Infrapatellar fat pad and knee osteoarthritis

Osteoarthritis (OA) is the most common and prevalent chronic joint disorder in older adults, characterized by progressive deterioration of joint structures. It affects not only the articular cartilage and subchondral bone but also other structures of the joint, such as menisci, synovial membrane, joint capsule, ligaments, muscles and infrapatellar fat pad (IPFP). IPFP, the biggest 'organ' in the knee and may play an important role in the incidence and progression of knee OA. This thesis aims to describe the associations of semi-quantitative and quantitative measures of IPFP signal intensity alterations assessed on magnetic resonance imaging (MRI) with knee structural and symptomatic changes in older adults or patients with symptomatic knee OA. This thesis is based on two established studies: Tasmanian Older Adults Cohort (TASOAC) study and Vitamin D Effects on Osteoarthritis (VIDEO) study. TASOAC is an ongoing prospective, population-based study, aimed at identifying the environmental, genetic, and biochemical factors associated with the development and progression of OA (assessed by both X-ray and MRI). Baseline measures were conducted from April 2002 to September 2004, and the first follow-up were conducted from September 2004 to February 2007 (mean 2.7 years, range 2.6-3.3 years). Subjects (n=1100) between the age of 50 and 80 years were randomly selected from the roll of electors in southern Tasmania (population, 229,000), a comprehensive population listing with an equal number of men and women. VIDEO is a multicentre, randomized, placebo-controlled double-blind clinical trial. The aim of this study is to compare the effects of vitamin D supplementation versus placebo on knee structural and symptomatic changes in patients with symptomatic knee OA over a 2-year period. Patients (n = 413) with symptomatic knee OA and low 25(OH)D levels were randomized to treatment and control groups in Hobart and Melbourne. Outcomes/predictors included knee symptoms assessed by WOMAC index and visual analogue scale (VAS), knee structural changes assessed by radiography or MRI, and serum biomarkers (IL-1, IL-6, TNF-˜í¬±). Chapter 4 describes the associations between semi-quantitative measures of IPFP high signal intensity alteration at baseline and knee symptoms and structural changes in older adults. These semi-quantitative measures of IPFP high signal intensity alterations at baseline are 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. Chapter 5 investigates the associations between semi-quantitative measures of IPFP hypointense signals and knee structural change and symptoms in older adults. These hypointense signals in the IPFP are associated primarily with increased knee cartilage defects and also with bone marrow lesions (BMLs) and knee symptoms in cross-sectional and longitudinal analyses, suggesting the abnormality represented by this signal has a potentially important role in OA process. Chapter 6 describes the associations between quantitative measures of IPFP high signal intensity alteration and knee structural abnormalities in patients with symptomatic knee OA. Quantitative measures of increased signal intensity in the IPFP are associated with knee structural abnormalities longitudinally, suggesting that these measurements could be used as an additional entry criteria in order to enrich for 'faster progressors' in studies of knee OA. Chapter 7 investigates the associations between serum levels of resistin, IPFP signal intensity alterations and other knee structural changes in patients with knee OA. Serum levels of resistin are significantly and positively associated with IPFP signal intensity alterations and other structural abnormalities, suggesting a potential role of resistin in knee OA. Chapter 8 describes the natural history of IPFP high signal intensity alteration (quantitative measures) and factors affecting its changes over 2 years. IPFP high signal intensity alterations were not static in patients with knee OA. Changes of these signal intensity alterations were age-related, independent of BMI, predicted by radiographic OA (ROA), cartilage volume and effusion-synovitis, as well as associated with changes in neighboring knee structures, suggesting therapeutic interventions aimed at these changes could be considered in clinical practice. In conclusion, age-related signal intensity alterations in the IPFP are associated with greater ROA progression, predict symptomatic and structural changes, and are related to neighboring knee structural abnormalities. Combined with its associations with pro-inflammatory mediators, these signal intensity alterations may represent age-related local adipose tissue inflammation, which contributes to the incidence and/or progression of knee OA. Furthermore, these signal intensity alterations may be used as imaging biomarkers in clinical research or practice.