Objective: analysis of the osteoarthritis (OA) comorbidity taking into account the microelement status and genetic polymorphisms of the examined patients, determination of the prospects for the OA prevention and therapy.Material and methods. A cross-sectional study of a multiethnic cohort (n=655, mean age 43±14 years, 95% CI 29–70) formed on the basis of the Institute of Microelements database, was carried out. For all participants, the content of the 62 elements of the Element Periodic Table profile in hair was identified and variants of 120 nucleotide polymorphisms associated with various pathologies were definedResults. The study found that 18 of the 27 ICD-10 diagnoses examined were comorbid with OA. Osteoarthritis was comorbid with pathologies with a pronounced component of inflammation (ulcerative colitis, atherosclerosis, unspecified encephalopathy, obesity, diabetes mellitus, essential (primary) hypertension, urine calculus, acute myocardial infarction, cholelithiasis, etc.). The core of OA comorbidity was established, which included following pathologies: chronic cerebral ischemia, diabetes mellitus, thrombophlebitis, atherosclerosis, cholelithiasis. Seven profiles of the most frequent combinations of these diagnoses were identified. The presence of 2 out of 5 of these pathologies was recorded in 92% of patients with OA (n=50) and only in 2% of control patients (n=600), which corresponded to an extreme increase in the risk of OA (OR 56.3, 95% CI 17.4–181.6, p<10–20). Analysis of the 62 elements profile of the Element Periodic Table content in hair showed that reduced levels of silicon, molybdenum, vanadium and calcium are significantly associated with OA. As a result of studying data on 120 nucleotide polymorphisms, OA was significantly associated with the LPL Ser447Stop CC, LPL N291S AA, NOS3 E298D GG, and MTHFR 677 CC genotypes, which regulate lipid metabolism and inflammation.Conclusion. Based on the obtained results the prospects for the use of chondroitin sulfate and glucosamine sulfate in patients with an increased risk of OA development are shown.