The current osteoarthrosis (OA) drugs such as non-steroidal anti-inflammatory agents (NSAIDs), paracetamol and tramadol, focus on pain amelioration but do not solve the underlying pathologies of the disease. Numerous preventive agents for OA are available in the market, such as glucosamine, chondroitin sulfate, curcumin and avocado soybean unsaponifiables but their efficacy remains elusive. Nutritional principles, such as vitamin D, vitamin E and polyphenols, have been reported to retard the progression of OA as well. Cartilage calcification plays an important role in the pathogenesis of OA: calcification of the articular cartilage at the hip and knee is highly prevalent among the general population. cartilage calcification in tandem with increased expression of tumor necrosis factor-alpha and interleukins from macrophages induced by wear-and-tear particles could lead to further cartilage breakdown and OA.
Matrix gamma-carboxyglutamic acid (GLA) protein (MGP) involved in calcification is expressed in chondrocytes, the cartilage forming cells. The biological activity of MGP is dependent on vitamin K, a cofactor to the enzyme -glutamyl carboxylase that converts the inactive uncarboxylated MGP to the active carboxylated MGP. MGP knockout animals developed spontaneous calcification of the blood vessels, while overexpression of MGP retarded the mineralization of bone. Carboxylation of matrix proteins, which is a functional activity of vitamin K, has been investigated as the action of vitamin K on chondrocytes. Chondrocytes from organ donors with OA produced mainly uncarboxylated MGP vesicles, while chondrocytes from normal donors produced fully carboxylated MGP. Since OA is a localized inflammatory event of the joint, protein carboxylation activities of vitamin K could prevent inflammation and prevent the progression of the condition.
Currently, the recommended dietary allowance or RDA of vitamin K is not established due to insufficient data. Therefore, average intake values derived from healthy representative populations have been used. The AI of vitamin K for adult men and women are 120 and 90 μg/day. Vitamin K supplementation is not associated with serious health effects, thus, its tolerable upper intake level has not been fixed. Therefore, long-term supplementation of vitamin K for preventing osteoarthrosis might be safe, but there is a paucity of trial data to support this claim. The effective dose of vitamin K in preventing OA remains elusive, but some data suggest that maintaining the circulating vitamin K concentration around 1.0 nmol/L is associated with better joint health. However, vitamin K showed interaction with drugs, notably warfarin (an anticoagulant) and some nutrients, like vitamin E. High tocopherols, indeed, could interfere with the enzyme epoxidase activating vitamin K.
Warfarin functions by suppressing hepatic vitamin K-epoxide reductase, which in turns inhibits the productions of vitamin K-dependent plasma clotting factors. Patients receiving warfarin are commonly advised to avoid taking vitamin K-rich food, like green leafy vegetables. A recent meta-analysis showed that interference might only occur at very high vitamin K intake (>150 μg/day). Human observational studies show that vitamin K could prevent OA but evidence from clinical trials is limited. Some important questions concerning the intake level, dose of supplementation, and vitamin K type that is the most effective against osteoarthrosis awaits further studies. Not mentioning the effects on blood coagulation. Indeed, very recently has been confirmed that the use of anticoagulants like warfarin or dicoumarol increase the incidence risk of OA or its progression in the elderly patients with cardiovascular conditions.
However, the problem could be overcome with the use of alternative and safer anticoagulants for patients, such as rivaroxaban, digabatran and newer molecules with a safer pharmacological profile.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
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