Correlates of hyaluronic acid and corticosteroid injections among patients with radiographically confirmed osteoarthritis

Objective: Despite the rapid proliferation of hyaluronate (HA) and corticosteroid (CO) injections and clinical guidelines regarding their use in osteoarthritis (OA), information on the characteristics of people receiving them is scarce. We described use of injections among adults with radiographically confirmed knee OA and identified correlates of injection use. Methods: We used publicly available data from Osteoarthritis Initiative and included participants with ≥ one radiographically confirmed knee OA (Kellgren-Lawrence grade (K-L) \u3e 2) at baseline. We matched 415 participants reporting HA and/or CO during the 6 month before one of the first 7 annual follow-up assessments to 1,841 non-injection users by randomly selecting a study visit to match the distribution observed in the injection users. Multinomial logistic regression models identified correlates of injection use including sociodemographics and clinical/functional factors. Results: Injections were common (16.9% -year 1, 13.7% -year 2, 16.6 % -year 3, 13.5% - year 4, 15.9% -year 5, 13.5 % -year 6 and 9.9% -year 7) with corticosteroid injections most common (68.4%). HA and CO were more commonly reported by those with higher income (e.g. adjusted Odds Ratio (aOR) HA \u3e $50k versus \u3c$25k: 3.63; (95% CI: 1.20-10.99)) and less common among blacks (aOR HA: 0.19; 95% CI: 0.06-0.55). Greater K-L grade (grade 4 versus 2) was associated with increased odds of HA (aOR: 4.79; 95% CI: 2.47-9.30), CO (aOR: 1.56; 95% CI: 1.04-2.34), or both (aOR: 4.94; 95% CI: 1.99-12.27). Conclusion: Hyaluronic acid or corticosteroid injections are associated with higher socioeconomic positioning and indicators of greater disease severity

Long-term Effects of Use of Prescription Non-steroidal Anti-inflammatory Agents on Symptoms and Disease Progression among Patients with Radiographically Confirmed Osteoarthritis of the Knee

Objective: To estimate the extent to which long-term use of prescription non-steroidal anti-inflammatory agents (NSAIDs) relieve symptoms and delay disease progression among patients with radiographically confirmed osteoarthritis (OA) of the knee. Methods: Using Osteoarthritis Initiative data, we identified participants with confirmed OA at enrollment and evaluated changes in symptoms measured using the Western Ontario and McMaster Universities Arthritis Index, WOMAC (n=1,846) and joint space width measured using serial x-rays and a customized software tool (n=1,116) over 4 years. Covariates included sociodemographics, OA clinical characteristics, indices of general health status, body mass index, and use of other treatments. We adjusted for baseline and time-varying confounders using marginal structural modeling. Results: Six percent initiated NSAID treatment at year one, with half of the initiators being regular users. After adjusting for time-varying confounders with marginal structural models, we found that compared to participants who never reported use of prescription NSAIDs, those reporting use for 3 years had on average 0.88 point decrease (95% Confidence Interval (CI): -0.46 to 2.22) in WOMAC Pain, 0.72 point decrease (95% CI: -0.12 to 1.56) in WOMAC Stiffness, 4.27 points decrease (95% CI: 0.31 to -8.84) in WOMAC Function, and 0.28mm increase (95% CI: -0.06 to 0.62) in joint space width. Conclusions: Long term NSAID use was associated with a priori defined minimally important clinical improvements in stiffness, function and structural degeneration, but not in pain

A Decline in Walking Speed is Associated with Incident Knee Replacement in Adults with and at Risk for Knee Osteoarthritis

OBJECTIVE: To determine if a one-year change in walking speed is associated with receiving an incident knee replacement during the following year in adults with and at risk for knee osteoarthritis (OA). METHODS: Using data from the Osteoarthritis Initiative, we determined a one-year change in 20- meter walk speed from three observation periods (i.e., 0-12, 12-24, and 24-36 month). We operationally defined one-year change in walking speed as either: 1) decline: \u3c -0.1 m/s change, 2) no change: between -0.1 and 0.1 m/s change, 3) increase: \u3e 0.1 m/s change. Incident knee replacement was defined using each subsequent one-year period (i.e., 12-24, 24- 36, and 36-48 month). Combining data from the three observation periods, we performed a Poisson regression with robust error variance to determine the relative risk between a change in walking speed (exposure) and incident knee replacement over the following year (outcome). RESULTS: Of the 4,264 participants included within this analysis (11,311 total person visits), 115 (3%) adults received a knee replacement. Decline in walking speed was associated with a 104% increase in risk [adjusted relative risk (RR)=2.04; 95% confidence interval (CI)= 1.40-2.98], while an increase in walking speed associated with a 55% decrease in risk (RR=0.45; 95% CI=0.22-0.93) of incident knee replacement in the following year compared to a person with no change in walking speed. CONCLUSION: A one-year decline in walking speed is associated with an increased risk, while one-year increase in walking speed is associated with a decreased risk of future incident knee replacement

Defining and evaluating a novel outcome measure representing end-stage knee osteoarthritis: data from the Osteoarthritis Initiative.

We described a definition of end-stage knee osteoarthritis (esKOA) and evaluated its association with health outcomes and osteoarthritis risk factors. We included Osteoarthritis Initiative participants with or at risk for knee osteoarthritis who had complete baseline data. We defined esKOA by adapting a validated appropriateness algorithm for total knee replacement based on data from baseline and the first four follow-up visits. We performed person-based analyses, including both knees from all participants. Participants met the definition of esKOA at the visit at which ≥1 knee reached the esKOA criteria. We assessed differences in individual characteristics between groups at baseline and over time and tested if incident esKOA (outcome) was associated with osteoarthritis risk factors (e.g., age, maximum adult weight, and quadriceps strength). The cohort consisted of 3916 participants with mean age of 61 (SD = 9) years and mean body mass index of 28.4 (4.7) kg/m(2); 59 % were female and 9.7 % developed incident esKOA. Those with incident esKOA had poorer health outcomes at baseline and greater declines in health outcomes, with the exception of SF-12 mental health score. Five out of nine tested risk factors were associated with incident esKOA in unadjusted analyses, with older age (≥65 years; odds ratio = 1.44, 95 % confidence interval = 1.19 to 1.83) and quadriceps weakness (odds ratio = 0.78, 95 % confidence interval = 0.71 to 0.86) remaining significant in adjusted models. Older age and quadriceps weakness predicted esKOA. esKOA is also characterized by poor health-related outcomes. This definition of esKOA could be a new clinically relevant outcome measure for osteoarthritis research

Magnetic Resonance Image Sequence Influences the Relationship between Bone Marrow Lesions Volume and Pain: Data from the Osteoarthritis Initiative

Subchondral bone marrow lesions (BMLs) are related to structural and symptomatic osteoarthritis progression. However, it is unclear how sequence selection influences a quantitative BML measurement and its construct validity. We compared quantitative assessment of BMLs on intermediate-weighted fat suppressed (IW FS) turbo spin echo and 3-dimensional dual echo steady state (3D DESS) sequences. We used a customized software to measure 30 knees' (24-and 48-month MR images) BMLs on both sequences. The results showed that the IW FS sequences have much larger BML volumes (median: IW FS = 1840 mm 3 ; DESS = 191 mm 3 ) and BML volume change (between 24 and 48 months) than DESS sequence and demonstrate more BML volume change. The 24-month BML volume on IW FS is correlated with BML volume on DESS ( = 0.83). BML volume change on IW FS is not significantly correlated with change on DESS. The 24-month WOMAC pain is correlated with the 24-month BMLs on IW FS ( = 0.39) but not DESS. The change in WOMAC pain is correlated with BML volume change on IW FS ( = 0.37) but not DESS. Overall, BML quantification on IW FS offers better validity and statistical power than BML quantification on a 3D DESS sequence

Individual patient data meta-analysis of trials investigating the effectiveness of intra-articular glucocorticoid injections in patients with knee or hip osteoarthritis:an OA Trial Bank protocol for a systematic review

BACKGROUND: Based on small to moderate effect sizes for the wide range of symptomatic treatments in osteoarthritis (OA), and on the heterogeneity of OA patients, treatment guidelines for OA have stressed the need for research on clinical predictors of response to different treatments. A meta-analysis to quantify the effect modified by the predictors using individual patient data (IPD) is suggested. The initiative to collect and analyze IPD in OA research is commenced by the OA Trial Bank. The study aims are therefore: to evaluate the efficacy of intra-articular glucocorticoids for knee or hip OA in specific subgroups of patients with severe pain and (mild) inflammatory signs, over both short-term and long-term follow-up, using IPD from existing studies; to reach consensus on the rules for cooperation in a consortium; and to develop and explore the methodological issues of meta-analysis with individual OA patient data. METHODS/DESIGN: For the current IPD analysis we will collect and synthesize IPD from randomized trials studying the effect of intra-articular glucocorticoid injections in patients with hip or knee OA. Subgroup analyses will be performed for the primary outcome of pain at both short-term and long-term follow-up, in the subgroups of patients with and without severe pain and with and without inflammatory signs. DISCUSSION: This study protocol includes the first study of the OA Trial Bank, an international collaboration that initiates meta-analyses on predefined subgroups of OA patients from existing literature. This approach ensures a widely supported initiative and is therefore likely to be successful in data collection of existing trials. The collaboration developed (that is, the OA Trial Bank) may also lead to future IPD analyses on subgroups of patients with several intervention strategies applied in OA patients

Association of subchondral bone texture on magnetic resonance imaging with radiographic knee osteoarthritis progression: data from the Osteoarthritis Initiative Bone Ancillary Study.

OBJECTIVES: To assess whether initial or 12-18-month change in magnetic resonance imaging (MRI) subchondral bone texture is predictive of radiographic knee osteoarthritis (OA) progression over 36 months. METHODS: This was a nested case-control study including 122 knees/122 participants in the Osteoarthritis Initiative (OAI) Bone Ancillary Study, who underwent MRI optimised for subchondral bone assessment at either the 30- or 36-month and 48-month OAI visits. Case knees (n = 61) had radiographic OA progression between the 36- and 72-month OAI visits, defined as ≥ 0.7 mm minimum medial tibiofemoral radiographic joint space (minJSW) loss. Control knees (n = 61) without radiographic OA progression were matched (1:1) to cases for age, sex, body mass index and initial medial minJSW. Texture analysis was performed on the medial femoral and tibial subchondral bone. We assessed the association of texture features with radiographic progression by creating a composite texture score using penalised logistic regression and calculating odds ratios. We evaluated the predictive performance of texture features for predicting radiographic progression using c-statistics. RESULTS: Initial (odds ratio [95% confidence interval] = 2.13 [1.41-3.40]) and 12- 18-month change (3.76 [2.04-7.82]) texture scores were significantly associated with radiographic OA progression. Combinations of texture features were significant predictors of radiographic progression using initial (c-statistic [95% confidence interval] = 0.65 [0.64-0.65], p = 0.003) and 12-18-month change (0.68 [0.68-0.68], p < 0.001) data. CONCLUSIONS: Initial and 12-18-month changes in MRI subchondral bone texture score were significantly associated with radiographic progression at 36 months, with better predictive performance for 12-18-month change in texture. These results suggest that texture analysis may be a useful biomarker of subchondral bone in OA. KEY POINTS: • Subchondral bone MRI texture analysis is a promising knee osteoarthritis imaging biomarker. • In this study, subchondral bone texture was associated with knee osteoarthritis progression. • This demonstrates predictive and concurrent validity of MRI subchondral bone texture analysis. • This method may be useful in clinical trials with interventions targeting bone

Lorecivivint, a Novel Intraarticular CDC‐like Kinase 2 and Dual‐Specificity Tyrosine Phosphorylation‐Regulated Kinase 1A Inhibitor and Wnt Pathway Modulator for the Treatment of Knee Osteoarthritis: A Phase II Randomized Trial

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162805/2/art41315_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162805/1/art41315.pd

Evaluation of bone marrow lesion volume as a knee osteoarthritis biomarker - longitudinal relationships with pain and structural changes: data from the Osteoarthritis Initiative

Abstract Introduction Bone marrow lesion (BML) size may be an important imaging biomarker for osteoarthritis-related clinical trials and reducing BML size may be an important therapeutic goal. However, data on the interrelationships between BML size, pain, and structural progression are inconsistent and rarely examined in the same cohort. Therefore, we evaluated the cross-sectional and longitudinal associations of BML volume with knee pain and joint space narrowing (JSN). Methods A BML volume assessment was performed on magnetic resonance images of the knee collected at the 24- and 48-month Osteoarthritis Initiative visits from a convenience sample of 404 participants in the progression cohort. During the same visits, knee pain was assessed with WOMAC pain scores and knee radiographs were acquired and scored for JSN. BML volume was summed to generate a total knee volume and an index tibiofemoral compartment volume (compartment with greater baseline JSN). Primary analyses included multiple linear regressions (outcome = pain, predictor = total knee BML volume) and logistic regressions (outcome = JSN, predictor = index tibiofemoral compartment BML volume). Results This sample was 49% female with a mean age of 63 (9.2 standard deviation (SD)) years, and 71% had radiographic osteoarthritis in the study knee. Larger baseline BMLs were associated with greater baseline knee pain (P = 0.01), the presence of JSN at baseline (odds ratio (OR) = 1.50, 95% confidence interval (CI) = 1.23 to 1.83), and JSN progression (OR = 1.27, 95%CI = 1.11 to 1.46). Changes in total knee BML volume had a positive association with changes in knee pain severity (P = 0.004) and this association may be driven by knees that were progressing from no or small baseline BMLs to larger BMLs. In contrast, we found no linear positive relationship between BML volume change and JSN progression. Instead, regression of medial tibiofemoral BML volume was associated with JSN progression compared to knees with no or minimal changes in BML volume (OR = 3.36, 95%CI = 1.55 to 7.28). However, follow-up analyses indicated that the association between JSN progression and BML volume change may primarily be influenced by baseline BML volume. Conclusion Large baseline BMLs are associated with greater baseline knee pain, the presence of JSN at baseline, and disease progression. Additionally, BML regression is associated with decreased knee pain but not a reduced risk of concurrent JSN progression

Incident hand OA is strongly associated with reduced peripheral blood leukocyte telomere length

[Abstract] Objective: To evaluate the relationship of telomere length to the prevalence and incidence of hand osteoarthritis in a longitudinal cohort. Design: We conducted a cross-sectional and longitudinal analysis of data from a subset of participants in the Osteoarthritis Initiative (OAI) recruited between February 2004 and May 2006. 274 individuals were eligible for the study based on availability of both baseline and 48-month hand radiographs and peripheral blood leucocyte telomere length data. Mean telomere length of peripheral blood leukocytes (PBL)s from the DNA samples was determined using a validated quantitative polymerase chain reaction (PCR)-based assay, and hand radiographs were analyzed and graded using the Kellgren-Lawrence scale. Results: In joint -level analyses, prevalent Interphalangeal Joint Osteoarthritis (IPJOA) was significantly associated with PBL telomere length in the baseline sample in unadjusted analyses (RR = 2.84; 95% CI:0.87-9.29) or in models adjusted for age, sex, and body mass index (aRR = 1.10; 95% CI: 0.96-1.27). The association in crude and adjusted analyses appeared slightly stronger with incident IPJOA, especially in the subset with normal hands at baseline (aRR = 1.62; 95% CI: 1.02-2.57). PBL telomere length was also associated with prevalent HOA at baseline (significant in unadjusted analysis: RR = 1.22; 95% CI 1.06-1.42), but not after adjusting for covariates: aRR = 1.12; 95% CI: 0.96-1.30). The magnitude of association was stronger for incident HOA, especially incident symptomatic HOA (aRR = 1.53; 95% CI: 1.09-2.15). Conclusions: In summary, the results of this exploratory analysis are confirmatory of previous work showing a cross-sectional relationship between telomere length and HOA and add to the field by demonstrating an even stronger association with incident IPJOA, both radiographic and symptomatic.info:eu-repo/grantAgreement/MINECO/Programa Estatal de I+D+I Orientada a los Retos de la Sociedad/PI16%2F02124/ES/Determinación de índices predictivos de diagnóstico y pronóstico de artrosis de rodilla mediante la validación de biomarcadores proteicosinfo:eu-repo/grantAgreement/ISCIII/Programa Estatal de Fomento de la Investigación Científica y Técnica de Excelencia/PI17%2F01987/ES/ANALISIS DINAMICO DE PARAMETROS DE FISIOLOGIA TELOMERICA, COMO MARCADORES DE INCIDENCIA Y/O PROGRESION DE OSTEOARTITI