores). Fully adjusted models also included all relevant COM predictors. Binary generalized estimating equations models predicting 3-year incidence were also adjusted for individual follow-up time between cycles.
Results
Significant predictors of prevalent MTF tenderness: medial femoral cartilage (fully adjusted odds ratio aOR 1.84; 95% confidence interval CI 1.11, 3.05), female (aOR = 3.05; 1.67, 5.58), BMI (aOR = 1.53 per 5 units BMI; 1.10, 2.11). Predictors of prevalent LTF tenderness: female (aOR = 2.18; 1.22, 3.90). There were no predictors of prevalent PF grind in the fully adjusted model. However, medial patellar osteophytes was predictive in the age-sex-BMI adjusted model. There were no predictors of 3-year incident MTF tenderness. Predictors of 3-year incident LTF tenderness: female (aOR = 3.83; 1.25, 11.77). Predictors of 3-year incident PF grind: lateral patellar osteophytes (aOR = 4.82; 1.69, 13.77). In the age-sex-BMI adjusted model, patellar cartilage was also a predictor.
Conclusion
We explored potential MRI predictors of prevalent and 3-year incident MTF/LTF knee joint tenderness and PF grind. These findings could guide preemptive strategies aimed at reducing these symptoms in the present and future (3-year incidence).
Abstract
Background
Low back pain (LBP) causes the highest morbidity burden globally. The purpose of the present study was to project and compare the impact of three strategies for reducing the ...population health burden of LBP: weight loss, ergonomic interventions, and an exercise program.
Methods
We have developed a microsimulation model of LBP in Canada using a new modeling platform called SimYouLate. The initial population was derived from Cycle 1 (2001) of the Canadian Community Health Survey (CCHS). We modeled an open population 20 years of age and older. Key variables included age, sex, education, body mass index (BMI), type of work, having back problems, pain level in persons with back problems, and exercise participation. The effects of interventions on the risk of LBP were obtained from the CCHS for the effect of BMI, the Global Burden of Disease Study for occupational risks, and a published meta-analysis for the effect of exercise. All interventions lasted from 2021 to 2040. The population health impact of the interventions was calculated as a difference in years lived with disability (YLDs) between the base-case scenario and each intervention scenario, and expressed as YLDs averted per intervention unit or a proportion (%) of total LBP-related YLDs.
Results
In the base-case scenario, LBP in 2020 was responsible for 424,900 YLDs in Canada and the amount increased to 460,312 YLDs in 2040. The effects of the interventions were as follows: 27,993 (95% CI 23,373, 32,614) YLDs averted over 20 years per 0.1 unit change in log-transformed BMI (9.5% change in BMI) among individuals who were overweight and those with obesity, 19,416 (16,275, 22,557) YLDs per 1% reduction in the proportion of workers exposed to occupational risks, and 26,058 (22,455, 29,661) YLDs averted per 1% increase in the proportion of eligible patients with back problems participating in an exercise program.
Conclusions
The study provides new data on the relationship between three types of interventions and the resultant reductions in LBP burden in Canada. According to our model, each of the interventions studied could potentially result in a substantial reduction in LBP-related disability.
To evaluate whether knee osteoarthritis (OA) manifestations predict depression and anxiety using cross-sectional and longitudinal prediction models.
A population-based cohort (n = 122) with knee ...pain, aged 40-79, was evaluated at baseline, 3 and 7 years. Baseline predictors were: age decade; sex; BMI ≥ 25; physical exam knee effusion; crepitus; malalignment; quadriceps atrophy; flexion; flexion contracture; Kellgren-Lawrence (KL) x-ray grade (0/1/2/3+); WOMAC pain ≥25; WOMAC stiffness ≥25; self-reported knee swelling; and knee OA diagnosis (no/probable/definite). Depression and anxiety, cutoffs 5+ and 7+ respectively, were measured via the Hospital Anxiety and Depression Scale. We fit logistic models at each cycle using multivariable models selected via lowest Akaike's information criterion.
Baseline depression model: sex (female OR = 0.27; 0.10, 0.76) and KL grade (KL 1 OR = 4.21; 1.31, 13.48). Three-year depression model: KL grade (KL 1 OR = 18.92; 1.73, 206.25). Seven-year depression model: WOMAC stiffness ≥25 (OR = 3.49; 1.02, 11.94) and flexion contracture ≥1 degree (OR = 0.23; 0.07, 0.81). Baseline anxiety model: knee swelling (OR = 4.11; 1.51, 11.13) and age (50-59 vs. 40-49 OR = 0.31 0.11, 0.85; 60-69 OR = 0.07 0.01, 0.42). Three-year anxiety model: WOMAC stiffness ≥25 (OR = 5.80; 1.23, 27.29) and KL grade (KL 1 OR = 6.25; 1.04, 37.65). Seven-year anxiety model: sex (female OR = 2.71; 0.87, 8.46).
Specific knee OA-related manifestations predict depression and anxiety cross-sectionally, 3 years in the future, and for depression, 7 years in the future. This information may prove useful to clinicians in helping to identify patients most at risk of present or future depression and anxiety, thus facilitating preemptive discussions that may help counter that risk.
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