A growing body of evidence suggests that vitamin K insufficiency is associated with several age-related diseases, including osteoarthritis (OA). Several vitamin K-dependent proteins are found in joint tissue, including matrix gla protein (MGP), which functions as a calcification inhibitor. In order for MGP to function it must be carboxylated, which requires vitamin K. Recently assays that measure plasma uncarboxylated MGP (ucMGP) in humans have been developed, and plasma ucMGP is reported to be elevated (reflective of low vitamin K status) in patients with arterial calcification. Since MGP is present n both vascular tissue and cartilage and the vitamin K-dependent mechanisms underlying arterial calcification and cartilage calcification are similar, it is plausible that plasma ucMGP also reflets OA pathology. However, plasma ucMGP has not been measured in persons well-characterized for OA progression. To advance our understanding of vitamin Ks role in joint health, the investigators propose to measure circulating ucMGP and vitamin K1 in archived samples from the Health, Aging and Body Composition (Health ABC) Knee OA Study, a cohort of 1141 black and white well-functioning community-dwelling men and women aged 70-79 yrs at baseline. The following specific aims will be addressed:
Specific aim 1 a: To determine the association between low vitamin K status (measured by plasma ucMGP and vitamin K1) and symptomatic knee OA in older adults.
Specific aims 2 a and 2b: To determine the association between vitamin K status and knee OA progression assessed radiographically and by MRI in older adults over 3 years of follow-up.
Specific aim 3 : To determine the cross-sectional and longitudinal association between vitamin K status and lower extremity function in older adults. Participants in the Health ABC Knee OA study underwent repeated bilateral knee x-rays and MRIs and are well characterized for lower-extremity function, making this study an ideal study to determine the associations between plasma ucMGP, vitamin K1 and OA. Our results will provide innovative evidence of the mechanisms underlying vitamin Ks role in OA in a cost-effective and efficient manner, and will be used to develop future proposals to carry out follow-up trials to clarify the vitamin Ks role in OA progression and related disability.

Public Health Relevance

Several vitamin K-dependent proteins are present in joint tissue, and a growing body of evidence suggests that vitamin K insufficiency is associated with several chronic diseases, including osteoarthritis (OA). However, vitamin Ks role in OA is not completely understood because available studies are limited to cross-sectional analyses and none have determined the association between multiple measures of vitamin K status and OA progression. Considering the public health burden of OA is high, a better understanding of the longitudinal relationship between vitamin K status and knee OA progression in older adults is of significant public health importance, since vitamin K insufficiency is correctable.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AR062284-02
Application #
8535608
Study Section
Special Emphasis Panel (AMSC)
Program Officer
Lester, Gayle E
Project Start
2012-08-22
Project End
2014-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
2
Fiscal Year
2013
Total Cost
$158,175
Indirect Cost
$51,300
Name
Wake Forest University Health Sciences
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157