Nutrition and Osteoporosis
What You Need To Know (and maybe a little more).
I am frequently asked, “Do I need to take calcium supplements to keep my bones strong?” The short answer is “probably no”, but I wish to take this opportunity to give a more thorough answer than “yes” or “no”. I believe in empowering you with the knowledge to take care of yourself. So here’s the long answer (If you are short of time, skip to the recommendations section at the end).
While it is true that bones contain much of the calcium in our bodies, and it is also true that bones tend to lose calcium and become weaker and more prone to fracture with age, it is not true that our bones fracture because of a lack of calcium. If you were to grind up a calcium tablet, you would hold a soft pile of powder in your hand. What gives bone structural integrity and flexibility, is the matrix of connective tissue and living cells that holds the calcium in place. Calcium by itself is like bricks without mortar.
Anatomically, bones are composed of:
1. The very hard outer surface (periosteum),
2. The fairly hard material that makes up the bulk of the bone (compact bone),
3. The softer inner marrow where blood cells and immune cells are made.
Bone is about one-third living cells. The rest is calcium phosphate, calcium carbonate and other minerals embedded in a mesh of tough, dense connective tissue. Though the other minerals make up a smaller proportion of the total mineral content in bone than does calcium, they are, nonetheless, essential. We are only as strong as our weakest link.
Why should we care about our bones? Thin bones (osteopenia) and porous bones (osteoporosis) are at greater risk of fracture than healthy bones. The National Osteoporosis Foundation says that “osteoporosis causes more than 1.5 million fractures annually: 700,000 vertebral, 300,000 hip, 250,000 wrist and 300,000 fractures at other sites”.i Furthermore, “an average of 24 percent of hip fracture patients aged 50 and over die in the year following their fracture.”ii Our bones reach their maximum strength in our early twenties and decline steadily every year thereafter.
Back to calcium. Yes, calcium is an important component of bone, but it is only necessary to supplement calcium if your diet is deficient in calcium relative to your needs. You may have read that the Recommended Daily Allowance (RDA) for calcium set by the United States government is 1,200 mg per day for women. However, a Swedish study of 61,433 women over a period of 19 years found that those taking 750 mg per day of calcium had the lowest risk of fracture. Increasing calcium intake beyond 750 mg did not confer additional benefit and in fact was associated with increased risk of fracture!iii A pregnant or lactating woman may need to take supplemental calcium because her need is high, but the average person eating a varied, whole-food diet should not need supplemental calcium. Of course, it is true that most Americans aren’t eating a varied, whole-food diet but even so, the calcium that comes in food is generally better absorbed than the calcium that comes in pills. Therefore, it is far better to change your diet than to take a pill.
Speaking of pills, most calcium pills are made from ground-up limestone. This is calcium carbonate from shells of ancient sea life that piled up on the ocean floor. Over millions of years of tons of compressive force these shells became the white cliffs of Dover or the Dolomite mountains. A lot of stomach acid is required to break down and absorb this form of calcium. This last fact is why “Tums” is such a terrible way to supplement calcium. The large amount of calcium in Tums neutralizes stomach acid, preventing absorption.
Just to expand on that topic for a moment, stomach acid declines as we ageiv. Could this be the reason for osteoporosis? Yes, lack of stomach acid does cause osteoporosis. That’s why people taking proton pump inhibitors to reduce acid reflux suffer from more spinal fractures than the average person.v It is likely why osteoporosis is more common as we age. It is also why many traditional cultures start the meal with an appetizer that stimulates the production of acid.
So Tip Number 1 is to eat whole foods in a relaxed, slow manner, following the customs of almost any traditional culture (starting the meal with appetizers that are sour, bitter or spicy).
Eating this way may also eliminate the need for the drugs to reduce acid reflux. Wait a minute! Stimulating acid production reduces acid reflux?
A curious thing about stomach acid is that the symptoms of “acid reflux” or GERD are actually caused by low acid, not by the high acid that most people assume is the cause. Adequate stomach acid is needed to close the ring of muscle (cardiac sphincter) that separates the stomach from the tube leading to it (the esophagus). Insufficient stomach acid (or simply eating too much) allows the food to push up into the esophagus. The esophagus cannot tolerate even a low amount of acid and so it will burn on contact with the mildly acidic food. This is how low stomach acid causes heartburn.
Hydrochloric acid (stomach acid) is of course needed to digest our food. Without it, we cannot digest and absorb protein, calcium, Vitamin B12 or a host of other nutrients. Hydrochloric acid is also needed to kill bacteria and other pathogens in the food. That’s why people on drugs to reduce stomach acid (proton pump inhibitors) are more likely to get pneumoniavi. One study found that 33,000 deaths a year are due to pneumonia acquired as a result of taking acid-reducing proton pump medicationsvii.
An even more important pathogen that flourishes in the stomach when there is insufficient acid is Helicobacter Pylori (known as H. pylori for short). Overgrowth of H. pylori due to insufficient stomach acid is the cause of stomach ulcers, gastritis, reflux, GERD and esophageal cancer.viii How common is this? It is estimated that 20 percent of individuals under the age of 40 are infected with H. pylori and 50 percent to 60 percent of individuals over the age of 60 are infected.ix Wow! That is really common. Remember, taking drugs that reduce stomach acid actually increases the risk of H. pylori infection, which in turn increases the risk of reflux, GERD, esophageal cancer, osteoporosis and pneumonia.
By the way, I noted earlier that low stomach acid impairs the absorption of Vitamin B12x. Lack of B12 is implicated in Alzheimer’s disease and heart diseasexi. Add that to the list of reasons to take care of your stomach without relying on anti-acid drugs. To learn more, read Your Bones: How You Can Prevent Osteoporosis & Have Strong Bones for Life Naturally by Lara Pizzorno and Jonathan Wright, M.D.
So, if you have enough calcium in your diet, how do you get it to become bone? I have seen many x-rays of patients whose bones in the lower back look osteoporotic, but their abdominal aorta looks calcified. The calcium that should be in the bones is not in the bone, but is in the blood vessels instead. Taking more calcium, without directing where it goes will only worsen the hardening of the arteries and stiffness in the muscles. This situation is more common than you would think. Plenty of calcium, but it is in the wrong places.
The arrows in the x-ray above are pointing to the abdominal aorta. It should not be visible. The reason we can see it is that it is calcified.
How does this happen? In addition to its role in bone, calcium helps nerves and muscles fire faster and stronger. When we are alert and active, calcium is drawn from the bones and directed to the soft tissues to help with these vital functions. The movement of calcium from the bones to the soft tissues is accomplished with the help of “fight or flight” hormones. At the end of the day, we are supposed to relax and let the “rest and digest” hormones (principally calcitonin from the thyroid gland) put the calcium back in the bones. That way, we rest comfortably at night (no twitching muscles or disturbed sleep). Picture for a moment, a traditional hunter-gatherer, farmer or laborer. Most of the day was consumed with routine physical activities. Probably a lot of sunlight, as these labors took place out doors. At night, a little story around the campfire after dinner for the hunter-gatherer, perhaps reading a book or having a nice conversation before going to bed in more recent times. How does this compare to our modern lives? We wake up to an alarm clock, grab some caffeine on the run, suffer high-stress all day, which we continue into the night with late emails, bills to pay and perhaps some graphic violence on the evening news before falling exhausted into bed. When are those “rest and digest” hormones going to be stimulated? The fight or flight hormones are turned on all the time. We can live life in the fast lane, but where are we going?
Tip Number 2: stop all work activities and overly stimulating television by dinnertime. Reconnect with your spouse. Read a book. Take a walk after dinner. Get creative. This is a time to nurture yourself and relax.
Let’s take a look at the effect of our ancestor’s labors on their bone density. The hard physical work of hunting or farming stresses and compresses the bones, stimulating the bone-forming cells (osteoblasts) to make more bone. That is why exercise is recommended to prevent osteoporosis (More on that later). As a rule, most of our ancestor’s work was done outdoors. Sun exposure causes the body to make Vitamin D in the skin, which helps move calcium into the bones, making the bones stronger. How much Vitamin D does a person make in their skin? Vacationers in Hawaii make 10,000 to 25,000 units of vitamin D in their skin per day.xii How much is that compared to what we normally get? The National Health and Nutrition Examination Survey found that over fifty million children and adolescents are getting below the recommended daily requirement of vitamin D.xiii How much is recommended? The United States government says that the Recommended Daily Allowance is 600 units. If that sounds low to you, that’s because it probably is. Research shows that an adequate supplemental intake to achieve optimal serum levels is a little over 2,000 IU’s per day.xiv
How can you know the right amount for you? There is a blood test for vitamin D that you can take to find out if you are deficient. You want to score on the high end of normal because even within the normal range, there is a strong correlation between lower (though still normal) levels of vitamin D and a host of diseases, including colon and breast cancer, xv xvi multiple sclerosis, Alzheimer’s, Parkinson’s disease, schizophrenia, diabetes, autoimmune disorders, hypertension, atherosclerosis and muscle weakness.xvii It is best to be sure that you have plenty of D, but not too much.xviii There is an optimal dose for you.
Tip Number 3 Take the blood test to check your vitamin D levels.
Is sunlight a safe way to get vitamin D? Yes, but only in the early morning or late afternoon. The sun’s rays can cause free-radical damage to your skin. Damage to the collagen in skin causes wrinkles. Damage to the DNA of skin cells can cause skin cancer. The cancer-causing rays are diminished by passing through the atmosphere. In the early morning or late afternoon, or midday during the winter, the sun’s rays are weakened by passing through more atmosphere than during the middle of a summer day. Melanin in the skin (the pigment that gives our skin color) is an antioxidant that protects against skin cancer. In other words, having a tan is protective. Eating fruits and vegetables that are rich in colorful antioxidants also protects against free-radical damage from the sun. Sunscreen unfortunately does not provide protection. After 20 to 30 minutes, the protective chemicals in sunscreen actually become free-radicals themselves.xix Furthermore, they provide a false sense of security, leading people to stay out in the sun longer than is safe. I recommend wearing a hat to protect the face and neck while getting some early morning or late afternoon sun to gradually build a tan. Stay out of the sun during the middle of the day or wear protective clothing and a broad-brimmed hat.
Tip Number 4 Get sunlight safely, several times a week if possible.
What about dietary sources of vitamin D? The highest food sources are oily fish such as salmon and swordfish, with lesser amounts in sardines, tuna and other fish. Unfortunately, those top predator fish contain large amounts of mercury.xx This is especially true of swordfish. Sardines have much lower levels of mercury because they aren’t so high on the food chain. There is some Vitamin D in meat, milk and eggs, but not very much. Land animals aren’t nearly as good a source because they are mainly composed of saturated fats and cholesterol, while the fish oil sources are very high in essential omega-3 fatty acids. These omega-3 fats are necessary to reduce blood pressure and risk of heart disease,xxi as well as improving cognitive function. The food source I recommend is Nordic Naturals cod liver oil, because it is certified mercury free.
Tip Number 5 Take one tablespoon of cod liver oil daily. In addition to providing essential omega-3 fatty acids, cod liver oil contains 1,360 IU’s of Vitamin D per tablespoon.xxii
What about all the hard work our ancestors performed? How does that help? Everyone knows that weight-bearing exercise is necessary to build and maintain bone.xxiii Why is that? The answer is that bone is continually remodeled by two types of cells. One of the cells continually eats bone. These are called osteoclasts. The other type of cell continually makes new bone. These are called osteoblasts. The eaters keep nibbling away all the time. Kind of like the adage, “Rust never sleeps”. The blasts (builders) work in response to electrical impulses created by compression on the bone. For instance, if you are walking, the compressive forces on the bones of your legs, hips and spine stimulates the blasts to make those bones stronger. To maintain the strength of bones in the arms, weight-lifting or pushups may be needed. The beauty of the way these cells work is that the bone is continually remade to serve the functions we do every day. If you were to lie in bed for an extended period of time, your bones would become weaker. It’s as if your body is saying, “If you don’t need that calcium in the bone, we’ll just use it for something else”. The body is very economical. It doesn’t maintain tissue that you aren’t using. Our bodies are active, dynamic processes, not things. We are verbs, not nouns.
This process works to our advantage. If we break a bone and it sets crooked, the “blasts” will keep strengthening where the compressive forces are and the “clasts” will keep eating the parts where there is no functional stress. This will eventually remodel the bone to become straight. (By the way, the only tissues the body keeps that are not functional are scar tissue and fat. This is because these tissues do not require energy to be maintained.)
Tip Number 6 Perform weight-bearing exercise at least three times a week.
I mentioned caffeine above. Caffeine acts like a fight or flight hormone. Drinking coffee and to a lesser extent, tea or decaf, is like taking liquid stress hormones. Caffeine moves calcium from your bones to your soft tissues. Caffeinated soft drinks are even worse. Not only do they contain caffeine and diabetes-inducing amounts of sugar, but they also have phosphoric or carbonic acid, which is what makes them fizzy. These acids dissolve calcium. If you have a child’s discarded tooth available, try dropping it into a coke and see what happens. It will dissolve and disappear pretty quickly. Tip Number Seven: Stay away from coffee and sodas.
What about drugs to strengthen bone? The bisphosphonate drugs (such as Fosomax, Boniva, etc.) commonly prescribed to treat or prevent osteoporosis work by killing osteoclasts. These drugs were originally developed to treat a kind of bone cancer called Paget’s Disease, which is a form of cancer involving over-production of osteoclasts. In other words, these drugs were a form of chemotherapy. Their half-life is ten years.xxiv In other words, ten years after taking one of these drugs, half of it is still in your system. “Okay,” you say. “So these are strong medicines. Why not take them? So what if they kill off the bone-destroying osteoclasts. What’s wrong with that?”
The problem with killing off the osteoclasts is that they are necessary for bone health. One of the functions the “clasts” perform is to keep the canals in the bone open so nutrients and wastes from the living cells in bone can flow freely. Without osteoclasts, the bone gradually becomes harder and more brittle because it is dying.xxv The bone looks better on a bone density test because it has a higher mineral content. Initially, a low dose of the drug may be helpful but continued use of bisphosphonates does not give increased benefits.xxvi The bone density test provides a false sense of reassurance at your annual physical, but harder is not always better. To get a sense of what I am talking about, imagine trying to break the “wishbone” of a turkey on Thanksgiving Day. The bone is so flexible, it is very hard to break. Wait a few days for the bone to dry out and it snaps easily. A dead bone is more brittle than living tissue. The osteoclasts that are killed by bisphosphonate drugs are needed for healthy bone remodeling. This is well stated in the Journal of Endocrinology and Metabolism, “Microcracks occur in normal bone after the kind of stresses encountered in day-to-day life. These cracks are detected by the osteocytes, which initiate a bone-remodeling unit to repair the damage. If bone resorption is strongly inhibited, the damage can’t be repaired because the osteoclasts won’t dissolve the bone.”xxvii Imagine you need to remodel your kitchen but you can’t take out the old cabinets or flooring. Putting more cabinets on top of the old ones doesn’t make sense, but that’s what you get with bisphosphanate drugs.
This bone weakening is not just theoretical. A known side-effect of bisphosphonate drugs is “osteornecrosis of the jaw”. Let’s break down that word. “Osteo” means bone. “Necrosis” means death. It is reportedly rare but I have seen two cases among my patients. Dentists I have talked with report they have seen it as well. A study in the Journal of Oral Maxillofacial Surgery reported that while most cases were due to high intravenous doses of bisphosphonates for cancer therapy, some were due to long-term oral use for osteoporosis.xxviii
Tip Number 8 Seriously question your doctor about your need for bisphosphonate drugs if they are prescribed.
I mentioned earlier that calcium isn’t the only material that makes up bone. Trace elements and other nutrients are needed to make and strengthen bone. Chief among these minerals is magnesium. Magnesium is the third most abundant mineral in your body and a very important element in bone. Trace elements needed for healthy bone formation include boron, strontium and silicon (More on these in a moment).
Magnesium is found in chlorophyll, so any colorful vegetable or fruit provides magnesium. Magnesium does compete with calcium for absorption, so excessive amounts such as found in laxatives can be harmful to calcium levels. Does magnesium increase bone density? Yes it does. One study showed a 1 to 8 percent rise in bone density when taking magnesium supplements.xxix Other studies show that severe magnesium deficiency “causes impaired bone growth, osteopenia and skeletal fragility.” xxx The average American diet is deficient in magnesium but then again, it is deficient in most nutrients. Once again, eat whole foods. I also suggest taking supplemental magnesium. I have been taking 200 mg magnesium gluconate twice a day since the early 1980s. It keeps my mind calm and muscles relaxed. How much should you take? Your body can only absorb so much magnesium at a time from your intestines. If you take more that what you need, the magnesium remaining in your intestines will attract water to itself and pass as loose stools or diarhea. Many clinicians recommend taking just short of that effect to find the optimal dose.
Magnesium is also great for insomnia. It helps prevent restless leg syndrome, muscle cramps, heart palpitations and of course constipation. Please note that magnesium is needed by your body to convert Vitamin D to the active form. If you increase your Vitamin D intake, you may need to increase your magnesium intake as well or you could suffer heart palpitations from magnesium deficiency.
Tip Number 9 Take magnesium citrate or gluconate (not oxide) 200 to 400 mg per day, or up to bowel tolerance.
Boron stimulates bone forming cells (osteoblast) and inhibits bone destroying cells (osteoclasts).xxxi Boron stabilizes and extends the half-life of vitamin D and estrogen.xxxii Furthermore, post-menopausal women who took 3 mg supplemental boron per day showed improved retention of calcium and magnesium in their kidneys.xxxiii Three milligrams isn’t much, but about half the population of the United States gets less than 1 mg boron per day.xxxiv Boron is found in raisins, almonds, hazel nuts, avocado, cashews, dates, peanut butter, Brazil nuts, walnuts, dried apricots, red kidney beans and many other foods.xxxv
Strontium is a trace element that has been proven to be very beneficial in preventing and treating osteoporosis. A research study published in the Journal of Clinical Endocrinology and Metabolism found a “39 percent reduction in vertebral fractures and a 36 percent risk reduction in hip fracture in post menopausal women over a 3-year time period. Bone mineral density increased 8.2 percent at the femoral neck and 9.8 percent at the hip.”xxxvi Strontium ranelate has been patented in Europe as a drug but is available over the counter as a nutritional supplement in this country, usually as strontium citrate or gluconate. It competes with calcium for absorption so is best taken at a different meal. Foods high in strontium include, whole grains, seafood, poultry, meats, vegetables and legumes.
Another mineral of interest is silicon. Studies have shown that 40 mg a day of dietary silicon or more is associated with increased bone density.xxxvii The average daily intake for women is around 18 mg. It is higher for men on average because it is contained in beer and men drink more beer. Before you think I’m advocated drinking a lot of beer, let me note that dietary sources include whole grains, carrots and green beans.
In addition to Vitamin D3 (the “Sunshine Vitamin”), there is another vitamin critical to bone health. That vitamin is K2 or menaquinone. This nutrient is very exciting because it not only helps to build bone, it does so by removing calcium from arteries and other places where it is causing problems. It is so effective in reducing plaque in the arteries that a 10-year study of 4,800 fifty-five-year-olds found that vitamin K2 reduced cardiac deaths by 50 percent and “all cause mortality” by 25 percent. This research is known as the Rotterdam Studyxxxviii. This correlates well with a Japanese study that found Vitamin K2 is effective as drugs in preventing osteoporotic fractures.xxxix Additionally, Vitamin K2 has been found to reduce risk of prostate cancer by 35 percentxl, Non-Hodgkins Lymphoma by 45 percentxli and hepatocellular carcinoma by 20 percentxlii.
How do you get K2? The highest food source is a Japanese food called natto. It is a slimy fermented soybean dish that I tried once (and will never try again). It is also found in fermented curds, cheeses, fish and high fat meats, dairy and eggs from pasture-raised animals. The lowest levels of Vitamin K2 were found in people who consumed the most polyunsaturated fatty acids (such as Canola oil). Smokers had the very lowest levels of K2, regardless of what they ate. The FDA recommends 90 mcg (micrograms) for women and 120 mcg for men, but researchers treating cancer have used doses as high as 45 mg (that’s 45,000 mcg) per day with good results and no side effects.xliii
I am currently taking liquid Vitamin K2 from Thorne Research. Each drop is 1 mg (1,000 mcg). I find it the easiest way to take K2, especially since I don’t eat a lot of high fat meats, cheeses or natto. Tip Number Ten: Take one drop of Thorne Vitamin K2 per day.
There is a blood test that indirectly measures Vitamin K2 deficiency. It is called uncarboxylated osteocalcin. It is a direct measure of how well the body is forming bone. However, since there appears to be no downside for overdosing Vitamin K2, I recommend taking at least 1 drop of the liquid Vitamin K2 from Thorne Research.
So in summary,
1. Eat a variety of whole foods in a relaxed manner. Use appetizers and seasonings that stimulate your appetite.
2. Take a walk or engage in another relaxing activity after dinner.
3. Get tested for your blood level of Vitamin D.
4. Get some late afternoon or early morning sunshine. Wear a hat rather than sunscreen.
5. Take one tablespoon of cod liver oil per day.
6. Do weight-bearing exercise at least three times a week.
7. Avoid coffee and carbonated beverages.
8. Question any recommendation to take bisphosphonate drugs, particularly more than a few years.
9. Consider taking 200 – 400 mg magnesium gluconate or citrate per day.
10. To get boron, strontium, silicon and other nutrients, eat whole foods. Remember, real food doesn’t have ingredients. If your grandmother wouldn’t recognize it, it isn’t food. This may require more money, time and effort (such as going to the Farmer’s Market and learning to cook from scratch, but it is worth it. The extra money will be saved in doctors bills and the extra time spent will be regained in years of good health).
11. Take one drop per day of Thorne Vitamin K2.
I hope you found this article informative and useful. I apologize if it is too technical, but I want to be accurate and I trust you have the intelligence to understand it. Thank you for reading it through.
David Wells, D.C., L.Ac., MS Nutrition
iii Dietary calcium intake and risk of fracture and osteoporosis: prospective longitudinal cohort study
BMJ 2011; 342 doi: http://dx.doi.org/10.1136/bmj.d1473 (Published 24 May 2011)
Cite this as: BMJ 2011;342:d1473
iv Assessment of gastric acidity of Japanese subjects over the last 15 years. Morihara M, Aoyagi N, Kaniwa N, Kojima S, Ogata H. Biol Pharm Bull. 2001 Mar;24(3):313-5.
National Institute of Health Sciences, Tokyo, Japan.
v Laura E. Targownik, MD MSHS, Lisa M. Lix, PhD, Colleen J. Metge, PhD, Heather J. Prior, MSc, Stella Leung, Msc. and William D. Leslie MD
Use of proton pump inhibitors and risk of osteoporosis-related fractures CMAJ August 12, 2008 179:319-326; doi:10.1503/cmaj.071330
vi Chun-Sick Eom, Christie Y. Jeon, Ju-Won Lim, Eun-Geol Cho, Sang Min Park and Kang-Sook Lee. Use of acid-suppressive drugs and risk of pneumonia: systematic review and meta-analysis. CMAJ, December 20, 2010 DOI: 10.1503/cmaj.092129
vii JAMA. 2009 May 27;301(20):2120-8. Acid-suppressive medication use and the risk for hospital-acquired pneumonia. Herzig SJ, Howell MD, Ngo LH, Marcantonio ER.
viii Kusters JG, van Vliet AH, Kuipers EJ (July 2006). “Pathogenesis of Helicobacter pylori Infection”. Clin Microbiol Rev 19 (3): 449–90.
xi J Alzheimers Dis. 2010;19(2):481-8. Vitamin B12 levels in Alzheimer’s disease: association with clinical features and cytokine production. Politis A, Olgiati P, Malitas P, Albani D, Signorini A, Polito L, De Mauro S, Zisaki A, Piperi C, Stamouli E, Mailis A, Batelli S, Forloni G, De Ronchi D, Kalofoutis A, Liappas I, Serretti A.
xii Holick, MF (1995). Environmental factors that influence the cutaneous production of vitamin D. Am. J. Clin. Nutr. 61 (3 Suppl): 638S–645S.
xiii Pediatrics. 2009 Sep;124(3):e362-70. Epub 2009 Aug 3.
Prevalence and associations of 25-hydroxyvitamin D deficiency in US children: NHANES 2001-2004. Kumar J, Muntner P, Kaskel FJ, Hailpern SM, Melamed ML. Children’s Hospital at Montefiore, Bronx, New York, USA.
xiv Heany R. The vitamin D requirement in health and disease. J Steroid Biochem Mol Biol. 2005;97:13–9. [PubMed]
xv Ann N Y Acad Sci. 1999;889:107-19. Calcium and vitamin D. Their potential roles in colon and breast cancer prevention. Garland CF, Garland FC, Gorham ED. Department of Family and Preventive Medicine, University of California, San Diego 92093, USA.
xvi Lappe JM, Travers-Gustafson D, Davies KM, et al. Vitamin D and calcium supplementation reduces cancer risk: Results of a randomized trial. American Journal of Clinical Nutrition 2007; 85(6):1586–1591.
xvii Tuohimaa P, Keisala T, Minasyan A, Cachat J, Kalueff A (December 2009). “Vitamin D, nervous system and aging”. Psychoneuroendocrinology 34 (Suppl 1): S278–86.
xviii Hsu, J. J.; Tintut, Y.; Demer, L. L. (2008). “Vitamin D and Osteogenic Differentiation in the Artery Wall”. Clinical Journal of the American Society of Nephrology 3 (5): 1542–7.
xix Free Radic Biol Med. 2006 Oct 15;41(8):1205-12. Epub 2006 Jul 6. Sunscreen enhancement of UV-induced reactive oxygen species in the skin. Hanson KM, Gratton E, Bardeen CJ. Department of Chemistry, University of California at Riverside, Riverside, CA 92506, USA.
xxi Current Opinion in Clinical Nutrition & Metabolic Care: March 2007 – Volume 10 – Issue 2 – p 129-135 Lipid metabolism and therapy
xxii NIH Office of Dietary Supplements Dietary Supplement Fact Sheet: Vitamin D. 2009/11/13;
xxiii Bull World Health Organ. 2003;81(11):827-30. Epub 2004 Jan 20.
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. email@example.com
xxiv Ensrud KE, Barrett-Connor EL, Schwartz A, Santora AC, Bauer DC, Suryawanshi S, Feldstein A, Haskell WL, Hochberg MC, Torner JC, Lombardi A, Black DM 2004 Randomized trial of effect of alendronate continuation versus discontinuation in women with low BMD: results from the Fracture Intervention Trial long-term extension. J Bone Miner Res 19:1259–1269
xxv Currey JD 1984 Effects of differences in mineralization on the mechanical properties of bone. Philos Trans R Soc Lond B Biol Sci 304:509–518
xxvi Bone. 2004 Apr;34(4):599-604. Changes in bone mineral density explain little of the reduction in vertebral or nonvertebral fracture risk with anti-resorptive therapy. Delmas PD, Seeman E. Claude Bernard University of Lyon and INSERM Research Unit 403, Lyon, France. firstname.lastname@example.org
xxvii Ott, Susan. The Long-Term Safety of Bisphosphonates. The Journal of Clinical Endocrinology & Metabolism March 1, 2005 vol. 90 no. 3 1897-1899
xxviii J Oral Maxillofac Surg. 2004 May;62(5):527-34. Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL. Division of Oral and Maxillofacial Surgery, Long Island Jewish Medical Center, New Hyde Park, NY 11040, USA.
xxix Magnes Res. 1993 Jun;6(2):155-63. 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.
xxx J Am Coll Nutr. 2009 Apr;28(2):131-41. Skeletal and hormonal effects of magnesium deficiency. Rude RK, Singer FR, Gruber HE. USC Keck School of Medicine, Los Angeles, CA.
xxxi Therapeutic effect of dietary boron supplement on retinoic acid-induced osteoporosis in rats. Xu P, Hu WB, Guo X, Zhang YG, Li YF, Yao JF, Cai QK. Department of Orthopedics, Xi’an Red Cross Hospital, Xi’an 710054, China. https://www.ncbi.nlm.nih.gov/pubmed/17259120
xxxii Volpe S, Taper LJ, Meacham S. The relationship between boron and magnesium status and bone mineral density in the human a review. Magnes Res. 1993;6(3 ):291–6. [PubMed]
xxxiii Nielsen F. Studies on the relationship between boron and magnesium which possibly affects the formation and maintenance of bones. Magnes Trace Elem. 1990;9(2 ):61–9. [PubMed]
xxxiv National Academy of Sciences. A Report of the Panel on Micronutrients. Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington DC: National Academy Press; 2001.
xxxvi J Clin Endocrinol Metab 2005 May;90(5):2816-22. Epub 2005 Feb 22.
Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study, Reginster, et al
xxxvii J Bone Miner Res. 2004 Feb;19(2):297-307. Epub 2003 Dec 16.
Dietary silicon intake is positively associated with bone mineral density in men and premenopausal women of the Framingham Offspring cohort. Jugdaohsingh R, Tucker KL, Qiao N, Cupples LA, Kiel DP, Powell JJ. Gastrointestinal Laboratory, The Rayne Institute, St Thomas’ Hospital, London, United Kingdom.
xxxviii Dietary Intake of Menaquinone is Associated with a Reduced Risk of Coronary Heart Disease: The Rotterdam Study. J. Nutr. November 1, 2004 vol. 134 no. 11 3100-3105
xxxix J Bone Miner Res. 2000 Mar;15(3):515-21.Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis. Shiraki M, Shiraki Y, Aoki C, Miura M. Research Institute and Practice for Involutional Diseases, Nagano Prefecture, Japan.
xl Am J Clin Nutr. 2008 Apr;87(4):985-92. Dietary intake of vitamin K and risk of prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg). Nimptsch K, Rohrmann S, Linseisen J. Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany.
xli Vitamin K may reduce cancer risk: EPIC study. JAMA. 2004 Jul 21;292(3):358-61.
xlii Vitamin K may reduce cancer risk: EPIC study JAMA. 2004 Jul 21;292(3):358-61.
xliii Habu D, Shiomi S, Tamori A, Takeda T, Tanaka T, Kubo S, Nishiguchi S. Role of vitamin K2 in the development of hepatocellular carcinoma in women with viral cirrhosis of the liver. JAMA, 2004 Jul 21;292(3):358-61.