Osteoarthritis (OA) is the most common form of arthritis affecting older adults in the United States. OA commonly affects the knee joint and leads to pain and lower limb functional limitations. Knee OA is the leading cause of lower extremity disability among older adults in the U.S. As the population is aging, the prevalence of knee OA is expected to increase substantially.
Currently, there are few therapeutic options available to treat symptoms of knee OA. Many of the pharmacologic therapies used to treat the condition are associated with side effects and have limited efficacy. Importantly, none of the treatments available at this time can prevent or halt the progression of knee OA. Thus, there is a crucial need to develop safe and effective therapeutic and prophylactic agents for knee OA.
Vitamin K’s Role
In clinical research, vitamin K has been identified as a potential target of interest in the care of patients with knee OA and in those at risk for it. “Vitamin K plays an important role in regulating bone and cartilage mineralization,” explains Devyani Misra, MD, MS. She adds that many older adults in America suffer from low vitamin K intake and subclinical deficiency, according to published research.
Subclinical deficiency refers to the detection of a low serum vitamin K level without signs of bleeding. “Some prior studies have shown an association of low vitamin K status, as assessed by biochemical measures and dietary intake, with prevalent radiographic OA,” Dr. Misra says. “However, none of these analyses have evaluated the association of vitamin K deficiency with incident (new-onset) radiographic OA. They also haven’t evaluated the structural components within the knee joint that are involved.”
A New Analysis
In the American Journal of Medicine, Dr. Misra and colleagues from Boston University Medical Center recently had a study published that examined the association of subclinical vitamin K deficiency with development of incident radiographic knee OA and MRI-based structural changes. “X-rays have limited utility in detecting early changes, such as cartilage abnormalities and early osteophyte formation,” says Dr. Misra. “Accordingly, we examined the association of vitamin K deficiency with incident cartilage lesions and osteophytes on knee MRIs.”
“Subclinical vitamin K deficiency appears to increase the risk of developing radiographic knee OA and MRI-based cartilage lesions.”
Using data from 1,180 participants enrolled in the Multicenter Osteoarthritis Study, Dr. Misra and colleagues reviewed readings of knee radiographs and MRI scans obtained at baseline and 30 months later. Plasma phylloquinone—vitamin K—was also measured at baseline. About one-third of patients were women. The average age of all participants was about 62 years, and their average BMI was 30.1 kg/m2. At baseline, 9.2% of study participants were subclinically vitamin K-deficient. Among the knees that were free of radiographic OA at baseline, 14.5% developed incident radiographic OA by the 30-month follow-up study visit.
In the knee-based analyses, the incidence of radiographic knee OA among vitamin K-deficient patients was 21.2%, compared with a 13.9% rate for those who were not deficient (Table 1). After adjusting for potential confounders, the risk of incident radiographic knee OA was 56.0% higher among those who were vitamin K deficient when compared with those who were not. In the person-based analysis, vitamin K deficiency correlated with a higher risk of having incident knee OA in one or both knees when compared with no OA in either knee, respectively.
Furthermore, 111 knees were eligible for the incident cartilage lesion analysis, and 197 knees were eligible for the incident osteophyte analysis, based on MRI outcomes. Vitamin K deficiency was significantly associated (risk ratio, 2.39) with incident cartilage lesions (Table 2). However, no significant association was found for incident osteophytes. The study team noted that it was unable to assess the effect of vitamin K on development of the earliest stage of osteophytes because data was not available on enough knees that were free of any osteophytes at baseline.
“The findings from our study demonstrate that subclinical vitamin K deficiency appears to increase the risk of developing radiographic knee OA and MRI-based cartilage lesions,” says Dr. Misra. “These results complement and extend findings from previous radiograph-based studies suggesting vitamin K’s role in the development of OA.”
According to Dr. Misra, the study group’s findings provide new insights into the potential mechanisms by which vitamin K may have its effects. “By using MRI data, our analysis identified a specific effect on cartilage rather than bone,” she says. “It’s possible that inadequate vitamin K concentrations could contribute to development of osteoarthritic changes. Thus, our findings form a premise for future studies that need to evaluate the therapeutic/prophylactic potential of vitamin K in OA.”
Readings & Resources (click to view)
Misra D, Booth SL, Tolstykh I, et al. Vitamin K deficiency is associated with incident knee osteoarthritis. Am J Med. 2013;126:243-248. Available at: http://www.amjmed.com/article/S0002-9343(12)00881-9/fulltext.
Booth S, Dallal G, Shea M, Gundberg C, Peterson J, Dawson-Huges B. Effect of Vitamin K supplementation on bone loss in elderly men and women. J Clin Endocrinol Metab. 2008;93:1217-1223.
Amin S, LaValley MP, Guermazi A, et al. The relationship between cartilage loss on magnetic resonance imaging and radiographic progression in men and women with knee osteoarthritis. Arthritis Rheum. 2005;52:3152-3159.
Booth S, Suttie J. Dietary intake and adequacy of vitamin K. J Nutr. 1998;128:785-788.
Oka H, Akune T, Muraki S, et al. Association of low dietary vitamin K intake with radiographic knee osteoarthritis in the Japanese elderly population: dietary survey in a population-based cohort of the ROAD study. J Orthop Sci. 2009;14:687-692.
Neogi T, Booth S, Zhang Y, et al. Low vitamin K status is associated with osteoarthritis in the hand and knee. Arthritis Rheum. 2006;54:1255-1261.
Altman R, Hochberg M, Murphy WJ, Wolfe F, Lequesne M. Atlas of individual radiographic features in osteoarthritis. Osteoarthritis Cartilage. 1995;3(Suppl A):3-70.