Vitamin K: Tool to control the osteophrosis


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Vitamin K: Tool to control the osteophrosis

  1. 1. Vitamin K: Tool to control osteoporosis Muhammad Yasin, Masood Sadiq Butt and Faqir Muhammad Anjum National Institute of Food Science and Technology University of Agriculture Faisalabad 12/28/10
  2. 2. Road map <ul><li>Introduction </li></ul><ul><li>Functions of vitamin K </li></ul><ul><li>Osteoporosis and vitamin K </li></ul><ul><li>Vitamin K-dependent carboxylation reaction </li></ul><ul><li>Vitamin K supplementation and bone health </li></ul><ul><li>Observations related to osteoporosis </li></ul><ul><li>Conclusions </li></ul>12/28/10
  3. 3. Vitamin K: Introduction <ul><li>Vitamin K, a fat-soluble vitamin is needed for the post-translational modification of certain proteins </li></ul><ul><ul><li>blood coagulation </li></ul></ul><ul><ul><li>metabolism pathways in bone and other tissue </li></ul></ul><ul><li>Vitamin K exist naturally in multiple dietary forms </li></ul>12/28/10
  4. 4. Types and sources Phylloquinone (K 1 ) Menaquinone (K 2 ) Menadione (K 3 ) <ul><li>Leafy green vegetables (spinach, Brassica, </li></ul><ul><li>Some fruits (avocado) </li></ul><ul><li>Colonic bacteria Staphylococcus aureus </li></ul><ul><li>Egg, </li></ul><ul><li>Fermented soybean (Natto) </li></ul><ul><li>Chicken meat </li></ul><ul><li>Cheese </li></ul><ul><li>Synthetic analogue </li></ul><ul><li>Menadion Sodium Bisulfie </li></ul><ul><li>Mendione Nictinamide Bisulfite </li></ul>12/28/10
  5. 5. Functions of vitamin K <ul><li>Blood coagulation </li></ul><ul><ul><li>Vitamin k is a factor for promoting blood coagulation by helping post-trancriptional modifications of blood factors </li></ul></ul><ul><ul><li>Vitamin K is responsible for the carboxylation or activation of clotting factors II, VII, IX, and X in the liver. </li></ul></ul><ul><ul><li>Vitamin K reductase enzymes keep the vitamin in an active (reduced) state </li></ul></ul>12/28/10
  6. 6. Cont… <ul><li>Calcium binding proteins (CBP) </li></ul><ul><ul><li>Vitamin K is found to carboxylated specific glutamate residues of CBP of bones, spleen, placenta and kidneys </li></ul></ul><ul><li>Vitamin K-dependent protein </li></ul><ul><ul><li>Matrix Gla-protein (mgp) </li></ul></ul><ul><ul><li>Growth arrest-specific gene 6 (gas6), </li></ul></ul><ul><ul><li>Endothelial protein C receptor (EPCR)- </li></ul></ul><ul><ul><li>Protease activated receptor 1 (PAR-1) </li></ul></ul><ul><ul><li>Thrombin (f2) </li></ul></ul><ul><ul><li>Growth arrest-specific gene 6 (gas6) </li></ul></ul>12/28/10
  7. 7. Cont… <ul><li>Poor vitamin K status is associated </li></ul><ul><ul><li>increased postmenopausal bone loss </li></ul></ul><ul><ul><li>bone fractures </li></ul></ul><ul><ul><li>artery calcification </li></ul></ul><ul><li>Inverse correlation between dietary vitamin K intake and </li></ul><ul><ul><li>bone fracture risk </li></ul></ul><ul><ul><li>cardiovascular mortality </li></ul></ul>12/28/10
  8. 8. Vitamin K dosage and toxicity <ul><li>There is no known toxicity associated with high doses </li></ul><ul><ul><li>phylloquinone </li></ul></ul><ul><ul><li>menaquinone </li></ul></ul><ul><ul><li>menadione </li></ul></ul><ul><ul><li>its derivatives </li></ul></ul><ul><li>High intake of vitamin K is not recommended </li></ul>12/28/10 Age RDI Males and females, 0-6 months 2µg Males and females, 7-12 months 2.5µg Males and females, 1-3 years 30µg Males and females, 4-8 years 55µg Males and females, 9-13 years 60µg Males and females, 14-18 years 75µg Males, 19 years and older 120µg Females, 19 years and older 90µg
  9. 9. Osteoporosis and vitamin K <ul><li>Osteoporosis is a disease of skeleton characterizes by decrease bone power and the bone are more vulnerable to fracture </li></ul><ul><li>Menaquinone reduce and stop </li></ul><ul><ul><li>bone loss </li></ul></ul><ul><ul><li>helpful to control the disorders of bone </li></ul></ul><ul><li>Vitamin K </li></ul><ul><ul><li>decreases the vertebral the hip fractures </li></ul></ul><ul><ul><li>rising bone mass </li></ul></ul>12/28/10
  10. 10. Cont… <ul><li>Pakistan has a rapidly growing population, with the percentage of elderly steadily increasing </li></ul><ul><li>Osteoporosis- medical fraternity as a significant health problem </li></ul><ul><li>Hip fractures in 2008 </li></ul><ul><ul><li>estimates based on ultrasound study </li></ul></ul><ul><ul><li>9.91 million people suffer with osteoporosis </li></ul></ul><ul><ul><ul><li>7.19 million women </li></ul></ul></ul><ul><ul><ul><li>2.71 million men </li></ul></ul></ul>12/28/10
  11. 11. Cont… <ul><ul><li>These numbers are estimated to rise </li></ul></ul><ul><ul><ul><li>11.3 million in 2020 </li></ul></ul></ul><ul><ul><ul><li>12.91 million in 2050 </li></ul></ul></ul><ul><li>Women aged (45-70 years) </li></ul><ul><ul><li>osteoporosis -16% </li></ul></ul><ul><ul><li>osteopenia - 34% </li></ul></ul><ul><li>Postmenopausal women in Peshawar- 75% at risk of osteoporosis (2002) </li></ul>12/28/10
  12. 12. Cont… <ul><li>Vitamin k – dependent proteins </li></ul><ul><ul><li>Osteocalcin </li></ul></ul><ul><ul><li>Matrix Gla-protein </li></ul></ul><ul><ul><li>activated and play role in bone metabolism </li></ul></ul><ul><ul><li>reduce the threat of hip breakage </li></ul></ul><ul><li>Incomplete carboxylation of osteocalcin results in </li></ul><ul><ul><li>an increased risk of osteoporosis </li></ul></ul><ul><ul><li>bone fractures </li></ul></ul><ul><li>Gla residues binds Ca 2+ ions and promotes a protein-Ca 2+ -phospholipid interaction </li></ul>12/28/10
  13. 13. The vitamin K-dependent carboxylation reaction 12/28/10 The enzyme is located at the luminal surface of the endoplasmic reticulum, and post-translationally carboxylates specific Glu residues of a limited number of proteins to ϒ -carboxyglutamyl (Gla) residues during protein processing glutamyl (Glu) 7-carboxyglutamyl (Gla) residues The vitamin K-dependent carboxylation reaction
  14. 14. Osteocalcin <ul><li>Osteocalcin </li></ul><ul><ul><li>low-molecular-weight protein (49-50 residues) </li></ul></ul><ul><ul><li>three Gla residues </li></ul></ul><ul><ul><li>mineral-binding properties </li></ul></ul><ul><li>Osteocalcin is produced by </li></ul><ul><ul><li>osteoblasts during bone matrix formation </li></ul></ul><ul><li>Osteocalcin concentration in bone </li></ul><ul><ul><li>is directly proportional to calcium in bone </li></ul></ul><ul><li>Osteocalcin indication of bone formation </li></ul>12/28/10
  15. 15. Relationship between vitamin K status and bone health <ul><li>Circulating and bone vitamin K concentrations </li></ul><ul><li>Vitamin K status and os teoporosis </li></ul><ul><ul><li>reduced plasma concentrations of </li></ul></ul><ul><ul><ul><li>Phylloquinone </li></ul></ul></ul><ul><ul><ul><li>MK-7 </li></ul></ul></ul><ul><ul><ul><li>MK-8 </li></ul></ul></ul><ul><ul><li>patients with recent femoral fractures or prior vertebral compression fractures </li></ul></ul><ul><li>Serum vitamin K concentration in elderly women after hip fracture </li></ul><ul><ul><li>significantly lowers than those in age-matched healthy control </li></ul></ul>12/28/10
  16. 16. Under- ϒ -carboxylated osteocalcin ( ucOC ) <ul><li>Circulating osteocalcin </li></ul><ul><ul><li>Adsorbed ca-phosphate (hydroxyapatite) gel </li></ul></ul><ul><ul><li>oral anticoagulant is less adsorbed hydroxyapatite in the presence of warfarin </li></ul></ul><ul><li>Osteocalcin converted in to fully ϒ -carboxylate in normal vitamin K-sufficient subjects </li></ul><ul><li>Circulating ucOC increase with advancing age in women </li></ul><ul><li>Serum osteocalcin and extent of its carboxylation is a </li></ul><ul><ul><li>marker of vitamin K status in </li></ul></ul><ul><ul><ul><li>pregnant women </li></ul></ul></ul><ul><ul><ul><li>newborn babies </li></ul></ul></ul>12/28/10
  17. 17. Vitamin K supplementation and bone health <ul><li>Phylloquinone (1 mg/d) </li></ul><ul><ul><li>undercarboxylated osteocalcin to normal level in a postmenopausal (55- to 75 years old) women </li></ul></ul><ul><ul><li>elevated ratios of urinary hydroxyprolinexreatinine and urinary calciumxreatinine, </li></ul></ul><ul><ul><li>rapid bone turnover </li></ul></ul><ul><li>Vitamin K supplementation led to significant reductions in both urinary calcium and hydroxyproline excretion </li></ul>12/28/10
  18. 18. Cont… <ul><li>MK-4 (45 mg) increase in </li></ul><ul><ul><li>metacarpal bone mineral density, </li></ul></ul><ul><ul><li>serum osteocalcin </li></ul></ul><ul><ul><li>reduced urinary calcium excretion </li></ul></ul><ul><li>Renal vitamin K-dependent protein activity decreased by insufficient vitamin K </li></ul><ul><ul><li>leading to excessive calcium loss in the urine </li></ul></ul><ul><li>Supplementation with MK-4 has positive effect in an in vitro bone mineralization system </li></ul>12/28/10
  19. 19. Observations relating to osteoporosis <ul><li>Low concentration of circulating vitamin K in patients with bone fractures </li></ul><ul><li>Concentration of circulating under- ϒ -carboxylated osteocalcin associated with age, low bone mineral density, and hip fracture risk </li></ul><ul><li>Anticoagulant therapy associated with decreased bone density </li></ul><ul><li>Vitamin K supplementation decreases bone loss and calcium excretion </li></ul>12/28/10
  20. 20. Conclusions <ul><li>Vitamin K should be mandatory to control osteoporosis </li></ul><ul><li>It is also indispensable for the formation of thrombin </li></ul><ul><li>Osteoporosis is not recognized by the government as a health problem </li></ul><ul><li>There are no policies or programs for prevention of osteoporosis and associated fractures in Pakistan </li></ul><ul><li>The level of awareness among allied heath professionals as well as the general population </li></ul>12/28/10
  21. 21. References <ul><li>Binkley, N. C and Suttie, J. W. 1995. Vitamin K Nutrition and Osteoporosis. Journal of nutrition, 125: 1812-1821. </li></ul><ul><li>Katarzyna  Billing-Marczak, Marcin  Krotkiewski. 2008. The role of vitamin K in bone metabolism.Terapia;16(5):41-46. </li></ul><ul><li>Habiba U, Ahmed S, Hassan L. 2002. Predisposition to osteoporosis in postmenopausal women. J Coll Physicians Surg Pak;12:297-301 </li></ul><ul><li>Riaz S, Alam M, Umer M. 2006.Frequency of osteomalacia in elderly patients with hip fractures. J Pak Med Assoc;56:273-276 </li></ul><ul><li>Lowe N, Bano Q, Bangash S A, et al. 2008.Dietary calcium intake and bone health in postmenopausal women in Nahaqi, North West Frontier Province, Pakistan. Proceedings of the Nutrition Society; 67:(OCE8), E369 </li></ul>12/28/10