Little Evidence of Link Between Vitamin K and Osteoarthritis Risk

Researchers evaluated the causal association between vitamin K and osteoarthritis using Mendelian randomization.

Scant statistical evidence has demonstrated that there is a causal association between genetically predicted vitamin K levels and the risk for development of osteoarthritis (OA), according to study results published in Seminar in Arthritis & Rheumatism. .

Researchers sought to estimate the causal association between vitamin K and risk for OA with the use of two-sample Mendelian randomization (MR). Data from a genome-wide association study (GWAS) of OA were used to evaluate the possible link.

Data from the GWAS (with up to 826,690 individuals) were used to assess the effect of genetically predicted vitamin K level (instrumented using 4 variants derived from a GWAS of 2138 individuals) on the risk for all types of OA (knee, hip, spine, and hand), as well as total joint replacement. The 4 variants selected explained 5.5% of the variance for circulating phylloquinone (vitamin K1), which corresponded to a mean F statistic of 27 (range, 18 to 23).

Genetically predicted vitamin K1 levels were not associated with the risk for OA overall (odds ratio [OR], 0.98; 95% CI, 0.96-1.01), knee OA (OR, 0.98; 95% CI, 0.92-1.03), hip OA (OR, 0.97; 95% CI, 0.88-1.07), spine OA (OR, 0.97; 95% CI, 0.90-1.04), hand OA (OR, 0.97; 95% CI, 0.91-1.04), early-onset OA (OR, 1.01; 95% CI, 0.90-1.14), total joint replacement (OR, 0.96; 95% CI, 0.89-1.04), total hip replacement (OR, 0.95; 95% CI, 0.85-1.07), or total knee replacement (OR, 0.94; 95% CI, 0.88-1.01). Study results were similar across all sensitivity analyses.

A limitation of the study included the fact that the current GWAS of vitamin K concentration discovered only a handful of associated variants at sub-genome-wide significance. During peer review, a major concern was the insufficient instrument strength.

The study authors concluded that future genetic and interventional studies are warranted to identify stronger instruments for vitamin K evaluation. These studies are also needed to mitigate the potential for “winners’ curse,” as observed in the current analysis, in which the same GWAS was used for instrument discovery and effect estimate. The study findings suggest that population level vitamin K supplementation is unlikely to reduce the incidence of OA.

Disclosure: None of the study authors has declared affiliations with biotech, pharmaceutical, and/or device companies.  


Zhao SS, Bovijn J, Hughes DM, Sha T, Zeng C, Lyu H. Genetically predicted vitamin K levels and risk of osteoarthritis: Mendelian randomization study. Semin Arthritis Rheum. Published online May 24, 2022. doi:10.1016/j.semarthrit.2022.152030