The New World of Bones – Thyroid, Leptin, Blood Sugar, and Bone Strength
Byron J. Richards, Board Certified Clinical Nutritionist
In 1994, with the discovery of leptin, the view of white adipose tissue was transformed from a warehouse whose primary role was the storage of extra calories into one of the most important endocrine organs in the human body. The explosion in leptin-related research, now involving over 16,000 studies, is a testament to the emerging reality that leptin regulates (as a top-level manager) almost everything in your body. In the past few years the leptin science has transformed our understanding of bone health and bone function.
The traditional understanding of bone as primarily a structural material has been transformed to the new understanding of bone as a vitally important endocrine organ – with leptin sitting right in the middle of everything. This new information yields immediate practical applications not only for improved metabolism but also for better bone health and strength.
In a nutshell the new science shows that bone formation and bone strength are managed by the efficient function of leptin and thyroid. Problems with either topic, such as overweight-related leptin resistance or sub-clinical hypothyroid (elevating TSH) directly impair healthy bones – making them weaker and more at risk for fracture. A new metabolic role for bone has also been discovered, indicating that healthy bone function has a primary impact on blood sugar levels, insulin function, and body weight. This newly identified role of bone as a metabolic endocrine organ is of primary importance in metabolism, not a secondary role of limited importance. Bone health and metabolic health are highly integrated, in a chicken and egg manner, and mastering them is central to healthy aging and longevity.
A focus by the medical profession on the issue of bone density, as “proven” to the patient with two-dimensional pictures that prove little, leads to the widespread abuse of highly toxic bone drugs that directly interfere with bone metabolism and fly in the face of the new science. These drugs cause swollen bone, like a sprained ankle, so of course it appears that bone density has improved when in reality the micro-architecture of the bone has been grossly disturbed and bones have been weakened. It is now proven that taking these drugs for a number of years, a good patient just following doctor’s orders, results in seriously compromised bone health and increased fractures.
Bone drugs can also cause life-threatening atrial fibrillation. I have already covered this issue in detail in my feature article, “The Delusion of Bone Drugs,” so it will not be the focus of this current article. I might point out that other commonly used drugs, such as antidepressants and diabetes medication directly induce bone loss as a side effect – not only compromising bone integrity but disturbing metabolism in fundamental ways. The disgusting practice of putting seniors on a cocktail of toxic medications to manage numbers on paper is a primary reason for poor quality of health in the elderly population.
Those who wish to take advantage of the new science will focus on bone strength, and not just bone density. A picture showing you that bone is there does not in any way show if that bone is metabolically healthy or strong, true predictors of fracture risk. There is no shortcut to healthy bones. There are no drugs that make them strong or metabolically fit. To the contrary, the majority of drugs work in the unhealthy direction for bones, including the majority of drugs taken for other reasons than bones. Western medicine likes everything to be very simple, so they can give you a questionable test and put you on a drug. Bones are not simple and understanding them is not a simple subject. Here is a basic overview, in English, that I hope you find useful.
Bones are in a constant state of regeneration, involving the breakdown of old or stressed bone and the replacement of it with new bone. Keeping this process going throughout your life is vital for bone strength and healthy metabolism. Anything that interferes with this process is stressful to optimal bone health. Common stressors include malnutrition during high growth (teenage years), malnutrition at any time, high emotional stress, a lack of stimulation (mechanical force such as strength training), chemical exposure (especially the common PCBs1), chronic inflammation, chronic illness, the drop in estrogen at menopause, and, unfortunately, bone drugs themselves.
A variety of primary nutrients are required for normal bone rejuvenation including protein, calcium, vitamin D, and magnesium (like plywood and 2 x 4s). In addition to these primary basic nutrients, many other co-factor nutrients participate in the integrity of bone including zinc, boron, silica, manganese, vitamin C, vitamin K, and strontium (like nails and screws). And nutrients that build connective tissue matrix, such as hyaluronic acid and glucosamine, have now been proven as vital in the bone building process (forming the blueprint to follow and linking it all together).
There are many options to support bone health with nutrition as part of an overall health program that offsets the stressors in your life. A diet adequate in protein and rich in fruits and vegetables is fundamental. Exercise, or at least lots of physical activity, is required, as is adequate sleep. In the final equation your bone regeneration checkbook must balance. It is a reflection of your entire life. No shortcuts. No quick fixes. Success is based on consistently doing the right things. It is never too late to get started; bone health can be improved at any age.
Bone Carpenters: Osteoblasts and Osteoclasts
Bones are constantly remodeling themselves. This requires coordination between the demolition crew (osteoclasts) and the new construction crew (osteoblasts). Osteoclasts and osteoblasts are the carpenters of bone.
In healthy function, osteoclasts survey the existing bone looking for small micro-cracks (as induced from exercise). Once they find a crack they clean it out by drilling a little hole through it, making room for new bone. Then osteoblasts come along and use raw materials (like calcium, hyaluronic acid, and protein) to fill in the hole with new bone, attaching new bone crystals into their proper place within the existing bone matrix.
During childhood the activity of osteoclasts and osteoblasts is set to a very high pace of both – governed by higher levels of growth hormone active in bones. Once you have finished growing, growth hormone activity declines and osteoclasts and osteoblasts work together to maintain the current size and strength of your bones for the duration of your life. The normal activity of both osteoclasts and osteoblasts is vital to maintaining strong and healthy bones.
In women, the hormone progesterone favors osteoblast activity and the hormone estrogen helps balance or slow down osteoclast activity.
A novel herb, cissus quadrangularis, has been in traditional use for a thousand years as part of Ayurvedic medicine. The Sanskrit name for this herb is Hadjod which translates literally to bone-union. It is now available as an organically grown standardized extract. Modern science confirms that it supports the bone building process, helping to activate one of the osteoblast’s key enzymes that triggers bone building, alkaline phosphatase2. Cissus quadrangularis has been shown to prevent osteoporosis3 in female rats that have had their ovaries removed. Interestingly, the nutrient has been shown to assist in healthy weight loss4 (more on the relationship of bones and metabolism later in this article).
A Startling Bone Breakthrough
It has long been known that bone exists as a matrix of protein mainly in the form of collagen to which minerals are attached. The protein matrix is responsible for the toughness and the minerals are responsible for the stiffness of bone. In order to have strong bones it is vital to have a healthy relationship between the protein matrix and the attached minerals.
Up until the end of 2007 it was taught in all bone biology classes that the minerals were directly attached to protein molecules. U.K. researchers from the University of Cambridge have quietly shocked the entire bone world and opened up a treasure-trove of natural options for individuals to strengthen bone.
In a recent study5 they showed that it was actually sugar molecules that linked the minerals to the collagen-protein matrix. These sugar molecules form the structural blueprint and the adhesive connections that make bone strength possible. This is a dramatic new discovery.
Specifically, the sugar molecules identified by the researchers are called glycosaminoglycans (GAGs), which means many sugars strung together in repeating units – a type of complex carbohydrate. Using advanced imaging technology, the researchers proved, for the very first time, that these sugar molecules are responsible for the linking attachments between proteins and minerals that enable bone to form. In fact, they are directly responsible for the symmetrical formation of bone that enables bone strength. GAGs are directly responsible for modulating mineral size and crystalline structure.
The most important GAG is called Hyaluronic Acid (HA). It is a combination of two sugars (D-Glucoronic Acid and N-Acetyl-Glucosamine) that form one unit referred to as a disaccharide. One molecule of HA has as many as 10,000 disaccharide units, making it a very large and long molecule. For many years scientists thought this simple long molecule didn’t do much of anything except fill space and provide joint lubrication. Now scientists understand that HA acts as a template to assist in the formation of new body structure, like a blueprint for the construction workers to follow. In other words, HA is to the human body what soil is to a crop.
HA is the fundamental GAG, but it is used as a building block to form other types of GAGs that play unique and important roles in different body structures. These other GAGs have an HA spine, and then use sulfur to form more specific GAG structures such as chondroitin sulfate (cartilage), keratin sulfate (cartilage and bone), dermatin sulfate (skin and blood vessels), and heparin sulfate (cell membranes). GAGs are the fundamental alphabet that enables any kind of body tissue to form and have shape.
The new research is groundbreaking as it proves that GAG molecules are the essential glue that not only holds bone together but also guides the formation of a bone’s proper three dimensional integrity and crystalline shape. Without enough GAGs bone crystals form in an unregulated manner resulting in weaker bones.
One newly identified risk factor for bone loss is a high homocysteine level, as it has been found that elevated homocysteine directly interacts with the collagen matrix of bone and disturbs the bone integrity. This problems is readily prevented by taking B vitamins, especially folic acid, B12, and B6.
Another Profound Discovery
One of the major problems in maintaining healthy bones over the course of a lifetime is keeping a proper balance between osteoclasts (the demo crew) and osteoblasts (the new construction crew). Both must act in harmony. In cases of bone-related stress or wear and tear it appears osteoclasts get carried away and osteoblasts take a nap.
An answer to this problem has emerged from the new field of osteoimmunology6. The data shows that excess inflammation, i.e., excessively turning on the NF-kappaB gene signal, is the direct cause of too many osteoclasts forming which results in excessive bone loss7.
This new science shows that macrophages (immune cells) and osteoclasts (the demo crew) come from the same parent cell. Thus, as cells begin to take form from basic stem cells there are options as to what they might become. A key switch has been identified called NF-kappaB8. If the NF-kappaB switch is too active, then too many osteoclasts are made. If the NF-kappaB switch is in more normal operation, then osteoclasts are produced at a healthier level, likely in better balance with its companion, osteoblasts.
The NF-kappaB switch is actually part of the intelligence of a cell. When it is on too often it means the cell is overheating or inflamed. Stress is a major factor that causes excessive NF-kappaB activation. Numerous nutrients interact with the NF-kappaB switch, and many have now been documented to interact specifically in bone to modulate healthy bone function by suppressing the excessive activity of osteoclasts.
One of the top nutrients in this regard is boswellia serrata9. This herbal extract is clearly shown to reduce excess osteoclasts formation by turning off NF-kappaB in bone (the source of the problem). Other nutrients proven to lend support in this way are quercetin10, curcumin11, guggul12, DHA13, tocotrienols14 (special vitamin E), R-alpha lipoic acid15, green tea catechins16, zinc17, and of course magnesium18. A diet rich in fruits and vegetables is conducive to supporting this principle of bone health.
Many of these nutrients help bones in multiple ways. For example, tocotrienols help calcium attach to bones19 as well as helping to prevent stress induced (high cortisol) bone loss - even bone loss induced by steroids20.
A nutrient like lactoferrin21 has been shown to partly work by inhibiting osteoclasts, yet also work by other mechanisms to significantly help boost the architectural integrity of the bone leading to better bone strength. A nutrient like vitamin K22 does not seem to slow down osteoclasts, but it does directly enhance the quality of bone once again leading to better bone strength (synergistic with the GAGs mentioned earlier).
Thyroid Health and Your Bones
A fundamental question arises: Who is managing the construction crew of osteoblasts and osteoclasts? Herein the plot thickens and the complexity of the issue increases by many orders of magnitude. I will try to keep this as easy to understand as possible, so that you can get the basic gist of what is going on and an understanding of where new science is taking us – as well as how you can use this information to your advantage.
TSH (Thyroid Stimulating Hormone) is generally thought of as a message going from your pituitary gland to your thyroid gland, telling your thyroid to get going. As TSH levels rise (subclinical hypothyroidism), it means your pituitary is yelling at your thyroid to get going, and your thyroid may or may not be responding.
In addition to this primary function of TSH, the new science shows that TSH is directly talking to the osteoblasts23 in bone (the bone building carpenters), which have TSH receptors on them. In fact, osteoblasts are listening for TSH instructions in order to pick up their hammers and go to work – while at the same time telling osteoclasts not to work too hard.
A number of studies, both animal and human, prove that a lack of TSH24 results in bone loss. On the other hand, too much TSH also shuts down osteoblasts, a problem we might call TSH resistance (similar to leptin resistance or insulin resistance). This problem has now been clearly demonstrated in postmenopausal women25.
This means that it is absolutely vital to have a correct amount of TSH signaling to your thyroid as well as to your bone, as a basic need for healthy bone rejuvenation.
It has also been proven that the presence of adequate T326 (active thyroid hormone) is needed for osteoblasts to perform. In this context think of TSH as the order to get to work and T3 as the signal the provides the energy to do a full day’s work.
Because individuals with hypothyroid, sub-clinical hypothyroid, or just plain sluggish thyroid function tend to have too much TSH and not enough T3, it is a double-negative bone-stressing situation that directly causes poor bone strength.
Prior to this new understanding it was simply thought that hyper thyroid induced bone loss due to an excessive metabolic state that “burned up” bone as an undesirable consequence (which is true). Now we see that virtually every shade of gray in terms of hypothyroid proneness is adverse to bone. This means fixing even small thyroid glitches is important for maintaining healthy bones.
Leptin is in Command
The overall function of thyroid hormone in your body is occurring with permission from the big hormone boss, leptin. Not surprisingly, leptin regulation of bone27 is even more important than thyroid regulation of bone. We now understand that leptin regulates bone in two primary ways:
1) Leptin signals your subconscious brain (hypothalamus) to turn on sympathetic nerves that directly regulate the activity of osteoblasts.
This may be one of the most complex regulatory systems in your body. The leptin-permitted message from your brain via your nerves actually slows down osteoblasts (meaning less bone formation). On the other hand, leptin simultaneously allows the increase in TSH that tells osteoblasts to get going. In health, this is some sort of a fitness system in signaling, a form or management flexibility to go either direction and to have a system of feedback that keeps the carpentry crew nimble yet under control.
In fact, it appears that leptin wants to make sure everything is working properly, so much so that leptin itself acts locally in bone, primarily to ensure bone building takes place. Thus, if you are normal body weight and have a normal appetite, then leptin will enter your brain in a normal amount and trigger complex signals that directly regulate your bone formation – as your body’s primary signal for doing such. You will also have leptin, in a normal amount, acting locally within your bones to ensure bone regeneration.
Leptin enables the human race to withstand starvation. Thus, situations that are similar to real starvation (malnutrition, anorexia, excessive exercise, mal-absorption of food, etc.) lower leptin levels to withstand the withering effect of not enough nutrition. Bone loss always accompanies this problem, and is always accompanied by low leptin activity within bone. Bone regeneration is energy intense and cannot proceed in times of true malnutrition, so leptin controls the process and puts bone regeneration on hold until more nutrition is available.
However, when a person is overweight bone metabolism starts to go haywire. An overweight person is leptin resistant, meaning there is too much leptin in their blood coming from the extra pounds of fat, yet that leptin isn’t getting into the brain (a false state of perceived starvation). This causes central nervous system and thyroid signals to behave as if starvation is going on, while local leptin within bone is excessive. This problem causes bone chaos with consequent bone weakening and disruption of overall body metabolism (discussed in the next section), even if bone density appears “normal” in a two-dimensional picture.
I mentioned previously that the parent cells of osteoclasts could either become macrophages or osteoclasts. If there is too much inflammation in bone then excessive osteoclasts are made that break down bone. Well, the parent cells of osteoblasts can either become osteoblasts or new fat cells. As a person gains weight then excess fat cells are formed within bone, depressing the formation of osteoblasts. Furthermore, inflammatory immune cell activity takes place as a result of the extra fat cells, in turn stimulating the formation of too many osteoclasts. This is how leptin problems damage bone health.
Believe it or not, this is a simple explanation of the complexity involved. While leptin is the primary signal in your brain regulating healthy bone regeneration, numerous related brain signals also modulate bone health. One in particular is worth mentioning, and that is the elevation of NPY (neuropeptide Y) which is invariably associated with excessive cravings for carbohydrates. NPY slows down osteoblasts and increases osteoclasts. Said another way, if you are overweight and craving food too often, especially carbohydrates, you are likely losing bone density and bone strength.
The bottom line is to keep leptin in good working order by following the Leptin Diet and you’ll be doing your bones a favor. This is especially important if you are trying to lose weight, as you can lose significant bone density by losing weight improperly. Any nutrients you use to help yourself stay on the Leptin Diet towards a successful outcome will be synergistically helping your bones even if you don’t think of such nutrients in the traditional bone-support category. If you would like to read a comprehensive scientific article explaining bones and leptin, click here28.
The Emerging Metabolic Picture
There is far more to this story. So far we have been discussing this issue from the perspective of making your bones strong and healthy. The new science shows that healthy bones play a major role in determining healthy metabolism.
It has been found that osteoblasts secrete a protein called osteocalcin that is not only involved in the formation of bone29 but acts as a hormone30, communicating to stored fat and increasing the production of adiponectin. Adiponectin is a vital hormone that enables your liver to be sensitive to insulin so that you do not become glucose intolerant and eventually type II diabetic. At the same time, ostecalcin also communicates to your pancreas and helps it make insulin in the first place, so that you have improved ability to transport sugar to places it needs to go.
On the other side of the coin is research showing that extra osteoclasts, the cells that drive inappropriate bone loss, make too much of a specific enzyme called tartrate resistant acid phosphatase or TRAP. They bred a strain of mice to generate excessive TRAP so they could study exactly what it did to bones – and much to their surprise it made the mice fat.
The research was able to show that macrophages (immune cells) acting within white adipose tissue (stored fat) used TRAP to generate new fat cells. Overweight people make 400% more TRAP than normal weight people. This lends novel proof to the existing body of science that the process which drives an expanding waistline is an inflammatory process, in no small part caused by immune cells operating within stored fat. It is also likely that excess TRAP production within bone helps fuel the production of fat cells within bone, at the expense of osteoblast formation and consequent osteocalcin production – though this hasn’t been demonstrated yet. It has been shown that the mineral boron31 lowers TRAP production by osteoclasts.
This problem of abnormally weak bones due to obesity has now been documented in children and teens. Considering the obesity epidemic in these young people, we can expect serious bone health issues in their later years. Messing up bones while you are growing is a huge problem that causes a failure to reach genetic potential – ground that will be very difficult, if not impossible, to make up later. It is also important to lose weight in a healthy way so that bone density is not lost while weight is lost.
The bottom line is that too many osteoclasts tilt metabolism towards bone loss, obesity, inflammation, and impaired insulin function. On the other hand, adequate osteoblasts help guard against obesity, excess inflammation, and help improve the function of insulin in multiple ways while at the same time building new bone.
This data means that anything you do to improve your bone health will have a profound effect on improving your overall metabolism. For example, by lifting weights you can stimulate osteoblasts32 to repair bone that you are now using more. As you stimulate osteoblasts, then osteocalcin levels will rise, in turn boosting adiponectin and helping to correct insulin resistance or reverse type II diabetes.
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