Osteoporosis Part 1

Osteoporosis Part 1

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Readers Summary

  1. Is osteoporosis tied to leptin biochemistry?
  2. Does your spine surgeon know what really causes bad bone?
  3. What dietary factors are tied to osteoporotic risk?
  4. Does your gut control your bone mass?
  5. What little known hormones control your bone mass?

In my day job as a neurosurgeon, I operate on a lot of diseased spines.  In the last 12 years, I have repaired over 1000 vertebral fractures from osteoporosis.  If you remember back to my podcast with Jimmy Moore, I mentioned in the talk that the changes I had seen in osteoporosis incidence and prevalence is what made me look for the underlying cause.  This ultimately led me to leptin and our diet.  Many people think since bones are hard and used for support that they are not an active tissue.  Bone is a very active tissue in the body that is constantly turned over. We constantly lay down new bone to stressors and resorb bone from areas that are not stressed.  Since bone is so active, it uses massive amounts of energy.  Energy is usually tied to a strong source of electrons.  This is where leptin comes in because it is our electron accountant in the brain.  Any tissue that requires a ton of energy is coupled to leptin biochemistry.  The story on bones and osteoporosis, however, is a very complicated one.  I am going to give you a flavor of just how complicated. This osteoporosis series will have many twists and turns.  Most seasoned spine surgeons wont know much of what you are going to learn here about bone.  Most don’t know that osteoporosis is caused by leptin resistance.  Just ask one and see if I am correct.  Most will tell you to take Calcium, Vitamin D, and exercise a bit to treat osteoporosis.  They may mention a Rx for a bisphosphonate class of drugs too.  I don’t use these drugs at all.  If you do just that, you can bet you won’t cure a thing and you might even make the problem worse.  Spine surgeons are taught a law called Wolff’s law in reference to bone metabolism.  It says the more stressed a bone is, the more bone is laid down and the stronger the bone is.  This law is why most spine surgeons don’t think that obese folks will have osteoporosis when they come to see us, much less test for it.  These are the people who are experiencing a silent epidemic of this condition.  Their numbers have exploded over the last thirty years.  I mentioned that in my career I have seen a tremendous increase in this disease.  In medical school, I think I had a one hour lecture on this disease.  Now it is involved in close to 80{a7b724a0454d92c70890dedf5ec22a026af4df067c7b55aa6009b4d34d5da3c6} of the cases I see in my clinic.  Few spine surgeons expect to see osteoporosis in our younger patients because most think this is predominantly a disease of old women with low estrogen levels.  We are not taught to look for it in its correct biologic context, so it is often missed as a diagnosis, but often found on MRI imaging as loss of mineral content and more fat present in the marrow space.  Spine surgeons must be more vigilant about this disease, because if it’s tied to the leptin hormone, it points to the fuels we are putting in our Ferrari’s!  I will show you why diet is a huge factor in the development of metabolic bone disease that you should consider.  This is why I treat osteopenia and osteoporosis a lot differently than conventional wisdom you will hear from other sources.

Here are some random dietary facts about osteoporosis in humans:  When your diet has a lot of…

  • Total protein: risk reduction of fractures is 3.6 times
  • Animal protein: risk reduction of fracture’s is 4.5 times
  • Vegetable protein: risk INCREASE of fracture’s is 2.9 times
  • Carbohydrate: risk INCREASE for fracture’s is 4.9 times

These basic facts point out why your spine surgeon or PCP needs to understand what you eat puts you at risk for your bones disappearing, no matter what age you are or what sex you are.  Diet affects the two main cells that are involved in bone metabolism. Osteoblasts lay bone down, and osteoclasts resorb bone.  Most of the bisphosphonate drugs only work on osteoclasts to stop them from resorbing the bone.  They are only two drugs that use anabolic mechanisms on making new bone. One is a human cloned hormone that does this and that is PTH, the other drug is Forteo.  Forteo is a very risky drug with many side effects.  Osteoporosis can be caused both by poor bone apposition, or by resorption of the bone or a combination of both.  These bone cells are controlled by hormones.  Leptin, testosterone, estrogen, progesterone and cortisol are some of the ones but there are many more major players as you will soon find out.

So if diet is so critical to osteoporosis, maybe we should start this journey in the gastrointestinal tract.  This month, an article showed up in the GI literature that gave more credence to my thoughts on how osteoporosis should be treated.  In this paper, from Gastroeneterology, we have the evidence that food absorption from the GI tract can directly influence bone mass.  That evidence  came from the study of ATF4, a transcription factor found in osteoblasts, the bone forming cells.  ATF4  is required for osteoblasts terminal differentiation and to function to make new bone.  ATF4 affects all known activities of the osteoblasts.  It affects bone formation, including extracellular matrix synthesis, osteoclast differentiation, and energy metabolism that is overseen by leptin function.  ATF4 is needed also for amino acid import into cells.  Experiments in mice and humans have also shown that high animal protein and fat diets tend to overcome the lowered ATF4 levels in the gut.  High fat diets are also protective of the bones, because fats are required to make the hormones that protect the bone namely the sex steroid hormones and vitamin D all are derived from LDL cholesterol.  This is another major reason I’m completely against the use of statins in humans.

The most important dietary issue in osteoporosis is that it appears high carbohydrate low fat and low protein diets cause osteoporosis.  This is precisely the diet outlined in the USDA pyramid or plate.  This clinically fits with my clinical findings over the last 15 years in my spine practice as well.  I found once I left residency and began a private practice that fat people have really bad bone.  This was not what I was taught to expect in medical school or my spine training. I was taught about an axiomatic bone metabolism doctrine called Wolff’s law.  Wolff’s law says that a stressed bone placed under a load should be made stronger over time.  Based upon Wolff’s law, I learned in medical school fat people should have great bones.  After all conventional wisdom says, the heavier one is the more stress is placed upon the bones.  Well, as a clinician within one year of being in practice, I was overwhelmed with many patients who had osteoporosis at all ages and many different body types.  I learned that if one is leptin resistant,  Wolff’s law is null and void.  This is rule number one of my osteoporosis Rx and everything flows from this rule.

Hormones you did not know were involved but are

Recently Gerard Karsenty, MD, PhD, and colleagues at Columbia University Medical Center discovered that osteoblasts (bone-forming cells) secrete a hormone that regulates insulin production and enhances insulin sensitivity.  This hormone is called osteocalcin.  If you remember my recent top ten paleo supplements post we talked about osteocalcin briefly when I mentioned Vitamin K2.  What does osteocalcin do?  The latest data from Columbia shows it regulates insulin release to protect our bone stores while also increasing our testosterone levels.  Testosterone levels increase our bone density in both men and women.  It is a hormone only secreted by the osteoblasts, and it is vital in forming bone and directing calcium ion homeostasis in bone, dentin and the arteries of our body.  Remember in the teeth blog we spoke of the hypothalamic pituitary axis and how it controlled flow in the dentinal tubules used to mineralize teeth.  Vitamin K2 and osteocalcin are also key factors in saliva and help maintain optimal dental health.  In essence, osteocalcin directs the calcium we absorb in guts from our diet to go to the correct tissues in our body.  In humans, osteocalcin has to be carboxylated to be active.  When someone is IR or has T2D they have a lot of uncarboxylated osteocalcin, and this won’t allow calcium into the bone collagen matrix.  Instead, it gets placed in tissues it should not be in like the heart valves and in many different arteries of our body.  This can be measured with a calcium index score.  A high calcium index score is not a good sign for your long term health.  This is particularly true for your heart.

So what carboxylates osteocalcin to make it active in humans?  Vitamin K2 carboxylates osteocalcin to make it an active hormone to direct which tissue the absorbed calcium should go to.  When K2 levels are low, we see calcification in places it should not be, like in your arteries in spine x-rays ,or in your mouth as tartar build up on your lingual surface of the bottom incisors.

All diabetics are very deficient in Vitamin K2. Most people who eat a SAD also are quite Vitamin K2 deficient too.  Because osteocalcin helps modulate insulin release,  vitamin K2 can also be used to treat T2D as well.  In this country it is not used often for any reason.  Most physicians and health providers do not know what it is much less what it does.  If you go into most pharmacies or supplement stores you will be hard pressed to find Vitamin K2.  I use Vitamin K2 a lot in my practice and this is why its in my top ten paleo supplement list.  Most vascular surgeons don’t even know what Vitamin K2 is.  Sadly, neither do most healthcare practitioners who take care of the patients with the highest risk of being K2 depleted.  The next time you go visit your doc ask them about K2 to see if I am right or wrong about this.  I use osteocalcin to quantify how much a patient’s diet is depleted in Vitamin K2.  Most of our endogenous Vitamin K is made from our gut bacteria when we are healthy.  Humans also have a very slick way of recycling Vitamin K too in our guts.  So if one has a leaky gut or gut dysbiosis you might not be able to recapture your Vitamin K2 and need a bigger dietary source constantly.  I believe this is the major reason we have a pandemic in Vitamin K2 losses.  I also think it is why cardiovascular disease is so prevalent these days on a SAD.  I think a SAD selects for a gut microflora that ensures Vitamin K2 depletion.

So if one has LR or has a leaky gut (dysbiosis), we should expect a major problem with osteocalcin and K2.  I always look at the patients HDL level to see if the gut maybe leaky.  If the patient is on coumadin, the problem is even bigger.  Why you ask?  Coumadin’s mechanism of action is to deplete our cells of vitamin K by blocking our ability to recycle Vitamin K.  By  blocking vitamin K epoxide reductase, this lowers the Vitamin K dependent clotting factors made in our liver to clot our blood.  Vitamin K2 is not only important to diabetics, patients with heart disease, and  patients with peripheral artery disease from atherosclerosis, but it is critical in those with osteopenia or osteoporosis too.  Vitamin K2 is used as a first line treatment of osteoporosis in Japan in doses up to 45 mgs a day.  Unlike the SAD, the Japanese diet, however, has a major source of Vitamin K2 in natto.  The best source of Vitamin K2 in the SAD, is pastured butter which most physicians advise their patients not to use ironically.

Dysbiosis is the major cause of osteocalcin problems in clinical medicine, because most of the Vitamin K2 a human gets is from our gut bacteria.  If the gut macrobiotic is not optimal,  we lose our ability to recycle our endogenous Vitamin K.  This creates an overall depletion of Vitamin K, that must be made up in our diet.  In America, our diets have been striped of Vitamin K2 because the process of pasteurization robs dairy products of its Vitamin K content. Raw dairy products contain a lot of vitamin K2.  This is why I tell my osteopenic patients to seek raw milk, and raw milk cheeses from other countries.  Our government wont let us have access to raw dairy either.  It makes you wonder why?  That is a topic for another blog. Vitamin K is also found in many green leafy plants but with newer farming techniques and with the advent of many pesticides in use the Vitamin K levels have dropped in most non organic foods that contain Vitamin K.

If we cant recycle our vitamin K2 and we have poor dietary sources, it means that the proteins that depend upon K2 are not going to work optimally in us.  When this happens, we see the effects in the heart, arteries, and in our bones.  So people who are deficient in K2 cannot activate osteocalcin.  Moreover, the data from the labs at Columbia University,  made it clear that osteocalcin tells our beta cells in the pancreas to produce more insulin and our pituitary gland to make more testosterone.  These two maneuvers help us form bone.  Osteocalcin also has another function.  Osteocalcin also instructs fat cells to release adiponectin, a hormone that increases our insulin sensitivity.  Adiponectin is inversely correlated with body weight.  It is highest in thin patients.  This hormone plays a role in the metabolic derangements that result in T2D, obesity, atherosclerosis, and fatty liver disease.  There is also a sexual dimorphism with adiponectin in that women have higher levels than men.  Women also display a sexual dimorphism in leptin too.  They have higher levels then men do.  When adiponectin is released from fat cells so is leptin.

Where does leptin fit into the Osteoporosis story?

You all should be leptin experts now.  But now we need to add some more detailed biochemical knowledge to your leptin foundation.  Leptin is a hormone secreted by fat cells, and leptin inactivates osteocalcin via the sympathetic nervous system, according to research by E. Hinoi et al.  Leptin also is released from fat cells when inflammation levels are high.  Leptin is very similar in structure to IL-6 the main inflammatory cytokine behind all neolithic diseases.  When a person has high levels of leptin, it eventually drives cortisol higher and this stimulates even more inflammatory cytokines from cells.  As this occurs LR develops all over the body.  Cortisol is one of the major hormones involved in the sympathetic nervous system.  When cortisol is chronically high, as I told you in the Hormone 101 blog,  it’s bad news.  When someone is leptin resistant, they block osteocalcin’s main function and this causes osteoporosis.  This is one major reason why fat people lose their bone.  It also definitely proves that Wolff’s law is null and void when your are LR.  The law is true when we are dealing with healthy conditions.  When cortisol is chronically elevated with insulin, you get major neolithic diseases that are deadly.  This is why leptin resistance leads to insulin resistance and then eventually to cortisol excess.  When I  make the diagnosis of osteoporosis or osteopenia, this is a sign to me that a person is dying slowly biochemically.  Leptin it turns out is the “Ferrari brake” that keeps osteocalcin and circulating insulin levels from becoming too high .  People who are LR (fat) have high leptin levels and this causes a rise in JNK (mitogen activated protein kinase).  JNK’s do many things in our bodies.  One major function is to respond to inflammatory cytokines like IL-6 and to leptin.  Remember from my first leptin blog I told you that leptin and IL-6 look chemically quite similar to one another.  In our GI tract, JNK directly inhibits ATF4 in the gut effectively turning off all osteoblastic formation!  So we cannot make anymore bone, even if our diet is loaded with good foods!  You all know that LR also leads to high cortisol levels, and these high levels also cause us to resorb bone in far greater amounts at the osteoclast footplate further worsening the osteopenia to osteoporosis.  Most people know that excessive steroid use can cause osteoporosis too.  Chronically elevated cortisol levels also does this to overweight people as well.

Obese individuals with diabetes often exhibit high blood levels of both leptin and insulin. Researchers are trying to understand the interaction among leptin, osteocalcin, and beta cells in the hope of developing new treatments for diabetes.  Anyone I see with this disease gets placed on vitamin K2 and now you can see why.  I also think anyone with T2D must consider taking Vitamin K2 as well as their other needs.  I don’t think we need to wait for more research on this issue.  We have 60 million T2D in the USA and 150 million who likely have it but don’t meet our current guidelines to diagnose the disease.  Ten years ago, the Vitamin D council was talking up D3 and telling us how important it was and why we need to be on it.  Dr. K is now telling you that Vitamin K depletion is likely a bigger deal than Vitamin D deficiency because no one, including most primal folks, recycle enough of K2 or replace it in their diets in this country.  If you doubt me, go get your osteocalcin checked if you eat a lot of carbs or PUFA’s.  Population studies have been done on K2 and it backs up what I found in my clinic over the last 12 years.  We have a major K2 deficiency problem, and it’s a lot more significant than the current D3 issue that is finally being addressed.  Why?  When we are depleted of K2, we tend to calcify our coronary arteries.  These plaques are the ones that kill us suddenly.  Last I checked, heart disease remains the number one cause of death for men and women in the USA.  The Jupiter trial data also showed that calcium index scores are probably the best clinical marker we have for silent heart disease.  Peter, over at Hyperlipid, wrote about this topic on his site that you should read.

What about carbs?

Here is one of the twists and turns I told ya was coming.  On our bone forming cells we have a special LDL receptor.  The surface molecule Lrp5 (LDL receptor related protein 5) is a gene of great interest to bone biology.  When Lrp5 is inactivated, we see the worst cases of osteoporosis in humans.  Surprisingly, the gene most highly expressed in micro arrays studies when Lrp5 is absent is Tph1, which encodes tryptophan hydroxylase 1.  This is the rate-limiting and initial enzyme in the synthesis of serotonin in enterochromaffin (EC) cells of the GI tract!  It turns out serotonin is not just a neurotransmitter.  Remember we make most of our serotonin from dietary carbohydrates and not protein. I went over this in my neurotransmitter blog.  Here is a quick reminder.  Remember tryptophan is the least common AA in our diets. This also complicates serotonin biochemistry. Tryptophan is found in fish, poultry, and dairy products, but eating these products does not necessarily increase serotonin levels. The reason for this paradox is because other foods compete with tryptophan for absorption in the gut! It has to compete with other AA. In fact, another paradox of serotonin production is that is eating carbohydrates raises its level in the body faster than does eating a protein diet!  The reason for this is that carbs stimulate insulin release, and this insulin spike favors the absorption of tryptophan in the gut over other amino acids.  Most serotonin is stored in the enterochromaffin cells of the gut lining (60{a7b724a0454d92c70890dedf5ec22a026af4df067c7b55aa6009b4d34d5da3c6}), and the balance is stored in the pineal gland of the brain.

Serotonin is now also categorized as a gut hormone that inhibits osteoblastic bone formation!  Yes, you read that right.  The gut hormonally regulates bone formation!  When I realized this, I finally put together why I was seeing so much osteoporosis.  It was the SAD and Leptin resistance at work directing our gut not to form any new bone.  The more of a SAD you eat, the worse you gut microflora becomes and the more Vitamin K2 you can’t recycle.  This requires a much higher K2 requirement from the diet.  In the US food supply Vitamin K2 is horrifically deficient.  The end result is you get depleted of K2 and you never can activate your osteocalcin by carboxylating it.

Serotonin begins with the AA tryptophan. It requires B6, Mg, B12 and folate as co factors in production. So high levels of serotonin block our ability to lay down new bone.   The data in the literature on this are pretty deep.  I am still amazed that few people in my world of spine surgery talks much about this at all.  I’m also puzzled that our orthopedic sports medicine folks and the general orthopedists never mention this at all to patients.  In fact,  they often tell people to carb load before and after exercise.  This completely is counterproductive to healing any bone!

So how does this all work?  Your head is getting ready to hurt.  Gut-derived serotonin regulates bone mass accrual in humans.  LDL receptor related protein 5 (Lrp5) favors bone formation by inhibiting tryptophan hydroxylase 1 (Tph1) expression in enterochromaffin cells of the duodenum.  The gut-derived serotonin, following its binding to Htr1B on the osteoblast cell, and this inhibits CREB expression, which results in a decrease in cyclin expression and leads to osteoblast proliferation and lots of new bone formation.  Most of my patients get told what they should eat pre and post op because of this science I read about.  I rarely go into the biochemistry of why this happens, but here it is for all of you to read about.  I have them eat a ton of pastured butter, raw dairy, coconut oil, eggs and grass fed meat and limit their carbs to less than 50 grams a day.  All these things support optimal bone function.

The implications of the new experimental news on Lrp5  is that inhibition of serotonin biosynthesis in EC cells may actually provide an anabolic treatment for osteoporosis!  This also explains why we see so much osteopenia and osteoporosis in our vegan and vegetarian friends. The effects of serotonin are remarkable for another reason.  One experiment suggested a broader clinical implication for enteric serotonergic regulation of bone mass.  In mice that totally lack Tph1,  researchers found virtually no detectable circulating plasma serotonin and a high bone mass phenotype because of an increase in bone formation parameters.  This was shocking.  Remarkably, even gonadectomized (ovaries removed) female Tph1 mice did not develop osteoporosis because their increase in bone formation parameters outperformed the increase in bone resorption caused by the gonadectomy.  This means that menopause may not mean automatic bone loss if we can get ladies to change their diets. Remember this could have major implications for post menopausal women if the same effect is found in humans.  So far the data seem to be pointing us in that direction. Because of this, I advocate this dietary advice for patients with this disease. This observation is potentially important clinically for humans, because the therapeutic drugs some use against osteoporosis that is currently in use, is mostly geared toward inhibiting bone resorption and not adding new bone.  Forteo and PTH are the only two substances used today that are anabolic treatments for osteoporosis.  Both have major side effects.  Using diet to do the same thing is a lot safer in my view and this is how I currently treat osteoporosis.

Does meal timing of the Leptin Rx play a role here too?

The short answer is yes it does.  I told you in the blog about how the Leptin Rx works that meal timing is more critical than even food choices.  Lets talk a bit about what happens at meals.  We eat and the food in our gut is sensed by the vagus nerve and also by the EC cells of the gut.  When food enters parts of the gut, it creates a intraluminal pressure.  This pressure is what causes our gut to release serotonin from our EC cells to stimulate bone formation.  Remember that diabetics are also prone to gut stasis, and this decreases serotonin release and is another cause of osteoporosis in diabetics.  Experiments by Edith Balbring and her colleagues have confirmed that EC cells secrete serotonin in response to increases in intraluminal pressure.  My morning 50 to 70 grams of protein creates a bigger intraluminal pressure because of the shear volume of food that enters your gut, and is also why we want to eat this large a portion in the AM for breakfast.  The big ass breakfast (BAB) also stimulates peristaltic waves in the gut and this further releases more serotonin from the gut that might hinder bone formation. This is offset by the fat and protein loads in the BAB. Another major effect of the BAB is that it is a big stimulus to the secretion of testosterone and growth hormone in the body when this occurs.  Both of these hormones are anabolic to bone and to muscle.  This is also why the BAB helps body composition when it is applied over long periods of time.  This can be followed with lab testing of testosterone levels and IGF-1 levels.  Intraluminal pressure also releases gut bile acids and some other hormones like NYY, CCK, and pancreatic enzymes too that are critical in creating the proper satiety signal in the brain to stop eating.

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Additional Resources

Cites

  • Yadav VK, Ryu JH, Suda N, et al. Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell 2008;135: 825-837.
  • GASTROENTEROLOGY 2011;141:439-442
  • http://care.diabetesjournals.org/content/34/9/e147.full
  • Shea MK, Booth SL, Gundberg CM, Peterson JW, Waddell C, Dawson-Hughes B, Saltzman E: Adulthood obesity is positively associated with adipose tissue concentrations of vitamin K and inversely associated with circulating indicators of vitamin K status in men and women.
  • J Nutr. 2010 May;140(5):1029-34
  • PMID: 17145139 [PubMed – indexed for MEDLINE]
  • Wu S, Liao AP, Xia Y, Li YC, Li JD, Sartor RB, Sun J: Vitamin D Receptor Negatively Regulates Bacterial-Stimulated NF-{kappa}B Activity in Intestine. Am J Pathol. 2010 Jun 21
  • http://www.ncbi.nlm.nih.gov/pubmed/16942519  (vegan osteopenics need to read this one)

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106 Comments

  1. Rodney November 1, 2011 at 4:16 am - Reply

    Wow! Ok, you are right that my head really does hurt right now. This is all so fascinating, but I definitely need to read this through a few more times.

    In terms of Vitamin K deficiency, how long does it take to replenish the body, and how does its fat soluble property play into this?

    I realize this is probably an individual thing, depending on how deficient and "ill" someone is and how much Vit K they are taking daily, but generalizations would be helpful.

    I suspect another lively set of comments on this one, Dr K! Keep the good stuff coming. Eventually the details will start to fall into place for all of us trying to keep up.

    Thank you!

  2. Jack November 1, 2011 at 4:33 am - Reply

    @Rodney If your Vitamin K recycling is broken you can never fully replenish it until you fix the gut dysbiosis. This a major problem in osteoporosis. The SAD really ruins this. Fat solubility plays a role too. There are no generalizations. It has to be custom to the carboxylated osteocalcin levels.

    Most people dont realize that serotonin is a bone hormone (and it has other hormonal actions too) and that the gut EC are directly additive to bone mass ability. Osteoporosis is really a gut disease and not a bone disease.

  3. Jeff November 1, 2011 at 4:43 am - Reply

    Another great post!

    Do you think people who eat a lot of grass-fed butter and organ meats, and have good vit D levels need K2 supplementation?

    thanks

    • Jack November 1, 2011 at 12:53 pm - Reply

      @Jeff It depends upon our guts. Think about our friend on PH. He is a perfect example of a paleo person who is ripped up but has a very low HDL and leaky gut. This means his K2 recycle is "busted". No matter how much of a good diet he eats he may not get its benefit with daily huge intakes. We are only what we absorb. This is where the advice of Dr. Guyenet kind of stopped when he recommended a need of only 45mcgs of K2 a day. That recommendation is totally made without a proper context. Our daily needs of Vitamin K2 are low if we are properly recycling it. Most of us are not. Most patients have never even heard of an osteocalcin test and most docs dont even know what it monitors. The story requires a deeper understanding to conquer it.

  4. Adriana G November 1, 2011 at 5:29 am - Reply

    Very interesting doc. What is th relationship between K2, osteoporosis and disc and joint issues?

    In my case, bone density studies and coronary calcification scans read normal, but bulging discs, arthritic hip, abnormal LDL and dental tartar buildup tell a different story.

    Are they different manifestations stemming from the same gut and K2 defficiency issues?

    • Jack November 1, 2011 at 12:49 pm - Reply

      @Adrianna The biggest link to disc and joint disease is leptin resistance……..which then leads to gut issues and this disrupts the Vitamin K cycle and its recycle and ultimately really affects activated osteocalcin. Low Vitamin D also is a major player with altered sex steroid hormones. It is complex but shows there is a major homeostatic balance problem behind this. Surgery might fix some of these issues…….but the homeostatic issues in the tissues must be fixed first before surgery to get to optimal outcomes.

  5. moreporkplease November 1, 2011 at 5:36 am - Reply

    I love my raw milk and when I lived in a state where it is illegal, I was part of a underground buying club. 🙂 Now I live in a state where it is legal. But since adopting the lifestyle change, eliminating grains, sugar, beans, etc., drinking whole raw milk is just a jolt to me – I might as well just down sugar. Even 1/3 cup gives me a sugar rush now. Will raw cream do?

    • Jack November 1, 2011 at 12:47 pm - Reply

      @moreporkplease I am a big fan of raw cream.

  6. Rachel November 1, 2011 at 9:16 am - Reply

    What a fascinating article! I was diagnosed with osteopenia many years ago. Now I'm on a paleo diet. What do you think about calcium supplements? (Dr. Davis doesn't recommend them, so I haven't been taking them.) Also, if high serotonin is part of the problem, does that mean SSRIs are a problem, too?

    • Jack November 1, 2011 at 12:38 pm - Reply

      @Rachel people on a paleo diet do not need any calcium supplementation in my view. This is also why you dont see Calcium on any of my top ten lists of supplements. Magnesium is far more important as we will soon explore. SSRI and the proton pump inhibitors are major no no's too in my book. All things coming in future blogs.

  7. August November 1, 2011 at 1:45 pm - Reply

    I've seen a few people on-line assume that, since K2 has a short half-life, taking smaller doses throughout the day makes more sense than taking the same amount once a day.

    Does this fit with how it actually works in the body? I tend to think certain dosing regimes are artificial because we'd never get such a steady state of anything in paleo times.

  8. Ryan November 1, 2011 at 3:31 pm - Reply

    "The gut-derived serotonin, following its binding to Htr1B on the osteoblast cell, and this inhibits CREB expression, which results in a decrease in cyclin expression and leads to osteoblast proliferation and lots of new bone formation." I'm not quite sure if I understand correctly… If LRP5 favors bone formation by inhibitsing TPH1, then how might gut-derived serotonin binding to HtrB1 exhibit a positive correlation with increased bone production?

    • Jack November 4, 2011 at 11:40 pm - Reply

      @Ryan Let me try to make it make some sense of it for you…….This study is saying Thanksgiving turkey may be bad for your bones! The specific activation of Lrp5, or inactivation of Tph1, increases bone mass and also prevents ovariectomy-induced bone loss. This means even in menopause we can make bone if we limit gut derived serotonin. Serotonin acts on osteoblasts through the Htr1b receptor and CREB to inhibit their proliferation. By identifying duodenum-derived serotonin as a hormone inhibiting bone formation in an Lrp5-dependent manner, this study has broadened my understanding of how bone mass accural (growth by apposition) occurs and it suggested to my mind that I adjust how I treat osteoporosis in my patients. I did this in 2009 and the results have been nothing short of remarkable. My osteoporosis Rx is alot cheaper than Forteo and PTH treatments and has no side effects as yet.

  9. Ceci November 1, 2011 at 5:27 pm - Reply

    Awesome article. Yes my brain is reeling a bit, but I think I can recover. 🙂 I do have a question or two though.

    In the "What about carbs?" section, paragraph 2 and 3 are clear that serotonin inhibits bone formation. But in the 4th paragraph, there's a sentence that seems to contradict this. (But I think that may be because the sentence appears to have a type/some words missing??) …quoted below….

    "The gut-derived serotonin, following its binding to Htr1B on the osteoblast cell, and this inhibits CREB expression, which results in a decrease in cyclin expression and leads to osteoblast proliferation and lots of new bone formation."

    FWIW I'm extremely interested in the serotonin information because I seem to need to eat some carbs in order to sleep. I used to need more than 50g/day, but now it's less and I'm still able to sleep (I'm trying to lose my last 10-15 pounds also, so I'm keeping my carbs lower for that as well as the leptin reset)

    I also wonder if there's any correlation between the pineal gland shrinking during puberty (I think I remember being told this)and the fact that people sleep less as they get older? (I developed insomnia as my "go to" symptom just before puberty…meaning if anything wasn't perfect in my body, my first symptom was usually insomnia. And it's my predominant symptom during my perimenopausal years.) I also wonder if the pineal gland could be affected by excessive flouride?

    thx!

  10. Indigogirl November 1, 2011 at 6:54 pm - Reply

    Really interesting!

    Like Rachel, I would like to know more about the role of SSRI's and osteoporosis.

    And if SSRI's are problematic what do people diagnosed with depression or seasonal affective disorder do?

  11. akman November 1, 2011 at 7:43 pm - Reply

    What should proper supplementation with K2 do for someone?

  12. Jack November 1, 2011 at 9:24 pm - Reply

    @August The half life of vitamin K2 subfractions is different. MK7 is longer and MK4 is shorter. It depends what the indications are for it in making a treatment recommendation.

  13. Jane November 1, 2011 at 11:25 pm - Reply

    Question, Dr. K: "If the patient is on coumadin the problem is even bigger. Why you ask? Coumadin's mechanism of action is to deplete our cells of vitamin K by blocking our ability to recycle Vitamin K. By blocking vitamin K epoxide reductase, this lowers the Vitamin K dependent clotting factors made in our liver to clot our blood." I get this, but need help understanding how it applies in my situation.

    I recently had an aortic valve replacement (congenital bicuspid valve replaced with a tissue valve, so I'm not on Coumadin, etc., but do take a baby aspirin every day. No cardiovascular disease, and an HDL of 80). When I first read your post on your top ten supplements, I was excited about K2, since it seems ideal for avoiding calcification of my shiny, new tissue valve for as long as possible. My cardiologist, however, had a different reaction: he noted that K2 would promote clotting, which is a concern, evidently, with all valve replacements, and not just for mechanical valves.

    So I'm stuck: should I take K2 to reduce calcification of the valve, or should I avoid it to lessen the risk of troublesome clots? Would appreciate your thoughts, Dr. K!

  14. steve November 2, 2011 at 12:38 am - Reply

    Would you please give some indication of what HDL level might indicate leaky gut?

  15. Gabriella November 2, 2011 at 3:21 am - Reply

    Cool post. Do you recommend both forms of K2?

    Also, I hope you respond to the below thread over on paleohacks that is uber-critical of you. I'm not sure what to think, as I love your ideas but am cautious now because of the strange inaccuracies/lies that they bring up…

    • Jack November 2, 2011 at 12:31 pm - Reply

      @gaby. I do use both forms for different indications. As for the thread, I think it is filled with it's own set of inaccuracies and but that is for you to decide not me. I left some replies over there.

    • Jack November 3, 2011 at 12:27 am - Reply

      @Gabriella I do but for different reasons. For Osteoporosis I like the MK4 side chain better because of its bone effects. In T2D with bad bone I love MK4 for this reason and the fact that it augments the beta cells of the pancreas. MK4 requires more dosing but I think it is a good choice. Many use MK-7 because of the longer half life. I use both but I customize the treatment plan based upon the case data

  16. Debbie Young November 2, 2011 at 4:22 am - Reply

    Dr K excellent info! I am eating more good fats raw milk and gf beef ! Feeling great!

    • Jack November 3, 2011 at 12:30 am - Reply

      @Debbie……Keep it up. I am glad this is working for you.

  17. Micah November 2, 2011 at 4:23 am - Reply

    Someone close to me has a chronic problem with disbiosis. She has celiac's as well. We both eat a fairly low carb and gluten free, paleo diet. We take probiotic, eat fermented veggies and yogurt, and take the supplements you recommend. What else can be done to improve gut health? Since having optimal gut health is so central to over all health I am very concerned about this.

  18. Dexter November 2, 2011 at 5:20 am - Reply

    Is it possible to stimulate the pancreas of a true type I diabetic (not type 1.5) into producing enough insulin by supplementation of 45mg or more of K2 MK4 daily along with the elimination of all neolithic foods? Or have the beta cells been totally destroyed and cannot be revived to produce insulin?

  19. Swingen November 2, 2011 at 10:38 am - Reply

    A head spinner for sure!!! Thanks for an exceptional article.

    One quick question please……what about women who have had a hysterectomy? Any change in protocol? Still No to calcium supplementation?

  20. Doug November 2, 2011 at 12:54 pm - Reply

    Your whole philosophy should be called "Sensitivity Training" (making our bodies more Leptin, Insulin sensitive). I am now a convert.

    I am a family doc in Maine and would love to ask you some other questions via email. Can you send me your address.

    • Jack November 3, 2011 at 12:23 am - Reply

      @Doug You can email me you number or contact and I will get with you at jack@neurosurgical.net. Reference this post for me with your email. I have your email here so I will know its you.

  21. Cú Chul November 2, 2011 at 3:54 pm - Reply

    some mob psychology & resentment on display over there

  22. Santiago November 2, 2011 at 5:36 pm - Reply

    @Jack,

    I hope you read this post… because you have touched one huge concern I've been having these weeks. My father (80) suffers from Wegener disease since 4 years ago. Fortunately the corticoids have stopped the progress of his illness, although the corticoids have reduced big way his muscles and he can barely walk with difficulty.

    But my real problem is another. He's been diagnosed some weeks ago from fibrillation at the heart. Seemingly it's not very serious at this stage but here comes the big problem: he's been put on coumadin!. The problem is that after struggling a lot with him and my mother I could change for better there diet and 'obligated' them to take D3, cod liver oil and vitamin K2!!!. So now, I don't know that to do, if keep giving him K2 (Super K of LEF) or stop it because of the coumadin. I'm very worried with the interactions. What's your take on this?.

    BTW if you could put a blog entry with 'helps' for blood circulation would be great.

    Thanks a lot. Santiago

  23. Jane November 2, 2011 at 6:03 pm - Reply

    @Santiago, I have a similar concern (see my post above (#17): how do folks with certain heart issues reconcile the benefits of K2 with its tendency to promote clotting? @Dr. K?

  24. Dan H November 2, 2011 at 6:54 pm - Reply

    Where do you get your raw milk/dairy from, Dr. Kruse? Do I have to go locally, because I can't seem to find a main commercial source like U.S. Wellness Meats.

  25. Jack November 2, 2011 at 9:57 pm - Reply

    @jane. Your cardiologist is making an error. Please show them this to stop the misinformation. K2 in high doses is safe for clotting from japenese data. If you take Coumadin, Heparin, or another anti-coagulant you should always consult your physician before taking vitamin K2 supplements so they are aware of it. Vitamin K2 helps normal coagulation of blood but does not cause excessive clotting when used in high doses. Vitamin K1 however does do this. I repeat!!!!!!!!!! High levels of K2 do not cause abnormal blood clotting. You should not be concerned about taking levels of 45 mg/day or less, as numerous Japanese studies have shown even this high level is safe for adults. Most vitamin K2 supplements offer 45 – 150 micrograms per day.

  26. Jack November 2, 2011 at 10:00 pm - Reply

    @ santiago……i face this too with my cardiologists and we now have an agreement that those people can take Pradaxa over coumadin to protect bone and heart! They need to be told what you want and it can happen. My cardiologist had zero problems with my request just last week on a big spine case in a patients on couumadin a-fib and with horrendous osteoporosis

  27. Jack November 2, 2011 at 10:01 pm - Reply

    @DanH. I have a local farm connection

  28. Jack November 2, 2011 at 10:03 pm - Reply

    @Cu…….i think they love me truthfully. I responded over there. Im on call so i am quite busy this week.

  29. Jack November 2, 2011 at 10:06 pm - Reply

    @dex. The mk4 version is concentrated in the beta cells and is not gut derived from bacteria so this is another reason i love mk4 version of K2 for my diabetic osteoporotics

  30. Jack November 2, 2011 at 10:07 pm - Reply

    @micah……i have a post called the leaky gut Rx…..read it

  31. Jack November 2, 2011 at 10:08 pm - Reply

    @swingen……uterus or not im not a calcium guy.

  32. Jack November 2, 2011 at 10:10 pm - Reply

    @steve. I have written about the leaky gut in blogs extensively in reference to HDL. Check them out

  33. JanSz November 2, 2011 at 11:22 pm - Reply

    Vitamin K2 is used as a first line treatment of osteoporosis in Japan in doses up to 45 mgs a day.

    lef.org have a two products containing same amounts of K2.

    Super K with Advanced K2 Complex

    Super Booster Softgels with Advanced K2 Complex

    Lef.or recomends 1 softgel/day

    45/2.1=21.4

    Japanese eat 21x more K2 than lef.org recomends.

    Comments??

    ———————————————————

    Serving Size 1 softgel, contains

    Vitamin K activity 2100 mcg

    From:

    Vitamin K1 (as phytonadione) 1000 mcg

    Vitamin K2 (as menaquinone-4) 1000 mcg

    Vitamin K2 (as menaquinone-7) 100 mcg

    • Jack November 3, 2011 at 12:02 am - Reply

      @JanSz I think I have made my thoughts clear on K2 above

  34. JanSz November 2, 2011 at 11:56 pm - Reply

    Lab gives range:
    Osteocalcin, Serum(3.2-39.6) ng/mL

    What is your preferred level?

    .

    • Jack November 3, 2011 at 12:01 am - Reply

      @JanSz depends upon clinical situation and it also depends upon the lab…….the reference for this test varies wildly from lab to lab. No generalizations can be made.

  35. Santiago Madruga November 3, 2011 at 10:59 am - Reply

    @Jack,

    from your answer to Jane and me I understand that supplementing with K2 (no other forms like k1) is OK with coumadin. Please, I interpret you right?.

    As for K2. I've seen two forms in supplemnts: Menatetrenone and Menaquinone. As for the concern of the interfering with Coumadin, should we prefer on these forms over the other?.

    Thanks a lot. Santiago

    • Jack November 3, 2011 at 12:27 pm - Reply

      @santiago…..no that is not what i intended. You can not take coumadin with any vitamin k. You must switch to another blood thinner like pradaxa or a combo of lovenox and aspirin then you can add back the K2. Coumadin is only used because it is familiar to the docs. Most have no idea how bad it is for bones and vessels. If they did they would seek alternatives. Today we have alternatives. In the past we had none.

  36. Smolls November 3, 2011 at 12:43 pm - Reply

    In lue of SSRI's in it ok to take 5-HTP?

  37. Santiago November 3, 2011 at 1:55 pm - Reply

    @Jack,

    thanks a lot the clarification. I've never been able to change the opinion of any doctor… anyway I'll try. So the prudent thing is to stop vitamin K whenever my father is on coumadin. At least I know now and I heartily appreciate your help to let me know and don't make the things worse.

    Best. Santiago

  38. Spooky November 3, 2011 at 8:14 pm - Reply

    I know this is a bit off topic, but this is the most recent post so I feel I have the best chance here.

    I am 23, male and in pretty good shape probably around 10% body fat (you can faintly see a six pack). Anyways, I have trouble with blood pressure (I range between 135-150/85-95). I stumbled onto your site after sifting through various low carb sites trying to figure a way to keep my BP down. I am trying to get into the military as a pilot so I will frequently be getting my BP taken for flight physicals, etc and I don't want to have to worry about it.

    But, a long story short: Would your leptin reset program lower BP? And what is the best way to keep it down ongoing? It does run in the family (father's side).

    • Jack November 3, 2011 at 9:31 pm - Reply

      @Spooky the cause of your HTN would need to be assessed to know for sure. Have they told what they think is driving it up? If the answer is cortisol it will certainly help in a major way. If it is adrenal in nature (aldosterone) it will help too. If it is essential HTN then maybe not. I still think discussing Magnesium and K2 for essential cases is not a bad idea because Dr. Janetta, who is the father of MVD of the vagus nerve, thinks essential HTN is caused by calcification of the PICA as it compresses the Vagus nerve at the CPA. That is all I have for you.

  39. Cú Chul November 3, 2011 at 9:25 pm - Reply

    Dr Kruse, you mentioned some time ago you might be writing something relevant to dysgraphia–any thoughts/suggestions would be welcome.

  40. David Collie November 4, 2011 at 6:20 am - Reply

    Vit K is important but the form it is in is equally as important.Search Vit K2 MK4 on the web and see why this is critical. Don't take the MK7 version.

    For more info on new osteoporosis product check out

    wwww.seniorhealthcare.co.nz

  41. Gene K November 4, 2011 at 3:25 am - Reply

    Dr Kruse,

    I hope you would also recommend your blog readers interested in heart disease the blog of Dr William Davis at http://www.trackyourplaque.com/blog/. Although his focus is a little different, I find it fascinating how much his conclusions agree with yours! Advice taken from these two blogs has made great positive impact on my life. Thank you so much!

    • Jack November 4, 2011 at 12:45 pm - Reply

      @gene i follow Dr. Davis and read his stuff. I have also commented over there. I have a few beefs with him but many have beefs with me. We agree on more things then we do not. Just so we are clear……most doctors dont agree with other doctors on much. That is why it is called a second opinion. I also find the closer the two doctors are in proximity the more they dont agree. The further apart they are the more agreement one will expect.

  42. Paul November 4, 2011 at 8:07 pm - Reply

    Dr. Kruse,

    I seem to recall a post in which you discussed high protein diets promoting an environment that can lead to demineralization of bone. Did I read this correctly? I have osteoporosis and am trying to follow a paleo diet. Am I on the right track? I take 5 mg. of K2 daily.

    • Jack November 4, 2011 at 8:18 pm - Reply

      @Paul. That would not have been me. I'm a high fat moderate protein guy when it comes to bone health

  43. Dan A November 4, 2011 at 6:51 pm - Reply

    Spooky, I think optimizing vitamin D status should also contribute to lowering blood pressure. Vitamin D inhibits the expression of renin (http://tinyurl.com/3v5zqdv), lowers blood pressure by decreasing production of angiotensin.

    This is similar to how ACE inhibitors work, which inhibit the enzyme that converts angiotensin I to the biologically active form angiotensin II. So this method of action is pretty well-established, although I didn't find good trials in a quick search.

    In addition to causing blood vessels to constrict, angiotensin II-IV also stimulate the release of aldosterone, so this might be a pretty effective treatment.

  44. moreporkplease November 5, 2011 at 3:57 am - Reply

    Oh Lawd luv a green-eyed duck – forget those children over at PH. It's hilarious that a bunch of 25-year-old geeks who apparently have never left Kansas to do anything except study PHP scripting have suddenly appointed themselves Nobel-prize level thinkers. Puh-leeze.

    Let them save the drama for overclocking their processors. Sheesh. Why do you even waste your time with them? (eyes roll). And just to be clear, no I don't agree with everything you say. But I hope to always disagree with you respectfully and in an adult manner. 🙂

  45. Adriana G November 5, 2011 at 2:25 pm - Reply

    Speaking of your Osteoporosis RX, Vitamin Research is a great place to buy 15 mg Vitamin K2. http://www.vrp.com/bone-and-joint/ultra-k2

    They have a constantly revolving series of weekly discounts with buy one get one free every couple of weeks. This week it's buy $100, get $50 off.

  46. Adriana G November 5, 2011 at 2:32 pm - Reply

    @morepork, I agree it's time for Dr. K to stop posting at Paleo Hacks and open an Ask Dr. K. tab here on his site. It gives him much more control over the questions that get published and may let him focus more specifically on key issues he wants to highlight.

    There were 5000 attendees to the party they gave this week to kick Dr. K around. I don't think you need to give them the pleasure of providing the food reward for their feeding frenzy. They need you, not the other way around. Bring it over here! Those who need you will come here.

  47. DH November 6, 2011 at 7:15 am - Reply

    Forget the passive-aggressive critics at PH. You are on a mission, Dr. K.

    Teddy Roosevelt:

    "It is not the critic who counts: not the man who points out how the strong man stumbles or where the doer of deeds could have done better. The credit belongs to the man who is actually in the arena, whose face is marred by dust and sweat and blood, who strives valiantly, who errs and comes up short again and again, because there is no effort without error or shortcoming, but who knows the great enthusiasms, the great devotions, who spends himself for a worthy cause; who, at the best, knows, in the end, the triumph of high achievement, and who, at the worst, if he fails, at least he fails while daring greatly, so that his place shall never be with those cold and timid souls who knew neither victory nor defeat."

    • Jack November 6, 2011 at 10:28 pm - Reply

      @DH I have found in my career that if you try to please everyone you wind up doing nothing well. Instead I focus in on what I can do and not on what I cant do. That way I improve my former self daily and become a better person and doctor in my view. No one is perfect but we must try to help if we can help.

  48. Heather November 6, 2011 at 10:34 am - Reply

    Oh how, I agree, Adriana. Dr K, you along with Mark and Robb have transformed my journey, and this bone post is fascinating. Going to look for some K2 here in Oz, meantime gardening in the sun and enjoying life,

    Cheers

    • Jack November 6, 2011 at 10:24 pm - Reply

      @Heather If i can help I will try. If not I will try to guide to places that may help you. I want everyone to get to optimal.

  49. moreporkplease November 6, 2011 at 11:56 pm - Reply

    And now it seems MDA is no better. I particularly loved this comment from the "Leptin not so grand thread" by branchiate about our host here: "He's a surgeon not a physician."

    Still pondering that one, JK! 🙂 But then all surgeons I've ever consulted have been Phd doctors and one was also a teaching professor in New York. So what would I know?

    Who'd a thunk that anybody can just pick up a bone saw and hang out a shingle. 😉

  50. JanSz November 7, 2011 at 8:05 pm - Reply

    http://www.mayomedicallaboratories.com/test-catal
    Unit Code 80579:

    Osteocalcin, Serum

    Method Name

    Electrochemiluminescence Immunoassay

    Osteocalcin is produced by osteoblasts and is widely accepted as

    a marker of bone osteoblastic activity. Osteocalcin, incorporated

    into the bone matrix, is released into the circulation from the matrix

    during bone resorption and, hence, is considered a marker of bone

    turnover, rather than a specific marker of bone formation. Osteocalcin

    levels are increased in metabolic bone diseases with increased bone

    or osteoid formation including osteoporosis, osteomalacia, rickets,

    hyperparathyroidism, renal osteodystrophy, thyrotoxicosis, and in

    individuals with fractures, acromegaly, and bony metastasis. By

    means of osteocalcin measurements, it is possible to monitor therapy

    with antiresorptive agents (bisphosphonates or hormone replacement

    therapy [HRT]) in, for example, patients with osteoporosis or hyper-

    calcemia.(1) Decrease in osteocalcin is also observed in some disorders

    (eg, hypoparathyroidism, hypothyroidism, and growth hormone deficiency).

    Reference Values

    or =18 years: 9-42 ng/mL

    Interpretation

    Elevated levels of osteocalcin indicate increased bone turnover.

    In patients taking antiresorptive agents (bisphosphonates or hormone

    replacement therapy [HRT]), a decrease of > or = 20% from baseline

    osteocalcin level (ie, prior to the start of therapy) after 3 to 6 months

    of therapy, suggests effective response to treatment.(2)

    Patients with diseases such as hyperparathyroidism, which can be

    cured, should have a return of osteocalcin levels to the reference

    range within 3 to 6 months after complete cure.(3)

    ================

    ================

    http://www.questdiagnostics.com/hcp/testmenu/jsp/

    Osteocalcin, N-MID

    Methodology

    Electrochemiluminescence(ECLIA)

    Performing Laboratory

    Quest Diagnostics Nichols Institute

    33608 Ortega Highway

    San Juan Capistrano, CA 92690-6130

    Setup Time

    Night

    Setup Days

    Sets up 5 days a week.

    Report Available

    Reports in 3 to 4 days.

    Reference Range(s)

    __Osteocalcin, N-MID (UOM ng/mL)

    Pediatric Reference Ranges for Osteocalcin,

    N-MID:

    5-9 years: 47-142 ng/mL

    10-13 years: 49-167 ng/mL

    14-17 years:

    Males: 26-203 ng/mL

    Females: 14-85 ng/mL

    Adult Reference Ranges for Osteocalcin,

    N-MID:

    Males: 9-38 ng/mL

    Females: 8-32 ng/mL

    Clinical Significance

    Osteocalcin, the most abundant non-collagen protein in bone

    matrix, is a bone-specific, calcium binding protein. Serum

    osteocalcin levels are related to the rate of bone turnover

    in various disorders of bone metabolism, e.g.,

    osteoporosis, primary and secondary hyperparathyroidism,

    and Paget's disease.

    ——–

    http://www.questdiagnostics.com/hcp/intguide/jsp/

    Osteocalcin, N-MID

    Clinical Use

    Determine efficacy of therapy in osteoporosis and metastatic bone disease

    Useful marker of bone formation and remodeling

    Clinical Background

    Osteocalcin is a 6-kd protein constituting 1% to 2% of total bone protein. It contains 3 gamma-carboxyglutamic acid (Gla) residues that bind hydroxylapatite. Osteocalcin is produced exclusively by bone osteoblasts, and production is dependent on 1,25-dihydroxyvitamin D, vitamin K, and vitamin C. Measurement provides a specific biochemical index of bone activity. As assessed by bone histomorphometry, serum osteocalcin levels correlate with bone formation and not directly with bone resorption. Serum osteocalcin is an important bone formation marker.

    Specimen Requirements

    1 mL frozen serum

    0.5 mL minimum

    Red top (no gel) preferred

    SST red top acceptable

    Avoid hemolysis.

    Methods

    Electrochemiluminescence (ECLIA)

    Analytical sensitivity: 5.0 ng/mL

    Analytical specificity: N-MID fragment (amino acids 1-43) and intact osteocalcin (amino acids 1-49); does not crossreact with β-CrossLaps, parathyroid hormone, or bone-specific alkaline phosphatase

    Reference Ranges ng/mL

    Men 9-38

    Women 8-32

    Interpretive Information

    Increased levels are associated with:

    Primary hyperparathyroidism

    Secondary osteosarcoma

    Healing bone fractures

    Hyperthyroidism

    Paget's disease

    Therapeutic agents such as phenytoin and 1,25-dihydroxyvitamin D

    Decreased levels are associated with:

    Hypoparathyroidism

    Cushing's syndrome

    ===============================================================

    =====================

    http://www.labcorp.com

    Osteocalcin, Serum

    Synonyms:

    BGP

    Bone GLA Protein

    Reference Interval:

    Male: 3.2-39.6 ng/mL

    Female:

    – Premenopausal: 4.9-30.9 ng/mL

    – Postmenopausal: 9.4-47.4 ng/mL

    Use:

    Evaluate bone disease. Increased levels of osteocalcin are found

    in bone diseases characterized by increased bone turnover.

    Osteocalcin has been found to be elevated in Paget disease of

    the bone, cancer accompanied by bone metastases, primary

    hyperparathyroidism and renal osteodystrophy. Osteocalcin levels

    may serve as useful index in evaluating the therapeutic management

    of the patient.

    Methodology:

    Enzyme-linked immunosorbent assay (ELISA)

    Additional Information:

    Osteocalcin, or bone Gla protein (BGP), is the major noncollagenous

    protein of bone matrix. It has a molecular weight of

    approximately 5.8 kilodaltons and consists of 49 amino acids,

    including three residues of gamma-carboxyglutamic acid. Osteocalcin

    is synthesized in bone by osteoblasts. After production, it is partly

    incorporated into the bone matrix and partly delivered to the

    circulatory system. The precise physiological function of osteocalcin

    is still unclear. A large number of studies have shown that the

    circulating level of osteocalcin reflects the rate of bone formation.

    Determination of serum osteocalcin has proven to be valuable as an

    aid in identifying women at risk of developing osteoporosis,

    for monitoring bone metabolism during perimenopause and postmenopause,

    and during antiresorptive therapy.

    ,,,,,,,

  51. Maurice November 9, 2011 at 10:43 am - Reply

    Great blog Dr Kruse cannot wait for your osteoporosis Rx

    Cheers

    My comment to Maurice: If you read the gastroenterology paper cited you can see figure one has it clearly laid out Maurice. No typo at all.

  52. m chris link November 12, 2011 at 10:43 pm - Reply

    Jack I'm confused about serotonin and bone mineral density:

    It appears from the research and your posts that peripheral serotonin decreases bone deposition, yet you write the following in the section about meal timing –

    "The big ass breakfast (BAB) also stimulates more peristaltic waves in the gut and this further releases more serotonin from the gut to help build bone."

    Please explain

    Many thanks and keep up the great blog!

    Chris

    • Jack November 13, 2011 at 2:04 am - Reply

      @m chris Its a typo and I will fix it.

  53. […] the first blog on osteoporosis we focused in on how to stimulate bone mass accrual via our diet.  This is by far the best way to […]

  54. […] OSTEOPOROSIS PART ONE You may find what Jack Kruse has to say on testosterone secretion interesting. […]

    • Jack December 3, 2011 at 10:44 am - Reply

      @Ted Hutchinson…….the real reason D3 works so well in high ranges is that when it is above 70ng/dl it acts as a potent aromatase inhibitor to protect testosterone levels and protect our bone stock.

  55. MimiDiet December 6, 2011 at 11:58 am - Reply

    Hi, Dr. Kruse. Welcome back!

    I was reading this article on Vitamin A. Some interesting studies regarding hip fractures & lung cancer. I can understand excess vitamin A competing with Vitamin D (I've read that A & D need to be in balance), but what else do you think is going on with these data? The studies had very interesting results!! Why a much higher death rate from lung cancer with Vit A? Why more hip fractures with excess retinol, and how do I get ample vit A without excess retinol??

    Thanks…looking fwd to your reply.

    http://ods.od.nih.gov/factsheets/vitamina

  56. MimiDiet December 6, 2011 at 1:58 pm - Reply

    Also wondering if cod liver oil would be an awesome way to get natural forms of Vits A & D, & in a good balance together?

  57. Line January 9, 2012 at 9:10 am - Reply

    Very interesting reading:)

    ou mention that one should stay under 50g carbs a day. I have been living on a LCHF diet for a year. I have been diagnosedwith hypothyroidsm, osteoporosis and is no longer producing oestrogen – I am 37 years old. I have refuced taking hormones or pille for my osteoporosis but I am taking Erfa Thyroid for my hypothyroidsm.

    My question is: now my diet is based on 20-30% protein, 5% fat and 60-70% fat. I am thinking off schwitching to Paleo or Primal but I am not sure wat is best. I have allways been overweight, bebn addicted to sugar and even on LCHF I have to count calories, proteins, carbs an fat ore I will gain weight. I need to loose about 10kg but I am not sure if my current diet is good for my bones – hov many % and gram protein, carbs and fat would you recomend?

    Line

  58. Line January 20, 2012 at 12:18 am - Reply

    One more question – Hov can I balance my diet so that the acid/bace balance is perfect for my osteoporosis bones? Since the 1/1-12 I have lost 2,6kg, so I am happy. 4 day a week I get up early – drink a cup of cofee and go to the gym where I do low cardio for about 30 minutes and then weight lifting for about 30-40 minutes. I love the early morning gym and when I come home I eat breakfast. Is that allright?

    Line

    • Jack January 20, 2012 at 8:09 am - Reply

      @Line you dont need to balance anything……just eat a paleolithic diet and you will win. This acid base thing is more CW and urban myth.

  59. Line January 20, 2012 at 8:22 am - Reply

    Thank you for your answer. I will keep reading and learn 🙂

    Is Loren Cordain´s book The Paleo Diet a good one or do you recomend another one? The reason is that I have that book in danish and was about to read it when I found your blog – so I havent read it yet becauce there is hours of reading in here for me :)Is Loren Cordain ok or is there a better one?

    • Jack January 20, 2012 at 9:29 am - Reply

      @Line…….the paleo diet is a bit out of date on the saturated fats especially and Cordain admits it in his new book. I cant stress to you enough of how good The Paleo Answer is……..it is loaded with nuggets of wisdom. It does not provide the paleo 1.0 diet……for that I would lean on Mark Sisson or Robb Wolf works.

  60. My New Favorite Vitamin: K2 « Bare 5 February 13, 2012 at 2:18 pm - Reply

    […] Osteoporosis Part 1 & Osteoporosis 2: The Vitamin K2 Story by Jack Kruse Like this:LikeBe the first to like this post. […]

  61. Susan March 10, 2012 at 10:20 am - Reply

    Like Line, I am osteoporotic.

    My doctors do have me on small doses of bioidentical hormones, vit K and boron. They all insist that testing my morning urine and keeping it in the alkaline pH range is critical to avoid further bone depletion.

    I need to lose a lot of weight and wanted to do Paleo in a ketogenic way and am worried the ensuing acidosis will cause calcium loss.

    • Jack March 10, 2012 at 10:24 am - Reply

      @Susan your Urine PH is a waste of time and you can tell them I said so. I treat thousands of people with it……The best way to reverse it is to eat a diet loaded in animal protein and fat and very low in carbbs while using cold…….Ketosis without cold has its own set of issues…..Most VLCers never get optimal body comp because they do not realize they are warm adapted. When they cool they become rock hard just like evolution says they should.

  62. Susan March 10, 2012 at 10:25 am - Reply

    Are we allowed to contact other readers who have posted on this blog? We are Danish Americans and visit DK regularly. I have been in touch with the Danish researchers studying Danish Nurses for 15+years.
    I would enjoy corresponding directly with Line if she were interested.

    • Jack March 10, 2012 at 11:50 am - Reply

      @Susan why not?

    • P.Birger October 13, 2017 at 7:37 am - Reply

      Dear Susan

      I came accross your name on Dr. Kruse’s blog.
      As you have connections in Denmark with health professionals I would like to ask you a favour.
      I am living in Hungary, in Europe and have osteoporosis.
      As unfortunately Dr. Jack Kruse’s ideas are refused and not accepted by the doctors I met in Hungary I try to find a practitioner, physician, doctor, clinician in Europe, mainly in Germany or in Austria who accepts, (fully or partially) understands, follows his osteoporosis treatment.
      I try to find a doctor who follows Dr. Kruse’s options with paleolithic diet options, (high fat and high protein diet,), bio-identical hormones (bio-identical estrogen or progesterone creams, DHEA) K2, magnesium.
      I try to find a doctor who replaces all sex steroid hormones to the top quartile found in young adults and using and preferring bio-identical hormon replacement therapy.
      I really try to find a doctor who is willing and able to prescribe me bioidentical hormones (and NOT synthetich hormones!).
      I try to find a doctor whom I can consult in Europe, especially in German speaking contries.
      I try to find a doctor who understands Dr. Kruse’s treatment, knows his theory, his methods, his lab testings, and who knows what lab test are needed to do and how to interpret the data.
      I try to find someone who can help me identify where am I in this whole process of trying regain my leptin sensitivity, to balance my hormones, and recover my health and what I do have to do?
      I try find a doctor who follows my osteoporosis treatment’s progress based on Dr. Kruse’s treatment options, checks my results and helps me to educate myself.
      I try to find a doctor who accepts and understands Dr. Kruse’s observations, recommendations resulting from quantum physics.
      I really need somebody to consult in Europe, especially in German speaking countries.
      As you have connections with healths professionals in Europe, in Denmark, they may have connections with German speaking doctor(s) in Europe (in Germany or in Austria) who accept(s) Dr. Kruse’s findings, treatments recommendations and who is treating osteoporosis according Dr. Kruse’s methods.
      You might have some connections or you might know Dr. Jack Kruse’s followers in Europe as well. I can not believe that his ideas are fully unrecognised by other researchers or by other health professionals in Europe. There must be somebody somewhere in Europe, who treats patients on the base of his finding, of his observations, of quantum biology, who is daring to follow his and Becker’s findings, who is daring to cross-think.
      I believe that there must be also in Europe a doctor who knows Dr. Jack Kruse and who follows his treatment recommendations and he also does not believe in just treating osteoporosis but he believes in curing it.
      Should you know somebody (doctors with out-of-box thinking, researchers, scientists interested in Dr.Kruse’s theories and observations) in Europe, mainly in Germany or in Austria, please contact me via email please. (pendriveholder@googlemail.com)

      Should you know any other person of the other commenters, blog readers, somebody (health professionals, health practitioners, researchers, scientists ) in Europe, especially in German speaking countries who follows Dr.Kruse’s treatment , please contact me.
      Although I am trying to educate myself on Dr. Kruse’s treatment recommendations and experiment on myself his treatment I’m just very overwhelmed and scared alone.
      I really need the help of a physician who accepts Dr. Kruse’s treatment recommendations and especially bioidentical hormone therapy on osteoporosis.i
      I read that your doctor in USA did you on bioidentical hormones, and boron. I tried to find in Hungary bioidentical hormones but they are not used. I asked about boron, nobody heard about it for treatment in osteoporosis although I have found some studies about the beneficaries of boron for bones. If you could tell me some names of bioidentical hormon products or drugs or of boron supplements , it would also useful for me, as I could at least search in the right direction.
      Thank you for taking the time to reading my post and thank you for your help with finding a doctor for me in Europe.

  63. Susan March 10, 2012 at 5:27 pm - Reply

    Thank you!

    I live in the South. Can I cold adapt simply by drinking ice water all day?

    Can I use a small amt of cheese, 1/2 & 1/2 in my coffee as part of my protein?

    Should I test my urine for ketones to ensure the diet is indeed ketogenic?

    • Jack March 10, 2012 at 6:49 pm - Reply

      @Susan no……drinking cold water helps but it wont allow for full adaption, no cheese, no half and half……you can use pure heavy cream in coffee.

  64. Susan March 12, 2012 at 7:36 am - Reply

    Thank you.

    How can I cold adapt? I Live in a small rural area, no plastic surgeons around here to perform Zeltiq :). Should I turn up the a/c?

  65. Maria March 12, 2012 at 2:03 pm - Reply

    If a person is successful in reversing osteopenia with your dietary recommendations, do you have them stay on 50g carb for life? I understand that increasing carbs too drastically would just restart the process one has corrected, but I wasn’t sure if the dietary recommendations change once the osteopenia is reversed. Also, how are you defining “moderate protein” in the context of treating someone with osteopenia. Could you give a gram protein/kg bodyweight guideline? Thanks in advance for your help. I have been on bisphosphonates and have also taken Forteo (stopped it after 18 months and did not have a remarkable change in bone density). I am going for a DEXA in about a week, but I won’t go back on drugs for something that I can modify through diet.

    Thank you.

    • Jack March 12, 2012 at 4:04 pm - Reply

      @Maria these are questions I answer after working a patient up in my clinic…..it is very detailed and is based upon many factors that are individual. The diet however is decidely animal based……and carbs are always limited with this disease.

  66. Maria March 13, 2012 at 10:36 am - Reply

    Thank you–I would appreciate you elaborating on this as I’m sure it would help others as well.

  67. Jack March 13, 2012 at 10:42 am - Reply

    @Maria the 4 part blog series is very comprehensive on osteoporosis. Anything more than this would require a work up by your doctor.

  68. Mark April 10, 2012 at 1:24 am - Reply

    Jack – I just recently started anticoag therapy for DVTs that were found in my leg. I’ve been eating Paleo, take many supplements, and have recently started Boluoke (lumbrokinase). I am not in favor of continuing long term with coumadin/warfarin for the reasons made very clear in your blog posts and elsewhere. The doc wants to do the usual 6-month coumadin protocol as a prophylactic. Is Pradaxa and a combo of Lovenox and aspirin then the only effective replacements you’d recommend? Isn’t there anything I can take naturally that will stabilize my INR between 2-3?

    • Jack April 10, 2012 at 6:38 am - Reply

      @Mark If youre only going to be on 6 months then using coumadin is not a bad gig. Once of it you need to consider a steady regimen of krill and or fish oil. Discuss that with your doc at your next visit

  69. Mark April 10, 2012 at 12:15 pm - Reply

    @Jack I was on 4g of fish oil, but my INR remained @ around 1.0. Once off coumadin, would you suggest I raise the dose to 6g? Also, would you say krill oil is a more effective anticoagulant than fish oil or about the same?

  70. Jasmin April 18, 2012 at 3:07 am - Reply

    Jack – I have been stressed a lot for several years and finally I got very very sick because I did not listen to my body. I now have low metabolism, osteoporosis ,perhaps lupus (will get the result next month) and havent had my period since januar 2009 (I am 38) – so my hormones is a mess.
    For a long time I have thought that the high cortisol, because of stress, could have caused osteoporosis, low metabolism and lupus. Am I totally wrong or is there any scientific studies that point in that direction that you know of? I am trying to find an explanation for my bad health – all my family is at very good health (thank god) and it is just me that have taken the bad cards. My doc has no explanation

    I started Leptin recet 24/1-2012 and CT 18/2-2012 and I love it, and take a lot of D3 and K2. I have followed the plan until easter where I was invited to brunch 2 times (only eating meat, fish, bacon, and cucumber, but I was eating too much. But I am back on track and will stay here for the next month or so until I have all the signs of being LS. But for now I have less hunger, sleep good, wake up before my alarm in the morning, less muscle soreness, no sweating, but I am still waiting for more energy, softer skin but Im on the road to get better because of you – thank you Jack 🙂
    I have written to you before and am following your advice but I changed my name when your forum opend – hope it is allright?

  71. Szara Loring May 3, 2012 at 7:33 am - Reply

    Dr K – My mom (64) fell and broke her humerus a couple days ago. She is uncertain if she is getting good care. She wrote me the following: “They re-xrayed my shoulder after 2 days in a cuff & collar that raised the hand up to my collar bone to realign ball & humerus. There was no improvement in alignment. The ball is currently at a 90, rather than a 120 degree angle to humerus. They said it was back somewhat as well. I was told that surgery was elective. There was no percentages of recovered range of motion with electing surgery over a sling. The resident described a different surgical procedure leaving hardware in as opposed to the surgeon’s procedure.”

    She is frustrated. Should she look for a second opinion? Are there any resources that would help her find a good doc? Are there certain tests she might want to ask for with respect to bone health?

    This is the second break she has had in recent history. I think it was approximately a year ago when she broke her wrist. Her primary doc wants to put her on Fossamax. I’ve been encouraging her to give up the grains and supplements with D, K2, and Mag at a minimum. I sent her a couple of LEF articles as well.

    • Jack May 3, 2012 at 8:07 am - Reply

      @Szara your mom really needs to listen to you in this area……and I would definitely suggest another opinion before she opts for surgery

  72. Szara Loring May 3, 2012 at 7:34 am - Reply

    Can you change my name to my forum name? thx

    • Jack May 3, 2012 at 8:06 am - Reply

      @SZara you have to come on the forum and ask the Marketing monkeys to do this.

  73. Sue Cummings August 25, 2012 at 10:12 am - Reply

    As I read the nut of this blog it’s VLC diet = low serotonin, therefore increased bone because serotonin produced from the EC cells in the gut inhibit bone formation. But I read elsewhere that serotonin produced in the brain increases bone. So do we know that low serotonin wherever it’s produced still = more bone? Did I miss something?

    • Jack August 25, 2012 at 10:19 am - Reply

      @Sue Serotonin has a storage depot in the gut…..any dietary source that leads to excessive serotonin levels will usually lead to a LR state and bone issues. You can find this by low free T3, high rT3, low alkaline phosphatase, low Mg. High carb diets produce this perfect storm.

  74. Don December 7, 2015 at 2:36 pm - Reply

    Hi Dr. K,

    I am curious about about the effects of SSRIs on bone formation. Do they have a positive effect or negative effect? Because i read somewhere that serotonin produced in the brain encourages bone formation while serotonin produced in the gut does not. Please do share yr insight. Thanks!

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