Xingzhong Jin

Circulating C reactive protein in osteoarthritis: a systematic review and meta-analysis

Background There is emerging evidence that the development and progression of osteoarthritis (OA) is associated with inflammation. C reactive protein (CRP), a systemic marker for inflammation, may be elevated in OA patients but the evidence is conflicting. Objective To systematically review the literature for the relationship between serum CRP levels measured by a high sensitivity method (high sensitive CRP (hs-CRP)) and OA, as well as the correlation between circulating CRP levels and OA phenotypes. Methods MEDLINE, EMBASE and CINAHL databases were systematically searched from January 1992 to December 2012. Studies were included when they met the inclusion criteria and data from studies were extracted. Two independent reviewers assessed study quality using a modified Newcastle-Ottawa Quality Assessment Scale. Meta-analyses were performed to pool available data from included studies. Results 32 studies met the inclusion criteria. Serum hs-CRP levels in OA were modestly but statistically significantly higher than controls (mean difference=1.19 mg/L, 95% CI 0.64 to 1.73, p<0.001) with significant heterogeneity between studies. Levels were significantly associated with pain (r=0.14, 95% CI 0.09 to 0.20, p<0.001) and decreased physical function (r=0.25, 95% CI 0.13 to 0.39, p<0.001). No significant associations were found between hs-CRP levels and radiographic OA. Conclusions Low-grade systemic inflammation may play a greater role in symptoms rather than radiographic changes in OA.

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.

Belimumab – an anti-BLyS human monoclonal antibody for rheumatoid arthritis

Introduction: B lymphocyte stimulator (BLyS) is a major regulatory factor that controls the development and survival of B cells. Elevated serum levels of BLyS have been associated with rheumatoid arthritis (RA). Belimumab is a fully human monoclonal antibody that inhibits BLyS and it is being developed for the treatment of RA. This review aims to summarize up-to-date pharmacological and clinical data of belimumab in the treatment of RA. Areas covered: A literature search was performed on PubMed using keywords, including belimumab, LymphoStat-B, benlysta, BLyS inhibitor, rheumatoid arthritis and autoimmune disease. References of relevant studies were searched by hand. Abstracts of international conferences up to October 2012 were also included. Belimumab was well tolerated in the treatment of RA over 24 weeks. It significantly increased American College of Rheumatology (ACR)20 responses at week 24, especially in patients with high disease activity, positive rheumatoid factor, no anti-TNF treatment experience and those who had failed methotrexate therapy. However, belimumab failed to demonstrate significantly improved ACR50 and ACR70 responses in the single Phase II clinical trial of RA. Expert opinion: These results suggest that the clinical efficacy of belimumab for RA needs to be further investigated in future clinical trials. Careful patient selection may be necessary for belimumab to achieve optimal clinical outcomes in RA.

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.

Do early life factors affect the development of knee osteoarthritis in later life: a narrative review

Osteoarthritis (OA) mainly affects older populations; however, it is possible that early life factors contribute to the development of OA in later life. The aim of this review is to describe the association between childhood or early adulthood risk factors and knee pain, structural imaging markers and development of knee OA in later life. A narrative overview of the literature synthesising the findings of literature retrieved from searches of computerised databases and manual searches was conducted. We found that only a few studies have explored the long-term effect of childhood or early adulthood risk factors on the markers of joint health that predispose people to OA or joint symptoms. High body mass index (BMI) and/or overweight status from childhood to adulthood were independently related to knee pain and OA in later life. The findings regarding the association between strenuous physical activity and knee structures in young adults are still conflicting. However, a favourable effect of moderate physical activity and fitness on knee structures is reported. Childhood physical activity and performance measures had independent beneficial effects on knee structures including knee cartilage in children and young adults. Anterior knee pain syndrome in adolescence could lead to the development of patellofemoral knee OA in the late 40s. Furthermore, weak evidence suggests that childhood malalignment, socioeconomic status and physical abuse are associated with OA in later life. The available evidence suggests that early life intervention may prevent OA in later life.

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.

Cross-Sectional and Longitudinal Associations Between Serum Levels of High-Sensitivity C-Reactive Protein, Knee Bone Marrow Lesions, and Knee Pain in Patients With Knee Osteoarthritis

To describe associations between serum high‐sensitivity C‐reactive protein (hsCRP), knee bone marrow lesions (BMLs), and knee pain, cross‐sectionally and longitudinally, in patients with knee osteoarthritis (OA).