Shuang Zheng

Association Between Infrapatellar Fat Pad Volume and Knee Structural Changes in Patients with Knee Osteoarthritis

Objective. The function of the infrapatellar fat pad (IPFP) in knee osteoarthritis (OA) remains uncertain. This study aimed to examine cross-sectional associations between IPFP volume and knee structures in patients with knee OA. Methods. The study included 174 patients with clinical knee OA (mean age, 55.5 yrs). Fat-suppressed 3-D T1-weighted spoiled gradient recall magnetic resonance imaging (MRI) was used to measure the IPFP and cartilage volume. T2-weighted fast spin echo MRI was used to assess cartilage defects and bone marrow lesions (BML). Radiographic knee osteophytes and joint space narrowing (JSN) were assessed using the Osteoarthritis Research Society International atlas. Results. After adjustment for potential confounders, greater IPFP volume was associated with greater tibial and patellar cartilage volume (all p < 0.05), and fewer cartilage defects at all sites (OR 0.88–0.91, all p < 0.05). IPFP volume was associated with presence of BML at lateral tibial and medial femoral sites (OR 0.88–0.91, all p < 0.05) and osteophytes at lateral tibiofemoral compartment (OR 0.88, p < 0.05). IPFP volume was not significantly associated with JSN. Conclusion. Greater IPFP volume was associated with greater knee cartilage volume and fewer structural abnormalities, suggesting a protective role of IPFP size in knee OA.

Association between circulating adipokines, radiographic changes, and knee cartilage volume in patients with knee osteoarthritis.

Objectives: To explore the associations between serum adipokine levels, radiographic osteoarthritis (ROA) severity, and articular cartilage volume in patients with knee OA. Method: A cross-sectional sample of 205 patients (aged 45–74 years) with knee OA were consecutively recruited to the Anhui Osteoarthritis (AHOA) study. ROA was assessed using the Kellgren–Lawrence (KL) grading system (grades 0–4). Knee cartilage volume was determined using fat-saturated T1-weighted magnetic resonance imaging (MRI). Serum levels of the adipokines leptin, adiponectin, and resistin were measured by using an enzyme-linked immunosorbent assay (ELISA). Results: Serum adiponectin, but not serum leptin or resitin, was significantly associated with reduced ROA severity in univariable analyses and this association remained significant after adjustment for age, sex, body masss index (BMI), and disease duration [β = −0.012, 95% confidence interval (CI) −0.021 to −0.002]. In ROA patients, leptin was significantly and positively associated with knee cartilage volume at patellar and medial tibial sites in both unadjusted and adjusted analyses (β = 0.006, 95% CI 0.02–0.010 for medial tibia and β = 0.009, 95% CI 0.001–0.018 for patella sites) but adiponectin and resistin had no significant associations with cartilage volume. In non-ROA patients, leptin, adiponectin, and resistin were not significantly associated with cartilage volume at any site. Conclusions: Serum levels of leptin are independently associated with increased knee cartilage volume. In addition, serum adiponectin is significantly and negatively associated with ROA severity, suggesting a potentially protective effect.

Associations between serum ghrelin and knee symptoms, joint structures and cartilage or bone biomarkers in patients with knee osteoarthritis

OBJECTIVE The roles of ghrelin in knee osteoarthritis (OA) are unclear. This study aimed to examine cross-sectional associations of ghrelin with knee symptoms, joint structures and cartilage or bone biomarkers in patients with knee OA. METHODS This study included 146 patients with symptomatic knee OA. Serum levels of ghrelin and cartilage or bone biomarkers including cartilage oligomeric matrix protein (COMP), cross linked C-telopeptide of type I collagen (CTXI), cross linked N-telopeptide of type I collagen (NTXI), N-terminal procollagen III propeptide (PIIINP), and matrix metalloproteinase (MMP)-3, 10, 13 were measured using Enzyme-linked immunosorbent assay (ELISA). Knee symptoms were assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Infrapatellar fat pad (IPFP) volume, IPFP signal intensity alternation, cartilage defects, bone marrow lesions (BMLs) and effusion-synovitis were assessed using the (MRI). Osteophytes and joint space narrowing (JSN) were assessed using the Osteoarthritis Research Society International atlas. RESULTS After adjustment for potential confounders, ghrelin quartiles were positively associated with knee symptoms including pain, stiffness, dysfunction and total score (quartile 4 vs 1: β 24.19, 95% CI 8.13-40.25). Ghrelin quartiles were also significantly associated with increased IPFP signal intensity alteration (quartile 4 vs 1: OR 3.57, 95% CI 1.55-8.25) and NTXI, PIIINP, MMP3 and MMP13. Ghrelin was not significantly associated with other joint structures and biomarkers. CONCLUSIONS Serum levels of ghrelin were significantly associated with increased knee symptoms, IPFP signal intensity alteration and serum levels of MMP3, MMP13, NTXI and PIIINP, suggesting that ghrelin may have a role to play in knee OA.

Serum levels of resistin and interleukin-17 are associated with increased cartilage defects and bone marrow lesions in patients with knee osteoarthritis.

Abstract Objectives: To investigate cross-sectional associations between serum levels of resistin and interleukin-17 (IL-17) and cartilage defects and bone marrow lesions (BMLs) in patients with knee symptomatic osteoarthritis (OA). Methods: One hundred and ninety-four consecutively-selected patients with knee symptomatic OA (mean 55.4 years, range 34–74, 87% females) were included in Anhui Osteoarthritis (AHOA) Study. Knee cartilage defects and BMLs were determined at different sites using T2-weighted fat-suppressed fast spin echo MRI. Serum resistin, IL-17, and high-sensitivity C-reactive protein (hs-CRP) levels were measured using ELISA. Results: In multivariable analyses, serum resistin was positively associated with cartilage defects at lateral femoral, lateral tibial, and medial tibial (all p < 0.05) sites. The significant associations were also present with BMLs at lateral femoral and tibial sites (ORs: 1.13–1.19, both p < 0.05). In patients with the highest quartile of hs-CRP (>2.45 pg/ml), IL-17 was positively and significantly associated with cartilage defect score at nearly all sites (ORs: 1.33–1.44, all p < 0.05), and BMLs at lateral and medial femoral sites (ORs: 1.26–1.51, both p < 0.05). Conclusions: Serum levels of resistin were positively and independently associated with cartilage defects and BMLs in patients with knee OA. Serum IL-17 was significantly associated with cartilage defects and BMLs in patients with an increased inflammatory status. These suggest that metabolic and inflammatory mechanisms may have a role to play in knee OA.

Monoclonal antibodies for the treatment of osteoarthritis

ABSTRACT Introduction: Osteoarthritis (OA) is a multifactorial chronic joint disease, and so far, there are no approved disease-modifying anti-OA drugs (DMOADs). There is an urgent need to develop therapies for different phenotypes of OA. Monoclonal antibodies (mAb) may slow structural progression, control inflammation and relieve pain, and thus have the potential to be DMOADs. Areas covered: In this review, the authors searched the literature on PubMed, EMBASE and the Cochrane Library using keywords, including mAbs, biological agents, OA and osteoarthritis, electronically up to May 2016. They also included abstracts of international conferences. Furthermore, they reviewed experimental and clinical studies of various mAbs targeting different pathological mechanisms of OA, including ADAMTS, Interleukine-1, tumour necrosis factor, never growth factor and vascular endothelial growth factor. Expert opinion: MAbs for the treatment of OA are under intense investigation and the results for some mAbs (e.g., anti-nerve growth factor mAbs, anti- vascular endothelial growth factor mAbs) are promising. The authors believe that mAb therapy can be a targeted therapeutic approach for the treatment of OA. Future clinical trials are required to evaluate the therapeutic efficacy of these agents by the appropriate selection of specific phenotype for targeted therapy based on the mechanism of drug action.

Associations between circulating adipokines and bone mineral density in patients with knee osteoarthritis: A cross-sectional study

BackgroundAssociations between adipokines and bone mineral density (BMD) in knee osteoarthritis (OA) remain indistinct. The aim of this study was to investigate the cross-sectional associations between serum levels of adipokines and BMD in patients with knee OA.MethodsThis study included 164 patients with symptomatic knee OA from the Anhui Osteoarthritis study. Serum levels of leptin, adiponectin, and resistin were measured using an enzyme-linked immunosorbent assay (ELISA). BMD at total body, spine, hip, and femur were measured by dual-energy X-ray absorptiometry (DXA).ResultsIn multivariable analyses, serum levels of leptin were significantly associated with reduced BMD at total body, hip, total femur, femoral neck, and femoral shaft (β = − 0.019, 95% CI -0.034 to − 0.005; β = − 0.018, 95% CI -0.034 to − 0.003; β = − 0.018, 95% CI -0.034 to − 0.002; β = − 0.016, 95% CI -0.032 to 0.000; β = − 0.026, 95% CI -0.046 to − 0.006; respectively). Serum levels of adiponectin were significantly and negatively associated with BMD at total femur and femoral shaft (β = − 0.007, 95% CI -0.013 to 0.000; β = − 0.011, 95% CI -0.018 to − 0.003; respectively). However, no significant associations were found between serum levels of resistin and BMD at any site measured.ConclusionsSerum levels of leptin and adiponectin were significantly and negatively associated with BMD, suggesting potentially detrimental effects of leptin and adiponectin on BMD in knee OA patients.

Association between quantitatively measured infrapatellar fat pad high signal intensity alteration and MRI-assessed progression of knee osteoarthritis

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).

FRI0528 Long-term effects of vitamin d supplementation and maintaining vitamin d sufficiency on knee osteoarthritis over 5 years

Background Epidemiological studies suggest that vitamin D deficiency is associated with knee symptoms and structural progression of knee osteoarthritis (OA). However, randomised controlled trials (RCTs) failed to demonstrate a significant effect of vitamin D supplementation on OA, probably due to selecting OA participants with and without vitamin D deficiency, short duration of follow-up and a large proportion of participants in the placebo group reaching vitamin D sufficiency (61.3% of patients in the placebo group achieved a serum 25(OH)D level of >60 nmol/L at 3 months of a clinical trial). Objectives To examine whether those maintaining sufficient serum vitamin D levels over 5 years had reduced knee symptoms compared with those who did not maintain adequate vitamin D levels in patients with knee OA. We also explored the effect of 2 year vitamin D supplementation on knee symptoms compared to placebo after 3 years of cessation of treatment. Methods Participants with symptomatic knee OA and low 25-hydroxyvitamin D [25(OH)D] (12.5–60 nmol/L) 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. 172 participants who enrolled in the study from Hobart were followed up after 3 years (5 years from baseline) of the cessation of the treatment to assess knee symptoms and vitamin D levels. Participants were classified as maintaining sufficient vitamin D group if they maintained serum 25(OH)D>50 nmol/L at month 3, 24 and 60 (n=79), and not maintaining sufficient vitamin D group (25(OH)D≤50 nmol/L at month 3, 26 and 60, n=62) groups. Knee symptoms were assessed at baseline, 3, 6, 12, 24 and 60 month using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Results The level of 25(OH)D dropped in the vitamin D group (87.0 nmol/L to 53.3 nmol/L) and slightly increased (53.3 nmol/L to 61.7 nmol/L) in the placebo group 3 years after the cessation of the treatment. Knee pain increased from the end of the study to 5 years of follow-up in the treatment (81.8 to 91.7) and placebo (75.8 to 101.1) groups. 16.7% of the participants in vitamin D and 18.5% of the participants in placebo group underwent total knee replacement (TKR) surgery. There were no significant differences in WOMAC symptoms, TKR rates or change in symptoms between Vitamin D and placebo groups after 3 years of cessation of the supplementation. Participants who maintained adequate vitamin D levels over 5 years had significantly less WOMAC knee pain (β:−38.4, 95% CI:−69.2,–7.7) and physical dysfunction (β:−98.5, 95% CI:−193.8,–3.1) than participants with vitamin D deficiency over 5 years in multivariable analyses. Conclusions Vitamin D supplementation over 2 years did not result in significant differences in change in knee symptom score over 5 years compared to placebo. However, knee OA patients maintaining sufficient serum vitamin D levels over long-term had more improvement in knee pain and physical function than those who did not maintain adequate vitamin D levels, suggesting a beneficial effect of maintaining sufficient serum vitamin D for knee OA. Disclosure of Interest None declared

FRI0522 Vitamin d supplementation improves depression in knee osteoarthritis patients over 24 months

Background Although depression is prevalent in osteoarthritis (OA) patients and the positive association between vitamin D deficiency and depression has been demonstrated, no study has examined the effect of vitamin D supplementation on depression in OA patients. Objectives To determine the effect of vitamin D supplementation and maintaining sufficient serum vitamin D on depression in patients with knee OA and vitamin D deficiency. Methods Participants with symptomatic knee OA and vitamin D deficiency were enrolled in a randomised, placebo-controlled trial and received 50,000IU vitamin D3 (n=209) or placebo (n=204) monthly for 24 months. Serum 25-hydroxyvitamin D [25(OH)D] was measured at baseline, month 3 and 24. Depression was measured using the patient health questionnaire (PHQ-9), and knee symptoms were assessed using Western Ontario and McMaster Universities Arthritis Index (WOMAC) at baseline, month 3, 6, 12 and 24. Multilevel mixed-effect models were used to estimate the association between exposures and outcomes adjusting for potential confounders. Results Over 24 months, 340 participants (82.3% retention rate) completed the study. The prevalence and incidence of depression were 25.4% and 11.2%, respectively. Depression improved more in the vitamin D supplementation group (β: −0.45, 95% CI: −0.84 to −0.07) compared to the placebo group (β: 0.21, 95% CI: −0.19 to 0.61) (p=0.02) and in those participants who maintained vitamin D sufficiency (β: −0.44, 95% CI: −0.88 to −0.00) compared to those who did not maintain sufficiency (β: 0.40, 95% CI: −0.18 to 0.97) (p=0.02) over 24 months.Abstract FRI0522 – Table 1 Effects of vitamin D supplementation over 24 months on change in PHQ-9 Mean change,(95% CI) Between-group difference change, mean (95% CI) P value Placebo Group(n=204) 0.21 (-0.19 to 0.61) −0.66 (-1.22 to −0.11) 0.02 Vitamin D Group(n=209) −0.45 (-0.84 to −0.07) Changes in outcomes are generated from mixed-effect models adjusted for age, sex and body mass index.Abstract FRI0522 – Table 2 Effects of vitamin D status over 24 months on change in PHQ-9 Mean change,(95% CI) Between-group difference change, mean (95% CI) P-value Not maintaining sufficient vitamin D (n=114) 0.40 (-0.18 to 0.97) −0.83 (-1.56 to −0.11) 0.02 Maintaining sufficient vitamin D (n=226) −0.44 (-0.88 to −0.00) Changes in outcomes are generated from mixed-effect models adjusted for age, sex and body mass index.Abstract FRI0522 – Figure 1 Flowchart of the study Conclusions These findings suggest that vitamin D supplementation and maintaining sufficient vitamin D levels over 24 months may have beneficial effects on depression in patients with knee OA. References [1] Stubbs B, Aluko Y, Myint PK, et al. Prevalence of depressive symptoms and anxiety in osteoarthritis: a systematic review and meta-analysis. Age Ageing2016;45(2):228–35. doi:10.1093/ageing/afw001 [2] Anglin RE, Samaan Z, Walter SD, et al. Vitamin D deficiency and depression in adults: systematic review and meta-analysis. Br J Psychiatry2013;202:100–7. doi:10.1192/bjp.bp.111.106666 Acknowledgements We 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. Disclosure of Interest None declared

Associations between systemic bone mineral density, knee cartilage defects and bone marrow lesions in patients with knee osteoarthritis

The relationship between bone mineral density (BMD) and osteoarthritis (OA) remains controversial. This study aimed to explore the cross‐sectional associations between BMD at the total body, hip and spine and joint structural abnormalities including cartilage defects and bone marrow lesions (BMLs) in patients with knee OA.