In women but not men, low serum levels of endogenous estradiol, progesterone and testosterone are associated with increased knee effusion-synovitis and possibly other OA-related structural changes. This may contribute to observed sex differences in knee OA.

the most-damaged tibiofemoral compartment evaluated from frontal weight bearing image. Gradings of joint space width (0-3), femoral osteophytes (0-3), tibial erosion (0-4) and subluxation (0-3) were combined for a total score from zero to 13. Trained readers were used to obtain the gradings. The decision for surgery was made without access to the DE or RG data. Results: 157 complete data sets have now been evaluated. Ages ranged from 38 to 91 (average 65.2) with an even sex distribution. WOMAC, scored out of a total 96, ranged from 1 to 86, mean 41.2 (Standard Deviation (SD) 17.3). The UCOAG ranged from 2 to 12 with a mean of 5.4 (SD 2). There was a weak positive relationship between an increasing DE and RG (r¼ 0.185, p¼0.027). 70 of the 157 cases were booked for surgery (60 TKA, 2 osteotomy and 5 arthroscopic surgeries). Average WOMAC score among the cases booked was 49.8 (SD 13.6) compared to 34.5 (SD 1.7) of those not booked (p<0.001). Cases for surgery had an average UCOAG score of 6.4 (SD 2.1) compared to 4.6 (SD 1.2) for non-surgical cases (p<0.001). For TKA and Osteotomy cases booked, RG were similar (6.7 and 8 respectively). Arthroscopy cases were significantly less (RG 4.6, p<0.001). Conclusions: These preliminary results suggest promise for the use of an evidence based triage tool based on the combination of Disability Evaluation and Radiographic Grading to index the need for knee surgery, in particular TKA.

BackgroundSynovial inflammation is commonly observed in osteoarthritis (OA). Vitamin D has showed anti-inflammatory properties in joint disorders which have not been reported in OA.ObjectivesTo examine the effect of vitamin D supplementation on synovial inflammation in patients with symptomatic knee osteoarthritis (OA) and low vitamin D levels over 24 months.MethodsIn a multi-center, randomized, placebo-controlled and double-blind trial, symptomatic knee OA patients with a low 25-(OH)D level (12.5–60 nmol/l) were recruited. 413 patients (age 63.2±7.0 years, 208 females) were allocated to either a 50,000IU monthly vitamin D3 capsule (n=209) or placebo (n=204) for 24 months. In this post-hoc analysis, changes in knee effusion-synovitis volume and score (0–3) were assessed using MRI (fig 1). A least significant criterion (LSC) was used to define an increase of effusion-synovitis volume by correcting measurement errors.ResultsAt baseline, total effusion-synovitis volume was 8.0 ml with a prevalence of 47.7% (score ≥2). Over 24 months, the total effusion-synovitis volume remained stable in vitamin D group (mean: 0.26 ml, 95% CI: -0.82, 1.34) but increased significantly in placebo group (mean: 2.20 ml, 95% CI: 1.01, 3.38) (difference between groups: -1.94 ml, 95% CI: -3.54, -0.33). This effect was evident in those with baseline effusion-synovitis (difference: -2.04 ml, 95%CI: -3.83, -0.25) and in suprapatellar pouch (difference: -2.49 ml, 95%CI: -4.74, -0.25). Increases in total (relative risk: 0.66, 95%CI: 0.49, 0.90) and suprapatellar (relative risk: 0.64, 95%CI: 0.44, 0.93) effusion-synovitis volume were less in vitamin D than placebo group.ConclusionsVitamin D supplementation over 24 months significantly reduced progression of effusion-synovitis in patients with knee OA and low 25-(OH)D level.AcknowledgementWe specially thank the participants who made this study possible, and we gratefully acknowledge the role of Vitamin D Effect on Osteoarthritis Study staff and volunteers in collecting the data. We thank the research assistants Jodi Barling, Kay Nguo, Judy Hankin and Alice Noone who were involved in the coordination of this study. Special thank to Yuelong Cao who wrote the study protocol. We also thank Rob Warren measured knee cartilage volume.Disclosure of InterestNone declared

BackgroundThere are no long-term studies that describe the independent association of radiographic and magnetic resonance imaging (MRI) based markers and cartilage volume loss and knee symptoms in population-based older adults.ObjectivesTo describe whether radiographic (joint space narrowing (JSN) and osteophytes) and MRI-based (cartilage defects, bone marrow lesions (BMLs), meniscal tears and meniscal extrusion) measures predict long-term cartilage volume loss and knee symptoms over 10.7 years.Methods983 participants (mean age 62.8 years, 50% female) were randomly recruited from the local community of Tasmania and followed up at 2.6 years, 5.1 years and 10.7 years later. Osteophytes and JSN were assessed using OARSI atlas. A 1.5T MRI scan of the right knee was acquired at baseline (n=930), 2.6 years (n=399) and 10.7 years (n=484). Tibial and patellar cartilage volume was acquired using a manual segmentation method on the T1-weighted fat-saturated 3D GRE images. Cartilage defects were assessed on T1-weighted MRI using a modified Outerbridge scoring system (grade 0–4). BMLs were measured on T2-weigthed fat saturated FSE images using a modified Whole-Organ MRI scoring system (grade 0–3). Meniscal extrusion (grade 0–2) and meniscal tears (grade 0–3) were measured using the T1- and T2-weighted MRI. Analyses were performed using linear mixed-effects models for symptoms and linear regression for cartilage volume loss.ResultsAfter adjustment for age, sex, BMI and radiographic KOA status, cartilage defects and BMLs were associated with total WOMAC score (β=4.81, p<0.01 and β=2.20, p<0.01, respectively) and subscale (pain, stiffness and function, all p<0.01) scores in a dose-response pattern. Participants who had higher grades of cartilage defects, particularly grade 3 and 4, had higher WOMAC scores and remained higher over 10.7 years (Figure 1). The association of cartilage defects was independent of BMLs, meniscal pathology and effusion-synovitis, whereas the association of BMLs was dependent on cartilage defects and meniscal pathology but independent of effusion-synovitis. Tibiofemoral cartilage volume loss (not patellar) (β=1.91, p<0.01) and meniscal extrusion (not tears) (β=3.21, p<0.01) were independently associated with total WOMAC scores and pain over 10.7 years.Baseline cartilage defects, BMLs and meniscal extrusion were significantly associated with annual loss of tibial cartilage volume over 10.7 years (β=0.27%, p<0.01, β=0.22%, p<0.01 and β=0.28%, p<0.01, respectively) independent of other structural abnormalities.Radiographic osteophytes (but not JSN) were significantly associated with WOMAC score (β=8.49, p<0.01) over 10.7 years after adjustment for age, sex, BMI and other structural lesions. Conversely, radiographic JSN (but not osteophytes) was significantly associated with annual tibial cartilage volume loss (β=0.28%, p<0.01) over 10.7 years. These associations were independent of MRI structural lesions.ConclusionsBaseline cartilage defects, cartilage volume loss, BMLs, meniscal extrusion, JSN and osteophy...

BackgroundVitamin D may have a protective role for both symptoms and structures in osteoarthritis (OA).ObjectivesThe aim of this study was to evaluate the effects of vitamin D supplementation versus placebo on knee pain and structural changes in knee OA patients with low vitamin D.MethodsA multicentre, parallel randomized, placebo-controlled and double-blind clinical trial was performed in patients with symptomatic knee OA and a low 25-hydroxy vitamin D level (12.5 nmol/L to 60 nmol/L, mean 43.8±12.2 nmol/L at baseline) in Melbourne and Hobart, Australia. A central randomization centre used computer-generated random numbers to allocate treatments. 413 patients (mean age 63.2±7.0 years, 208 females) were randomized to either a single 50,000 IU monthly vitamin D3 capsule (n=209) or identical inert placebo (n=204) and followed for 2 years. The primary outcome measures were change in knee tibial cartilage volume by magnetic resonance imaging (MRI) and change in total knee pain assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary analyses included ≥20% and ≥50% improvement in total WOMAC knee pain, change in knee pain assessed by visual analogue scale (VAS), change in cartilage defects and change in bone marrow lesions (BMLs). Analyses were performed on an intention-to-treat basis using mixed models and multiple imputation by chained equations for missing data.ResultsAfter 24 months, serum 25(OH)D level increased by a mean of 40.6 nmol/L in the vitamin D group compared to 6.7 nmol/L in the placebo group. There was no statistically significant difference in changes of total tibial cartilage volume (-3.44% p.a. versus -4.23% p.a., p=0.132) or total WOMAC pain score (-49.9 versus -35.1, p=0.102). In secondary analyses, knee pain decreased more in the vitamin D group than the placebo group for VAS pain over 2 years (mean difference -5.4, 95% CI -10.7 to -0.1, p=0.048). The vitamin D group was associated with a tendency to greater response for ≥20% improvement (64% versus 57%, p=0.164) and greater response for ≥50% improvement (50% versus 39%, p=0.036) in total WOMAC pain from baseline to month 24. There were no significant differences between two groups in changes of tibiofemoral cartilage defects (0.29 versus 0.47, p=0.159) and tibiofemoral BMLs (-0.59 versus -0.21, p=0.087); however, the vitamin D group had less increase in tibiofemoral BMLs (17% vs 27%, p=0.03). Adverse events were minor but were more common in the vitamin D group (42 versus 26). Severe adverse events were infrequent and similar (14 versus 12).ConclusionsIn patients with symptomatic knee OA with vitamin D insufficiency, vitamin D supplementation over 2 years markedly increased serum levels but did not meet either primary endpoint. Secondary analyses suggest there may be modest benefits on knee pain and BMLs.AcknowledgementsWe especially thank all participants who made this study possible. We acknowledge Jodi Barling, Kay Nguo, Judy Hankin and Alice Noon for coordinating this study, and Robert Warren for reading M...

Patients were randomized to receive oral 1200 mg CS plus 1500 mg of GS or placebo once a day for 6 months. The primary outcome was the mean change in VAS global pain from baseline to 6 months. Secondary outcomes included the mean change in the investigator global assessment (IGA), WOMAC total, WOMAC pain and WOMAC function, as well as the proportion of responders to the OMERACT-OARSI 2004 criteria and the consumption of rescue medication. Adverse events (AEs) were also recorded for safety purposes. Results: Placebo showed a significantly greater VAS pain reduction (20.5 ± 2.4 mm; 33.0%) than combined CS/GS (11.8 ± 2.4 mm; 19.0%) in patients with symptomatic knee OA for the modified Intention to Treatment (mITT) population (D ¼ À8.7; À14.2%; p<0.03), but no for per protocol completers. Our secondary outcomes showed similar results. Placebo was similar to CS/GS for improving WOMAC total, WOMAC pain or WOMAC function in both mITT and per-protocol completer patients. Furthermore, neither the proportion of patients who met the OMER-ACT-OARSI responder criteria or the consumption of rescue medication differed significantly between placebo and CS/GS groups. AEs were low and similarly distributed in both groups. AEs mainly consisted of abdominal complaints such as diarrhoea, upper abdominal pain, and constipation. Conclusions: CS/GS failed to demonstrate superiority over placebo in reducing pain and functional limitation in patients with symptomatic knee OA at 6 months of treatment. This is the first ramdomized clinical trial that evaluates the efficacy of a SYSADOA sponsored by a pharmaceutical company but independently monitored by a DSMB.

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