Association of long-term use of non-steroidal anti-inflammatory drugs with knee osteoarthritis: a prospective multi-cohort study over 4-to-5 years.

This study examines the long-term impact of non-steroidal anti-inflammatory drugs (NSAIDs) on the progression of symptoms and structural deterioration of the joint in knee osteoarthritis. The study analyzes data from 4197 participants (8394 knees) across the Osteoarthritis Initiative (OAI), Multicenter Osteoarthritis Study (MOST), and Cohort Hip and Cohort Knee (CHECK) over 4-to-5 years. Adjustments were made for major covariates. We focussed on binary outcomes to assess the presence or absence of significant changes. We found that, relative to non-users, individuals using NSAIDs long-term were significantly more likely to experience aggravated symptoms exceeding the minimally clinically important difference, specifically, pain (OR: 2.04, 95% CI: 1.66-2.49), disability (OR: 2.21, 95% CI: 1.74-2.80), and stiffness (OR: 1.58, 95% CI: 1.29-1.93). Long-term users also faced a higher probability than non-users of having total knee replacement (OR: 3.13, 95% CI: 2.08-4.70), although no significant difference between long-term users and non-users was observed for structural deterioration in the knee joint (OR: 1.25, 95% CI: 0.94-1.65). While acknowledging the limitations of this study due to its observational design and the potential for bidirectional causality, these findings suggest that long-term NSAID use could accelerate the progression to total knee replacement by markedly exacerbating symptoms.

Predicting the onset of end-stage knee osteoarthritis over two- and five-years using machine learning.

OBJECTIVE: Identifying participants who will progress to advanced stage in knee osteoarthritis (KOA) trials remains a significant challenge. Current tools, relying on total knee replacements (TKR), fall short in reliability due to the extraneous factors influencing TKR decisions. Acknowledging these limitations, our study identifies a critical need for a more robust metric to assess severe KOA. The end-stage KOA (esKOA) measure, which combines symptomatic and radiographic criteria, serves as a solid indicator. To enhance future trials that use esKOA as an endpoint, our study focuses on developing and validating a machine-learning tool to identify individuals likely to develop esKOA within 2 to 5 years. DESIGN: Utilizing the Osteoarthritis Initiative (OAI) data, we trained models on 3,114 participants and validated them with 606 participants for the right knee, and similarly for the left knee, with external validation from the Multicentre Osteoarthritis Study (MOST) involving 1,602 participants. We aimed to predict esKOA onset at 2-to-2.5 years and 4-to-5 years, defining esKOA by severe radiographic KOA with moderate/severe symptoms or mild/moderate radiographic KOA with persistent/intense symptoms. Our analysis considered 51 candidate predictors, including demographics, clinical history, physical examination, and X-ray evaluations. An online tool predicting esKOA progression, based on models with ten and nine predictors for the right and left knees, respectively, was developed. RESULTS: External validation (MOST) for the right knee at 2.5 years yielded an Area Under Curve (AUC) of 0.847 (95 % CI 0.811 to 0.882), and at 5 years, 0.853 (95 % CI 0.823 to 0.881); for the left knee at 2.5 years, AUC was 0.824 (95 % CI 0.782 to 0.857), and at 5 years, 0.807 (95 % CI 0.768 to 0.843). Models with fewer predictors demonstrated comparable performance. The online tool is available at: https://eskoa.shinyapps.io/webapp/. CONCLUSION: Our study unveils a robust, externally validated machine learning tool proficient in predicting the onset of esKOA over the next 2 to 5 years. Our tool can lead to more efficient KOA trials.

Investigation of the association of long-term NSAID use with radiographic hip osteoarthritis over four to five years: Data from the OAI and CHECK studies.

Objective: To examine the relationship between long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) and the incidence and progression of radiographic hip osteoarthritis (RHOA), as well as the degeneration of individual radiographic features. Methods: We analyzed data from the Osteoarthritis Initiative (OAI) and the Cohort Hip and Cohort Knee (CHECK) study. Our exposure was the number of years of NSAID use over a 4-to-5-year follow-up period. Our outcomes were the incidence and progression of RHOA over a 4-to-5-year follow-up as assessed using a modified Croft grade in OAI and the Kellgren-Lawrence (K/L) grade in CHECK. The incidence of RHOA was defined as having RHOA (grade ≥2) at follow-up and investigated in "incidence cohorts" of hips without RHOA at baseline (grade <2). The progression of RHOA was defined as an increase of ≥1 grade at follow-up from baseline and investigated in "progression cohorts" of hips with RHOA at baseline (grade ≥2). Additionally, we assessed the degeneration of nine specific radiographic features, such as joint space narrowing and osteophytes, defined by a grade increase of ≥1 â€‹at follow-up from baseline, in all cohorts. Results: In the incidence cohorts, there were 5153 hips in OAI and 1011 in CHECK; in the progression cohorts, there were 285 and 106 hips, respectively. There was no association between NSAID use and the outcomes investigated. Conclusion: Over 4-to-5 years, long-term NSAID use showed no association with the incidence or progression of RHOA, or with the degeneration of individual radiographic features.

Investigation of the Associations of Smoking With Hip Osteoarthritis: A Baseline Cross-Sectional and Four- to Five-Year Longitudinal Multicohort Study.

OBJECTIVE: This study aimed to investigate the effect of smoking on the prevalence, incidence, and progression of hip osteoarthritis (OA). We used data from the Osteoarthritis Initiative (OAI) and the Cohort Hip and Cohort Knee (CHECK) studies. METHODS: We analyzed 9,386 hips from 4,716 participants (OAI cohort) and 1,954 hips from 977 participants (CHECK cohort). The primary exposure was smoking status at baseline, categorized as current, former, or never smoker. Outcomes of radiographic hip OA (RHOA) and symptomatic hip OA were evaluated both cross-sectionally at baseline and longitudinally over a 4- to 5-year follow-up, with adjustments for major covariates. RESULTS: No significant differences were observed between current or former smokers and never smokers for any of the outcomes examined, either at baseline or at the 4- to 5-year follow-up. In the cross-sectional analysis, the odds ratios with 95% confidence intervals for the prevalence of RHOA for current and former smokers were 1.29 (0.68-2.46) and 0.99 (0.70-1.40) in the OAI cohort and 1.38 (0.78-2.44) and 0.85 (0.54-1.32) in the CHECK cohort, respectively. In the longitudinal analysis, odds ratio with 95% confidence intervals for the incidence of RHOA were 1.03 (0.23-4.50) and 0.92 (0.46-1.85) in the OAI cohort and 0.61 (0.34-1.11) and 1.00 (0.69-1.44) in the CHECK cohort, respectively. CONCLUSION: Our study found no clear association between smoking and the prevalence, incidence, or progression of RHOA or symptomatic hip OA, either at baseline or over a 4- to 5-year period.

Evaluation of a measure of end-stage knee osteoarthritis compared to total knee replacement: An observational study using multicohort data.

OBJECTIVES: To determine if an end-stage knee osteoarthritis (esKOA) measure, based on symptomatic and radiographic criteria, can indicate progression to severe KOA earlier and with fewer research participants than total knee replacement (TKR). We employed both interventional and observational study designs as examples to estimate the required sample sizes. EsKOA in a knee was declared if either of the following two conditions were met: 1) moderate, intense, or severe symptoms of KOA indicated by pain and disability measurement and severe KOA indicated by radiographically-assessed knee structure; 2) intense or severe symptoms of KOA indicated by pain and disability measurement and frequent knee pain with mild or moderate KOA as indicated by radiographically-assessed knee structure. METHODS: We examined the association between weight loss from baseline to 2-to-2.5-year and 4-to-5-year follow-ups and the odds of esKOA and TKR in 5,593 participants (10,357 knees) from the Osteoarthritis Initiative (OAI) and the Multicenter Osteoarthritis Study (MOST). We also estimated the sample sizes needed for interventional and observational study designs to detect a 10, 20, or 50% reduction in the incidence of esKOA and TKR. RESULTS: The association of weight loss with both esKOA and TKR was detected at the 4-to-5-year follow-up. However, at the 2-to-2.5-year follow-up, the association was detected for esKOA but not TKR. The required sample sizes for detecting associations of weight loss with the incidence of esKOA were 85% to 93% smaller than those for TKR at the 4-to-5-year and 2-to-2.5-year follow-ups, respectively. CONCLUSION: The esKOA measure enables shorter and smaller studies compared to using TKR as an outcome.

Association of Weight Loss and Weight Gain With Structural Defects and Pain in Hand Osteoarthritis: Data From the Osteoarthritis Initiative.

OBJECTIVE: Our aim was to define the association of weight change (weight loss or weight gain) with the incidence and progression of hand osteoarthritis (OA), assessed either by radiography or by pain, using data from the Osteoarthritis Initiative. METHODS: Among the 4,796 participants, we selected 4,598 participants, excluding those with cancer or rheumatoid arthritis or a body mass index under 18.5 kg/m2. We investigated the association of weight change with incidence and progression of radiographic hand OA and the development and resolution of hand pain. Using multivariable logistic regression, we investigated the association of weight change from baseline to the 4-year follow-up with the incidence and progression of radiographic hand OA at the 4-year follow-up. Additionally, multivariable repeated-measure mixed-effects logistic regression analyzed the association of weight change with the development and resolution of hand pain across 2-year, 4-year, 6-year, and 8-year follow-ups. RESULTS: No statistically significant associations were observed between weight change and the investigated outcomes. Specifically, for each 5% weight loss, the odds ratios for the incidence and progression of radiographic hand OA were 0.90 (95% confidence interval [95% CI] 0.67-1.23) and 0.92 (95% CI 0.84-1.00), respectively. Similarly, for each 5% weight loss, the odds ratios for the development and resolution of hand pain at the 8-year follow-up were 1.00 (95% CI 0.92-1.09) and 1.07 (95% CI 0.91-1.25), respectively. CONCLUSION: Our study found no evidence of an association between weight change and the odds of incidence or progression of radiographic hand OA over 4 years, nor the development or resolution of hand pain over 8 years.

Is binge eating associated with poor weight loss outcomes in people with a high body weight? A systematic review with meta-analyses.

OBJECTIVES: This systematic review aimed to compare the weight change in people with or without binge eating who underwent various weight loss treatments. METHODS: We searched for studies in PubMed, American Psychological Association, and Embase from inception to January 2022. The studies selected included assessment of binge eating and body weight before and after weight loss treatment in people of any age. The meta-analyses were conducted using Comprehensive Meta-Analysis (CMA). We used Egger's regression test, the funnel plot, and the Trim and Fill test to assess the risk of publication bias. RESULTS: Thirty-four studies were included in the systematic review, with a total of 10.184 participants. The included studies were divided into three categories according to types of weight loss treatments, namely, (1) bariatric surgery; (2) pharmacotherapy isolated or combined with behavioral interventions; and (3) behavioral and/or nutritional interventions. The meta-analyses showed no significant difference in weight loss between people with or without binge eating engaged in weight loss treatments, with an overall effect size of - 0.117 (95% CI - 0.405 to 0.171; P = 0.426). CONCLUSIONS: Our findings showed no difference in weight loss in people with or without pre-treatment binge eating who received various weight loss treatments. Weight loss treatments should not be withheld on the basis that they will not be effective in people with pre-treatment binge eating, albeit their safety and longer term impacts are unclear. LEVEL OF EVIDENCE: Level I, at least one properly designed randomized controlled trials; systematic reviews and meta-analyses; experimental studies.

Researchers in rheumatology should avoid categorization of continuous predictor variables.

BACKGROUND: Rheumatology researchers often categorize continuous predictor variables. We aimed to show how this practice may alter results from observational studies in rheumatology. METHODS: We conducted and compared the results of two analyses of the association between our predictor variable (percentage change in body mass index [BMI] from baseline to four years) and two outcome variable domains of structure and pain in knee and hip osteoarthritis. These two outcome variable domains covered 26 different outcomes for knee and hip combined. In the first analysis (categorical analysis), percentage change in BMI was categorized as ≥ 5% decrease in BMI, < 5% change in BMI, and ≥ 5% increase in BMI, while in the second analysis (continuous analysis), it was left as a continuous variable. In both analyses (categorical and continuous), we used generalized estimating equations with a logistic link function to investigate the association between the percentage change in BMI and the outcomes. RESULTS: For eight of the 26 investigated outcomes (31%), the results from the categorical analyses were different from the results from the continuous analyses. These differences were of three types: 1) for six of these eight outcomes, while the continuous analyses revealed associations in both directions (i.e., a decrease in BMI had one effect, while an increase in BMI had the opposite effect), the categorical analyses showed associations only in one direction of BMI change, not both; 2) for another one of these eight outcomes, the categorical analyses suggested an association with change in BMI, while this association was not shown in the continuous analyses (this is potentially a false positive association); 3) for the last of the eight outcomes, the continuous analyses suggested an association of change in BMI, while this association was not shown in the categorical analyses (this is potentially a false negative association). CONCLUSIONS: Categorization of continuous predictor variables alters the results of analyses and could lead to different conclusions; therefore, researchers in rheumatology should avoid it.

Investigation of the association of weight loss with radiographic hip osteoarthritis in older community-dwelling female adults.

OBJECTIVE: Most guidelines recommending weight loss for hip osteoarthritis are based on research on knee osteoarthritis. Prior studies found no association between weight loss and hip osteoarthritis, but no previous studies have targeted older adults. Therefore, we aimed to determine whether there is any clear benefit of weight loss for radiographic hip osteoarthritis in older adults because weight loss is associated with health risks in older adults. METHODS: We used data from white female participants aged ≥65 years from the Study of Osteoporotic Fractures. Our exposure of interest was weight change from baseline to follow-up at 8 years. Our outcomes were the development of radiographic hip osteoarthritis (RHOA) and the progression of RHOA over 8 years. Generalized estimating equations (clustering of 2 hips per participant) were used to investigate the association between exposure and outcomes adjusted for major covariates. RESULTS: There was a total of 11,018 hips from 5509 participants. There was no associated benefit of weight loss for either of our outcomes. The odds ratios (95% confidence intervals) for the development and progression of RHOA were 0.99 (0.92-1.07) and 0.97 (0.86-1.09) for each 5% weight loss, respectively. The results were consistent in sensitivity analyses where participants were limited to those who reported trying to lose weight and who also had a body mass index in the overweight or obese range. CONCLUSION: Our findings suggest no associated benefit of weight loss in older female adults in the structure of the hip joint as assessed by radiography.

A systematic review with meta-analyses of the relationship between recurrent binge eating and sleep parameters.

BACKGROUND: Sleep problems are known to compound the negative effects of other health issues, such as eating disorders and the associated behavior of binge eating. Previous studies suggested associations between binge eating and sleep problems, but the strength of the relationship is unknown. METHODS: We conducted a systematic review with meta-analyses examining the relationship between binge eating and sleep parameters. We searched for studies in Scopus, PubMed, and PsycInfo. The quality of evidence, including risk of bias, was assessed with adaptations of the Newcastle-Ottawa Scale and the Joanna Briggs Institute Critical Appraisal Checklist for Quasi-Experimental Studies, depending on study design. Data was synthesized as the difference in sleep between people who did or did not have binge eating. RESULTS: Thirty-one reports of studies met our eligibility criteria. Results are presented in 12 meta-analyses. In the 7 reports of studies (with 4448 participants) that assessed poor overall sleep quality, we found poorer overall sleep quality in people with binge eating compared to people without binge eating, with a standardized mean difference of 0.77 (95% confidence interval [CI] 0.61-0.92; P < 0.001), which is a large effect size. In addition, we found evidence that people with binge eating had significantly greater hypersomnia/daytime sleepiness (7 reports of studies with 4370 participants), insomnia (5 reports of studies with 12,733 participants), and difficulty falling asleep (3 reports of studies with 4089 participants) compared to people without binge eating, with moderate effect sizes (standardized mean differences of 0.57-0.66). CONCLUSIONS: People with binge eating exhibit poorer overall sleep quality compared to people without binge eating, and may also exhibit greater hypersomnia/daytime sleepiness, insomnia, and difficulty falling asleep. It is recommended that healthcare professionals routinely screen for poor overall sleep quality when treating people with binge eating-and address sleep difficulties when present.

Association Between Change in Body Mass Index and Knee and Hip Replacements: A Survival Analysis of Seven to Ten Years Using Multicohort Data.

OBJECTIVE: To define the association between change in body mass index (BMI) and the risk of knee and hip replacement. METHODS: We used data from 3 independent cohort studies: the Osteoarthritis Initiative (OAI), the Multicenter Osteoarthritis Study (MOST), and the Cohort Hip and Cohort Knee (CHECK) study, which collected data from adults (45-79 years of age) with or at risk of clinically significant knee osteoarthritis. We conducted Cox proportional hazards regression analysis with clustering of both knees and hips per person to determine the association between change in BMI (our exposure of interest) and the incidence of primary knee and hip replacement over 7-10 years' follow-up. Change in BMI (in kg/m2 ) was calculated between baseline and the last follow-up visit before knee or hip replacement, or for knees and hips that were not replaced, the last follow-up visit. RESULTS: A total of 16,362 knees from 8,181 participants, and 16,406 hips from 8,203 participants, were eligible for inclusion in our knee and hip analyses, respectively. Change in BMI was positively associated with the risk of knee replacement (adjusted hazard ratio [HRadj ] 1.03 [95% confidence interval (95% CI) 1.00-1.06]) but not hip replacement (HRadj 1.00 [95% CI 0.95-1.04]). The association between change in BMI and knee replacement was independent of participants' BMI category at baseline (i.e., normal, overweight, or obese). CONCLUSION: Public health strategies incorporating weight loss interventions could reduce the burden of knee but not hip replacement surgery.

Association of Change in Body Mass Index With Incidence and Progression of the Structural Defects of Hip Osteoarthritis: Data From the Osteoarthritis Initiative and the Cohort Hip and Cohort Knee study.

OBJECTIVE: To define the association between change in body mass index (BMI) and the incidence and progression of structural defects of hip osteoarthritis as assessed by radiography. METHODS: We used data from 2 independent cohort studies: the Osteoarthritis Initiative (OAI) and the Cohort Hip and Cohort Knee (CHECK) study. Our exposure was change in BMI from baseline to 4-5 years' follow-up. Our outcomes were the incidence and progression of structural defects of hip osteoarthritis as assessed using a modified Croft grade in OAI and the Kellgren/Lawrence grade in the CHECK study. To study incidence, we created incidence cohorts of hips without definite overall structural defects at baseline (i.e., grade <2) and then investigated the odds of hips having definite overall structural defects at follow-up (i.e., grade ≥2). To study progression, we created progression cohorts of hips with definite overall structural defects at baseline (i.e., grade ≥2) and then investigated the odds of having a grade increase of ≥1 from baseline to follow-up. RESULTS: There was a total of 5,896 and 1,377 hips in the incidence cohorts, and 303 and 129 hips in the progression cohorts for the OAI and CHECK study, respectively. Change in BMI (decrease or increase) was not associated with any change in odds of the incidence or progression of definite structural defects of hip osteoarthritis in either the OAI or CHECK cohorts. CONCLUSION: Weight loss may not be an effective strategy for preventing, slowing, or delaying the structural defects of hip osteoarthritis over 4-5 years.

Association of Decrease in Body Mass Index With Reduced Incidence and Progression of the Structural Defects of Knee Osteoarthritis: A Prospective Multi-Cohort Study.

OBJECTIVE: To define the association between change in body mass index (BMI) and the incidence and progression of the structural defects of knee osteoarthritis as assessed by radiography. METHODS: Radiographic analyses of knees at baseline and at 4-5 years of follow-up were obtained from the following 3 independent cohort studies: the Osteoarthritis Initiative (OAI) study, the Multicenter Osteoarthritis Study (MOST), and the Cohort Hip and Cohort Knee (CHECK) study. Logistic regression analyses using generalized estimating equations, with clustering of both knees within individuals, were used to investigate the association between change in BMI from baseline to 4-5 years of follow-up and the incidence and progression of knee osteoarthritis. RESULTS: A total of 9,683 knees (from 5,774 participants) in an "incidence cohort" and 6,075 knees (from 3,988 participants) in a "progression cohort" were investigated. Change in BMI was positively associated with both the incidence and progression of the structural defects of knee osteoarthritis. The adjusted odds ratio (OR) for osteoarthritis incidence was 1.05 (95% confidence interval [95% CI] 1.02-1.09), and the adjusted OR for osteoarthritis progression was 1.05 (95% CI 1.01-1.09). Change in BMI was also positively associated with degeneration (i.e., narrowing) of the joint space and with degeneration of the femoral and tibial surfaces (as indicated by osteophytes) on the medial but not on the lateral side of the knee. CONCLUSION: A decrease in BMI was independently associated with lower odds of incidence and progression of the structural defects of knee osteoarthritis and could be a component in preventing the onset or worsening of knee osteoarthritis.

Effect of severe compared with moderate energy restriction on physical activity among postmenopausal female adults with obesity: a prespecified secondary analysis of the Type of Energy Manipulation for Promoting optimum metabolic health and body composition in Obesity (TEMPO) Diet randomized controlled Trial.

BACKGROUND: An under-explored strategy for increasing physical activity is the dietary treatment of obesity, but empirical evidence is lacking. OBJECTIVES: We aimed to compare the effects of weight loss via severe as opposed to moderate energy restriction on physical activity over 36 mo. METHODS: A total of 101 postmenopausal female adults (45-65 y, BMI 30-40 kg/m2, <180 min/wk of structured exercise) were randomly assigned to either 12 mo of moderate energy restriction (25%-35% of energy requirement) with a food-based diet, or a severe intervention involving 4 mo of severe energy restriction (65%-75% of energy requirement) with a total meal replacement diet, followed by 8 mo of moderate energy restriction. Physical activity was encouraged, but no tailored or supervised exercise prescription was provided. Physical activity was assessed with an accelerometer worn for 7 d before baseline (0 mo) and 0.25, 1, 4, 6, 12, 24, and 36 mo after intervention commencement. RESULTS: Compared with the moderate group, the severe group exhibited greater mean: total volume of physical activity; duration of moderate-to-vigorous-intensity physical activity (MVPA); duration of light-intensity physical activity; step counts, as well as lower mean duration of sedentary time. All these differences (except step counts) were apparent at 6 mo [e.g., 1006 metabolic equivalent of task (MET)-min/wk; 95% CI: 564, 1449 MET-min/wk for total volume of physical activity], and some were also apparent at 4 and/or 12 mo. There were no differences between groups in the 2 other outcomes investigated (self-efficacy to regulate exercise; and proportion of participants meeting the WHO's 2020 Physical Activity Guidelines for MVPA). When the analyses were adjusted for weight at each time point, the differences between groups were either attenuated or abolished. CONCLUSIONS: Among female adults with obesity, including a dietary component to reduce excess body weight-notably one involving severe energy restriction-could potentially enhance the effectiveness of physical activity interventions.This trial was registered at www.anzctr.org.au as ACTRN12612000651886.

Weight loss is associated with reduced risk of knee and hip replacement: a survival analysis using Osteoarthritis Initiative data.

OBJECTIVE: To describe the association between body weight change and the risk of knee replacement and hip replacement. DESIGN: Time-to-event survival analysis from a population-based cohort of participants who had or were at risk of clinically significant knee osteoarthritis at baseline. SETTING: Data from the Osteoarthritis Initiative (OAI), which collected data from four clinical centres in the United States. PARTICIPANTS: A total of 8069 knees from 4081 participants, and 8076 hips from 4064 participants (59.3% female) aged 45-79 years, with mean ± SD body mass index (BMI) of 28.7 ± 4.8 kg/m2, were included in the knee and hip analyses, respectively. EXPOSURE: Body weight change from baseline as a percentage of baseline at repeated follow-up visits over 8 years. MAIN OUTCOME MEASURE: Incidence of primary knee or hip replacement during 8-year follow-up. RESULTS: Body weight change had a small, positive, linear association with the risk of knee replacement (adjusted hazard ratio [HR] 1.02; 95% confidence interval [CI] 1.00-1.04). Body weight change was also positively and linearly associated with the risk of hip replacement in hips that were persistently painful at baseline (adjusted HR 1.03; 95% CI 1.01-1.05), but not in hips that were not persistently painful at baseline. There were no significant interactions between body weight change and baseline BMI in the association with knee or hip replacement. CONCLUSIONS: In people with or at risk of clinically significant knee osteoarthritis, every 1% weight loss was associated with a 2% reduced risk of knee replacement and - in those people who also had one or more persistently painful hips - a 3% reduced risk of hip replacement, regardless of baseline BMI. Public health strategies that incorporate weight loss interventions have the potential to reduce the burden of knee and hip replacement surgery.