Abstract
Introduction:
The risk factors for degenerative joint disease are well established: increasing age, obesity, joint abnormalities, trauma and overuse, together with female gender, ethnic and genetic factors. That obesity is a significant risk factor for developing osteoarthritis in non-weight-bearing as well as weight-bearing and joints was one of the first indications that the risk was nor purely that of aberrant biomechanical loading. Low grade chronic systemic inflammation is a component of each of ageing and obesity, atherosclerosis and diabetes, culminating in Metabolic Syndrome. In our study of 1684 patients with joint degeneration 85% were overweight or obese and 65% older than 65 years with 62% being both, 73% of patients were taking medications for serious, ‘non-orthopaedic’ health problems such as cardiovascular or respiratory disease, obesity or NIDDM. Monocytes are a major component of chronic inflammation, approximately 10% of white blood cells are monocytes which circulate for 2–3 days, before being recruited into tissues as inflammatory macrophages or undergoing apoptosis. Circulating S100A8/A9 (MRP8/14) is a measure of monocyte recruitment being shed during monocyte transmigration across the endothelium. The higher the S100A8/A9 the more monocytes being recruited giving an indirect measure of chronic inflammatory status.
Methods:
2154 blood samples were collected from arthroplasty patients (first or second joint replacement), 1135 Female and 1019 Male, age 29–93 years, body mass index (BMI) 18–56, with hip or knee osteoarthritis (primary, post-traumatic and secondary), 589 before a primary arthroplasty, 1187 patients >1 year post-arthroplasty, 101 patients before revision for aseptic loosening and 237 patients >1 year post-revision. All study patients received metal on UHMWPE implants. Plasma S100A8/A9 was measured using BMA Biomedicals Elisa kit, normal levels in healthy adults are 0.5–3 mg/ml. The data were analysed using SPSS, p values were calculated using Spearman's test.
Results:
Pre-surgery (primary or revision), plasma concentrations of S100A8/A9 were significantly higher in overweight and obese patients 4.9 + 3.0 mg/ml and those over 65 years of age 5.0 + 3.0 mg/ml than in normal weight patients of any age 4.2 + 2.1 mg/ml. Further analysis revealed that in pre-operative lower limb arthroplasty patients >65 years and with a BMI >25, taking typical prescription NSAIDS (e.g. diclofenic, ibruprofen) circulating S100A8/A9 was 5.9 + 2.5 mg/ml while administration of anti-platelet/anti-coagulant therapies lowered plasma S100A8/A9 concentrations to 4.4 + 2.2 mg/ml, (p < 0.001). More than one year following an arthroplasty, circulating S100A8/A9 levels were significantly reduced including in overweight and obese patients >65 years of age regardless of their medication 4.2 + 2.2 mg/ml. Post-operative levels of S100A8/A9 were close to the normal healthy range in normal weight patients and only marginally higher in older obese patients.
Discussion:
These data suggest that osteoarthritis is a significant driver of the chronic inflammation associated with obesity. Platelet activation and aggregation may underpin this as administration of low dose aspirin for cardiovascular diseases significantly reduces S100A8/A9.
