Effects of Vitamin K on Lower-extremity Function in Adults with Osteoarthritis: a Randomized Controlled Pilot Trial

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PROJECT SUMMARY Knee osteoarthritis (OA) is a leading cause of lower-extremity disability in adults. There is no known cure, so the identification of effective strategies to reduce the consequences of knee OA is important to delay disability and reduce associated cost burden. Multiple lines of biologic, genetic, and epidemiologic evidence support a critical role for vitamin K and vitamin K-dependent proteins (VKDPs) in maintenance of joint health. Vitamin K is an established shortfall nutrient. Preclinical models indicate that vitamin K insufficiency adversely affects articular cartilage. In observational knee OA studies, older adults with low circulating concentrations of vitamin K have poorer lower-extremity function. Vitamin K is required to produce functional VKDPs found in the joint and there is emerging evidence that it regulates transcription of genes in articular cartilage through the nuclear receptor SXR/PXR. Therefore, there are strong physiological underpinnings to support a protective role for vitamin K in knee OA. However, no clinical trials have yet been conducted. To address critical parameters required to design a larger clinical trial, we propose a randomized controlled pilot study in adults with mild to moderate knee OA and low baseline vitamin K status to: (1) Pilot study procedures and assess the feasibility of implementing a larger scale definitive clinical trial of vitamin K supplementation in adults with mild to moderate knee OA and low baseline vitamin K status at two clinical sites; and (2) Determine the responsiveness of performance-based tests of physical function in adults with low vitamin K status and mild to moderate knee osteoarthritis. This randomized pilot study will generate critical data to guide the design of a larger clinical trial to evaluate vitamin K as a potential therapy to mitigate the decline in lower-extremity function among adults with symptomatic knee OA and low vitamin K status. Identifying a single well-tolerated intervention that favorably reduces knee OA progression would represent an important therapeutic breakthrough.