Background and purposeTotal knee replacements (TKRs) are being increasingly performed in patients aged ≤ 65 years who often have high physical demands. We investigated the relation between age of the patient and prosthesis survival following primary TKR using nationwide data collected from the Finnish Arthroplasty Register.MaterialsFrom Jan 1, 1997 through Dec 31, 2003, 32,019 TKRs for primary or secondary osteoarthritis were reported to the Finnish Arthroplasty Register. The TKRs were followed until the end of 2004. During the follow-up, 909 TKRs were revised, 205 (23%) due to infection and 704 for other reasons.ResultsCrude overall implant survival improved with increasing age between the ages of 40 and 80. The 5-year survival rates were 92% and 95% in patients aged ≤ 55 and 56–65 years, respectively, compared to 97% in patients who were > 65 years of age (p < 0.001). The difference was mainly attributable to reasons other than infections. Sex, diagnosis, type of TKR (condylar, constrained, or hinge), use of patellar component, and fixation method were also associated with higher revision rates. However, the differences in prosthesis survival between the age groups ≤ 55, 56–65, and > 65 years remained after adjustment for these factors (p < 0.001).InterpretationYoung age impairs the prognosis of TKR and is associated with increased revision rates for non-infectious reasons. Diagnosis, sex, type of TKR, use of patellar component, and fixation method partly explain the differences, but the effects of physical activity, patient demands, and obesity on implant survival in younger patients warrant further research.

Obesity is an important risk factor for osteoarthritis (OA) in weight-bearing joints, but also in hand joints, pointing to an obesity-related metabolic factor that influences on the pathogenesis of OA. Leptin is an adipokine regulating energy balance, and it has recently been related also to arthritis and inflammation as a proinflammatory factor. In the present paper, the effects of leptin on human OA cartilage were studied. Leptin alone or in combination with IL-1 enhanced the expression of iNOS and COX-2, and production of NO, PGE2, IL-6, and IL-8. The results suggest that the effects of leptin are mediated through activation of transcription factor nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathway c-Jun NH2-terminal kinase (JNK). Interestingly, inhibition of leptin-induced NO production with a selective iNOS inhibitor 1400 W inhibited also the production of IL-6, IL-8, and PGE2, and this was reversed by exogenously added NO-donor SNAP, suggesting that the effects of leptin on IL-6, IL-8, and PGE2 production are dependent on NO. These findings support the idea of leptin as a factor enhancing the production of proinflammatory factors in OA cartilage and as an agent contributing to the obesity-associated increased risk for osteoarthritis.

IntroductionAdiponectin is an adipokine that regulates energy metabolism and insulin sensitivity, but recent studies have pointed also to a role in inflammation and arthritis. The purpose of the present study was to investigate the association and effects of adiponectin on inflammation and cartilage destruction in osteoarthritis (OA).MethodsCartilage and blood samples were collected from 35 male OA patients undergoing total knee replacement surgery. Preoperative radiographs were evaluated using Ahlbäck classification criteria for knee OA. Circulating concentrations of adiponectin and biomarkers of OA, that is, cartilage oligomeric matrix protein (COMP) and matrix metalloproteinase 3 (MMP-3), were measured. Cartilage samples obtained at the time of surgery were cultured ex vivo, and the levels of adiponectin, nitric oxide (NO), IL-6, MMP-1 and MMP-3 were determined in the culture media. In addition, the effects of adiponectin on the production of NO, IL-6, MMP-1 and MMP-3 were studied in cartilage and in primary chondrocyte cultures.ResultsPlasma adiponectin levels and adiponectin released from OA cartilage were higher in patients with the radiologically most severe OA (Ahlbäck grades 4 and 5) than in patients with less severe disease (Ahlbäck grades 1 to 3). Plasma adiponectin concentrations correlated positively with biomarkers of OA, that is, COMP (r = 0.55, P = 0.001) and MMP-3 (r = 0.34, P = 0.046). Adiponectin was released by OA cartilage ex vivo, and it correlated positively with production of NO (r = 0.43, P = 0.012), IL-6 (r = 0.42, P = 0.018) and MMP-3 (r = 0.34, P = 0.051). Furthermore, adiponectin enhanced production of NO, IL-6, MMP-1 and MMP-3 in OA cartilage and in primary chondrocytes in vitro in a mitogen-activated protein kinase (MAPK)-dependent manner.ConclusionsThe findings of this study show that adiponectin is associated with, and possibly mediates, cartilage destruction in OA.