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Management of OA is primarily focused on palliative relief using agents such as nonsteroidal anti\u2010inflammatory drugs (NSAID) and analgesics. However, such an approach is limited by a narrow therapeutic focus that fails to address the progressive and multimodal nature of OA. Given the favorable safety profile of most nutritional interventions, identifying disease\u2010modifying pharmaconutrients capable of improving symptoms and also preventing, slowing, or even reversing the degenerative process in OA should remain an important paradigm in translational and clinical research. The goals of pharmaconutrition for metabolic optimization are to drive biochemical reactions in a desired direction and to meet health condition\u2013specific metabolic demands. Applying advances in nutritional science to musculoskeletal medicine remains challenging, given the fluid and dynamic nature of the field, along with a rapidly developing regulatory climate over manufacturing and commerce requirements. The purpose of this article is to review the available literature on effectiveness and potential mechanism for OA of micronutrient vitamins; minerals; glycosaminoglycans; avocado\u2010soybean unsaponifiable fractions; methylsulfonylmethane; s\u2010adenosylmethionine; undenatured and hydrolyzed collagen preparations; phytoflavonoid compounds found in fruits, vegetables, spices, teas, and nuts; and other nutrients on the horizon. There also is a discussion on the concept of rational polysupplementation via the strategic integration of multiple nutraceuticals with potential complementary mechanisms for improving outcomes in OA. As applied nutritional science evolves, it will be important to stay on the forefront of proteomics, metabolomics, epigenetics, and nutrigenomics, because they hold enormous potential for developing novel therapeutic and prognostic breakthroughs in many areas of medicine, including OA.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.pmrj.2012.02.023","type":"journal-article","created":{"date-parts":[[2012,5,23]],"date-time":"2012-05-23T16:43:52Z","timestamp":1337791432000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Nutritional Interventions to Prevent and Treat Osteoarthritis. 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