Vitamin K2, but Not Vitamin K1, is Helpful for Bone Density

The importance of vitamin K in the prevention and treatment of osteopenia/osteoporosis has just been discounted in a WebMD review ("Vitamin K: No Help for Bone Density") of research published Oct. 14, 2008, in PLoS Medicine (Cheung A, et al.) In the study, Canadian researchers, not surprisingly, found that taking 5 mg per day of vitamin K1 does not protect postmenopausal women from age-related declines in bone density.

What is surprising is that the researchers, despite noting that vitamin K is a family of compounds, and that vitamin K2 is the form which is an approved treatment for osteoporosis in Japan, chose to use vitamin K1 in their clinical trial.

It is well known that vitamin K1 (phylloquinone) is involved in blood coagulation. It is also well documented that vitamin K2 (menaquinone) is the essential cofactor for the carboxylation (activation) of the (gamma-carboxyglutamic acid) Gla-containing proteins involved in calcium regulation.

Numerous peer-reviewed studies have shown that vitamin K2 - given either as the synthetic form MK-4 (a short-chain version called menatetrenone) at a dosage of 45 mg/day, or as the natural form, MK-7 (a long-chain menaquinone derived from natto) at a dosage of 45 mcg/day - is a highly effective activator of osteocalcin, the Gla-containing protein integral to calcium deposition in bone. This body of research conclusively demonstrates that vitamin K2 not only lessens fracture incidence and improves bone density but also, via the carboxylation of another Gla protein (matrix Gla protein), inhibits arterial calcification.

Finally, even though they did not use the right form of vitamin K, looking at the research more closely shows that in the treatment group fractures were down - only 9 women getting vitamin K1 vs. 20 getting placebo had fractures (which is why we want higher bone density!). In addition, surrogate markers of bone production were up and the trends were toward higher density at several points during the intervention.

Why Cheung et al. did not use the optimal form of vitamin K remains a mystery, as does the lack of critical analysis and incomplete conclusion provided by the review. Hopefully, the outcome of this misleading publication will not be an increased incidence of osteopenia/osteoporosis in women at risk of these conditions who are dissuaded from supplementing with vitamin K2.

References:

Cheung A, Tile L, Lee Y, et al. Vitamin K Supplementation in Postmenopausal Women with Osteopenia (ECKO Trial): A Randomized Controlled Trial, PLOS Medicine, Oct. 14, 2008; Vol 5: p. e196.

Pizzorno L, Pizzorno J. Vitamin K: Beyond Coagulation to uses in Bone, Vascular, and Anti-Cancer Metabolism. IMCJ, Apr/May 2008, Vol 7:No. 2, p.24-30.

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• Men: New Guidelines for Osteoporosis Tests
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Strong Bones for Life - Naturally (Part 2)

Your Bones, Your Choice

Of course, even old decrepit bone is better than no bone, the situation seen in osteoporosis, which results when osteoclasts' demolition work greatly outpaces osteoblasts' new construction. Fortunately, this unbalanced situation, which can develop if the body becomes chronically pro-inflammatory and/or lacks a good supply of all the materials needed to build new bone, can be prevented and treated without drugs.

Here's what you need to build strong bones for life, naturally.

Calcium
Daily calcium needs:

• Women 19-50: 1,000 mg


• Women 51+: 1,200 mg


• Postmenopausal women not taking HRT: 1,500 (if on HRT, 1,200 mg daily; if you are taking HRT, it should be bio-identical bi-est and progesterone compounded specifically for you after you have had your hormone levels - all three estrogen fractions and progesterone - checked, not Premarin and Provera! If your physician is not aware of this, switch physicians.)

Remember, you get calcium from both food and supplements, so keep a food diary for a week or two to estimate your typical calcium intake and then take enough supplemental calcium to reach the above amounts.

If you regularly eat dairy products (from cows, sheep, or goats), soyfoods with added calcium, sesame seeds, and greens such as spinach, collard greens, Swiss chard, or broccoli, you are likely getting about 600 mg calcium from food each day.

Choosing a Calcium Supplement
You will see different forms of calcium in supplements. Choose either chelated calcium or hydroxyapatite (#3 or #4 below). Here's why:

1. Naturally-derived calcium: may appear on labels as bone meal, oyster shell, limestone, or dolomite (clay). Avoid these supplements since naturally derived calcium may contain significant amounts of lead.


2. Calcium carbonate: the most commonly used form and the least expensive, but not nearly as well absorbed as chelated calcium. If taking calcium carbonate, take with meals when your stomach will be secreting hydrochloric acid to digest the food as it will also help you break down and absorb calcium carbonate.


3. Chelated calcium: will appear on the label as calcium-citrate, calcium-malate, calcium-gluconate or calcium-aspartate. In these chelated forms, the calcium is bound to an organic acid (citrate, malate, gluconate) or amino acid (aspartate), which improves its absorption. Chelated forms of calcium are more expensive than calcium carbonate, but build more bone for the buck, so are worth it.


4. Hydroxyapatite: sometimes appears as MCHC (microcrystalline hydroxyapaptite). The most expensive form of calcium, hydroxyapatite, is a complex crystalline compound that contains calcium linked with phosphorus in a pre-formed building block of the bone mineral matrix. MCHC contains hyrdoxyapatite plus bone-derived growth factors and all the trace minerals that comprise healthy bone. If you are at high risk of osteoporosis or have osteopenia, you should be taking MCHC.

Vitamin D
Vitamin D is essential for calcium's absorption both from the intestines and into bone.

You want vitamin D3, the natural form. The fully activated form of the vitamin in the body is titled 1,25-dihydroxycholecalciferol as know as "calcitriol".

Some supplements (especially the less expensive ones) contain synthesized D2 (called ergocalciferol). Current research shows this is not as biologically effective as the natural D3. (Houghton L, Vieth R. The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr. 2006 Oct;84(4):694-7).

Anyone living in northern latitudes (e.g., the Pacific Northwest or New England) is at high risk for vitamin D deficiency and should have her or his blood levels of 25(OH)D3 checked. 25(OH)D3 is the major circulating form of vitamin D in the blood and the best barometer of vitamin D status. Be sure this is the vitamin D test your doctor orders for you; many labs/doctors test D2.

Adequate blood levels of vitamin D to provide for bone health (as well as protecting against colon and breast cancer, multiple sclerosis, inflammatory bowel disease, depression - and a host of other ailments) begin at 75 nmol/L of 25OH-D3. Blood levels of vitamin D between 90 and 100 nmol/L are optimal.

The amount of vitamin D you need will depend on the results of your blood test. A daily intake for all adults of >/=1000 IU vitamin D is needed to bring vitamin D concentrations up to 75 nmol/L in at least 50% of the population. If you live in northern latitudes or live in the south but get little sun exposure or wear sunscreen, you can start taking 1,000 IU of D3 daily right away. However, you may need 2,000 or even 5,000 IU of D3 daily for 6-8 months to restore adequate levels of this critical nutrient.

We are currently involved in a corporate wellness program in Canada. We found that 82% of the employees have low levels of vitamin D in their blood.

Magnesium
If your blood test reveals that you are significantly vitamin D-deficient (we've seen vitamin D levels around 30 nmol in many patients and levels as low as 13 nmol in several), and your physician recommends you take more than 2,000 IU/day for an extended period of time, you will also need to supplement with magnesium citrate, 500 mg, twice daily.

Calcium and magnesium counterbalance one another in numerous cellular activities. If you are taking high levels of vitamin D, you will be absorbing significantly more calcium and will need to ensure your magnesium levels are sufficient to maintain this balance.

This is very important: symptoms of magnesium deficiency include migraines and tension headaches, muscle weakness, leg cramps, restless legs, elevated blood pressure, transient ischemic attacks, and heart arrhythmia.

Vitamin K
Vitamin K, specifically vitamin K2 or menaquinone, activates a group of proteins (the Gla-proteins), which are responsible for where calcium gets delivered in the body. Vitamin K2 ensures that the calcium you consume (and which will be getting into your circulation in higher amounts now that you are taking vitamin D) is deposited where you want it—in your bones, and not where you don't—in your blood vessels and other soft tissues.

When your vitamin K2 levels are adequate, two of the Gla-proteins that are activated are: (1) osteocalcin, the protein responsible for anchoring calcium within bone, and (2) matrix Gla-protein, which prevents calcium from depositing in the heart, arteries, breast and kidneys.

Both vitamin K1 (phylloquinone) and vitamin K2 (menaquinone) are available as supplements. Vitamin K1 is primarily involved in helping your blood clot normally, although our bodies are able to convert a small amount of K1 into K2.

For bone health, K2 (menaquinone), particularly natural menaquinone derived from natto, which may be labeled MK-7 (menaquinone-7) is the most potent form. You may also see K2 as menatretrenone; this is MK-4, a synthetic version that must be taken in much higher doses because its half-life in the body is quite a bit shorter.

If you are taking MK-7, a daily dose of 45 mcg is sufficient. If taking MK-4, take 5 mg daily.

Best food sources of vitamin K (K1) include kale, spinach, Swiss chard, broccoli, Brussels sprouts, parsley and romaine lettuce. Natto, from soy, is an excellent source of K2, but is not easily available in the U.S., nor would the taste appeal to most Americans.

Boron
Boron protects against calcium loss by helping to maximize the activity of both estrogen and vitamin D in bone.

The drop in estrogen levels that occurs during menopause triggers an increase in the production of a pro-inflammatory mediator called interleukin-6, which stimulates the production and activity of osteoclasts. Boron is needed for the conversion of estrogen to its most potent form, 17-beta-estradiol, which allows the body to make the most use of its remaining estrogen.

Boron is also involved in the reaction in the kidneys in which vitamin D is converted to its most active bone-building form, (1,25-(OH)2D3)—a compound that is even 10 times more potent than D3.

In one study of postmenopausal women, supplementation with 3 mg/day of boron reduced urinary calcium excretion by 44%!

Best food sources of boron are apples, pears and grapes. Leafy greens, legumes and nuts can also be good sources of this mineral; however, since the boron content of fruits and vegetables depends upon that provided by the soil in which they were grown, which can vary dramatically, boron supplementation with 3 mg/day is recommended.

Omega-3s
Inflammation-related activation of osteoclasts plays a key role in osteoporosis. Not only do the omega-3 fatty acids lessen the production of pro-inflammatory cytokines that activate osteoclasts acids, these fats also stimulate the activity of osteoblasts. In contrast, the pro-inflammatory omega-6 fats so abundant in the typical American diet stimulate osteoclasts. (Fernandes G, Lawrence R, Sun D. Protective role of n-3 lipids and soy protein in osteoporosis. Prostaglandins Leukot Essent Fatty Acids. 2003 Jun;68(6):361-72; Heaney RP, Carey R, Harkness L. Roles of vitamin D, n-3 polyunsaturated fatty acid, and soy isoflavones in bone health. J Am Diet Assoc. 2005 Nov;105(11):1700-2; Watkins BA, Li Y, Lippman HE, Feng S. Modulatory effect of omega-3 polyunsaturated fatty acids on osteoblast function and bone metabolism. Prostaglandins Leukot Essent Fatty Acids. 2003 Jun;68(6):387-98.)

Experts suggest the optimal ratio of omega 6:omega 3 fatty acids is 4:1 or even 2:1. The standard American diet delivers a ratio somewhere between 10 and 20:1.

In a recent study, subjects consumed each of three diets for a period of 6 weeks. The first, a typical American diet, delivered a 9.6:1 ratio of omega 6:omega 3 fats. The second and third diets provided ratios of 3.5:1 and 1.6:1 omega 6 to omega 3 fats, respectively. Walnuts, a rich source of both omega 6 and the omega 3 fats, were the primary sources of omega-3s in the second diet; a little more than one ounce (37 grams) of walnuts and ½ ounce (15 grams) of walnuts were included in each day's meals in the form of walnut granola, walnut butter, walnut pesto or plain walnuts as a snack. The third diet contained about 20 grams (2/3 ounce) per day of flaxseed oil, a highly concentrated source of the omega 3 fat, alpha linolenic acid.

Indicators of bone loss called N-telopeptides (NTx, which are produced when osteoclasts break down bone collagen, were measured and found to be significantly lowered by the diets containing a lower ratio of omega 6 to omega 3 fats. The second diet, in which the ratio of omega 6: omega 3 was 3.5:1 reduced NTx 11.5%, while the third diet dropped NTx levels by 15.3%.

The researchers also measured levels of a pro-inflammatory cytokine called TNF-a (tumor necrosis factor alpha), which increases osteoclast production and activity. As the ratio of omega 6: omega 3 dropped, levels of TNF-a also dropped substantially. (Griel AE, Kris-Etherton PM, Hilpert KF, et al. An increase in dietary n-3 fatty acids decreases a marker of bone resorption in humans. Nutr J. 2007 Jan 16;6:2.)

In other research, a few weekly servings of salmon (14 ounces per week), has been shown to raise omega 3 levels more effectively than taking a daily fish oil supplement while also lowering blood levels of a number of pro-inflammatory chemicals including TNF-a. Researchers think omega-3s may be better absorbed from fish because fish contains these fats in the form of triglycerides, while the omega-3s in almost all refined fish oils are in the ethyl ester form. Once absorbed, omega-3s are converted by the body from their triglyceride to ester forms as needed. (Elvevoll EO, Barstad H, Breimo ES, Brox J, Eilertsen KE, Lund T, Olsen JO, Osterud B. Enhanced incorporation of n-3 fatty acids from fish compared with fish oils. Lipids. 2006 Dec;41(12):1109-14.)

Your Bones, Your Choice
You only have one body. Doesn't supporting its inherent drive to maintain strong, healthy bones by supplying the natural compounds it uses in normal bone remodeling make better sense than giving it a drug that poisons your osteoclasts and puts you at risk for abnormal heart rhythms and jaw bone death? Your bones, your choice.

~Joseph Pizzorno, ND and Lara Pizzorno, MDiv, MA, LMT

Part 1: Bisphosphonate Drugs

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Strong Bones for Life - Naturally (Part 1)

Bisphosphonate Drugs

It's true, as Sally Fields emphasizes in her TV ads for Boniva, that you have only one body; it's not true that Boniva and the other bisphosphonate drugs commonly prescribed to prevent osteoporosis offer the best way to take care of it!

Although prescribed to 30 million Americans each year, the bisphosphonates (e.g., Fosamax, Boniva, Actonel), have now been linked to serious potential complications.

A recent FDA alert warned physicians that all bisphosphonate drugs may cause "severe and sometimes incapacitating bone, joint, and/or muscle (musculoskeletal) pain...[that] may occur within days, months or years" after starting the medication, and in some patients, may not resolve even after discontinuing the drug.

Even more frightening are recent studies conclusively linking bisphosphonate use with jaw osteonecrosis or bone death. Osteonecrosis occurs when bone damaged as a result of poor blood flow or trauma is not removed and replaced with new bone. Initial symptoms include numbness, heaviness, swelling, pain and infection in the jaw, and progress to loosening of the teeth, decay and death of the jaw bone. Bisphosphonates accumulate in bones, particularly in the jawbone, and inhibit the bone's natural ability to repair everyday damage.

A Cochrane Review noted that age = or > 60 years, female sex and previous invasive dental treatment were the most common characteristics of patients taking bisphosphonates who developed osteonocrosis. (Pazianas M, Miller P, Blumentals WA, et al. A review of the literature on osteonecrosis of the jaw in patients with osteoporosis treated with oral bisphosphonates: prevalence, risk factors, and clinical characteristics. Clin Ther. 2007 Aug;29(8):1548-58.) Considering that the target population for bisphosphonate drug use is postmenopausal women, and many women now 60 or older have had some kind of invasive dental procedure in their lifetime, these risk traits for osteonecrosis with bisphosphonate use are far too common for comfort; so common that concerned dentists are highly reluctant to perform any type of dental surgery on women taking these drugs.

In one of the most recent studies, published in the Journal of Oral Maxillofacial Surgery in April 2008, researchers at the University of Southern California's School of Dentistry found a direct correlation between the development of microbial biofilms (bacterial colonies that cause chronic infections) in affected bone and the use of bisphosphonates. (Sedghizadeh PP, Kumar SK, Gorur A, et al. Identification of microbial biofilms in osteonecrosis of the jaws secondary to bisphosphonate therapy. J Oral Maxillofac Surg. 2008 Apr;66(4):767-75.)

Just how many people now have osteonecrosis of the jaw caused by bisphosphonates? Incidence of osteonecrosis among cancer patients, who are given an intravenous and more potent variety of these drugs (e.g., Zometa and Aredia), is estimated at between 1% and 10%. Among those with osteopenia/osteoporosis taking the lower-dose pill forms (Fosamax, Actonel, Boniva), no one knows for sure. Studies to provide firm answers are just beginning, but it has been established that invasive dental procedures, such as tooth extractions or root canals, greatly increase risk of osteonecrosis in women taking bisphosphonates. As for treatments, cutting away the dead bone just worsens the situation, so antibiotic rinses are used, but frequently fail to remedy the condition. And since bisphosphonates remain in bones for years, no one knows how long the risk of osteonecrosis remains, even if the drug is no longer being taken. (Kolata G. Drug for Bones is Newly Linked to Jaw Disease, New York Times, June 2, 2006)

Recent studies have also reported bisphosphonate use as a risk factor for atrial fibrillation (abnormal heart rhythm) in women. One study estimates that 3% of atrial fibrillation cases might have been due to bisphosphonate (specifically, alendronate) use. (Heckbert SR et al.) Physicians are warned that bisphosphonate use needs to be closely monitored in certain populations at high risk of serious adverse effects from atrial fibrillation (such as patients with heart failure, coronary artery disease, or diabetes). In other words, those at risk for serious side effects from bisphosphonates also include anyone with heart disease or diabetes, a significant percentage of the U.S. population. (Heckbert SR, LiG, Cummings SR, et al. Arch Intern Med. 2008 Apr 28;168(8):826-31; Cummings SR, Schwartz AV, Black DM. N Engl J Med. 2007 May 3;356(18):1895-6.)

Not surprisingly, hundreds of lawsuits have now been filed against the manufacturers of biophosphonate drugs, and a class action suit appears likely.

Manufacturers of Bisphosphonates

• Fosamax - Merck & Company
• Boniva - Roche and GlaxoSmithKline, popularized by Sally Field commercials
• Actonel - Proctor & Gamble Pharmaceuticals, Sanofi Pharmaceuticals
• Skelid - Sanofi Pharmaceuticals
• Didronel - Proctor & Gamble Pharmaceuticals
• Reclast and Zometa - Novartis Pharmaceuticals

How Bisphosphonates Work

Even if the bisphosphonates did not put you at risk for severe musculoskeletal pain, the loss of your jaw, or abnormal heart rhythms, these drugs would still not be your best choice for strong healthy bones. Why? Because all they do is suppress bone turnover and remodeling.

Our bones, unless inhibited by bisphosphonates, are constantly rebuilding themselves throughout our lives. Cells called osteoclasts break down old or damaged bone, signaling other cells called osteoblasts to replace it with strong new bone. Bisphosphonates kill osteoclasts. Bone density goes up on these drugs, but the bone they leave in place is worn out tissue your body would normally clear out and replace with strong new bone.

This is why bisphosphonates put people at risk for osteonecrosis (jaw bone death). Because these drugs suppress osteoclastic activity, damaged bone is left in place rather than resorbed, so the amount of damaged old tissue accumulates until it reaches a level when any trauma or insult will result in extremely poor healing, the exposure of necrotic bone to the oral environment, development of pain, and increased risk of microbial infection, which is precisely what is seen in bisphosphonate-associated cases of osteonecrosis of the jaw.

Next: Part 2 - Your Bones, Your Choice

~Joseph Pizzorno, ND and Lara Pizzorno, MDiv, MA, LMT

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• Quiz: How Much Do You Know About Bones?