Vitamin K: Tool to control the osteophrosis
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Vitamin K: Tool to control the osteophrosis

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    Vitamin K: Tool to control the osteophrosis Vitamin K: Tool to control the osteophrosis Presentation Transcript

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