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Objective: To describe the cross-sectional and longitudinal associations between quantitative measures of infrapatellar fat pad (IPFP) signal-intensity alteration and knee structural abnormalities in patients with symptomatic knee osteoarthritis (OA)., Methods: A total of 261 patients (mean ± SD age 63.0 ± 7.2 years) with symptomatic knee OA were selected from a randomized controlled trial with a follow-up of 2 years. IPFP signal-intensity alterations at baseline were quantitatively measured on T2-weighted fat-saturated magnetic resonance imaging using MATLAB. These quantitative measures included the SD of whole IPFP signal intensity measurement, the upper quartile value of high signal intensity (UQ H ), the ratio of volume of high signal-intensity alteration to volume of whole IPFP (percentage H ), and the clustering effect of high signal intensity (clustering-factor H ). Cartilage volume and defects and bone marrow lesions (BMLs) were assessed using validated measures., Results: Higher baseline SD of the IPFP, UQ H , and clustering-factor H were associated with greater loss of tibial cartilage volume and larger increases in tibiofemoral cartilage defects over 2 years. Patients with high and medium tertiles of clustering-factor H had greater loss of cartilage volume per annum compared with those with a low tertile (for high 4.9%, for medium 4.6%, and for low 3.3% annually). Baseline percentage H and clustering-factor H were positively and significantly associated with increases in tibiofemoral BMLs over 2 years. Cross-sectional associations between IPFP measures and knee structures were similar but more consistent., Conclusion: Quantitative measures of increased signal intensity in the IPFP were associated with knee structural abnormalities in the tibiofemoral compartment, suggesting that these measurements could be used as an additional entry criterion to enrich studies for faster progressors of knee OA., (© 2018, American College of Rheumatology.)

The aim of this study is to describe the association of bone marrow lesions (BMLs) present on two different MRI sequences with clinical outcomes, cartilage defect progression, cartilage volume loss over 2.7 years, and total knee replacement (TKR) over 13.3 years. 394 participants (50-80 years) were assessed at baseline and 2.7 years. BML presence at baseline was scored on T1-weighted fat-suppressed 3D gradient-recalled acquisition (T1) and T2-weighted fat-suppressed 2D fast spin-echo (T2) sequences. Knee pain, function, and stiffness were assessed using WOMAC. Cartilage volume and defects were assessed using validated methods. Incident TKR was determined by data linkage. BMLs were mostly present on both MRI sequences (86%). BMLs present on T2, T1, and both sequences were associated with greater knee pain and functional limitation (odds ratio = 1.49 to 1.70; all p < 0.05). Longitudinally, BMLs present on T2, T1, and both sequences were associated with worsening knee pain (β = 1.12 to 1.37, respectively; p < 0.05) and worsening stiffness (β = 0.45 to 0.52, respectively; all p < 0.05) but not worsening functional limitation or total WOMAC. BMLs present on T2, T1, and both sequences predicted site-specific cartilage defect progression (relative risk = 1.22 to 4.63; all p < 0.05) except at the medial tibial and inferior patellar sites. Lateral tibial and superior patellar BMLs present on T2, T1, and both sequences predicted site-specific cartilage volume loss (β = - 174.77 to - 140.67; p < 0.05). BMLs present on T2, T1, and both sequences were strongly associated with incident TKR. BMLs can be assessed on either T2- or T1-weighted sequences with no clinical predictive advantage of either sequence.

Objective: Hip morphology plays a significant role in the incidence and progression of hip osteoarthritis (OA). We hypothesized that hip shape would also be associated with other key factors and tested this in a longitudinal community-based cohort combining radiographic, magnetic resonance imaging (MRI), dual-energy x-ray absorptiometry (DXA), and clinical data., Methods: Baseline DXA images of the left hip of 831 subjects from the Tasmanian Older Adult Cohort were analyzed using an 85-point statistical shape model. Hip pain was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index, and muscle strength was measured using a dynamometer. Hip structural changes were assessed using MRI and radiographic OA using plain radiographs., Results: Six shape modes accounted for 68% of shape variation. At baseline, modes 1, 2, 4, and 6 were associated with radiographic hip OA; modes 1, 3, 4, and 6 were correlated with hip cartilage volume; and all except mode 2 were correlated with muscle strength. Higher mode 1 and lower mode 3 and mode 6 scores at baseline predicted hip pain at followup and higher mode 1 and mode 2 scores were associated with hip effusion-synovitis. Higher scores for mode 2 (decreasing acetabular coverage) and lower scores for mode 4 (nonspherical femoral head) at baseline predicted 10-year total hip replacement (THR), while mode 4 alone was correlated with bone marrow lesions (BMLs), effusion-synovitis, and increased cartilage signal., Conclusion: Hip shape is associated with radiographic OA, THR, hip pain, effusion-synovitis, BMLs, muscle strength, and hip structural changes. These data suggest that different shape modes reflect multiple facets of hip OA., (© 2017, American College of Rheumatology.)

Objective: To describe the associations between infrapatellar fat pad (IPFP) signal intensity alteration at baseline and knee symptoms and structural changes in older adults., Methods: A total of 874 subjects (mean 62.1 years, 50.1% female) selected randomly from local community were studied at baseline and 770 were followed up (only 357 had MRI at follow-up) over 2.6 years. T1-weighted or T2-weighted fat suppressed MRI was used to assess IPFP signal intensity alteration (0-3), cartilage volume, cartilage defects and bone marrow lesions (BMLs) at baseline and 2.6 years later. Knee pain was assessed by self-administered Western Ontario and McMaster Osteoarthritis Index questionnaire. Radiographic osteoarthritis (OA) was assessed., Results: In cross-sectional analyses, IPFP signal intensity alteration was significantly and positively associated with total knee pain as well as knee cartilage defects, BMLs and knee radiographic OA and negatively associated with patellar cartilage volume after adjustment for age, sex, body mass index and/or radiographic OA. Longitudinally, baseline signal intensity alteration within IPFP was significantly and positively associated with increases in knee pain when going upstairs/downstairs as well as increases in tibiofemoral cartilage defects and BMLs, and negatively associated with change in lateral tibial cartilage volume in multivariable analyses., Conclusions: IPFP signal intensity alteration at baseline was associated with knee structural abnormalities and clinical symptoms cross-sectionally and longitudinally in older adults, suggesting that it may serve as an important imaging biomarker in knee OA., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: The aim of this study was to examine whether cartilage volume as measured by MRI and radiographic osteoarthritis (OA) at baseline predict cartilage volume loss over ten years independent of each other and other structural co-pathologies., Methods: 219 participants [mean-age 45(26-61); 57 % female] were studied at baseline and ten years. Approximately half were the adult offspring of subjects who underwent knee replacement for OA and the remainder were randomly selected controls. Joint space narrowing (JSN) and osteophytes were assessed on radiographs and cartilage volume (tibiofemoral), cartilage defects, bone marrow lesions and meniscal tears/extrusion were assessed on MRI., Results: Mean absolute and percentage per annum cartilage volume loss was 1284 mm(3) and 1.91 % respectively in the medial compartment and 1007 mm(3) and 1.38 % respectively in the lateral compartment. Higher baseline tibiofemoral cartilage volume was independently associated with greater absolute cartilage volume loss in both medial (β(95 % CI) = -300 (-399,-200)) and lateral (β = -338 (-443,-233)) compartments and percentage per annum loss in the lateral compartment(β = -0.15 (-0.29, -0.01)). Baseline JSN and osteophytes were associated with cartilage volume loss in the univariable analysis, however these associations did not persist after adjustment for other structural co-pathologies., Conclusion: Cross-sectional cartilage volume measurement independently predicts cartilage volume loss over 10 years and can be used to identify fast progressors in clinical trials. Radiographic JSN and osteophytes on the other hand are a reflection of other co-pathologies assessed on MRI and do not independently predict cartilage volume loss over 10 years.

Objective: To compare the responsiveness of magnetic resonance imaging (MRI)-derived measures of knee osteoarthritis over 2.7 years., Methods: There were 430 community-based participants (mean age 63.0 yrs, range 51-79 yrs; 51% female) measured at baseline and 2.7 years later. MRI of the right knee at both timepoints was performed to assess cartilage volume, cartilage defects, bone marrow lesions (BML), meniscal pathology, and tibial bone area. Global measurements were calculated as the sum of tibial and femoral measures. Standardized response mean (SRM) was calculated as the mean of change divided by the SD of change., Results: Global tibiofemoral cartilage volume and cartilage defects had the best SRM of -0.80 and 0.62, respectively. Site-specific measurements were lower (SRM range for cartilage volume -0.48 to -0.54 and cartilage defects 0.33 to 0.49). The SRM for BML was 0.12, meniscal pathology 0.39, and tibial bone area -0.09. Cartilage volume and/or defects tended to be more responsive in those with knee pain, those who were obese, those who were older, and those with radiographic osteoarthritis., Conclusion: Global cartilage volume demonstrated the best sensitivity to change, suggesting that if we relied solely on SRM to optimize clinical trial design, then cartilage volume would be the best outcome measure. However, clinical trials have shown that cartilage volume may be less responsive to treatment compared to other measures that have lower SRM (such as BML). Therefore, although one can optimize trial efficiency by finding more responsive endpoints, both sensitivity to change and magnitude of benefit should be considered.

Objective To describe the association between change in subchondral bone marrow lesions (BMLs) and change in tibiofemoral cartilage volume and knee symptoms in patients with symptomatic knee OA. Methods In total, 251 participants (mean 61.7 years, 51% female) were included. Tibiofemoral cartilage volume was measured at baseline and 24 months, and BML size at baseline, 6 and 24 months. Knee pain and function scores were evaluated at baseline, 6 and 24 months. Change in total and compartment-specific BML size was categorized according to the Least Significance Criterion. Linear mixed-effects models were used to evaluate the associations of change in BMLs over 6 and 24 months with change in cartilage volume over 24 months and knee symptoms over 6 and 24 months. Results Total BML size enlarged in 26% of participants, regressed in 31% and remained stable in 43% over 24 months. Compared with stable BMLs in the same compartment, enlarging BMLs over 24 months were associated with greater cartilage loss (difference: −53.0mm3, 95% CI: −100.0, −6.0), and regressing BMLs were not significantly associated with reduced cartilage loss (difference: 32.4mm3, 95% CI: −8.6, 73.3) over 24 months. Neither enlargement nor regression of total BML size over 6 and 24 months was associated with change in knee pain and function over the same time intervals. Conclusions In subjects with symptomatic knee osteoarthritis and BMLs, enlarging BMLs may lead to greater cartilage loss but regressing lesions are not associated with reduced cartilage loss while neither is associated with change in knee symptoms. [ABSTRACT FROM AUTHOR]

Background: Current pharmacologic therapies for patients with osteoarthritis are suboptimal.Objective: To determine the efficacy of Curcuma longa extract (CL) for reducing knee symptoms and effusion-synovitis in patients with symptomatic knee osteoarthritis and knee effusion-synovitis.Design: Randomized, double-blind, placebo-controlled trial. (Australian New Zealand Clinical Trials Registry: ACTRN12618000080224).Setting: Single-center study with patients from southern Tasmania, Australia.Participants: 70 participants with symptomatic knee osteoarthritis and ultrasonography-defined effusion-synovitis.Intervention: 2 capsules of CL (n = 36) or matched placebo (n = 34) per day for 12 weeks.Measurements: The 2 primary outcomes were changes in knee pain on a visual analogue scale (VAS) and effusion-synovitis volume on magnetic resonance imaging (MRI). The key secondary outcomes were change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and cartilage composition values. Outcomes were assessed over 12 weeks.Results: CL improved VAS pain compared with placebo by -9.1 mm (95% CI, -17.8 to -0.4 mm [P = 0.039]) but did not change effusion-synovitis volume (3.2 mL [CI, -0.3 to 6.8 mL]). CL also improved WOMAC knee pain (-47.2 mm [CI, -81.2 to -13.2 mm]; P = 0.006) but not lateral femoral cartilage T2 relaxation time (-0.4 ms [CI, -1.1 to 0.3 ms]). The incidence of adverse events was similar in the CL (n = 14 [39%]) and placebo (n = 18 [53%]) groups (P = 0.16); 2 events in the CL group and 5 in the placebo group may have been treatment related.Limitation: Modest sample size and short duration.Conclusion: CL was more effective than placebo for knee pain but did not affect knee effusion-synovitis or cartilage composition. Multicenter trials with larger sample sizes are needed to assess the clinical significance of these findings.Primary Funding Source: University of Tasmania and Natural Remedies Private Limited. [ABSTRACT FROM AUTHOR]

Background: Hip effusion-synovitis may be relevant to osteoarthritis (OA) but is of uncertain etiology. The aim of this study was to describe the cross-sectional and longitudinal associations of hip effusion-synovitis with clinical and structural risk factors of OA in older adults.Methods: One hundred ninety-six subjects from the Tasmanian Older Adult Cohort (TASOAC) study with a right hip STIR (Short T1 Inversion Recovery) Magnetic Resonance Imaging (MRI) on two occasions were included. Hip effusion-synovitis CSA (cm2) was assessed quantitatively. Hip pain was determined by WOMAC (Western Ontario and McMaster Universities Osteoarthritis) while hip bone marrow lesions (BMLs), cartilage defects (femoral and/or acetabular) and high cartilage signal were assessed on MRI. Joint space narrowing (0-3) and osteophytes (0-3) were measured on x-ray using Altman's atlas.Results: Of 196 subjects, 32% (n = 63) had no or a small hip effusion-synovitis while 68% (n = 133) subjects had a moderate or large hip effusion-synovitis. Both groups were similar but those with moderate or large hip effusion-synovitis were older, had higher BMI and more hip pain. Cross-sectionally, hip effusion-synovitis at multiple sites was associated with presence of hip pain [Prevalence ratio (PR):1.42 95%CI:1.05,1.93], but not with severity of hip pain. Furthermore, hip effusion-synovitis size associated with femoral defect (βeta:0.32 95%CI:0.08,0.56). Longitudinally, and incident hip cartilage defect (PR: 2.23 95%CI:1.00, 4.97) were associated with an increase in hip effusion-synovitis CSA. Furthermore, independent of presence of effusion-synovitis, hip BMLs predicted incident (PR: 1.62 95%CI: 1.13, 2.34) and worsening of hip cartilage defects (PR: 1.50 95%CI: 1.20, 1.86). While hip cartilage defect predicted incident (PR: 1.11 95%CI: 1.03, 1.20) and worsening hip BMLs (PR: 1.16 95%CI: 1.04, 1.30).Conclusions: Hip effusion-synovitis at multiple sites (presumably reflecting extent) may be associated with hip pain. Hip BMLs and hip cartilage defects are co-dependent and predict worsening hip effusion-synovitis, indicating causal pathways between defects, BMLs and effusion-synovitis. [ABSTRACT FROM AUTHOR]

Resistin acts as an endogenous ligand of Toll-like receptor (TLR)-4 that triggers major inflammatory pathways and mediates inflammatory processes. The role of resistin in osteoarthritis (OA) pathogenesis is unclear. The aim of this study is to describe the longitudinal associations of serum levels of resistin with knee synovitis measures and structural abnormalities in patients with knee OA. A prospective cohort study. Patients (n = 200) with symptomatic knee OA (mean age 63.1 years, range 49-79; female 46.5%) participated. All measures were performed at baseline and 2 years later. Serum resistin was measured using enzyme-linked immunosorbent assay. Infrapatellar fat pad (IPFP) high signal intensity alteration and effusion synovitis were measured from magnetic resonance imaging (MRI). Knee structures including cartilage volume, cartilage defects, and bone marrow lesions (BMLs) were also assessed by MRI semiquantitatively or quantitatively. Linear or logistic mixed effects regression analyses were used in longitudinal analyses. Serum resistin was positively associated with high signal intensity alteration measures of IPFP as well as the presence [relative risk = 1.06, 95% confidence interval (CI) 1.02, 1.10] and volume (β = 0.77, 95% CI 0.01, 1.53) of effusion synovitis in multivariable analyses. Serum levels of resistin were also positively associated with higher tibiofemoral cartilage defect (β = 1.98, 95% CI 0.34, 3.57) and BML scores (β = 3.18, 95% CI 0.99, 5.37) after adjustment for covariates. Higher serum levels of resistin are associated with knee synovitis surrogate measures and structural abnormalities, suggesting that obesity may promote OA not only by increasing weight loading on joints but also by triggering 1 or more inflammatory pathways. [ABSTRACT FROM AUTHOR]

Objective To identify and validate knee pain phenotypes in an older population across different pain-related domains over 10.7 years. Methods A total of 963 participants (mean age 63 years) from a population-based older adult cohort study were studied at baseline and followed up at 2.6 (n = 875), 5.1 (n = 768) and 10.7 years (n = 563). Baseline demographic, psychological, lifestyle and comorbidities data were obtained and MRI was performed to measure knee structural pathology. WOMAC pain and pain at multiple sites were assessed by questionnaires at each time-point. Latent class analysis was used to identify knee pain phenotypes, considering sex, BMI, emotional problems, education level, comorbidities, number of painful sites and knee structural pathology. Results Three pain phenotypes were identified: Class 1: high prevalence of emotional problems and low prevalence of structural damage (25%); Class 2: high prevalence of structural damage and low prevalence of emotional problems (20%); Class 3: low prevalence of emotional problems and low prevalence of structural damage (55%). Participants within Class 1 and 2 had greater BMI, more comorbidities, a higher prevalence of radiographic knee OA and knee structural pathology compared with Class 3. Furthermore, compared with Class 2 and 3, WOMAC pain and number of painful sites were consistently greater at each time-point over 10.7 years in Class 1. Results were similar when the analyses were restricted to participants with radiographic knee OA. Conclusion Psychological and structural factors interact with each other to exacerbate pain perception, suggesting that tailored treatment approaches for older people with knee pain in clinical practice are needed. [ABSTRACT FROM AUTHOR]

ABSTRACT: The aim of this study was to evaluate the effect of zoledronic acid (ZA) and denosumab on low back pain (LBP) and Modic change (MC) over 6 months. Adults aged ≥40 years with significant LBP for at least 6 months duration and MC (type 1, 2, or mixed) were randomized to receive ZA (5 mg/100 mL), denosumab (60 mg), or placebo. LBP was measured monthly by visual analogue scale (VAS) and the LBP Rating Scale (RS). MC was measured from MRIs of T12–S1 vertebrae at screening and 6 months. A total of 103 participants with moderate/severe LBP (mean VAS = 57 mm; mean RS = 18) and median total MC area 538 mm2 were enrolled. Compared to placebo, LBP reduced significantly at 6 months in the ZA group for RS (–3.3; 95% CI, –5.9 to –0.7) but not VAS (–8.2; 95% CI, –18.8 to +2.4) with similar findings for denosumab (RS, –3.0; 95% CI, –5.7 to –0.3; VAS, –10.7; 95% CI, –21.7 to +0.2). There was little change in areal MC size overall and no difference between groups with the exception of denosumab in those with type 1 Modic change (–22.1 mm2; 95% CI, –41.5 to –2.7). In post hoc analyses, both medications significantly reduced VAS LBP in participants with milder disc degeneration and non‐neuropathic pain, and denosumab reduced VAS LBP in those with type 1 MC over 6 months, compared to placebo. Adverse events were more frequent in the ZA group. These results suggests a potential therapeutic role for ZA and denosumab in MC‐associated LBP. © 2018 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the associations of knee structural abnormalities with different patterns of pain. A total of 891 participants (average age 63 years; range 50 to 80 years) participated in this study. Presence of pain at the neck, back, hands, shoulders, hips, knees, and feet was assessed by questionnaire. Participants were categorized as having no pain at any site (no pain), pain only at the knee (KP), pain at other sites but not the knee (OP), and pain at the knee and other sites (KOP). T1-weighted or T2-weighted MRI of the right knee was performed to measure cartilage defects, bone marrow lesions (BMLs), and effusion-synovitis. Osteophytes and joint space narrowing were assessed by X-ray. KP, KOP, and OP were, respectively, present in 3, 43, and 42% of the participants. In multivariable analyses, KOP was associated with the presence of cartilage defects, BMLs, and osteophytes (OR 3.57 (95% CI 1.78 to 7.14), 2.37 (1.27 to 4.43), and 2.87 (1.10 to 7.51), respectively) in those with radiographic knee OA. KP was also associated with presence of these structural abnormalities as well as effusion-synovitis, and these associations were much stronger. The associations between structural abnormalities and KOP were weaker than those with KP in those with radiographic knee OA. This suggests that mechanisms mediating the association between structural pathology, localized, and generalized pain may be different, and central sensitization is possibly involved in generalized pain. Pain at other sites needs to be considered in the management and treatment of OA-related pain. [ABSTRACT FROM AUTHOR]

Objective: To describe the associations between infrapatellar fat pad (IPFP) signal intensity alteration at baseline and knee symptoms and structural changes in older adults.Methods: A total of 874 subjects (mean 62.1 years, 50.1% female) selected randomly from local community were studied at baseline and 770 were followed up (only 357 had MRI at follow-up) over 2.6 years. T1-weighted or T2-weighted fat suppressed MRI was used to assess IPFP signal intensity alteration (0-3), cartilage volume, cartilage defects and bone marrow lesions (BMLs) at baseline and 2.6 years later. Knee pain was assessed by self-administered Western Ontario and McMaster Osteoarthritis Index questionnaire. Radiographic osteoarthritis (OA) was assessed.Results: In cross-sectional analyses, IPFP signal intensity alteration was significantly and positively associated with total knee pain as well as knee cartilage defects, BMLs and knee radiographic OA and negatively associated with patellar cartilage volume after adjustment for age, sex, body mass index and/or radiographic OA. Longitudinally, baseline signal intensity alteration within IPFP was significantly and positively associated with increases in knee pain when going upstairs/downstairs as well as increases in tibiofemoral cartilage defects and BMLs, and negatively associated with change in lateral tibial cartilage volume in multivariable analyses.Conclusions: IPFP signal intensity alteration at baseline was associated with knee structural abnormalities and clinical symptoms cross-sectionally and longitudinally in older adults, suggesting that it may serve as an important imaging biomarker in knee OA. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to describe the correlation between changes in structural abnormalities assessed on magnetic resonance imaging (MRI) and change in radiographic osteoarthritis (OA) over 10 years in a midlife cohort.Methods: A total of 211 participants (mean age 45 years [range 26-61 years], 57% female) were studied at baseline, 2 years, and 10 years. Approximately one-half were adult offspring of subjects who had undergone knee replacement for OA and the remainders were randomly selected controls. Joint space narrowing (JSN) and osteophytes were assessed from radiographs, while cartilage volume, cartilage defects, and meniscal tears/extrusion were assessed from MRI. Spearman ranked correlation analysis was used to describe the correlation between structural changes assessed on MRI and radiographs. Only medial tibiofemoral compartment results are presented, as the lateral compartment had limited change.Results: Over 10 years, change in meniscal tears showed a moderate independent correlation with change in both JSN (ρ = +0.37, P < 0.01) and osteophytes (ρ = +0.31, P < 0.01) in the adjusted analysis. Meniscal extrusion (ρ = +0.22, P < 0.01) and cartilage defects (ρ = +0.16, P < 0.04) showed a slightly weaker independent correlation with JSN in the adjusted analysis, whereas cartilage volume loss showed no significant correlation with either of the 2 radiographic outcomes.Conclusion: Change in JSN is correlated with change in meniscal tears and, to a lesser extent, with meniscal extrusion and cartilage defects. In this sample, change in JSN is a composite measure that does not reflect cartilage volume loss, prompting the review of the use of JSN as an outcome measure in chondro-protective drug trials. [ABSTRACT FROM AUTHOR]

Background: There is limited longitudinal data available on the natural history of meniscal tears especially in middle-aged adults with a low prevalence of osteoarthritis (OA). The aim of this study was to describe the natural history of meniscal tears over 8 years and the relationship with change in knee pain and structures.Methods: One hundred ninety eight participants [mean age 47 (28-63); 57% female] were studied at baseline and 8 years later. Approximately half were the adult offspring of subjects who had a knee replacement performed for knee OA and the remainder were randomly selected controls. Meniscal tears/extrusion, cartilage volume/defects, bone marrow lesions (BMLs) and effusion were assessed on MRI. Knee pain was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index.Results: 22% of the participants had at least one meniscal tear at any site at baseline. Over 8 years, 16% of the participants had an increase in severity of meniscal tears while none improved. Increase in meniscal tear score was associated with worsening knee pain (β = +2.81 (+1.40, +4.22)), with offspring having a significantly greater increase in pain severity compared to controls. BMI and presence of osteophytes at baseline, but not knee injury, predicted change in tears, whereas change in meniscal tears was independently associated with cartilage volume loss, change in BMLs and change in meniscal extrusion.Conclusion: Change in meniscal tears shares risk factors with knee OA and is independently associated with worsening knee pain and structural damage suggesting that meniscal tears are on the knee OA causal pathway. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether high-dose fish oil is superior to low-dose supplementation for symptomatic and structural outcomes in knee osteoarthritis (OA).Methods: A randomised, double-blind, multicentre trial enrolled 202 patients with knee OA and regular knee pain. They were randomised 1:1 to high-dose fish oil (4.5 g omega-3 fatty acids) 15 mL/day or (2) low-dose fish oil (blend of fish oil and sunola oil; ratio of 1:9, 0.45 g omega-3 fatty acids) 15 mL/day. The primary endpoints were Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score at 3, 6, 12 and 24 months, and change in cartilage volume at 24 months. Secondary outcomes included WOMAC function, quality of life, analgesic and non-steroidal anti-inflammatory drug use and bone marrow lesion score.Results: Although there was improvement in both groups, the low-dose fish oil group had greater improvement in WOMAC pain and function scores at 2 years compared with the high-dose group, whereas between-group differences at 1 year did not reach statistical significance. There was no difference between the two groups in cartilage volume loss at 2 years. For other secondary endpoints, there was no difference between the two groups at 2 years.Conclusions: In people with symptomatic knee OA, there was no additional benefit of a high-dose fish oil compared with low-dose fish oil. The combination comparator oil appeared to have better efficacy in reducing pain at 2 years, suggesting that this requires further investigation.Trial Registration Number: Australian New Zealand Clinical Trials Registry (ACTRN 12607000415404). [ABSTRACT FROM AUTHOR]

The aim of this cross-sectional study was to describe the associations between history of knee injury and knee structure using magnetic resonance imaging (MRI). This study included two population-based samples: the Tasmanian Older Adult Cohort (TASOAC) study ( n = 430; mean age, 63.0 years; range, 51-79 years; 51 % female) and the Offspring study ( n = 372; mean age, 45.0 years; range, 26-61 years; 57.5 % female). In both studies, 1.5 T MRI scans of the right knee were performed to measure bone marrow lesions (BMLs), cartilage volume, tibial bone area, cartilage defects and meniscal pathology. History of knee injury was assessed using a self-administered questionnaire. The association between knee injury and knee structure was determined using multiple linear and log binomial regression models. Nineteen percent of the middle-aged and 12 % of the older adults reported a history of knee injury. In middle-aged adults, BML presence (prevalence ratio (PR) = 1.6 (95 % CI, 1.2; 2.1)), tibial bone area (difference of means (DM) = +86 (+23, +149)) and meniscal extrusion presence (PR = 2.7 (1.1, 6.8)) were significantly higher in those with knee injury. In older adults, cartilage defect presence (PR = 1.3 (1.0, 1.7)), lateral (DM = −265 (−439, −92)) and total tibial (DM = −325 (−600, −51)) cartilage volume, BML presence (PR = 1.4 (1.0, 1.9)) and tibial bone area (DM = +140 (+19, +260)) were significantly associated with knee injury. Meniscal tears showed no significant associations in either cohorts. The association between knee injury and MRI-assessed structural pathology in the knee joint is moderate and appears to be stronger in older adults compared to middle-aged adults. [ABSTRACT FROM AUTHOR]

Objective. Cartilage loss is a key pathological feature of OA and can be assessed indirectly using radiography or directly through MRI. A number of cross-sectional studies have suggested that primary generalized osteoarthritis (PGOA) may be a distinct disease, but despite the high frequency of involvement of the hip and the knee joints in OA, very few studies have looked at the radiographic association between these two joints, and none has done so using MRI. The aim of this study was to examine the association of hip and knee cartilage measured by both radiography and MRI.Methods. We studied 151 participants from the Tasmanian Older Adult Cohort (TASOAC) study, who were selected randomly from the southern Tasmanian electoral rolls. MRI was used to assess hip and knee cartilage volume and radiography was used to assess joint space narrowing (JSN). Correlation analyses were used to compare cartilage volume measurements and JSN.Results. In adjusted analysis, there was a consistent, positive association between knee and hip cartilage volume that was best for total knee cartilage volume (r = 0.16–0.40, all P < 0.05). In contrast, there was at best a weak correlation, depending on the site, between hip and knee JSN (r = −0.01 to 0.21).Conclusion. Hip and knee cartilage volume are more strongly associated than hip and knee JSN, suggesting a commonality of cartilage volume at different anatomic sites. The weaker radiographic association may reflect less measurement error with MRI or the contribution of multiple structures to joint space in the knee. [ABSTRACT FROM PUBLISHER]

Background: Bisphosphonates are a class of drugs that slow bone loss and are a promising candidate to treat knee osteoarthritis (OA) patients. In a pilot study, we demonstrated that zoledronic acid reduced knee pain and size of subchondral bone marrow lesions (BMLs) over 6 months in knee OA patients with significant knee pain and BMLs. A longer, larger study is required to assess whether decreases in BML size will translate to reductions in cartilage loss over time. We are currently conducting a multicentre, randomised, double-blind, placebo-controlled trial over 24 months that aims to compare the effect of annual infusions of zoledronic acid to placebo on knee structural change (assessed using magnetic resonance imaging (MRI)) and knee pain in knee OA patients.Methods: Two hundred sixty-four patients with clinical knee OA, significant knee pain and subchondral BMLs present on MRI will be recruited in Hobart, Melbourne, Sydney and Adelaide. They will be randomly allocated to the two arms of the study, receiving an annual identical intravenous infusion of either 100 mL of fluid containing zoledronic acid (5 mg/100 mL) or placebo (0.9% NaCl 100 mL), at baseline and 1 year later. MRI of the study knee will be performed at screening, month 6 and 24. Knee structure, symptoms and function will be assessed using validated methods. The primary outcome is absolute change in tibiofemoral cartilage volume (mm3) over 24 months. Secondary outcomes include improvement in knee pain over 3, 6, 12, 18, and 24 months and reductions in BML size over 6 and 24 months. The primary analyses will be intention-to-treat analyses of primary and secondary outcomes. Per protocol analyses will be performed as the secondary analyses.Discussion: This study will provide high-quality evidence to assess whether zoledronic acid has a novel disease modifying effect in OA by slowing cartilage loss and reducing pain. If zoledronic acid proves effective, it suggests great potential for cost savings through a delay or reduced need for joint replacement surgery, and potential for great improvements in quality of life for OA suffers.Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12613000039785 , registered on 14 January 2013. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to describe whether maintaining sufficient serum vitamin D levels in people with knee osteoarthritis and baseline vitamin D insufficiency has an association with change in knee structures and symptoms over 2 years.Methods: Participants (n = 413, mean age 63.2 years) with symptomatic knee osteoarthritis and vitamin D insufficiency were enrolled in a clinical trial. In all, 340 participants (82.3%) completed the study, with 25-hydroxyvitamin D [25(OH)D] measurements at baseline and months 3 and 24. Participants were classified as consistently insufficient [serum 25(OH)D ≤50 nmol/L at months 3 and 24, n = 45], fluctuating [25(OH)D >50 nmol/L at either point, n = 68), and consistently sufficient [25(OH)D >50 nmol/L at months 3 and 24, n = 226] groups. Knee cartilage volume, cartilage defects, bone marrow lesions, and effusion-synovitis volume were assessed using MRI at baseline and month 24. Knee symptoms were assessed at baseline and months 3, 6, 12, and 24 using the Western Ontario and McMaster Universities Arthritis Index.Results: The consistently sufficient group had significantly less loss of tibial cartilage volume (β 2.1%; 95% confidence interval [CI], 0.3%, 3.9%), less increase in effusion-synovitis volume (β -2.5 mL; 95 CI%, -4.7, -0.2 mL), and less loss of Western Ontario and McMaster Universities Arthritis Index physical function (β -94.2; 95% CI, -183.8, -4.5) compared with the consistently insufficient group in multivariable analyses. In contrast, there were no significant differences in these outcomes between the fluctuating and consistently insufficient groups. Changes in cartilage defects, bone marrow lesions, and knee pain were similar between groups.Conclusion: This post hoc analysis suggests beneficial effects of maintaining vitamin D sufficiency on cartilage loss, effusion-synovitis, and physical function in people with knee osteoarthritis. [ABSTRACT FROM AUTHOR]