ABSTRACT
BACKGROUND: Osteoarthritis (OA) of the hip is a frequent and debilitating joint disease. Only few clinical risk factors for hip OA are established and clinically applicable biomarkers to identify patients at risk are still lacking. The glycoprotein vascular cell adhesion molecule 1 (VCAM-1) is expressed by chondrocytes and synovial tissue and was a predictive marker for development of severe large joint OA in a previous study. OBJECTIVE: It was tested whether increased serum levels of VCAM-1 are prevalent in patients with severe OA of the hips. METHODS: In this prospective, multicenter, cross-sectional study, risk factors of severe hip OA were investigated in patients scheduled for hip joint arthroplasty and 100 patients were randomly selected for validation of VCAM-1 as a potential biomarker for hip OA. Serum samples were analyzed by an enzyme-linked immunosorbent assay and compared with a sex and age-matched control cohort. RESULTS: The groups were similar in age, gender ratio and prevalence of diabetes. Serum concentrations of VCAM-1 were 8% higher in OA patients compared to controls, without reaching statistical significance (818â¯ng ml-1, 95% confidence interval, CI 746-891â¯ng ml-1 versus 759â¯ng m-1, 95% CI 711-807â¯ng ml-1; Pâ¯= 0.4839). CONCLUSION: The results of this study show that serum concentrations of VCAM-1 cannot distinguish patients with severe hip OA from age and sex-matched controls.
Subject(s)
Biomarkers/blood , Osteoarthritis, Hip , Vascular Cell Adhesion Molecule-1/blood , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Male , Osteoarthritis, Hip/blood , Osteoarthritis, Hip/diagnosis , Osteoarthritis, Knee , Prevalence , Prospective StudiesABSTRACT
OBJECTIVE: Despite the high frequency of HFE gene mutations in Western Europe, widespread screening for HFE hemochromatosis is not recommended due to its variable phenotype. Joint pain and a premature osteoarthritis-like disease including the hip joints are the most frequent manifestation in patients with HFE hemochromatosis and iron overload. Therefore, screening of patients with severe osteoarthritis of the hip could identify patients with HFE hemochromatosis. METHODS: In this prospective cross-sectional study, 940 patients aged <70 years with end-stage osteoarthritis of the hip undergoing elective joint replacement surgery were screened for HFE hemochromatosis and compared to age- and sex-matched controls. RESULTS: No greater prevalence of C282Y homozygosity mutation or elevated serum ferritin or transferrin saturation levels was found in the study cohort with severe osteoarthritis of the hip than in controls from the general population. CONCLUSION: Our screening approach could not identify an increased prevalence of HFE gene mutations and iron overload in younger patients with severe osteoarthritis of the hip.
Subject(s)
Hemochromatosis Protein/genetics , Hemochromatosis/diagnosis , Iron Overload/diagnosis , Osteoarthritis, Hip/diagnosis , Aged , Arthroplasty, Replacement/methods , Female , Ferritins/blood , Genotype , Hemochromatosis/complications , Hemochromatosis/physiopathology , Hemochromatosis/surgery , Humans , Iron Overload/complications , Iron Overload/physiopathology , Male , Middle Aged , Mutation , Osteoarthritis, Hip/complications , Osteoarthritis, Hip/physiopathology , Osteoarthritis, Hip/surgery , Severity of Illness IndexABSTRACT
BACKGROUND: Aging has been associated with various alterations of immune functions, the musculoskeletal system and a decline of sex hormone levels. Estradiol has a central role in the regulation of bone turnover and also modulates the production of cytokines such as interleukin-1 and -6 and tumor necrosis factor-alpha. We therefore studied the effect of age and gender on cytokine production by mononuclear cells and markers of bone metabolism. METHODS: Peripheral blood mononuclear cells were isolated from young and elderly subjects; intracellular detection of cytokine production after stimulation with ionomycine and PMA (T cells) or LPS (monocytes) was performed by four color flow cytometry. Sex hormone levels and markers of bone metabolism were measured by RIA or ELISA: RESULTS: When we compared elderly to young women we found an increased proportion of T cells that were positive for interferon-gamma, interleukin-2, -4, -10 and -13. Also the percentage of cells producing interleukin-4 or interferon-gamma within the CD8(+) population was higher in the group of elderly women. In contrast, proportionally fewer monocytes of elderly women were positive for tumor necrosis factor-alpha or interleukin-6 than those of young women. In elderly men a higher percentage of T cells produced interleukin-2, -4 and -13. In the group of aged men we found a higher frequency of cells that produced interleukin-4 within the CD4(+) or CD8(+) population. Moreover, within monocytes of elderly men we found an increased percentage of cells positive for both interleukin-1beta and tumor necrosis factor-alpha. The data on markers of bone metabolism indicated an increase of bone turnover in old age. CONCLUSION: Our data demonstrate that aging is associated with significant alterations of bone metabolism and cytokine production by T cells and monocytes. For particular cytokines (interferon-gamma and interleukin-10 in T cells, interleukin-6 and tumor necrosis factor-alpha in monocytes) these changes are gender specific.