Vitamin K and equine osteocalcin: an enigma explored

Abstract

Vitamin K has received considerably less attention over the past 50 years compared to other fat soluble vitamins. Intakes of vitamin K beyond that required for normal blood coagulation were believed to confer no additional benefits, and therefore rarely investigated. The requirements and physiological role of vitamin K appeared to be secure. This view of vitamin K has changed recently following the delineation of its cofactor role in protein carboxylation, and the growing awareness of its interactions with other essential metabolic functions, beyond that of blood coagulation; there is much to be discovered. At present, seventeen vitamin Kdependent proteins (VKDPs) have been characterised, but the functionality of some still remains to be elucidated. Vitamin K has recently been implicated in osteoarthritis and accumulating evidence from human studies supports a protective role for vitamin K. To date however, little research into the role vitamin K may play in equine bone development exists. Developmental orthopaedic disease (DOD) is a term that encompasses a number of bone related conditions in the horse. It is a significant cause of lameness and wastage in a number of breeds, in particular Thoroughbreds and Warmbloods. It has clinical features in common with that of osteoporosis and osteoarthritis in the elderly. The VKDP osteocalcin is one of the few that has been extensively studied in humans and rodents. Located within bone, this protein plays a vital role in bone metabolism, facilitating the binding of bone minerals with protein. Decreased functionality of this protein has been found to be associated with increased fracture risk and osteoporosis in humans. The studies in this program were initiated to establish the relationship between vitamin K status and the development of DOD in foals. As bone development begins in utero, the first step was to examine placental transfer of the vitamin and then determine availability to the foal through milk. It was found in the initial experiments (Chapter 3), that foals at birth, had negligible concentrations of vitamin K1 (<0.01ng/mL) in both umbilical cord and foal plasma. The results clearly demonstrated that there is limited trans-placental transfer of vitamin K in the horse. It was also shown that milk can be enriched with vitamin K by supplementation of the mare with the vitamin. These studies confirmed that plasma concentrations were not a reliable measure of overall vitamin K status. Circulating osteocalcin and, its carboxylation status, has been proposed as one of the indicators of vitamin K status and a 'biomarker' of bone metabolism. Current assays available to measure Publications included in this thesis "No publications included". v