A role for vitamin K in the treatment of osteoarthritis

The importance of vitamin K for normal blood clotting and bone integrity in the prevention of osteoporosis is well known. There is also evidence for the importance of of vitamin K in the treatment of osteoarthritis. Consider research published in the journal Arthritis & Rheumatism in which the authors state:

"Poor intake of vitamin K is common. Insufficient vitamin K can result in abnormal cartilage and bone mineralization. Furthermore, osteophyte growth, seen in osteoarthritis (OA), may be a vitamin K–dependent process. We undertook this study to determine whether vitamin K deficiency is associated with radiographic features of OA."

They correlated radiographic (x-ray) findings with levels of phylloquinone (vitamin K) in 672 subjects, taking into consideration the degree of degenerative joint pathologies by prevalence ratios (PR) and variables such as vitamin D, bone mineral density, body mass index, age, etc. What did their data show?

"The PRs for OA, osteophytes, and JSN [joint space narrowing] and adjusted mean number of joints with all 3 features in the hand decreased significantly with increasing plasma phylloquinone level...For the knee, only the PR for osteophytes and the adjusted mean number of knee joints with osteophytes decreased significantly with increasing plasma phylloquinone levels."

Thus their conclusion:

"These observational data support the hypothesis of an association between low plasma levels of vitamin K and increased prevalence of OA manifestations in the hand and knee."

A clinical trial reported in the Annals of the Rheumatic Diseases highlights the practical importance of using objective laboratory tests to discriminate when may expect to see meaningful improvements from taking vitamin K (or any other intervention). The authors state:

"Vitamin K has bone and cartilage effects, and previously shown to be associated with radiographic osteoarthritis. We evaluated vitamin K's effect on hand osteoarthritis in a randomised controlled trial."

They observed the effects of vitamin K supplementation versus placebo on hand x-ray features of osteoarthritis regardless of their initial vitamin K status. Then they further examined a subgroup restricted to those that were vitamin K insufficient at baseline. Not surprisingly...

"There were no effects of randomisation to vitamin K for radiographic osteoarthritis outcomes." BUT..."Those with insufficient vitamin K at baseline who attained sufficient concentrations at follow-up had trends towards 47% less joint space narrowing."

Another study published in the Journal of Orthopaedic Science takes a closer look at vitamin K intake associated with knee osteoarthritis:

"The present study sought to identify dietary nutrients associated with the prevalence of radiographic knee osteoarthritis (OA) in the Japanese elderly of a population-based cohort of the Research on Osteoarthritis Against Disability (ROAD) study."

The authors analyzed a number of dietary factors and correlated them with the severity of radiographic (x-ray) osteoarthritic degenerative changes in the knees among 719 subjects. The association with vitamin K stood out in the data:

"Among the dietary factors, only vitamin K intake was shown to be inversely associated with the prevalence of radiographic knee OA by multivariate logistic regression analysis. The presence of joint space narrowing of the knee was also inversely associated with vitamin K intake. The prevalence of radiographic knee OA for each dietary vitamin K intake quartile decreased with the increased intake."

We can also appreciate a paper published in the journal Osteoarthritis and Cartilage that examines a mechanism by which vitamin K deficiency contributes to degenerative joint disease (osteoarthritis). The authors observe:

"Mineralization has been observed in osteoarthritic cartilage but the mechanisms are incompletely understood. Vitamin K is an essential cofactor in post-translational modification of proteins where specific Glu residues become modified to Ca++ binding γ-carboxyglutamic acid residues (Gla). One such protein, matrix Gla protein (MGP), is a known mineralization inhibitor. This study determined if synthesis of MGP and formation of a fetuin–MGP protein complex was altered in chondrocytes and vesicles from osteoarthritis (OA) cartilage."

They examined cartilage cells from osteoarthritic and normal joints to determine the presence of the fully γ-carboxylated form of MGP (cMGP) and non-γ-carboxylated MGP (ucMGP) as well as fetuin and MGP–fetuin complexes. This is significant because vitamin K is necessary for the production of cMGP and of the cMGP–fetuin complex, the absence of which results in the abnormal mineralization of cartilage. What did their data reveal?

"Chondrocytes and vesicles from osteoarthritic tissue produced significantly less cMGP compared to those from normal cartilage. This correlated with significantly less vitamin K-dependent γ-carboxylase enzyme activity in OA chondrocytes...A fetuin–MGP complex was identified in normal chondrocytes and in vesicles shed from these cells but not in OA cells or vesicles."

Thus their conclusion puts the spotlight on an important vitamin K dependent mechanism  for maintaining joint cartilage:

"The absence of cMGP and of the cMGP–fetuin complex in OA cells and OA vesicles may be an important mechanism for increased mineralization of osteoarthritic cartilage."

Clinicians and patients alike may ask the questions: Who will benefit from vitamin K supplementation and for whom will it not make a significant difference. How do we know, for each individual, what is the right amount? Measure it.