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Recent Advances in Nutritional Alternative to Parathyroid Hormone for Osteoporosis
- Joseph M Mercola (26 February 2002)
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Human parathyroid hormone and rat osteosarcoma
- Eric G Colman, Gemma Kuijpers, Bruce Schneider, Bruce Stadel (28 February 2002)
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Joseph M Mercola, Medical Director Optimal Wellness Center Schaumburg, IL 60194
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Dr. Reeve’s assertion that parathyroid hormone is the most effective current treatment for osteoporosis fails to take into account the wealth of recent research documenting the effectiveness of vitamin K for the prevention and treatment of osteoporosis.
Osteocalcin is a protein specifically produced by the osteoblasts, and is utilized within the bone as an integral part of the process of its formation. However, osteocalcin requires carboxylation before it can be effective in bone formation. Vitamin K is essential for the carboxylation of osteocalcin. In addition to the carboxylation of bone proteins, vitamin K has also been shown to inhibit the normal cell death of osteoblasts and help maintain the number of osteoblasts.1 Low vitamin K intakes have been associated with an increased incidence of hip fractures in elderly men and women and with osteoporosis in those with longstanding Crohn's Disease.2 While both vitamin D and vitamin K are important for bone growth, it appears that vitamin K may be more important. Women with low vitamin K but high vitamin D intakes have been shown to have a greater risk of hip fracture than women with high vitamin K and low vitamin D intakes.3 Bisphosphonates exhibit their clinical effect by disrupting osteoclastic activity, thus impairing the normal dynamic balance between bone resorbption and formation. A vitamin K analog was recently compared to etidronate in osteoporotic women for two years and no difference was found in the bone fracture rates between the two groups.4 Vitamin K may also help to counteract the microgravity-induced loss of bone mass during long lasting space missions.5 Fermented foods typically have the highest concentration of vitamin K found in the human diet and can provide several milligrams of vitamin K on a daily basis. This level far exceeds the amount found in dark green vegetables. Natto is a fermented soy product and contains a significant amount of food-based vitamin K2, which seems to be better absorbed than vitamin K1. Circulating vitamin K2 concentrations after the consumption of natto have been shown to be about 10 times higher than those of vitamin K1 after eating spinach.6 The current RDA of vitamin K is 1 mcg/kg. There are no comparative studies on different doses of vitamin K, but it is likely that a dose of 1-5 mg daily (1000-5000 mcg) would approximate the levels seen in Japanese women who regularly consumed natto or those who consumed fermented foods and dark green vegetables and had a low incidence of osteoporosis. Other compelling evidence for an increased requirement for vitamin K is that nearly half of newborns were shown to have low vitamin K, despite their mothers consuming dietary levels equal to the RDA of 1 mcg/kg.7 It would seem logical to pursue and advocate an inexpensive and non-toxic vitamin K alternative to a parathyroid hormone recommendation for osteoporosis that would result in a prohibitively costly long-term solution due to the enormous prevalence in the population. 1. Urayama S, Kawakami A, Nakashima T, et. al. Effect of vitamin K2 on osteoblast apoptosis: vitamin K2 inhibits apoptotic cell death of human osteoblasts induced by Fas, proteasome inhibitor, etoposide, and staurosporine.J Lab Clin Med 2000 Sep;136(3):181-93 2. Schoon EJ, Muller MC, Vermeer C . et. al. Low serum and bone vitamin K status in patients with longstanding Crohn's disease: another pathogenetic factor of osteoporosis in Crohn's disease? Gut 2001 Apr;48(4):473-7 3. Zittermann A. Effects of vitamin K on calcium and bone metabolism. Curr Opin Clin Nutr Metab Care. 2001 Nov;4(6):483-7. 4. Iwamoto J, Takeda T, Ichimura S. Effect of menatetrenone on bone mineral density and incidence of vertebral fractures in postmenopausal women with osteoporosis: a comparison with the effect of etidronate. J Orthop Sci 2001;6(6):487-92 5. Vermeer C, Wolf J, Craciun AM, Knapen MH. Bone markers during a 6-month space flight: effects of vitamin K supplementation.J Gravit Physiol 1998 Oct;5(2):65-9 6. Schurgers LJ, Vermeer C. Determination of phylloquinone and menaquinones in food. Effect of food matrix on circulating vitamin K concentrations. Haemostasis. 2000 Nov-Dec;30(6):298-307. 7. Greer FR. Are breast-fed infants vitamin K deficient? Adv Exp Med Biol. 2001;501:391-5. |
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Eric G Colman, Medical Officer - U.S. FDA 20857, Gemma Kuijpers, Bruce Schneider, Bruce Stadel
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Human parathyroid hormone and rat osteosarcoma Editor — As members of the U.S. Food and Drug Administration’s (FDA) Division of Metabolic and Endocrine Drug Products responsible for the review of Eli Lilly’s teriparatide (PTH1-34) application, we would like to respond to Dr. Jonathan Reeve’s 2/23/2002 editorial, Recombinant human parathyroid hormone1. Although the FDA’s Advisory Committee concluded that the company provided sufficient evidence to support the efficacy of teriparatide in the treatment of postmenopausal osteoporosis and idiopathic and hypogonadal osteoporosis in men, the committee did voice concern about osteosarcomas that developed in rats treated with the drug. In contrast to Dr. Reeve’s assertion that rats received “huge doses” of teriparatide, some animals developed osteosarcomas when treated with doses that were approximately 3 times the expected daily human exposure – a relatively small safety margin by conventional standards of drug development. While several factors limit the ability to extrapolate the rat findings to humans, we did not dismiss the preclinical data as clinically irrelevant and believe that they should be factored into the drug’s benefit-to-risk profile. A complete discussion of teriparatide’s efficacy and safety can be found in the transcript of the July 2001 FDA Advisory Committee Meeting2: http://www.fda.gov/ohrms/dockets/ac/01/transcripts/3761t2.htm The views expressed above are those of the authors and do not necessarily reflect the official position of the U.S. FDA Competing interests: None 1. Reeve J. Recombinant human parathyroid hormone. BMJ 2002; 324: 435 -436. 2. Endocrinologic and Metabolic Drugs Advisory Committee meeting transcript. Web site accessed February 25, 2002. http://www.fda.gov/ohrms/dockets/ac/01/transcripts/3761t2.htm Gemma Kuijpers, PhD Bruce Schneider, MD Bruce Stadel, MD, MPH Eric Colman, MD U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Division of Metabolic and Endocrine Drug Products, 5600 Fishers Lane, Rockville, MD 20857 Corresponding author:
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