W. Han

A longitudinal study of the association between infrapatellar fat pad maximal area and changes in knee symptoms and structure in older adults

Background The infrapatellar fat pad (IPFP) is of uncertain significance for knee osteoarthritis. The aim of this study was to describe the longitudinal associations between baseline IPFP maximal area and changes in knee pain, knee cartilage volume and cartilage defects in older adults. Methods 356 community-dwelling male and female adults aged 50–80 years were measured at baseline and approximately 2.6 years later. T1-weighted or T2-weighted fat-suppressed MRI was used to assess maximal IPFP area, cartilage volume and cartilage defects at baseline and/or follow-up. Knee pain was assessed by the self-administered Western Ontario McMaster Osteoarthritis Index questionnaire. Results After adjustment for confounders, IPFP maximal area in women was significantly and negatively associated with changes in knee pain (β: −0.18 to −0.86 for total knee pain, pain at night while in bed, pain when sitting/lying and pain when standing upright, all p<0.05) but not with other knee pain subscales. IPFP maximal area in women was beneficially associated with change in tibial cartilage volume per annum (β: +1.56% per cm2 at medial site; +0.86% per cm2 at lateral site, both p<0.05), but not with change in patellar cartilage volume. Further, it was significantly associated with reduced risks of increases in medial cartilage defects (relative risk: 0·46 at tibial site, relative risk: 0.59 at femoral site; both p<0.05) but not with increases at other sites in women. No significant associations were found in men. Conclusions While the associations are not fully consistent, IPFP maximal area appears to have a protective role for knee symptoms and cartilage damage in older female adults.

Effect of vitamin D supplementation on tibial cartilage volume and knee pain among patients with symptomatic knee osteoarthritis: a randomized clinical trial

IMPORTANCE Observational studies suggest that vitamin D supplementation is associated with benefits for knee osteoarthritis, but current trial evidence is contradictory. OBJECTIVE To compare the effects of vitamin D supplementation vs placebo on knee pain and knee cartilage volume in patients with symptomatic knee osteoarthritis and low vitamin D levels. DESIGN, SETTING, AND PARTICIPANTS A multicenter randomized, double-blind, placebo-controlled clinical trial in Tasmania and Victoria, Australia. Participants with symptomatic knee osteoarthritis and low 25-hydroxyvitamin D (12.5-60 nmol/L) were enrolled from June 2010 to December 2011. The trial was completed in December 2013. INTERVENTIONS Participants were randomly assigned to receive monthly treatment with oral vitamin D3 (50,000 IU; n = 209) or an identical placebo (n = 204) for 2 years. MAIN OUTCOMES AND MEASURES Primary outcomes were change in tibial cartilage volume (assessed using magnetic resonance imaging [MRI]) and change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score (0 [no pain] to 500 [worst pain]) from baseline to month 24. Secondary outcomes were cartilage defects and bone marrow lesions (assessed using MRI). RESULTS Of 413 enrolled participants (mean age, 63.2 years; 50% women), 340 (82.3%) completed the study. The level of 25-hydroxyvitamin D increased more in the vitamin D group (40.6 nmol/L) than in the placebo group (6.7 nmol/L) (P < .001) over 2 years. There were no significant differences in annual change of tibial cartilage volume or WOMAC pain score. There were no significant differences in change of tibiofemoral cartilage defects or change in tibiofemoral bone marrow lesions. Adverse events (≥ 1 per patient) occurred in 56 participants in the vitamin D group and in 37 participants in the placebo group (P = .04). [table: see text]. CONCLUSIONS AND RELEVANCE Among patients with symptomatic knee osteoarthritis and low serum 25-hydroxyvitamin D levels, vitamin D supplementation, compared with placebo, did not result in significant differences in change in MRI-measured tibial cartilage volume or WOMAC knee pain score over 2 years. These findings do not support the use of vitamin D supplementation for preventing tibial cartilage loss or improving WOMAC knee pain in patients with knee osteoarthritis. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01176344; anzctr.org.au Identifier: ACTRN12610000495022.

Association between MRI-detected knee joint regional effusion-synovitis and structural changes in older adults: a cohort study

Objective To describe the cross-sectional and longitudinal associations between knee regional effusion-synovitis and structural changes in older adults. Methods A total of 977 subjects were randomly selected from the local community (mean 62 years, 50% female) at baseline and 404 were followed up 2.6 years later. T2-weighted MRI was used to assess knee effusion-synovitis in four subregions: suprapatellar pouch, central portion, posterior femoral recess and subpopliteal recess. Knee cartilage defects, cartilage volume and bone marrow lesions (BMLs) were measured using MRI at baseline and follow-up. Results Cross-sectionally, effusion-synovitis in most subregions was significantly associated with a higher risk of cartilage defects, BMLs and reduced cartilage volume. Longitudinally, suprapatellar pouch effusion-synovitis at baseline predicted an increase in cartilage defects (p<0.01), loss of cartilage volume (p=0.04) and an increase in BMLs (p=0.02) in multivariable analyses. The significant associations of effusion-synovitis with cartilage volume and BMLs disappeared after adjustment for cartilage defects. Effusion-synovitis in whole knee joint (p<0.01) and subpopliteal recess (p<0.05) was consistently associated with longitudinal changes in cartilage defects but not in cartilage volume and BMLs. Conclusions There are independent associations between knee joint effusion-synovitis and knee cartilage defects in both cross-sectional and longitudinal analyses, suggesting a potential causal relationship. The associations of effusion-synovitis with BMLs and cartilage volume were largely dependent on cartilage defects, suggesting potential causal pathways.

Signal intensity alteration in the infrapatellar fat pad at baseline for the prediction of knee symptoms and structure in older adults: a cohort study

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.

Mass effect and signal intensity alteration in the suprapatellar fat pad: associations with knee symptoms and structure

OBJECTIVE To describe cross-sectional associations between mass effect or signal intensity alteration of the suprapatellar fat pad (SPFP) with knee symptoms and structure in older adults. METHODS A cross-sectional sample of 904 randomly selected subjects (mean 62.4 years, 49.9% female) was studied. T1- or T2-weighted fat suppressed magnetic resonance imaging (MRI) was used to assess mass effect or signal intensity alteration of SPFP, cartilage volume, cartilage defects, and bone marrow lesions (BMLs). Knee pain was assessed by self-administered Western Ontario McMaster Osteoarthritis Index (WOMAC) questionnaire. The Osteoarthritis Research Society International (OARSI) atlas was used to assess knee osteophyte, joint space narrowing (JSN) and radiographic osteoarthritis (ROA). Univariable and multivariable linear or logistic regression analyses were used to examine the associations. RESULTS After adjustment for confounders including age, sex, body mass index (BMI), disease status, tibial bone area and/or ROA, the presence of SPFP mass effect was significantly associated with any knee pain (OR: 2.39; 95% confidence interval (CI): 1.54, 3.70) and ROA (OR: 2.10; 95% CI: 1.33, 3.31) but not with cartilage volume, cartilage defects or BMLs. The presence of SPFP signal intensity alteration was significantly associated with any knee pain (OR: 1.90; 95% CI: 1.43, 2.53), ROA (OR: 1.83; 95% CI: 1.37, 2.45), any BMLs (OR: 1.55; 95% CI: 1.17, 2.06) but not with cartilage volume and cartilage defects. Significant associations with knee pain and BMLs were more evident in subjects with ROA. Presence of SPFP mass effect and/or signal intensity alteration combined was associated with any tibial cartilage defects (OR: 1.45; 95% CI: 1.04, 2.04). CONCLUSIONS SPFP mass effect and/or signal intensity alterations are deleteriously associated with knee pain, radiographic OA and BMLs in this cross-sectional study, suggesting that SPFP abnormalities may contribute to pain and structural abnormalities in the knee.

Cross-sectional and Longitudinal Associations between Knee Joint Effusion Synovitis and Knee Pain in Older Adults

Objective. To describe the cross-sectional and longitudinal associations between knee regional effusion synovitis and knee pain in older adults. Methods. Data from a population-based random sample (n = 880, mean age 62 yrs, 50% women) were used. Baseline knee joint effusion synovitis was graded (0–3) using T2-weighted magnetic resonance imaging (MRI) in the suprapatellar pouch, central portion, posterior femoral recess, and subpopliteal recess. Effusion synovitis of the whole joint was defined as a score of ≥ 2 in any subregion. Other knee structural (including cartilage, bone marrow, and menisci) lesions were assessed by MRI at baseline. Knee pain was assessed by the Western Ontario and McMaster Universities Osteoarthritis Index questionnaire at baseline and 2.6 years later. Multivariable analyses were performed after adjustment for age, sex, body mass index, and other structural lesions. Results. The prevalence of effusion synovitis was 67%. Suprapatellar pouch effusion synovitis was significantly and independently associated with increased total and nonweight-bearing knee pain in both cross-sectional and longitudinal analyses (for an increase in total knee pain of ≥ 5, RR 1.26 per grade, 95% CI 1.04–1.52), and increased weight-bearing knee pain in longitudinal analysis only. Effusion synovitis in posterior femoral recess and central portion were independently associated with increases in nonweight-bearing pain (RR 1.63 per grade, 95% CI 1.32–2.01 and RR 1.29 per grade, 95% CI 1.01–1.65, respectively) in longitudinal analyses only. Conclusion. Knee joint effusion synovitis has independent associations with knee pain in older adults. Suprapatellar pouch effusion synovitis is associated with nonweight-bearing and weight-bearing knee pain, while posterior femoral recess and central portion effusion synovitis are only associated with nonweight-bearing pain.

Quantitative Assessment of Knee Effusion-Synovitis in Older Adults: Association With Knee Structural Abnormalities

To describe the natural history of quantitatively measured knee effusion‐synovitis and the longitudinal associations between effusion‐synovitis and knee structural factors, including cartilage defects, cartilage volume, subchondral bone marrow lesions, and meniscal pathology, in older adults.

Systemic and Local Adipose Tissue in Knee Osteoarthritis

Knee osteoarthritis (OA) is the most common joint disease. Body adipose tissue has been shown to be related to the development and progression of knee OA. Among systemic adipose tissues, subcutaneous adipose tissue is significantly and negatively associated with muscle mass and forces, and could be related to the presence and progression of knee OA. Visceral adipose tissue is associated with increased cartilage loss and production of pro-inflammatory cytokines. Intra-muscular adipose tissue is associated with knee osteoarthritic changes, but it remains controversial if inter-muscular adipose tissue has a role to play in the pathogenesis for knee OA. Knee local adipose tissue such as infrapatellar fat pad (IPFP) can interact with neighbouring tissues, and may have a biphasic effect in knee OA. The underlying mechanisms for the roles of the systemic and local fat in knee OA could be related to biomechanical, metabolic, inflammatory factors and fat fibrosis, which may have a separated or combined effect on OA. Tissue engineering from systemic or local adipose tissue is a new research direction, and adipose tissue-derived stem cells from systemic or local adipose tissue may be beneficial for OA cartilage repair. Research on systemic and local adipose tissue would provide novel approaches for prevention and treatment of knee OA, but further studies are required to explore the roles of different adipose tissues in knee OA and the effects of stem cells derived from different adipose tissues on knee OA.

Strontium Ranelate, A Promising Disease Modifying Osteoarthritis Drug.

ABSTRACT Introduction: The articular cartilage and subchondral bone may have potential crosstalk in the development and progression of osteoarthritis (OA). Strontium ranelate (SrR) has the ability to dissociate the bone remodeling process and to change the balance between bone resorption and bone formation. Its effect on subchondral bone makes it a potential disease- modifying osteoarthritis drug (DMOAD) in the treatment of OA. The aim of the current review is to summarize up-to-date pharmacological and clinical data of SrR for OA treatment. Areas covered: A literature search was performed on PubMed and European Medicines Agency (EMA) website for all publications and documents related to SrR and OA. References of related studies were searched by hand. Treatment with SrR, especially at the dosage of 2 g/day, was associated with reduced radiographic knee OA progression, and with meaningful clinical improvement. It was also significantly associated with decreased MRI-assessed cartilage volume loss (CVL) and bone marrow lesions (BMLs). Expert opinion: SrR could be a promising DMOAD particularly for OA patients with bone phenotypes. The clinical efficacy and side effects of SrR for OA treatment need to be further investigated in future clinical trials before clinical application.

OP0064 Cross Sectional and Longitudinal Associations between Knee Joint Effusion and Osteoarthritic Structural Changes in Older Adults

Background Multiple joint pathological changes such as synovial effusion, cartilage and subchondral bone lesions are involved in osteoarthritis (OA). The causal relationship between joint effusion and other knee structural changes was not clear. Objectives This study aimed to determine the cross-sectional and longitudinal associations between knee joint effusion at different compartments and knee osteoarthritic changes in older adults. Methods A cohort of 976 randomly selected subjects from local community (mean 62 years, 50% female) was studied at baseline and 416 followed up 2.7 years later. Radiographic knee osteophyte and joint space narrowing (JSN) were assessed using the OARSI atlas. T2-weighted fat saturated magnetic resonance imaging (MRI) was utilized to assess knee effusion at 4 compartments: suprapatellar pouch, central portion, posterior femoral recess, and subpopliteal recess. Cartilage volume, cartilage defects, and bone marrow lesions (BMLs) were measured using MRI at baseline and 2.7 years later. Multivariable generalized linear models with Poisson regression analyses or linear regression were used to estimate prevalence ratios (PR) relative risks (RR) or regression coefficient (β). Results Cross-sectionally, knee effusion at suprapatellar pouch was associated with total cartilage volume (β=-0.23, p=0.05), cartilage defect presence at any compartment (PR: 1.17, p<0.01), BML presence at any compartment (PR: 1.23, p<0.01), any moderate to severe JSN (PR: 1.44, p<0.01) and any osteophyte (PR: 1.54, p<0.001). Effusion at central portion was associated with cartilage defect presence at any compartment (PR: 1.08, p=0.05), BML presence at any compartment (PR: 1.19, p<0.01). Effusion at posterior femoral recess was associated with cartilage defect presence at any compartment (PR: 1.12, p<0.01). Lastly, effusion at subpopliteal recess was associated with cartilage defect presence at any compartment (PR: 1.10, p<0.01), BML presence at any compartment (PR: 1.12, p=0.02), moderate to severe JSN (PR: 1.28, p<0.01) and osteophyte (PR: 1.27, p=0.03). Longitudinally, suprapatellar pouch effusion was associated with change in cartilage volume (β=-0.33%, p=0.05), increases in cartilage defects (RR: 1.24, p<0.01), and an increase in BML (RR: 1.24, p=0.04). Effusion at posterior femoral recess was associated with change in cartilage volume (β=-0.48%, p<0.01) increases in cartilage defects (RR: 1.11, p=0.03). Effusion at subpopliteal recess was associated with change in cartilage volume (β=-0.36%, p=0.01), increases in cartilage defects (RR: 1.15, p<0.01). In contrast, effusion at central portion was not significantly associated with any of the above structural changes. All these analyses were performed after adjustment for age, gender, BMI, rheumatoid arthritis, and/or radiographic osteoarthritis (ROA). Conclusions Knee joint effusions are associated with knee osteoarthritic structural changes suggesting a potential causal relationship. While suprapatellar pouch effusion is most consistently associated with knee structural changes, central portion effusion is not associated with changes in knee structures over time. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3882