In this blog post I’ll be looking at some of the research that has been conducted to evaluate whether osteoporosis can be supported through good diet or nutritional supplements.
First of all though it is a little easier to understand the research with a bit of background knowledge:
Bone is a dynamic tissue being continually broken down and rebuilt in a process known as “remodelling”. Cells called osteoclasts, made in bone marrow break down and reabsorb bone tissue liberating calcium and other minerals stored in the bone matrix. Bone stores calcium phosphate and growth factors. Cells called osteoblasts, derived from cells associated with blood vessels, move in and make new bone tissue, known as osteoid which is predominantly made of collagen. Minerals crystallise around the collagen matrix to form hydroxyapatite, the major inorganic constituent of bone containing calcium phosphate. As the osteoblasts form new bone tissue some become embedded in the bone tissue and differentiate into osteocytes.
Bone Mass Density (BMD) begins to decrease in our early 20’s. After age 30 most people have a decreased bone mass due to increased orthoclastic activity compared to osteoblastic activity. Decreased BMD means decreased bone strength and fracture risk.
Osteoporosis is decreased bone density, which means it is porous and weakened at risk of fracture. It is common in postmenopausal women because oestrogen regulates osteoclasts removal of dead demineralised bone and progesterone is required by osteoblasts to build new bone, so decreased oestrogen means increased bone resorption, and decreased progesterone means less bone building.
Genetic, hormonal and lifestyle factors such as exercise all impact on BMD.
Now I will review some of the studies that have been conducted on a range of different nutrients.
Calcium - Calcium is the main component of bone and 99% of the body’s calcium resides in bone. Skeletal calcium also acts as a reserve supply of calcium to meet the body's metabolic needs in states of calcium deficiency and calcium is lost through the bowels, skin and kidneys. Several studies have concluded that calcium supplementation improves bone density in perimenopausal women [1] and slows the rate of bone loss in postmenopausal women by 30-50%, thus reducing the risk of hip fracture and also elderly postmenopausal women [2]. Loss of bone starts in women at the time of the menopause, with urinary calcium excretion increasing [3]. It starts in men at about age 55 and leads to an increase in fracture rates in both sexes.
Vitamin D3 - It is essential for the absorption and metabolism of calcium. Vitamin D has also been shown to reduce the occurrence of fractures within the first year of supplementation, before it has had a significant effect on bone density. Researchers concluded that Vitamin D reduced incidence rate of falls by improving muscle strength and balance [4].
Vitamin K2 – when vitamin D is given with calcium, it is my personal recommendation that vitamin K2 should always be included as it is required to “direct” the calcium to the bones. A study from the University of California has even concluded that supplementation with vitamin D3 and calcium in an absence of vitamin K can lead to cardiovascular calcification [5]. There are numerous research studies which have found that vitamin K2 deficiency is associated with high levels of undercarboxylated osteocalcin [6], decreased bone density and increased fracture risk and that supplementation with vitamin K2 reduces bone loss and fractures [7]. There are also a number of clinical trials which have found that vitamin D3/K2 combination supplementation is more effective [8] in preventing bone loss than either alone. In one study involving osteoporotic postmenopausal women that were given a D3/K2 combo, researchers showed a 4.92% increase in bone density compared to 0.13% in those receiving just K2 This was supported by further evaluation. In postmenopausal women receiving only calcium, lumbar bone density decreased, those given either D3 or K2 increased bone density slightly and those given a combination had the greatest increase in bone density [9].
Magnesium - 50% of the body’s magnesium is found in bones. New studies increasingly uncover new functions of magnesium, some of which include:
- The absorption and metabolism of calcium.
- The conversion of Vitamin D into its active form ( 25-(OH)D3 to 1,25-(OH)2D3) [10].
- Stimulating the thyroid’s production of calcitonin, which helps to regulate blood calcium by slowing down the amount of calcium released from the bones, slowing bone resorption [11].
- Regulating parathyroid hormone, which is a regulator of bone breakdown.
- Activate the enzyme required for production of new bone.
- Regulating calcium transport.
Magnesium has been shown to be in decreased concentration in the blood in post menopausal women with osteoporosis [12]. Osteoporotic women have been shown to have decreased serum levels of magnesium [13], and lower bone magnesium content. Another study showed that magnesium supplementation improved bone mineral density [14].
Boron
- Boron is involved in the conversion of vitamin D [15].
- Boron also stabilises and extends the half life of vitamin D [16] and oestrogen. As oestrogen drops at menopause there is an Increase in certain inflammatory chemicals (a cytokine called interleukin 6) which stimulates osteoclast production. Boron is required for oestrogen to convert to 17 beta oestrodiol which is more potent than oestrogen, so prolonging the beneficial effects of oestrogen. One study where postmenopausal women were supplemented with 3mg daily of boron, significantly decreased urinary excretory calcium and increased levels of 17 beta estrodiol [17].
- Boron is also involved in converting vitamin D to bone building calcitriol.
- Boron also has an interactive role with calcium and magnesium and vitamin D [18].
Manganese – Manganese stimulates the production of mucopolysaccharides (the organic bone matrix), manganese seems to be important for the enzymatic activity of glycosyltransferases (enzymes required for the synthesis of proteoglycans) which play a vital role in mucopolysaccharide synthesis. Impaired activity of these enzymes, due to manganese deficiencies, can result in abnormal cartilage formation. Studies on the role of manganese in bone formation concluded that deficiency of manganese in cartilage (in chicks) resulted in alteration of mucopolysaccharide resulting in bone changes, including less rigidity [19]. Women with osteoporosis were found to have decreased serum manganese, which increased with manganese supplementation.
The EFSA ruled that “Manganese is needed for the structure of strong bones”
High calcium and phosphorus decrease manganese absorption, which is why it is important in this Osteomax (osteoporosis support formula) to maintain levels of manganese, due to the calcium content.
Vitamin B12 – B12 plays an important role in maintaining bone integrity. As explained above, as we age, osteoclastic activity (bone breakdown) exceeds osteoblastic (bone build up) activity. B12 helps form new red blood cells in the bone marrow. Also B12 is arguably the most important factor in homocysteine metabolism, without which homocysteine levels can rise. Homocysteine can interfere with collagen cross linking and weaken bone matrix [20], increasing bone fragility [21]. Homocysteine has also been shown to increase Reactive Oxygen Species (ROS) in osteoblasts, so leading to cell death (apoptosis). High homocysteine has also been shown to increase osteocalcin and to be related to increased hip fracture rates [22]. The most well known study on B12 and its role in bone density is the Framingham Osteoporosis study from 1987 which concluded low levels of B12 exist in people with osteoporosis [23].
Silicon – Silicon is a major trace element in the body. Silicon is high in hops and barley and therefore high in beer! We ingest 20-50mg /day, although post menopausal women absorb silica less easily than younger women, and it is excreted in the same amount as calcium. Silicon is 25 times more concentrated in bone forming protein than in mature bone. It appears to act as a catalyst to make the bone calcify and then leaves so there is no harmful build up. Accumulated evidence over the last 30 years suggests an important role in bone formation and bone and connective tissue health. Mechanisms are unclear but evidence exists of its involvement in collagen synthesis and/or its stabilization and in matrix mineralization [24]. Researchers found that short term supplementation with silicon improved bone mineral density in osteoporosis in animals [25].
Beta Carotene - There are two sources of vitamin A, Retinol found in animal products and beta carotene found in carrots and deep green leafy vegetables. Excess intake of Retinol is associated with a risk of osteoporosis and increased bone fracture [26], whereas high intake of beta carotene is not. It is thought that excessive amounts of vitamin A trigger an increase in osteoclasts and osteoclastic activity and slow the growth of osteoblasts. Vitamin A also stimulates osteoblasts to secrete osteocalcin which helps bind calcium into the bone matrix and there is a delicate balance between vitamin A and vitamin D3. Vitamin D on its own stimulates osteocalcin but together with A has an enhanced synergistic effect [27].
Beta carotene is the precursor to make vitamin A and is considered safe without increasing fracture risk. Beta carotene is the precursor of retinoic acid which has been shown to induce Matrix GLA Protein [28] and is therefore why we choose to use beta carotene and NOT vitamin A in Metabolics products.
Green Tea – There is a large body of evidence supporting the role of green tea in bone health, both in research and epidemiologically. The main bioactive component of green gea is epigallocatechin (EGCG). Research has shown that EGCG can improve bone density by enhancing osteoblastic activity while suppressing osteoclastic activity (by increasing osteoclast apoptosis) at the same time as decreasing oxidative stress (ROS) and proinflammatory chemicals. This results in enhanced mineralization and decreased risk of fracture [29].
Metabolics uses a powerful 90% EGCG green tea in its formulations. Further reading on essential nutrients for bone health can be found in the paper “Essential Nutrients for Bone Health and a Review of their Availability in the Average North American Diet” [30].
Exercise - It is also important to remember that modest exercise should always be recommended as part of a bone health program. 20 minutes of modest impact activity or resistance training [31], or vibrational therapy [32] 3 times a week has been shown to improve bone mineral density.
References
1. Long-term effect of calcium supplementation on bone loss in perimenopausal women.
Elders PJ, Lips P, Netelenbos JC, van Ginkel FC, Khoe E, van der Vijgh WJ, van der Stelt PF.
Department of Endocrinology, Academisch Ziekenhuis Vrije Universiteit, Amsterdam, The Netherlands.
2. A 4-year follow-up study of the effects of calcium supplementation on bone density in elderly postmenopausal women.
Devine A, Dick IM, Heal SJ, Criddle RA, Prince RL.
Department of Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia.
3. Calcium and osteoporosis.
Nordin BE, Polley KJ, Need AG, Morris HA, Horowitz H.
Department of Nutrition & Dietetics, Royal Adelaide Hospital, South Australia.
4. Effect of Vitamin D on Falls
Heike A. Bischoff-Ferrari, MD, MPH; Bess Dawson-Hughes, MD; Walter C. Willett, MD, DrPH; Hannes B. Staehelin, MD; Marlet G. Bazemore, MD; Robert Y. Zee, MD; John B. Wong, MD
5. Vitamins D and K as pleiotropic nutrients: clinical importance to the skeletal and cardiovascular systems and preliminary evidence for synergy.
Kidd PM.
University of California, Berkeley, USA.
6. Vitamin K and bone health in adult humans.
Bügel S.
Department of Human Nutrition, University of Copenhagen, Rolighedsvej 30, DK-1958 Frederiksberg C, Denmark.
7. Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials.
Cockayne S, Adamson J, Lanham-New S, Shearer MJ, Gilbody S, Torgerson DJ.
York Trials Unit, Department of Health Sciences, University of York, York YO10 5DD, England.
8. Effect of combined administration of vitamin D3 and vitamin K2 on bone mineral density of the lumbar spine in postmenopausal women with osteoporosis.
Iwamoto J, Takeda T, Ichimura S.
Department of Sports Clinic, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
9. Effect of continuous combined therapy with vitamin K(2) and vitamin D(3) on bone mineral density and coagulofibrinolysis function in postmenopausal women.
Ushiroyama T, Ikeda A, Ueki M.
Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, Japan.
10. Low serum concentrations of 1,25-dihydroxyvitamin D in human magnesium deficiency.
Rude RK, Adams JS, Ryzen E, Endres DB, Niimi H, Horst RL, Haddad JG Jr, Singer FR.
11. Magnesium, zinc, copper, manganese, and selenium levels in postmenopausal women with osteoporosis. Can magnesium play a key role in osteoporosis?
Odabasi E, Turan M, Aydin A, Akay C, Kutlu M.
Gulhane School of Medicine, Department of Medical Ecology and Hydroclimatology, Ankara, Turkey.
12. Magnesium, zinc, copper, manganese, and selenium levels in postmenopausal women with osteoporosis. Can magnesium play a key role in osteoporosis?
Odabasi E, Turan M, Aydin A, Akay C, Kutlu M.
Gulhane School of Medicine, Department of Medical Ecology and Hydroclimatology, Ankara, Turkey.
13. Low serum concentrations of 1,25-dihydroxyvitamin D in human magnesium deficiency.
Rude RK, Adams JS, Ryzen E, Endres DB, Niimi H, Horst RL, Haddad JG Jr, Singer FR.
14. Trabecular bone density in a two year controlled trial of peroral magnesium in osteoporosis.
Stendig-Lindberg G, Tepper R, Leichter I.
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Israel.
15. The relationship between boron and magnesium status and bone mineral density in the human: a review.
Volpe SL, Taper LJ, Meacham S.
Department of Nutritional Sciences, University of California at Berkeley.
16. Essential Nutrients for Bone Health and a Review of their Availability in the Average North American Diet
Charles T Price,* Joshua R Langford, and Frank A Liporace
17. Effect of dietary boron on mineral, estrogen, and testosterone metabolism in postmenopausal women.
Nielsen FH, Hunt CD, Mullen LM, Hunt JR.
United States Department of Agriculture, Grand Forks Human Nutrition Research Center, North Dakota 58202.
18. The relationship between boron and magnesium status and bone mineral density in the human: a review.
Volpe SL, Taper LJ, Meacham S.
Department of Nutritional Sciences, University of California at Berkeley.
19. Studies on the Role of Manganese in Bone Formation
I. EFFECT UPON THE MUCOPOLYSACCHARIDE CONTENT OF CHICK BONE
R. M. LEACH, JR. ANDANNA-MARIE MUENSTER
U.S. Plant, Soil and Nutrition Laboratory, Soil and Water Conservation Research Division, Agricultural Research Service, U. S. Department of Agriculture, Ithaca, New York
20. Homocysteine as a Predictive Factor for Hip Fracture in Older Persons
Robert R. McLean, M.P.H., Paul F. Jacques, D.Sc., Jacob Selhub, Ph.D., Katherine L. Tucker, Ph.D., Elizabeth J. Samelson, Ph.D., Kerry E. Broe, M.P.H., Marian T. Hannan, D.Sc., L. Adrienne Cupples, Ph.D., and Douglas P. Kiel, M.D.
21. Homocysteine Levels and the Risk of Osteoporotic Fracture
Joyce B.J. van Meurs, Ph.D., Rosalie A.M. Dhonukshe-Rutten, M.Sc., Saskia M.F. Pluijm, Ph.D., Marjolein van der Klift, M.D., Ph.D., Robert de Jonge, Ph.D., Jan Lindemans, Ph.D., Lisette C.P.G.M. de Groot, Ph.D., Albert Hofman, M.D., Ph.D., Jacqueline C.M. Witteman, Ph.D., Johannes P.T.M. van Leeuwen, Ph.D., Monique M.B. Breteler, M.D., Ph.D., Paul Lips, M.D., Ph.D., Huibert A.P. Pols, M.D., Ph.D., and André G. Uitterlinden, Ph.D.
22. Plasma homocysteine, folate, and vitamin B 12 and the risk of hip fracture: the hordaland homocysteine study.
Gjesdal CG, Vollset SE, Ueland PM, Refsum H, Meyer HE, Tell GS.
Department of Public Helath and Primary Health Care, University of Bergen, Bergen, Norway.
23. Application of the National Osteoporosis Foundation Guidelines to Postmenopausal Women and Men: The Framingham Osteoporosis Study
Sarah D. Berry, MD MPH,1,2 Douglas P. Kiel, MD MPH,1,2 Megan G. Donaldson, PhD,3 Steven R. Cummings, MD FACP,3 John A. Kanis, MD FRCP,4 Helena Johansson,4 and Elizabeth J. Samelson, PhD1,2
24. SILICON AND BONE HEALTH
R. JUGDAOHSINGH
25. Short-term administration of water-soluble silicon improves mineral density of the femur and tibia in ovariectomized rats.
Bae YJ, Kim JY, Choi MK, Chung YS, Kim MH.
Department of Food and Nutrition, Sookmyung Women's University, Seoul, South Korea.
26. Vitamin A intake and osteoporosis: a clinical review.
Crandall C.
Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California 90095-7023, USA.
27. Effect of retinoic acid on osteocalcin gene expression in human osteoblasts.
Oliva A, Della Ragione F, Fratta M, Marrone G, Palumbo R, Zappia V.
Institute of Biochemistry of Macromolecules, Medical School, Second University of Naples, Italy.
28. Retinoic acid induces matrix Gla protein gene expression in human cells.
Cancela ML, Price PA.
Department of Biology, University of California-San Diego, La Jolla 92093.
29. Green tea and bone metabolism.
Shen CL, Yeh JK, Cao JJ, Wang JS.
Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX 79430-9097, USA.
30. Essential Nutrients for Bone Health and a Review of their Availability in the Average North American Diet.
Price CT, Langford JR, Liporace FA.
Orlando Health, 1222 Orange Avenue, 5 Floor, Orlando, Florida 32806, USA.
31. Exercise interventions: defusing the world's osteoporosis time bomb.
Kai MC, Anderson M, Lau EM.
Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, SAR, China.
32. The effects of whole-body vibration training in aging adults: a systematic review.
Merriman H, Jackson K.
DPT Program, Department of Health & Sport Science, University of Dayton, 300 College Park, Dayton, Ohio 45469-2925, USA.
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