The dissertation is dedicated to improvement of diagnostics and treatment of knee osteoarthritis by recognition of special features of the circadian rhythms of melatonin and galectin-3 production and association thereof with clinical-laboratory markers of the disease course, the indicators of quality of life and the efficacy of anti-arthrosis pharmacotherapy. Clinical and pathogenetic features of patients with OA of the knee were determined depending on the circadian rhythms of melatonin and galectin-3 production, and approaches to increasing the effectiveness of OA pharmacotherapy were justified.In patients with OA, there is a decrease in the excretion of 6-sulfatoxymelatonin in the urine (mainly at night) and the level of galectin-3 in the blood (without circadian character) compared with healthy individuals. The decrease in the excretion of 6-sulfatoxymelatonin and the increase in the level of galectin-3 were associated with age, duration of the disease and the X-ray stage of the disease, increased levels of cartilage oligomeric matrix protein (COMP), interleukin-1?. Individuals with low 6-SMT excretion rates (<13.7 ng/mg creatinine) were more common to patients > 60 years of age (54.9% versus 25.6% in patients aged ? 60 years, p <0.01) and patients with radiographic grade III (56.3% versus 19.5% in patients with OA grade II; p <0.01). The average daily level of 6-SMT excretion was statistically significantly correlated with age (r = 0.40; p <0.001), less closely - with duration of the disease (r = 0.18, p <0.05), and was not at all - with the concomitant synovitis. Patients with knee joint OA presented with an increase of mean daily serum levels of galectin-3, interleukin-1? and COMPby 64.0; 33.9 and 114%(p <0.001). The suppression of melatonin production and the increase in production of galectin-3 was accompanied by increased pain syndrome, deterioration of physical functions and quality of life of patients with OA. Also among patients with OA with aberrant excretion of 6-sulfatoxymelatonin, individuals with severe insomnia and depressive disorders were more common. Unlike patients with unchanged excretion of 6-SMT (> 19.4 ng/mg creatinine), patients with low excretion of 6-SMT (<13.7 ng/mg creatinine) had a moderate increase of the clinical severity of the disease (1.15-1.26 times; p <0.05) under Lequesne, WOMAC, KOOS, and HAQ indices, deterioration of the quality of life indicators under SF-36 scale and the total psychological health component (by 11.2%, p <0.05), a greater manifestation of insomnia (OR - 7.8; 95% CI - 3.01-18.6), daytime drowsiness under the Epworth scale (OR - 2.68; 95% CI - 1.18-6.10), and Beck's depression self-rating scale (OR-2.57; 95% CI-1.02-6.46). The patients with OA had elevated levels of galectin-3 associated with a significant deterioration of clinical symptoms (1.4-1.6 times; p <0.001) under Lequesne, WOMAC, KOOS, HAQ indices, worsening of quality of life under SF-36 scale, and a decrease in the total physical health component (by 27%, p <0.05), but less statistically significantly reflected on the quality of sleep and the severity of depressive disorders. The proportion of individuals with a total WOMAC index > 50 points in OA patients with high levels of galectin-3 (> 15.8 ng/ml) was 3.24 times higher (74.2 versus 22.9%; p <0.01) than in patients with normal levels of galectin-3 (<12.1 ng/ml). High serum levels of galectin-3 and low levels of 6-SMT excretion were found to be predictors of insufficient clinical response to standard pharmacotherapy in OA patients. 6-SMT level proved to be a more informative predictor of the "responder" status at the cut-off point > 17.6 ng/mg creatinine (sensitivity - 0.875, specificity - 0.600), while galectin-3 level appeared to be more informative predictor of the "non-responder" status at the cut-off point > 14.0 ng/ml (sensitivity - 0.742, specificity - 0.769).OA patients with normal melatonin production had significantly higher chances of achieving WOMAC 20 in a 12-week standard therapy than patients with suppressed hormone secretion (OR-3.12; 95% CI-1.04 - 9.33).The inclusion of melatonin in the treatment regimen improved sleep quality, a decrease in depressive disorders, increased the regression of clinical symptoms, and tripled the chances of achieving WOMAC 20 in OA patients with aberrant excretion of 6-sulfatoxymelatonin.
