Osteoarthritis Bone Marrow Lesions.

Assessment and treatment of Bone Marrow Lesions (BMLs) could ultimately make step changes to the lives of people with osteoarthritis (OA). We here review the imaging and pathological characteristics of OA-BMLs, their differential diagnosis and measurement, and cross-sectional and longitudinal associations with pain and OA structural progression. We discuss how biomechanical and cellular factors may contribute to BML pathogenesis, and how pharmacological and non-pharmacological interventions that target BMLs might reduce pain and OA structural progression. We critically appraise semiquantitative and quantitative methods for assessing BMLs, and their potential utilities for identifying people at risk of symptomatic and structural OA progression, and evaluating treatment responses. New interventions that target OA-BMLs should both confirm their importance, and reduce the unacceptable burden of OA.

Who are likely to benefit from the Good Life with osteoArthritis in Denmark (GLAD) exercise and education program? An effect modifier analysis of a randomised controlled trial.

OBJECTIVE: To identify contextual factors that modify the treatment effect of the 'Good Life with osteoArthritis in Denmark' (GLAD) exercise and education programme compared to open-label placebo (OLP) on knee pain in individuals with knee osteoarthritis (OA). METHODS: Secondary effect modifier analysis of a randomised controlled trial. 206 participants with symptomatic and radiographic knee OA were randomised to either the 8-week GLAD programme (n = 102) or OLP given as 4 intra-articular saline injections over 8 weeks (n = 104). The primary outcome was change from baseline to week 9 in the Knee injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale (range 0 (worst) to 100 (best)). Subgroups were created based on baseline information: BMI, swollen study knee, bilateral radiographic knee OA, sports participation as a young adult, sex, median age, a priori treatment preference, regular use of analgesics (NSAIDs or paracetamol), radiographic disease severity, and presence of constant or intermittent pain. RESULTS: Participants who reported use of analgesics at baseline seem to benefit from the GLAD programme over OLP (subgroup contrast: 10.3 KOOS pain points (95% CI 3.0 to 17.6)). Participants with constant pain at baseline also seem to benefit from GLAD over OLP (subgroup contrast: 10.0 points (95% CI 2.8 to 17.2)). CONCLUSIONS: These results imply that patients who take analgesics or report constant knee pain, GLAD seems to yield clinically relevant benefits on knee pain when compared to OLP. The results support a stratified recommendation of GLAD as management of knee OA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03843931. EudraCT number 2019-000809-71.

Does gabapentin provide benefit for patients with knee OA? A benefit-harm and cost-effectiveness analysis.

OBJECTIVE: Gabapentin can treat neuropathic pain syndromes and has increasingly been prescribed to treat nociplastic pain. Some patients with knee osteoarthritis (OA) suffer from both nociceptive and nociplastic pain. We examined the cost-effectiveness of adding gabapentin to knee OA care. METHOD: We used the Osteoarthritis Policy Model, a validated Monte Carlo simulation of knee OA, to examine the value of gabapentin in treating knee OA by comparing three strategies: 1) usual care, gabapentin sparing (UC-GS); 2) targeted gabapentin (TG), which provides gabapentin plus usual care for those who screen positive for nociplastic pain on the modified PainDETECT questionnaire (mPD-Q) and usual care only for those who screen negative; and 3) universal gabapentin plus usual care (UG). Outcomes included cumulative quality-adjusted life years (QALYs), lifetime direct medical costs, and incremental cost-effectiveness ratios (ICERs), discounted at 3% annually. We derived model inputs from published literature and national databases and varied key input parameters in sensitivity analyses. RESULTS: UC-GS dominated both gabapentin-containing strategies, as it led to lower costs and more QALYs. TG resulted in a cost increase of $689 and a cumulative QALY reduction of 0.012 QALYs. UG resulted in a further $1,868 cost increase and 0.036 QALY decrease. The results were robust to plausible changes in input parameters. The lowest TG strategy ICER of $53,000/QALY was reported when mPD-Q specificity was increased to 100% and AE rate was reduced to 0%. CONCLUSION: Incorporating gabapentin into care for patients with knee OA does not appear to offer good value.

Exercise and education vs intra-articular saline for knee osteoarthritis: a 1-year follow-up of a randomized trial.

OBJECTIVE: To assess the longer-term effect of the Good Life with osteoarthritis in Denmark (GLAD) exercise and education program relative to open-label placebo (OLP) on changes from baseline in core outcomes in individuals with knee osteoarthritis (OA). METHODS: In this 1-year follow-up of an open-label, randomized trial, patients with symptomatic and radiographically confirmed knee OA were monitored after being randomized to either the 8-week GLAD program or OLP given as 4 intra-articular saline injections over 8 weeks. The primary outcome was the change from baseline in the Knee injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale after 1 year in the intention-to-treat population. Key secondary outcomes were the KOOS function and quality of life subscales, and Patients' Global Assessment of disease impact. RESULTS: 206 adults were randomly assigned: 102 to GLAD and 104 to OLP, of which only 137 (63/74 GLAD/OLP) provided data at 1 year. At one year the mean changes in KOOS pain were 8.4 for GLAD and 7.0 for OLP (Difference: 1.5 points; 95% CI -2.6 to 5.5). There were no between-group differences in any of the secondary outcomes. CONCLUSIONS: In this 1-year follow-up of individuals with knee OA, the 8-week GLAD program and OLP both provided minor longer-term benefits with no group difference. These results require confirmation given the significant loss to follow-up. TRIAL REGISTRATION NUMBER: NCT03843931.

Effectiveness of vitamin D supplementation on knee osteoarthritis - A target trial emulation study using data from the Osteoarthritis Initiative cohort.

OBJECTIVE: To assess the real-world effectiveness of vitamin D supplementation in patients with knee osteoarthritis (KOA) by replicating a randomized controlled trial (RCT) design in an observational study. METHOD: This study emulated a target trial using data from the Osteoarthritis Initiative (OAI). Eligible participants were ≥45 years, had symptomatic KOA and did not take vitamin D supplements in the past 30 days. A participant can enter the trial more than once. Participants were included in vitamin D group if they took ≥1,000 IU/day for ≥4 days/week in the past 30 days at the first follow-up visit after baseline. The control group did not use vitamin D in the past 30 days. Optimal propensity score matching at 1:1 ratio was performed. The primary outcome was change in knee pain 2 years after baseline measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes included WOMAC physical function and quantitative joint space width (JSW). Standardized mean difference (SMD) was used to compare the findings with previous RCTs. RESULTS: A total of 236 person-trials in the vitamin D group were pair-matched with a control. Compared to the control group, vitamin D supplementation did not reach significant changes in WOMAC pain (SMD = -0.04, 95%CI [-0.21, 0.13]), physical function and radiographic JSW over 2 years. The SMDs were consistent with the effect sizes reported in previous RCTs. CONCLUSION: Target trial emulation in the OAI cohort demonstrated findings close to published RCTs. This supports the future use of target trial emulation in evaluating other systemic therapies for KOA.

Synovitis mediates the association between bone marrow lesions and knee pain in osteoarthritis: data from the Foundation for the National Institute of Health (FNIH) Osteoarthritis Biomarkers Consortium.

OBJECTIVES: Although subchondral bone marrow lesions (BMLs) and synovitis have been well acknowledged as important sources of pain in knee osteoarthritis (KOA), it is unclear if synovitis plays the mediating role in the relationship between BMLs and knee pain. METHODS: We analyzed 600 subjects with magnetic resonance imaging (MRI) in the Foundation for National Institutes of Health Osteoarthritis Biomarkers Consortium (FNIH) cohort at baseline and 24-month. BMLs and synovitis were measured according to the MRI Osteoarthritis Knee Score (MOAKS) scoring system. BMLs were scored in five subregions. A summary synovitis score of effusion and Hoffa-synovitis was calculated. Knee pain was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Linear regression models were applied to analyze the natural direct effect (NDE) of BMLs and synovitis with knee pain, respectively, and natural indirect effect (NIE) mediated by synovitis. RESULTS: 590 participants (58.8% females, with a mean age of 61.5) were included in the present analyses. For NDE, knee pain was cross-sectionally associated with medial femorotibial BMLs (ß = 0.23, 95% CI: 0.09, 0.38) and synovitis (ß = 0.40, 95% CI: 0.20, 0.60). Longitudinal associations retained significant [medial femorotibial BMLs (ß = 0.37, 95% CI: 0.21, 0.53); synovitis (ß = 0.72, 95% CI: 0.45, 0.99)]. In the NIE analyses, synovitis mediated the association between medial femorotibial BML and knee pain at baseline (ß = 0.051, 95% CI: 0.01, 0.09) and over 24 months (ß = 0.079, 95% CI: 0.023, 0.15), with the mediating proportion of 17.8% and 22.4%, respectively. CONCLUSION: Synovitis partially mediates the association between medial femorotibial BMLs and knee pain.

Development and validation of the Flare-OA questionnaire for measuring flare in knee and hip osteoarthritis.

OBJECTIVE: Ability to assess flares in osteoarthritis (OA) of the knee and hip (KHOA) is important in clinical care and research. Using mixed methods, we developed a self-reported instrument measuring flare and assessed its psychometric properties. METHODS: We constructed questionnaire items from semi-structured interviews and a focus group (patients, clinicians) by using a dual-language (English-French) approach. A Delphi consensus method was used to select the most relevant items. Patients with OA from Australia, France and the United States completed the preliminary Flare-OA, HOOS, KOOS and Mini-OAKHQOL questionnaires online. We used a factor analysis and content approach to reduce items and determine structural validity. We tested the resulting questionnaire (score 0-100) for internal consistency, convergent and known-groups validity. RESULTS: Initially, 180 statements were generated and reduced to 33 items in five domains (response 0 = not at all, to 10 = absolutely) by Delphi consensus (50 patients, 116 professionals) and an expert meeting. After 398 patients (mean [SD] age 64 [8.5] years, 70.4% female, 86.7% knee OA) completed the questionnaire, it was reduced to 19 items by factor analysis and a content approach (RMSEA = 0.06; CFI = 0.96; TLI = 0.94). The Cronbach's alpha was >0.9 for the five domains and the whole questionnaire. Correlation coefficients between Flare-OA and other instrument scores were as predicted, supporting construct validity. The difference in Flare-OA score between patients with and without flare (31.8) largely exceeded 2 SEM (10.2). CONCLUSION: Flare-OA is a valid and reliable patient-reported instrument for assessing the occurrence and severity of flare in patients with KHOA in clinical research.

Efficacy and safety of a supplement combination on hand pain among people with symptomatic hand osteoarthritis an internet-based, randomised clinical trial the RADIANT study.

OBJECTIVE: The RADIANT study aimed to investigate the efficacy and safety of a complementary medicine supplement combination in people with hand osteoarthritis (HOA). METHOD: This was an internet-based, double-blind, randomised, placebo-controlled trial. Participants aged over 40 years with symptomatic HOA with radiographic confirmation (Kellgren Lawrence grade ≥ 2) throughout Australia were recruited and randomly assigned (1:1) to receive either a supplement combination composed of Boswellia serrata extract 250 mg/day, pine bark extract 100 mg/day, methylsulfonylmethane 1,500 mg/day and curcumin 168 mg/day or placebo for 12 weeks. The primary outcome was change in hand pain assessed using a visual analogue scale (VAS 0-100) from baseline to week 12. A range of secondary outcomes and additional measures were recorded. Adverse events were monitored weekly. RESULTS: One hundred and six participants were included with mean age 65.6 years and 81% were women. 45% of the participants were graded as KLG 4, 40% KLG three and 39 (37%) had erosive OA. There was no significant difference in pain VAS reduction between groups. The adjusted between group difference in means (95%CI) was 5.34 (-2.39 to 13.07). Five participants (10%) in the supplement combination group discontinued study treatment due to AE vs four participants (7%) in the placebo group. CONCLUSION: There were no significant differences in symptomatic relief between the two groups over 12 weeks. These findings do not support the use of the supplement combination for treating hand pain in people with HOA. REGISTRATION: Prospectively registered (Australian New Zealand Clinical Trials Registry ACTRN12619000835145, 31/05/2019).

Cost-effectiveness of duloxetine for knee OA subjects: the role of pain severity.

OBJECTIVE: Establish the impact of pain severity on the cost-effectiveness of generic duloxetine for knee osteoarthritis (OA) in the United States. DESIGN: We used a validated computer simulation of knee OA to compare usual care (UC) - intra-articular injections, opioids, and total knee replacement (TKR) - to UC preceded by duloxetine in those no longer achieving pain relief from non-steroidal anti-inflammatory drugs (NSAIDs). Outcomes included quality-adjusted life years (QALYs), lifetime medical costs, and incremental cost-effectiveness ratios (ICERs). We considered cohorts with mean ages 57-75 years and Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain 25-55 (0-100, 100-worst). We derived inputs from published data. We discounted costs and benefits 3% annually. We conducted sensitivity analyses of duloxetine efficacy, duration of pain relief, toxicity, and costs. RESULTS: Among younger subjects with severe pain (WOMAC pain = 55), duloxetine led to an additional 9.6 QALYs per 1,000 subjects (ICER = $88,500/QALY). The likelihood of duloxetine being cost-effective at willingness-to-pay (WTP) thresholds of $50,000/QALY and $100,000/QALY was 40% and 54%. Offering duloxetine to older patients with severe pain led to ICERs >$150,000/QALY. Offering duloxetine to subjects with moderate pain (pain = 25) led to ICERs <$50,000/QALY, regardless of age. Among knee OA subjects with severe pain (pain = 55) who are unwilling or unable to undergo TKR, ICERs were <$50,600/QALY, regardless of age. CONCLUSIONS: Duloxetine is a cost-effective addition to knee OA UC for subjects with moderate pain or those with severe pain unable or unwilling to undergo TKR. Among younger subjects with severe pain, duloxetine is cost-effective at WTP thresholds >$88,500/QALY.

Greater efficacy of a combination of conservative therapies for thumb base OA in individuals with lower radial subluxation - a pre-planned subgroup analysis of the COMBO trial.

OBJECTIVE: To investigate heterogeneous effects of a combination of conservative therapies compared with an education comparator for thumb base (TB) osteoarthritis (OA) according to clinically relevant characteristics. METHODS: Pre-planned subgroup analysis of the COMBO trial (n = 204) which compared a combination of education on self-management and ergonomic principles, a prefabricated neoprene splint, hand exercises, and diclofenac sodium gel, with education alone for radiographic and symptomatic TB OA. Primary outcomes were change in pain (visual analogue scale [VAS], 0-100 mm) and hand function (Functional Index for Hand Osteoarthritis questionnaire, 0-30) from baseline to week-6. Other outcomes were grip and tip-pinch strength and patient's global assessment (PGA) (VAS, 0-100 mm). Possible treatment effect modifiers were the presence of interphalangeal joint pain, erosive hand OA, radiographic thumb carpometacarpal joint subluxation (higher vs equal or lower than the sample mean), and baseline radiographic OA severity (Kellgren Lawrence grade). Linear regression models were fitted, adding interaction terms for each subgroup of interest. RESULTS: The treatment effects of the combined intervention at 6 weeks were greater in participants with lower joint subluxation compared with those with greater subluxation (pain -11.6 [95%CI -22.2, -9.9] and 2.6 [-5.5, 10.7], respectively, difference between the subluxation groups 14.2 units (95% CI 2.3, 26.1), p-value 0.02; and PGA -14.0 [-22.4, -5.5] and 1.5 [-6.2, 9.3), respectively, difference between the subluxation groups 15.5 units (95% CI 4.2, 26.8), p-value 0.03). There was no statistically significant heterogeneity for the other subgroups. CONCLUSION: A combination of conservative therapies may provide greater benefits over 6 weeks in individuals with lower joint subluxation, although the clinical relevance is uncertain given the wide confidence intervals. Treatment strategies may need to be customized for those with greater joint subluxation. TRIAL REGISTRATION NUMBER: ACTRN 12616000353493.

Can pain flares in knee osteoarthritis be predicted?

Objectives: This study examined whether risk factors for knee osteoarthritis (KOA) pain such as age, gender, body mass index (BMI), baseline pain, and other putative risk factors for knee osteoarthritis pain flares (KOAF) (e.g. knee buckling, injury, mood/stress/social support scores, and footwear) could predict KOAF.Method: People with KOA and previous history of KOAF were selected from a 3 month web-based longitudinal study. KOAF was defined as an increase of ≥ 2 points on a numeric rating scale (compared with background pain) which resolved within 20 days. Predictors assessed at baseline were gender, age, duration of KOA, BMI, pain, knee injury (7 days before), knee buckling (2 days before), Lubben Social Support, Knee Injury and Osteoarthritis Outcome Score, Intermittent and Constant Osteoarthritis Pain score (ICOAP), Positive/Negative Affect Score, and footwear stability/heel height. Outcome was occurrence of any KOAF during the ensuing 30 days. The combined ability of the above variables to predict occurrence of any KOAF was evaluated by multiple logistic regression with a 10-fold cross-validation method to build and internally validate the model. Variables that assessed similar domains were eliminated using receiver operating characteristics curve assessment for best fit.Results: Complete data were available for 313 people (66.6% female, mean ± sd age 62.3 ± 8.2 years, BMI 29.7 ± 6.5 kg/m2). Increasing age, years of osteoarthritis, BMI, background/worst levels of pain, knee injury, knee buckling, ICOAP, and footwear category/heel height significantly predicted the occurrence of KOAF during the following 30 days, with an area under the curve of 0.73 (95% confidence interval 0.67-0.80).Conclusion: A combination of risk factors assessed at baseline, including exposures with potential to vary, successfully predicts the KOAF in the ensuing 30 days.

Association of weather factors with the risk of pain exacerbations in people with hip osteoarthritis.

Objectives: Our objective was to evaluate the association of weather factors with the risk of pain exacerbations in people with symptomatic hip osteoarthritis (OA). Method: Eligible participants with symptomatic hip OA were instructed to log on to the study website and complete questionnaires every 10 days and additionally whenever they considered they were experiencing a pain exacerbation (case period) during the 90 day follow-up. Pain exacerbation was defined as an increase of two points in pain intensity on an 11-point numeric rating scale (0-10) during the follow-up compared with baseline. Each case period was anchored to four control periods within a 35 day interval using a time-stratified approach. Weather data were obtained for both periods from the publicly available meteorological database of the Australian Bureau of Meteorology. We examined the association of weather factors across 72 h before the index date with the risk of pain exacerbation, using conditional logistic regression. Results: Among 252 participants recruited, 129 participants had at least one episode of pain exacerbation and were included in the analysis. A significant dose-response relationship was found between average daily temperature variation in the prior 72 h and risk of pain exacerbations (p = 0.04 for linear trend). There was no significant association between maximum daily temperature, minimum daily temperature, relative humidity, precipitation, or barometric pressure and hip pain exacerbations. Conclusion: The overall results suggest that only daily temperature variation among different weather factors was associated with hip pain exacerbations in people with symptomatic hip OA.

The art and science of priority-setting: assessing the value of Public Health England's Prioritization Framework.

BACKGROUND: Findings are presented from the evaluation of Public Health England's (PHE) Prioritization Framework (PF) aimed to assist local authority commissioners with their public health investment and disinvestment decisions. The study explored the take up of the PF in three early adopter local authority settings. METHODS: Semi-structured interviews (n = 30) across three local authorities supplemented by participant observation of workshops. RESULTS: Participants acknowledged that the PF provided a systematic means of guiding priority-setting and one that encouraged transparency over investment and disinvestment decisions. The role performed by PHE and its regional teams in facilitating the process was especially welcomed and considered critical to the adoption process. However, uptake of the PF required a significant investment of time and commitment from public health teams at a time when resources were stretched. The impact of the political environment in the local government was a major factor determining the likely uptake of the PF. Ensuring committed leadership and engagement from senior politicians and officers was regarded as critical to success. CONCLUSIONS: The study assessed the value and impact of PHE's PF tool in three early adopter local authorities. Further research could explore the value of the tool in aiding investment and disinvestment decisions and its impact on spending.

Long-term clinical and economic outcomes of a short-term physical activity program in knee osteoarthritis patients.

OBJECTIVE: Physical activity (PA) in the US knee osteoarthritis (OA) population is low, despite well-established health benefits. PA program implementation is often stymied by sustainability concerns. We sought to establish parameters that would make a short-term (3-year efficacy) PA program a cost-effective component of long-term OA care. METHOD: Using a validated computer microsimulation (Osteoarthritis Policy Model), we examined the long-term clinical (e.g., comorbidities averted), quality of life (QoL), and economic impacts of a 3-year PA program, based upon the SPARKS (Studying Physical Activity Rewards after Knee Surgery) Trial, for inactive knee OA patients. We determined the cost, efficacy, and impact of PA on QoL and medical costs that would make a PA program a cost-effective addition to OA care. RESULTS: Among the 14 million with knee OA in the US, >4 million are inactive. Participation of 10% in the modeled PA program could save 200 cases of cardiovascular disease, 400 cases of diabetes, and 6,800 quality-adjusted life-years (QALYs). The program had an incremental cost-effectiveness ratio (ICER) of $16,100/QALY. Tripling PA program cost ($860/year) raised the ICER to $108,300/QALY; varying QoL benefits from PA yielded ICERs of $8,800/QALY-$99,900/QALY; varying background cost savings from PA did not qualitatively impact ICERs. Offering the PA program to any adults with knee OA (not only inactive) yielded $31,000/QALY. CONCLUSION: A PA program with 3-year efficacy in the knee OA population carried favorable long-term clinical and economic benefits. These results offer justification for policymakers and payers considering a PA intervention incorporated into knee OA care.

Association of baseline and change in tibial and femoral cartilage thickness and development of widespread full-thickness cartilage loss in knee osteoarthritis - data from the Osteoarthritis Initiative.

OBJECTIVE: To investigate whether baseline cartilage thickness and its longitudinal change are associated with incident widespread full-thickness cartilage loss (wsFTCL) in knee osteoarthritis, and whether there are optimal cut-off values for predicting wsFTCL. METHODS: Central medial tibial (cMT) and femoral (cMF) cartilage were assessed using quantitative magnetic resonance imaging data from the Osteoarthritis Initiative cohort (N = 600 knees). Cartilage thickness was measured at baseline and 12 months. wsFTCL was defined semi-quantitatively (scores 2 and 3 from the MRI Osteoarthritis Knee Score) and its incidence at 24 months recorded. Logistic regression was used to determine the odds of developing wsFTCL for baseline and for each 0.1 mm decrease in cartilage thickness. Cut-off values were investigated using the minimal-p method and area under the Receiver Operating Characteristic curves (AUC). RESULTS: Incident wsFTCL was observed in 66 (12%) and 73 (14%) knees in cMT and cMF, respectively. Lower baseline cMT and cMF cartilage thickness values were associated with wsFTCL (OR = 1.20; 95% CI: 1.11, 1.28 and OR = 1.15; 95% CI: 1.06 to 1.24, respectively). Optimal cut-off AUCs for the tibia and femur were 0.64 (0.57-0.70) and 0.63 (0.57-0.69), respectively. Longitudinal decrease in femoral, but not tibial, cartilage thickness was associated with incident wsFTCL (OR = 1.77; 95% CI: 1.30 to 2.40); optimal cut-off AUC 0.65 (95% CI: 0.58-0.72). CONCLUSION: Lower baseline cMT and baseline/change (decrease) over 12 months in cMF cartilage thickness were associated with incident, location-specific, wsFTCL at 24 months. Optimal cut-off values were relatively low and of uncertain utility for predicting incident wsFTCL.

The morphology of proximal tibiofibular joint (PTFJ) predicts incident radiographic osteoarthritis: data from Osteoarthritis Initiative.

OBJECTIVE: To determine whether the morphology of proximal tibiofibular joint (PTFJ) is associated with increased risk of incident radiographic osteoarthritis (iROA) over 4 years in the OA Initiative (OAI) study. METHODS: A nested matched case-control study design was used to select participants from OAI study. Case knees were defined as those with iROA. Control knees were matched one-to-one by sex, age and radiographic status with case knees. T2-weighted MR images were assessed at P0 (the visit when incident ROA was found on radiograph), P1 (1 year prior to P0) and at OAI baseline. The contacting area of PTFJ (S) and its projection areas onto the horizontal (load-bearing area, Sτ), sagittal (lateral stress-bolstering area, Sφ) and coronal plane (posterior stress-bolstering area, Sυ) were assessed, respectively. RESULTS: 354 case knees and 354 matched control knees were included, with a mean age of 60 and a mean body mass index (BMI) of 28 kg/m2. Baseline PTFJ morphological parameters (S, Sτ and Sυ) were significantly associated with iROA over 4 years, and these associations remained unchanged after adjustment for BMI, number of knee bending activities, self-reported knee injury and surgery. S, Sτ and Sυ were also significantly associated with iROA at P1 and P0. In subgroup analysed, S, Sτ and Sυ were associated with risks of incident joint space narrowing in the medial, but not the lateral tibiofemoral compartment. CONCLUSION: Greater contacting area, load-bearing area and posterior stress-bolstering area of PTFJ were associated with increased risks of iROA, largely in the medial tibiofemoral compartment.

Qualitative and quantitative measures of prefemoral and quadriceps fat pads are associated with incident radiographic osteoarthritis: data from the Osteoarthritis Initiative.

OBJECTIVE: To determine if qualitative and quantitative measures of prefemoral fat pad (PFP) and quadriceps fat pad (QFP) are associated with incident radiographic osteoarthritis (iROA) over 4 years in the Osteoarthritis Initiative (OAI) study. DESIGN: Participants in this nested case-control study were selected from the OAI study with knees that had Kellgren Lawrence grades (KLG) of 0 or 1 at baseline. Case knees were defined by iROA (KLG≥ 2) over 4 years. Control knees without iROA were matched 1:1 with case knees. Magnetic resonance images (MRIs) were read at P0 (time of onset of iROA), P-1 (1 year prior to P0) and baseline, and used to assess PFP (i.e., prefemoral hyperintensity alteration, patellofemoral hyperintensity alteration, maximum axial area) and QFP (i.e., hyperintensity alteration, mass effect, maximum axial area). Conditional logistic regression analyses were performed to study the associations between PFP/QFP measures and iROA, after adjustment for covariates. RESULTS: 354 case knees with iROA were matched to 354 control knees. 66.9% of the participants were female, with an average age of 60.1 years. PFP prefemoral hyperintensity alteration measured at three time points (OR [95%CI]: 1.46 [1.18-1.82], 1.50 [1.20-1.88], 1.52 [1.22-1.89] respectively), PFP maximum axial area (OR [95%CI]: 1.07 [1.01-1.14], 1.08 [1.01-1.15], 1.08 [1.02-1.15] respectively) and QFP hyperintensity alteration (OR [95%CI]: 1.59 [1.27-2.00], 1.44 [1.13-1.82], 1.38 [1.09-1.73] respectively) were significantly associated with iROA in multivariable conditional logistic analyses. QFP mass effect measured at BL and P-1 (OR [95%CI]: 1.42 [1.11-1.82], 1.33 [1.01-1.73] respectively) were significantly associated with iROA. CONCLUSIONS: Qualitative and quantitative measures of PFP and QFP are associated with increased iROA over 4 years.

MRI-based screening for structural definition of eligibility in clinical DMOAD trials: Rapid OsteoArthritis MRI Eligibility Score (ROAMES).

PURPOSE: Our aim was to introduce a simplified MRI instrument, Rapid OsteoArthritis MRI Eligibility Score (ROAMES), for defining structural eligibility of patients for inclusion in disease-modifying osteoarthritis drug trials using a tri-compartmental anatomic approach that enables stratification of knees into different structural phenotypes and includes diagnoses of exclusion. We also aimed to define overlap between phenotypes and determine reliability. METHODS: 50 knees from the Foundation for National Institutes of Health Osteoarthritis Biomarkers study, a nested case-control study within the Osteoarthritis Initiative, were selected within pre-defined definitions of phenotypes as either inflammatory, subchondral bone, meniscus/cartilage, atrophic or hypertrophic. A focused scoring instrument was developed covering cartilage, meniscal damage, inflammation and osteophytes. Diagnoses of exclusion were meniscal root tears, osteonecrosis, subchondral insufficiency fracture, tumors, malignant marrow infiltration and acute traumatic changes. Reliability was determined using weighted kappa statistics. Descriptive statistics were used for determining concordance between the a priori phenotypic definition and ROAMES and overlap between phenotypes. RESULTS: ROAMES identified 43 of 50 (86%) pre-defined phenotypes correctly. Of the 50 participants, 27 (54%) had no additional phenotypes other than the pre-defined phenotype. 18 (36%) had one and 5 (10%) had two additional phenotypes. None had three or four additional phenotypes. All features of ROAMES showed almost perfect agreement. One case with osteonecrosis and one with a tumor were detected. CONCLUSIONS: ROAMES is able to screen and stratify potentially eligible knees into different structural phenotypes and record relevant diagnoses of exclusion. Reliability of the instrument showed almost perfect agreement.

Differences between race and sex in measures of hip morphology: a population-based comparative study.

OBJECTIVE: This paper aims to (i) identify differences in measures of hip morphology between four racial groups using anteroposterior (AP) hip x-rays, and (ii) examine whether these differences vary by sex. METHODS: 912 hip x-rays (456 individuals) from four racial groups (European Caucasians, American Caucasians, African Americans and Chinese) were obtained. Males and females (45-75 years) with no radiographic hip OA (Kellgren and Lawrence < Grade 2 or Croft < Grade 1) were included. Eleven features of hip joint morphology were analysed. Linear regression with generalised estimating equations (GEE) was used to determine race and sex differences in hip morphology. Post-hoc Bonferroni procedure was used to adjust for multiple comparisons. RESULTS: The final analysis included 875 hips. Chinese hips showed significant differences for the majority of measures to other racial groups. Chinese were characterised by more shallow and narrow acetabular sockets, reduced femoral head coverage, smaller femoral head diameter, and a lesser angle of alignment between the femoral neck and shaft. Variation was found between other racial groups, but with few statistically significant differences. The average of lateral centre edge angle, minimum neck width and neck length differed between race and sex (p-value for interaction < 0.05). CONCLUSIONS: Significant differences were found in measures of morphology between Chinese hips compared to African Americans or Caucasian groups; these may explain variation in hip OA prevalence rates between these groups and the lower rate of hip OA in Chinese. Sex differences were also identified, which may further explain male-female prevalence differences for OA.

The effect of weight loss on the progression of meniscal extrusion and size in knee osteoarthritis: a post-hoc analysis of the Intensive Diet and Exercise for Arthritis (IDEA) trial.

OBJECTIVE: Weight loss has beneficial effects on clinical outcomes in knee osteoarthritis (OA), but the mechanism is still unclear. Since meniscus extrusion is associated with knee pain, this study assessed whether weight loss by diet and/or exercise is associated with less progression in meniscus extrusion measures over time. DESIGN: The Intensive Diet and Exercise for Arthritis trial (IDEA) was a prospective, single-blind, randomized-controlled trial including overweight and obese older adults with knee pain and radiographic OA. Participants were randomized to 18-month interventions: exercise only, diet only or diet + exercise. In a random subsample of 105 participants, MRIs were obtained at baseline and follow-up. The medial and lateral menisci were segmented and quantitative position and size measures were obtained, along with semiquantitative extrusion measures. Linear and log-binomial regression were used to examine the association between change in weight and change in meniscus measures. Between-group differences were analyzed using an analysis of covariance. RESULTS: Weight loss was associated with less progression over time of medial meniscus extrusion as measured by the maximum (ß: -24.59 µm, 95%CI: -41.86, -7.33) and mean (ß: -19.08 µm, 95%CI: -36.47, -1.70) extrusion distances. No relationships with weight loss were observed for lateral meniscus position, medial or lateral meniscus size or semiquantitative measures. Change in meniscus position and size did not differ significantly between groups. CONCLUSIONS: Weight loss was associated with beneficial modifications of medial meniscus extrusion over 18 months. This may be one of the mechanisms by which weight loss translates into a clinical benefit. CLINICAL TRIAL REGISTRATION: NCT00381290.