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