Vitamin K2 in bone metabolism and osteoporosis

ABSTRACT

This article covers in vitro, in vivo, and human data on the positive effect of vitamin K2 on osteoporosis. Data is available on vitamin K2 for osteoporosis caused by a number of conditions, including postmenopausal osteoporosis, Parkinson's disease, biliary cirrhosis, stroke, and drug-induced osteoporosis. The activity of vitamin K2 involves both an increase in the bone-building process and a separate decrease in the bone-loss process. Vitamin K2 exerts a more powerful influence on bone than vitamin K1, and should be considered for prevention or treatment in those conditions known to contribute to osteoporosis. (Altern Med Rev 2005; 10(1):24-35)

Introduction

Vitamin K2 exerts a powerful influence on bone building, especially in osteoporosis, and has been cited as one of the most frequently prescribed treatments for osteoporosis in Japan. (1)

The ability to better facilitate bone growth, especially in osteoporosis and fracture, has long been of interest. Repair of non-pathogenic fracture is a normal process, generally engaged in without difficulty. Osteoporosis, a pathogenic process, is increasingly occurring in developed countries, and pathologic fracture due to osteoporosis in the elderly can be a life-shortening event. A five-year prospective study on fracture and mortality rate in men and women age 60 and older found all major fractures were associated with increased mortality, especially in men. (2)

Osteoporosis, a multifactorial pathology, has been reviewed extensively in recent years. (3-7) A review by Gaby of nutritional and hormonal management of osteoporosis is an excellent and well-referenced source for further edification. (8)

Evaluation of the etiology of osteoporosis in a particular individual can involve examination of hormonal aspects, exercise patterns, nutrient intake, digestion, and nutrient absorption. This article addresses the aspects of vitamin K2 in bone formation. The subject of nutrient absorption is pertinent because the vitamin Ks are lipid soluble; therefore, fat malabsorption may create a deficiency. Recent reviews revealing celiac disease is common (1 in 266) (9-11) underscore its involvement in the etiology of osteoporosis due to malabsorption of necessary bone factors, including vitamin K. (12) Documentation is plentiful illustrating the importance of vitamin K in bone maintenance. Its importance is easily evidenced by the osteoporosis and fractures resulting from long-term use of the anticoagulant drug warfarin, which inhibits the bone-building effect of vitamin K. (13-18)

The Vitamin Ks

Vitamin K is a family of structurally similar, fat-soluble, 2-methyl-l,4-naphthoquinones, including phylloquinone (K1), menaquinones (K2), and menadione (K3). The structural difference is in the substituent R group (Figure 1).

The best-known member of the vitamin K family is phylloquinone (K1), also known as phytonadione because of its relationship with photosynthesis. Phylloquinone is found in higher plants and algae, with the highest concentrations found in green leafy vegetables. (19)

Menaquinones (K2) also occur naturally, but are produced by an array of bacteria, not by higher plants. Recent studies have determined menaquinones can be produced in limited quantities by animals, and probably by humans, from the conversion of other forms of vitamin K. (20,21) The most common form of vitamin K2 in animals is menaquinone 4 (menatetrenone;...