The association between vitamin K status and knee osteoarthritis features in older adults: The Health, Aging and Body Composition Study

Objective Osteoarthritis (OA) is the most common form of arthritis and the leading cause of disability in the elderly. Of all the joints, genetic predisposition is strongest for OA of the hand; however, only few genetic risk loci for hand OA have been identified. Our aim was to identify novel genes associated with hand OA and examine the underlying mechanism. Methods We performed a genome-wide association study of a quantitative measure of hand OA in 12 784 individuals (discovery: 8743, replication: 4011). Genome-wide significant signals were followed up by analysing gene and allele-specific expression in a RNA sequencing dataset (n=96) of human articular cartilage. Results We found two significantly associated loci in the discovery set: at chr12 (p=3.5 × 10−10) near the matrix Gla protein (MGP) gene and at chr12 (p=6.1×10−9) near the CCDC91 gene. The DNA variant near the MGP gene was validated in three additional studies, which resulted in a highly significant association between the MGP variant and hand OA (rs4764133, Betameta=0.83, Pmeta=1.8*10−15). This variant is high linkage disequilibrium with a coding variant in MGP, a vitamin K-dependent inhibitor of cartilage calcification. Using RNA sequencing data from human primary cartilage tissue (n=96), we observed that the MGP RNA expression of the hand OA risk allele was significantly lowercompared with the MGP RNA expression of the reference allele (40.7%, p<5*10−16). Conclusions Our results indicate that the association between the MGP variant and increased risk for hand OA is caused by a lower expression of MGP, which may increase the burden of hand OA by decreased inhibition of cartilage calcification.

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“…It has been shown that low vitamin K intake is correlated with OA 40. Thus, vitamin K intake may be a potential therapeutic treatment in OA.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association and functional studies identify a role for matrix Gla protein in osteoarthritis of the hand

Hollander

Boer

Hart

et al. 2017

Annals of the Rheumatic Diseases

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“…A recent meta-analysis found no association between serum vitamin D levels and prevalence or incidence of hip, knee, or hand OA [130], despite early studies on vitamin D and OA suggesting a possible relationship [131, 132]. Low vitamin K has been associated with knee and hand OA in a small number of studies [133–135]; however, supplementation with vitamin K has not demonstrated any effect on disease progression [136]. Vitamin C and various other antioxidants have also been investigated for a possible association with OA but results have been inconclusive [137–139].…”

Section: Etiology and Risk Factors For Hip Oamentioning

confidence: 99%

Hip Osteoarthritis: Etiopathogenesis and Implications for Management

2016

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Highly prevalent among the elderly, hip osteoarthritis (OA) carries a heavy burden of disease. Guidelines for the management of hip OA are often extrapolated from knee OA research, despite clear differences in the etiopathogenesis and response to treatments of OA at these sites. We propose that hip OA requires specific attention separate from other OA phenotypes. Our understanding of the etiopathogenesis of hip OA has seen significant advance over the last 15 years, since Ganz and colleagues proposed femoroacetabular impingement (FAI) as an important etiological factor. This narrative review summarizes the current understanding of the etiopathogenesis of hip OA and identifies areas requiring further research. Therapeutic approaches for hip OA are considered in light of the condition’s etiopathogenesis. The evidence for currently adopted management strategies is considered, especially those approaches that may have disease-modifying potential. We propose that shifting the focus of hip OA research and public health intervention to primary prevention and early detection may greatly improve the current management paradigm.

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“…In the Health Aging and Body Composition (Health ABC) Study (mean±SD age = 74±3 yrs), older community-dwelling adults with very low plasma phylloquinone (defined as below the assay limit of detection, <0.2 nmol/L) had a 1.7-and 2.6-fold higher odds of worsening cartilage damage and meniscal damage over 3 years. This analysis also suggested participants with very low phylloquinone were more likely to have bone attrition, subarticular cyst, and osteophyte progression, but statistical significance was not reached [OR (95% CI): 1.9(0.9–3.6); 1.5(0.8–2.7); 1.5(0.8–2.8) respectively] [73]. In this same study, individuals with elevated (dp)ucMGP (reflecting low vitamin K status) were more likely to have osteophytes, bone marrow lesions, subarticular cysts, and meniscus damage cross-sectionally, but this was not associated with progression of any structural abnormalities in the longitudinal analysis [73].…”

Section: Vitamin K and Osteoarthritismentioning

confidence: 99%

“…This analysis also suggested participants with very low phylloquinone were more likely to have bone attrition, subarticular cyst, and osteophyte progression, but statistical significance was not reached [OR (95% CI): 1.9(0.9–3.6); 1.5(0.8–2.7); 1.5(0.8–2.8) respectively] [73]. In this same study, individuals with elevated (dp)ucMGP (reflecting low vitamin K status) were more likely to have osteophytes, bone marrow lesions, subarticular cysts, and meniscus damage cross-sectionally, but this was not associated with progression of any structural abnormalities in the longitudinal analysis [73]. This may suggest vitamin Ks role in these pathologies is independent of its function as an enzymatic co-factor in the carboxylation of MGP.…”

Section: Vitamin K and Osteoarthritismentioning

confidence: 99%

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The Role of Vitamin K in Chronic Aging Diseases: Inflammation, Cardiovascular Disease, and Osteoarthritis

Harshman

Shea

2016

Curr Nutr Rep

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Vitamin K is an enzyme cofactor required for the carboxylation of vitamin K dependent proteins, several of which have been implicated in diseases of aging. Inflammation is recognized as a crucial component of many chronic aging diseases and evidence suggests vitamin K has an anti-inflammatory action that is independent of its role as an enzyme co-factor. Vitamin K-dependent proteins and inflammation have been implicated in cardiovascular disease and osteoarthritis, which are leading causes of disability and mortality in older adults. The purpose of this review is to summarize observational studies and randomized trials focused on vitamin K status and inflammation, cardiovascular disease, and osteoarthritis. Although mechanistic evidence suggests a protective role for vitamin K in these age-related conditions, the benefit of vitamin K supplementation is controversial because observational data are equivocal and the number of randomized trials is few.

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The association between vitamin K status and knee osteoarthritis features in older adults: The Health, Aging and Body Composition Study

Cited by 84 publications

References 41 publications

Genome-wide association and functional studies identify a role for matrix Gla protein in osteoarthritis of the hand

Genome-wide association and functional studies identify a role for matrix Gla protein in osteoarthritis of the hand

Hip Osteoarthritis: Etiopathogenesis and Implications for Management

The Role of Vitamin K in Chronic Aging Diseases: Inflammation, Cardiovascular Disease, and Osteoarthritis

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