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Purpose of Review Osteoarthritis (OA) is the most common forms of arthritis in the general population, accounting for more pain and functional disability than any other musculoskeletal disease. There are currently no approved disease modifying drugs for OA. In the absence of effective pharmacotherapy, many patients with OA turn to nutritional supplements and nutraceuticals, including collagen derivatives. Collagen hydrolyzates and ultrahydrolyzates are terms used to describe collagens that have been broken down into small peptides and amino acids in the presence of collagenases and high pressure. Recent Findings This article reviews the relevant literature and serves as a White Paper on collagen hydrolyzates and ultrahydrolyzates as emerging supplements often advertised to support joint health in OA. Collagen hydrolyzates have demonstrated some evidence of efficacy in a handful of small scale clinical trials, but their ability to treat and reverse advanced joint disease remains highly speculative, as is the case for other nutritional supplements. Summary The aim of this White Paper is to stimulate research and development of collagen-based supplements for patients with OA and other musculoskeletal diseases at academic and industrial levels. This White Paper does not make any treatment recommendations for OA patients in the clinical context, but simply aims to highlight opportunities for scientific innovation and interdisciplinary collaboration, which are crucial for the development of novel products and nutritional interventions based on the best available and published evidence.

There is still no definitive treatment for knee osteoarthritis (OA). We are certainly far from a consensus on the best form of treatment or on an effective treatment recommendation. There are reasons for the current equivocal treatment recommendations in the face of this very serious health problem. The greatest of these reasons, undoubtedly, is the great complexity of the factors involved in the development and progression of knee OA and the complex pathophysiology including mechanical, inflammatory, metabolic, post-traumatic, molecular, genetic, and psychological changes. For several years, an attempt has been made to correlate different patient phenotypes to different patterns of response to treatment, thus creating the possibility of developing specific treatments for certain groups of patients and theoretically allowing better treatment efficacy. However, in practice we still find totally different responses and evolutions even in individuals belonging to the same phenotype. Thus, classification by phenotypes, despite being an advance, is not sufficient. The present article proposes a fragmented look at each of the many factors or targets involved in the genesis and evolution of OA. Therefore, we propose not the treatment of OA per se but the management of an individual set of targets to achieve personalized OA management. We believe that, paradoxically, by fragmenting the view of the disease we will be able to treat our patients more holistically in an individualized way.