Recently there has been a lot of coverage in the press regarding postmenopausal treatment of women to prevent osteoporosis. It is all based on this original publication February 26, 2013.
Essentially, a number of studies were compared (a meta-analysis of several trials) where 400 IU of vitamin D and 1000 mg of calcium were given to postmenopausal women and osteoporotic fractures were measured as the end point for osteoporosis. The conclusion was that there was no value in taking these supplements to prevent osteoporosis. Many other media publications carried this story.
Just two days earlier (Feb. 24, 2013) another study was released with a much larger patient base of 36,282 postmenopausal women of the Women’s Health initiative in the US who were followed up for 7 years. Initially there was some confusion as to how compliant the patients were in taking the required 1000 mg of calcium carbonate and 400 IU of vitamin D3. The supplement compliant group when compared 7 years into the trial had 35% to 38% less fractures of the hip than the placebo group. This supplementation did not cause kidney stones in the study group as is often cited by some physicians as the reason why they do not want to recommend supplementing with vitamin D3 and calcium. In other words all of these kidney stone concerns you have so often read in the media are not true.
In order to make sense of supplementation for osteoporosis prevention I will first review what is known about bone metabolism, then I will comment on what is missing in some of the studies and why it still makes sense to supplement to prevent osteoporosis. I also will outline at the end of this blog what would be a sensible supplementation regimen based on a balanced review of the medical literature.
The skeleton of an average adult contains 1–1.3 kg of calcium and 99% of this is mostly in the form of hydroxyapatite. In order to absorb calcium from our food we need vitamin D3 to absorb calcium into the blood from the small intestine (Ref.1). To transport calcium from the blood into the bone we require both vitamin D3 and vitamin K2 (=menaquinone). This blog explains that several studies have shown that vitamin K2 (or MK-7) plays a double role of preventing calcification of the arteries and bringing the calcium into the bones of osteoporotic women.
Apart from Vitamin K2 that is necessary for osteoporosis prevention other factors have shown to be of importance. For instance, testosterone is an anabolic hormone (meaning a hormone that builds up) and it has clearly been shown that it is bone building: It does so by stimulating osteoblasts, which are bone producing cells that reside inside the bone.
But vitamin D3, vitamin K2 and strontium together have also been shown to build up bone density within one year.
So, how does vitamin K2 deposit calcium into the bone? It does so by stimulating a hormone, called calcitonin, which is produced by specialized C cells (parafollicular cells) inside the thyroid gland and released into the blood stream. Calcitonin arrives in the bone where it binds firmly with receptors of osteoclasts (bone remodeling cells), which stops breakdown of bone. Calcitonin is helped by another hormone, called osteocalcin, which is produced by the bone producing cells, called osteoblasts:
Osteocalcin levels in the blood can be measured and used as a research tool to see whether a medication is effective in building up bone mass density (BMD). Osteocalcin is a calcium-regulating hormone that is controlled by vitamin K2. If vitamin K2 is present, carboxylation of osteocalcin will lead to mineralization of the bone (new bone formation); if vitamin K2 is absent, osteoporosis sets in.
Vitamin K2 has a second function: it removes calcium from the arterial walls and tissues. How does it do this?
Matrix GLA protein is found in tissues of the heart, lungs, kidneys and blood vessels. When vitamin K2 stimulates carboxylation of this protein, it will function like a broom and clean out calcium deposits (calcification) from blood vessels and organ tissues. As vitamin K2 is needed for this carboxylation process, it appears that nature had in mind to remove calcium from soft tissue organs and blood vessels and form hydroxyapatite in the bone for bone strength. It seems that vitamin K2 is the key vitamin necessary to do this job. Another player is magnesium that is required for the normal function of more than 300 cellular enzyme systems. In terms of hormones the three hormones parathyroid hormone (PTH), vitamin D3 and calcitonin need to interact normally, all requiring magnesium as cofactor. In addition to this zinc, copper, boron, and manganese are needed as trace minerals to act as cofactors with regard to specific enzymes related to bone metabolism (Ref. 1).
In the aging person hormonal deficiencies are also factors for causing osteoporosis to develop. As this link shows, Dr. John Lee found bioidentical progesterone topical cream very helpful in women with respect to increasing bone mass density by 15% over 3 years.
In men bioidentical testosterone needs to be replaced when it is found to be low as well. So, bioidentical hormone replacement in both men and women is part of a bone health management program to prevent osteoporosis.
Some trials that demonstrate how you can build up bone
1) In this paper a protein similar to parathyroid hormone (parathyroid hormone–related peptide or PTH-rP) was used in combination with 1000 mg of calcium and 400 IU of vitamin D3 in a group of postmenopausal women with osteoporosis. Within 3 month of treatment there was an increase of bone mass density in the lower back (lumbar spine) of 4.7%, which translates into a yearly increase of bone mass density of 18.8%. In the past this has never been achieved with other agents. A variation regarding this topic is a medication, which is a parathyroid hormone look-alike, called Teriparatide (PTH 1-34), which is given once daily as an injection of 20 mcg up to 2 years. It has been found useful in treating fractures of the vertebrae and other fractures in osteoporotic postmenopausal women (Ref.2).
2) This publication tells the story of how bone was built up just by adding vitamin K2 to the diet in a varied patient population from children to middle aged and older individuals with a variety of osteoporotic conditions in Mumbai, India.
3) In this paper the various effects of estrogens, selective estrogen receptor modulators, calcitonin and strontium ranelate were investigated with regard to their ability to build up bone when severe bone loss was caused by end stage osteoarthritis.
4) Postmenopausal women who received 800mg/day of calcium citrate, along with various levels of intensity of a structured exercise program, increased their muscle mass by 11% to 21% and increased their BMD by approximately 2%.
5) Calcitonin is very effective in reducing bone pain when the patient has compression fractures from osteoporosis; it is given as an intranasal spray of 200 units daily (Ref. 2). However on March 5, 2013 the FDA announced that salmon calcitonin would not be safe for humans as there is a slight risk that cancer can develop as a “side-effect”.
6) According to Ref. 2 strontium ranelate has been used in Europe in the treatment of postmenopausal osteoporosis. It was shown to build up bone and to decrease the amount of bone resorption. Side effects include nausea and diarrhea.
The team players of bone metabolism to build strong bone
We are now in a position to analyze why the researchers of the first paper cited in the beginning of this blog came to the conclusion that calcium and vitamin D3 supplementation were not enough to make a statistical difference in the treatment of postmenopausal women when compared to placebos. As explained bone metabolism is a complex process involving several team players, where the key player is vitamin K2, which was completely ignored in that study. The examples I mentioned above in point form show that exercise and calcium are also important. Vitamin K2 by itself worked quite well as it is so powerful. Hormones like PTH and calcitonin are effective, but more difficult to take for the average consumer and the FDA now has banned calcitonin. Vitamin D3 has been shown to be important both for absorption of calcium from the intestine and also for depositing calcium into the bone together with vitamin K2. The WHI study mentioned above is highly significant because of a 1/3 reduction of hip fractures after 7 years of vitamin D3 and 1000 mg of calcium per day supplementation. If you add vitamin K2, exercise and bioidentical hormone replacement in postmenopausal women who need it, the prevention of hip fractures, wrist fractures and vertebral compression fractures likely will be as high as 50% in those who are taking their supplements regularly (compliance issues like forgetting the supplements or deliberately not taking them were mentioned in several of the studies). With the right supplementation, which includes vitamin K2 as mentioned above, you achieve that you lower your heart attack and stroke risk as the vitamin K2 removes the calcium from the blood vessels and deposits it into the bones, while at the same time strengthening your bones. Attention to proper nutrition, exercise and your hormone balance (using only bio-identical hormones to replace what’s missing) will also reinforce osteoporosis prevention. The bonus of using bioidentical hormone replacement therapy is that you prevent heart attacks and strokes in addition to preventing osteoporosis. I think that this is a good deal!
An easy-to-follow osteoporosis prevention program
The best combination is 1000 mg (or 1200 mg as per National Osteoporosis Foundation recommendation) of calcium per day together with 400 to 800 IU of vitamin D3 (for cancer prevention you may want to take 4000 IU to 5000 IU of vitamin D3 per day instead monitored by a 25-hydroxyvitamin D blood level test through your physician) and 100 to 200 micrograms of vitamin K2 (also called MK-7). In the age group above 50 missing hormones such as bioidentical testosterone in men and bioidentical progesterone/estrogen combinations in women should be given as well. This works best, if you also watch your weight, cut down your alcohol consumption to a minimum (or better cut alcohol out altogether), exercise regularly (this builds up bone and muscle strength) and stick to a balanced diet resembling a Mediterranean or zone type diet (low-glycemic, low fat, wheat free and no sugar).
If you want to age gracefully, you need not only a healthy heart and a healthy brain, but also healthy bones as this prevents disabilities.
- McPherson: Henry’s Clinical Diagnosis and Management by Laboratory Methods, 22nd ed. Copyright © 2011 Saunders, An Imprint of Elsevier
- Rakel: Integrative Medicine, 3rd ed. Copyright © 2012 Saunders, An Imprint of Elsevier
I received the following feedback on Nov. 10, 2013:
Dr Ray, I read your March 17 Blog entry which suggested 100 ug of Vitamin K2 with 5000 IU of D3. I have atherosclerosis and have radically changed my diet (plant only), but also now take an average of about 3000 IU of Vitamin D3. Dr. Kate Rhéaume-Bleue (book on K2) recommended taking about 200 ug per day of K2, but increasing K2 to about 1,000 ug if taking around 5,000 IU of D3 to ensure proper activation of MGP. What is your opinion with regard to a D3/K2 ration? Thank you
Answer from Dr. Ray on Nov. 12, 2013:
I appreciate your question about what doses of vitamin K2 to take. There are varied recommendations, but I like to go by human trials and what they have actually shown. In this review in 2010 from the Life Extension Magazine a study is cited that showed that only 45 micrograms of vitamin K2 was enough to get the calcium out of the arterial walls and into the bones.
Dr. Mercola has reviewed the literature and found that most investigators were now using 180 to 200 micrograms, but he added that there is no real good literature substantiating that. I like to go by the golden rule to “do no harm”, so I myself take 100 micrograms per day of vitamin K2 along with 5000 IU of vitamin D3. I have my 25-hydroxy-vitamin D3 levels done every few months to make sure the vitamin D level is well above 50, but not too high.
Remember that other risks for cardiovascular disease are sugar and starch consumption (the liver turns this into triglycerides and too much LDL cholesterol). I also avoid wheat because of the gliadin content, which gets you addicted to wheat and sugary foods, and the lectin content, which can cause leaky gut syndrome and autoimmune illnesses. I also stay away from too much beef (I only eat grass fed, antibiotic free beef), but rather prefer to eat organic chicken, turkey and lean pork. I understand that you have a plant only based diet, but I would recommend to you to reconsider that. At least have your ferritin level checked from time to time, so you do not miss an iron deficiency that could develop. For other readers: Don’t forget your vegetables (organic, please).
More information about osteoporosis: http://nethealthbook.com/arthritis/osteoporosis/
Last updated Nov. 6, 2014