So oft in theologic wars,
The disputants, I ween,
Rail on in utter ignorance,
Of what each other mean,
And prate about an Elephant,
Not one of them has seen!

–John Godfrey Saxe

hose of us seeking to maintain our health in modern times will often be well-served to remember the age-old story from which the above quote is taken - The Blind Men and the Elephant.

According to this parable, which has been continually invoked and subtly altered throughout the ages, a group of blind men each attempt to reach an understanding of what an elephant “is” by using their sense of touch alone.

The first man, touching the elephant’s side likens the mighty beast to a wall, whereas the second man, feeling only the smoothness and sharpness of its tusk, becomes certain that the elephant is much like a spear. Each blind man, in turn, perceives the creature differently – the man touching the trunk is sure that the elephant is like a snake, while the men touching the elephant’s leg is sure that the elephant is like a tree, the man touching the ear likens the elephant to a fan, and so forth. In most versions of the story throughout history, the blind men then proceed to argue fiercely, each believing that their interpretation of the creature constitutes the one and only truth.

Yet, to put the blind men’s experience into somewhat scientific terms, their findings were all equally valid - but each lacked the conceptual framework to see the bigger picture. Though each man was technically “correct,” the end result was still confusion and hostility, instead of useful, practical knowledge.

As the scientific exploration of biochemistry and molecular biology has expanded greatly in recent years, we can often see a parallel phenomenon in popular interpretations of biological, medical, and nutritional research. Many of today’s “health experts” and alternative medicine gurus could be said to suffer from a similar sort of blindness (and complicating matters further, of course, is the fact that, unlike the blind men of the ancient parable, many of these modern day experts stand to benefit financially if their limited perceptions are widely accepted as truth).

This helps to explain why, as relates to nutritional science, the lay public has been constantly bombarded with little more than meaningless clichés and half-truths – substitutes for meaningful thought which have combined into the “conventional wisdom” of our time. These clichés often become firmly ingrained in cultural consciousness, and their unquestioned acceptance makes rational thinking on issues of health infinitely more difficult than it would otherwise be.

The biology of healthy bone is a perfect example.

The dominant cultural clichés surrounding bone health can be difficult to combat. Take calcium, for example. The marketing behind calcium-containing foods, and more recently, calcium supplements, has been so strong over the past several decades, that many people simply assume osteoporosis to be, fundamentally, a calcium-deficiency disorder.

But, though calcium certainly plays a role in bone-building, for most women, calcium supplements alone represent, at best, a modest amount of damage control against the ravages of age-related bone loss. For most women, in fact, calcium supplements do very little to rectify this increasingly common problem.

Indiscriminately consuming massive amounts of calcium, as is often recommended, makes about as much sense as trying to build a house by dropping off more and more lumber at a construction site. Without many other elements and the workers present to do the actual construction, a house won’t magically appear simply because one of its structural elements is present. The same is true when it comes to the building of bone.

In fact, studies comparing several countries have shown that American women have the highest rate of hip fracture despite eating a food supply which is among the highest in calcium worldwide. While at the same time, many groups of women throughout the world who consume far less calcium than American women seem to be protected from osteoporosis:

Study Link – Calcium and Osteoporosis.

Quote from the above study:

…according to currently available information, hip fractures are more frequent in populations where dairy products are commonly consumed and calcium intakes are relatively high… If women in general required 800 mg calcium/d or more, calcium deficiency and osteoporosis would be rampant throughout the world.

Such research makes it overwhelmingly clear that truly preventing or actually reversing bone loss requires a far greater depth of understanding than can be obtained by merely listening to the “conventional wisdom” of our day.

To begin to find workable answers, it’s important to address a few of the most common and deeply-entrenched misconceptions. The following are a few facts on bone health which have yet to receive the widespread attention they deserve:

1. Bone-building requires much more than just calcium.

Many nutrients are needed for bone building in addition to calcium. Non-calcium bone-building nutrients are often more apt to be deficient in the diet than calcium itself, and many of these nutrients are needed for the proper handling and storage of calcium. In aging (in both men and women), bone calcification decreases, while calcification and hardening of soft tissues (heart, arteries, kidneys, muscle, liver, skin) increases. Any person consuming calcium supplements should familiarize themselves with exactly which nutrients are necessary for calcium to be deposited in bone instead of the soft tissues. We’ll find that often times, the foods we exclude or limit in our diets will be just as important as the foods and nutrients we add.

2. Estrogens (including “natural” estrogens and food-based phytoestrogens) are not the answer to bone loss.

The fact that estrogen, and some plant-based estrogens (like those from soy, flax, clover, black cohosh, et al.) may inhibit the cells which break down bone has led to the widespread assumption that these compounds are able to build bone. Even leaving aside the potential side effects of these compounds throughout the rest of the body, it’s likely that estrogenic chemicals, as a group, may actually impair the building of strong, healthy bone – especially as we age. In aging and bone loss, a relative imbalance of hormones (which can be worsened by high amounts of phytoestrogens) may amplify the effects of estrogen, and of bone-destroying hormones such as cortisol and prolactin. Ensuring proper levels of protective hormones, such as progesterone and DHEA, is likely to be a major factor not only in inhibiting bone loss, but in actually building new bone.

3. Proper thyroid function and proper thyroid hormone metabolism are needed to build healthy bone.

Most conventionally-trained physicians are apt to warn their menopausal patients about the danger of thyroid medications causing osteoporosis. But, in truth, proper levels of the active thyroid hormones are very important for bone turnover (the breakdown of old bone, and its replacement with new, stronger, bone). In conjunction with several nutritional factors, thyroid hormone, because it improves mitochondrial respiration, is also likely to prevent the harmful calcification of soft tissues. For those who are taking thyroid medications, there are several strategies which can see to it that this thyroid hormone is metabolized properly. For those who aren’t, these same strategies will help to ensure the proper production and metabolism of the thyroid hormone produced by the body.

4. Reducing systemic inflammation and oxidative stress helps to build bone.

In previous Integrated Supplements Newsletters, we’ve written about the overlapping toxicity of excess iron and polyunsaturated fats. As we age, the body’s level of both of these substances tends to increase, predisposing us to oxidative stress, inflammation, and the calcification of soft tissues instead of bone. Addressing these phenomena will afford us protection against all degenerative diseases, including osteoporosis.

Much like the blind men and the elephant, we’ll need several different perspectives in order to see the big picture of why bone loss occurs and what we can do about it. In the end, we’ll find that a multi-faceted approach to bone-building will positively impact every aspect of our health.

The Coming Osteoporosis Epidemic

As the worldwide population ages, researchers are already sounding the alarm of the coming osteoporosis epidemic.

According to the U.S. Surgeon General’s report of 2004, by the year 2020, a full 50% of Americans over the age of 50 will have, or be at significant risk of developing osteoporosis of the hip alone – the risk of developing osteoporosis in any site of the skeleton is even greater.

And even Asian population - who are sometimes thought to be relatively resistant to the ravages of aging which affect Western cultures – can expect a dramatic increase in the incidence of osteoporosis in the coming decades. It has been estimated that, by the year 2050, almost 50% of all hip fractures worldwide will occur in Asia:

Study Link - World-wide Projections for Hip Fracture.

Quote from the above study:

The major demographic changes will occur in Asia. In 1990, 26% of all hip fractures occurred in Asia, whereas this figure could rise to 37% in 2025 and to 45% in 2050. We conclude that the socioeconomic impact of hip fractures will increase markedly throughout the world, particularly in Asia, and that there is an urgent need to develop preventive strategies, particularly in the developing countries.

Of course, it’s logical to assume that as populations live longer, that the overall incidence of age-related disorders such as osteoporosis will increase, but to make matters still worse, it seems that even the age-adjusted incidence of osteoporosis and fragility fractures may be increasing as well. This means that the bone health of older people today is generally becoming worse than the bone health of people in the same age group in years past.

Study Link - Increasing age-adjusted risk of fragility fractures: A sign of increasing osteoporosis in successive generations?

Quote from the above study:

The age-adjusted incidence of fragility fractures is increasing. This is the outcome of almost all epidemiologic studies that have been done throughout the world during the last 40 years.

As medical interventions against osteoporosis seem to continually come up short, it may be helpful to take a fresh perspective on the multi-faceted aspects of bone metabolism.

A Little Background on Bone Building

When we understand the process by which bone is built, it becomes easier for us to weed out many of the useless and potentially harmful “bone-building” products and strategies promoted by the pharmaceutical and nutritional supplement industries.

The first thing to realize is that bone isn’t a static tissue like a stone or a pillar of marble. There’s actually a continuous yin and yang-type balance between the breakdown of old fragile bone and the building of new, strong, healthy bone. In youth, the building of bone exceeds its breakdown – the result being an increase in bone mass during late adolescence and early adulthood. In a person’s early thirties, the breakdown of bone is usually roughly equal to the formation of new bone, keeping bone density mostly stable; and in middle age and beyond (especially in women after menopause) bone loss begins to outpace bone building, often resulting in the bone-loss disorders of osteopenia and ultimately, osteoporosis.

The scientific literature on bone remodeling centers around some key concepts:

Resorption:
The natural breakdown of bone. Resorption of bone isn’t a bad thing per se – it’s a necessary part of removing old, fragile bone so new stronger bone can take its place. It’s only when bone resorption outpaces the production of healthy, strong bone, that bone-loss becomes an issue.

Osteoclasts:
Immune cells which remove old bone tissue.

Osteoblasts:
Immune cells which begin the formation of new bone tissue.

Bone Mineral Density or Bone Mass Density (BMD):
A measurement of the density of bone, often used to diagnose osteopenia or osteoporosis. It’s important to note that BMD can often be a misleading indicator of bone health. Some drugs (like the currently popular bisphosphonates) can increase BMD, while, perhaps, compromising the structural integrity of bone. Similarly, estrogen is known to alter the water and fat content of cells in such a way as to give the false impression that bone mineral density is increasing when measured using x-ray testing. This sort of pharmaceutical and technological “hocus-pocus” is a major reason to question the validity of BMD-testing as the end-all-be-all of bone health.

Estrogen, Progesterone, Cortisol, and Bone

For decades, the medical community has repeated the cliché that osteoporosis, and even menopause itself, are both caused by the age-related cessation of estrogen production by a women’s ovaries. It was largely this simplistic assumption which led directly to the commercially-driven concept of estrogen replacement therapy; and ultimately, to the wider concept of hormone replacement therapy (i.e. HRT, usually employing patentable and profitable synthetic hormones).

Only in recent years, as the negative effects of this “hormone replacement therapy” have become too great for even the pharmaceutical companies to ignore, have estrogen drugs lost a bit of their luster as safe and viable treatments for menopausal symptoms. Although originally promoted as a strategy to reduce cardiovascular disease and cancer in post menopausal women, hormone replacement therapy is increasingly being shown to actually contribute to the development of these disorders. As such, the pharmaceutical industry has quickly switched their focus to the promotion of HRT for other disorders of menopause like osteoporosis and dementia. But the question still remains: Are the supposed benefits worth the risks?

As in the story of the blind men and the elephant, the evidence, at first, seems contradictory – that is, until we gain a broader perspective of the many factors involved.

Confounding the issue is the fact that the remnants of decades’ worth of incessant estrogen marketing remain embedded in the cultural consciousness. Even the widely-held concept of estrogen as “the female hormone” needs to be questioned if we are to gain the proper perspective of the hormonal milieu of osteoporosis.

First off, menopause isn’t, in fact, characterized by declining estrogen levels in quite the way the dominant cultural cliché implies. Of course, when the functioning of a woman’s ovaries declines in menopause, estrogen synthesis does decline as a result. But many tissues of the body can produce estrogen – not just the ovaries. Adipose (fat) tissue is a very well-known estrogen producing tissue (in both men and women) but its contribution to estrogen production in men, and in women after menopause, is often ignored.

In menopause, as the functioning of the ovaries declines, so too does the production of the protective hormone, progesterone. Unlike estrogen, the other “female hormone,” progesterone, is scarcely produced when ovarian functioning ceases (though a bit is produced by the adrenal glands). While levels of estrogen may drop 40-60% at menopause, it’s often the case in many women, that progesterone production drops nearly to zero. Knowing this, many thinking researchers have begun to characterize menopause not as a time of estrogen deficiency, but rather, as a time of relative estrogen excess compared to the anti-estrogenic effects of progesterone.

Many people, if they are familiar with progesterone at all, simply associate the hormone with pregnancy (i.e. its role as the pro-gestational hormone). The presence of somewhat progesterone-like progestins (which are NOT progesterone, as we shall see) in birth control drugs and HRT, hints at progesterone’s generally protective nature against the cancer-causing, and cardiotoxic effects of estrogen. When estrogen-containing drugs were first marketed to women without any protective progesterone-like components, the results were often disastrous, and included cancers, fatal blood clots, and birth defects.

But the body’s natural progesterone (which unlike progestins, can be metabolized into many other protective hormones), is one of the most far-reaching regulators of cellular function. Although the two hormones work together in many ways, progesterone can be said to protect against many of the toxic effects of estrogen. Immune function, liver/gallbladder/gastrointestinal function, anxiety and panic, inflammation and autoimmune disorders, have all been improved by progesterone therapy, while an estrogen excess tends to exacerbate or even cause such disorders. And as research continues, there are a growing number of researchers who believe that we may be able to add bone loss to the list of disorders caused by a lack of protective hormones, such as progesterone.

The fact that bone loss begins and increases progressively in women during the time when estrogen levels are increasing considerably (roughly between the ages of 20 to 40), is clear evidence that the menopausal onset of osteoporosis cannot so simply be attributed to an “estrogen deficiency.” Progesterone levels begin to decline several years before the onset of menopause, while estrogen production is still relatively high. This decline in progesterone directly parallels the most rapid period of bone loss for women.

Osteoporosis is much more common in women than in men, and it’s probably no coincidence that a man’s progesterone levels throughout his life are usually much greater than those of postmenopausal women. But even still, in aging, a man’s estrogen level can increase dramatically. The rate of osteoporosis in elderly men correlates directly with increasing estrogen levels - yet another reason to seriously question the conventional dogma that osteoporosis is caused by a lack of estrogen.

In men and women, progesterone is likely to protect against not just estrogen itself, but several stress-related hormones which increase in aging. It has been proposed that without sufficient progesterone, which is an antagonist to the destructive hormone, cortisol, that the bone-destroying effects of cortisol progress unabated. While progesterone triggers the building of bone, cortisol blunts this same process. It has been well-documented that the use of cortisol-like glucocorticoid drugs greatly increases the risk of osteoporosis; and, even in men, elevated levels of circulating cortisol are directly related to lowered bone density and an increased rate of bone loss:

Study Link - Profiles of Endogenous Circulating Cortisol and Bone Mineral Density in Healthy Elderly Men.

Quote from the above study:

These observations suggest that the endogenous cortisol profile of healthy elderly men is a determinant of their bone mineral density and their rate of involutional bone loss.

And a similar scenario of cortisol excess has been shown to play a role in osteoporosis of pre-menopausal women suffering from anorexia nervosa:

Study Link - Mechanisms of osteoporosis in adult and adolescent women with anorexia nervosa.

Quote from the above study:

We found a negative correlation between spinal bone density and duration of amenorrhea (P = 0.006; r = -0.53)… the cortisol excess that occurs in [anorexia nervosa] patients may contribute to the development of osteoporosis in these patients.

Note: Anorexia nervosa and the often-concomitant amenorrhea, characterized by the lack of menstrual flow for 180 days or more, exhibits hormonal changes very similar to those of menopause i.e., estrogen dominance relative to progesterone despite lower than normal estrogen levels, and elevated cortisol.

Bone loss is known to occur largely at night, in direct parallel to the circadian increase in cortisol levels. Elevated cortisol and related stress hormones at night may play a role in the sleeplessness and restlessness many people experience – especially in aging. Progesterone, as a cortisol antagonist, is known for its calming, restorative effect, and the only known side effect is sedation if too large of a dose is taken.

The medical disorder known as Cushing’s syndrome is characterized by chronically elevated cortisol levels, either as a result of adrenal cortisol overproduction, or the long-term use of glucocorticoid drugs. As a result of the tissue-destroying effects of cortisol, it’s not surprising that Cushing’s syndrome is well-known to lead to osteoporosis. Some researchers have noted a marked similarity between the hormonal changes which take place in Cushing’s syndrome and those which take place in menopause. Somewhat ironically, it has been found that supplementation with several of the hormonal precursors of cortisol (such as progesterone) have been found to have profoundly anti-cortisol, and bone-protecting effects.

Note: It’s worth noting as well that progesterone is perhaps the only hormone for which supplemental doses don’t inhibit its production by the body. Progesterone-containing creams are commonly available over the counter in the U.S., and low to moderate amounts applied to the skin appear to have a normalizing effect on the hormonal status of both men and women.

Another adrenal hormone, dehydroepiandrosterone (DHEA), declines so steadily with aging, that some researchers suspect it to be the most important anti-aging hormone. DHEA is able to be converted into both androgens and estrogens, but in low doses, DHEA appears to restore balance to the hormonal cascade. In the context of bone health, DHEA has been shown to reduce cortisol levels significantly, and to protect and rebuild bone even when administered in remarkably small doses.

The following study found that just 10 milligrams of DHEA per day, given to postmenopausal women for one year led to a significant decrease in cortisol levels. When DHEA was given with standard HRT, the reduction of cortisol was less than with DHEA alone:

Study Link - One-year therapy with 10mg/day DHEA alone or in combination with HRT in postmenopausal women: effects on hormonal milieu.

Quote from the above study:

Moreover, DHEA alone induced a significantly lower increase in estrogens and beta-endorphin levels and a higher decrease in cortisol levels than HRT.

Additionally, some research conducted in older individuals shows that DHEA holds promise for increasing bone mineral density in both men and women:

Study Link - Effects of dehydroepiandrosterone replacement therapy on bone mineral density in older adults: a randomized, controlled trial.

Quote from the above study:

DHEA replacement therapy for 1 yr improved hip BMD in older adults and spine BMD in older women.

In women suffering from anorexia nervosa, who, as we have seen, exhibit similar hormonal changes to those of menopausal women, DHEA supplementation helps to protect bone, and has even been found to restore proper menstrual function in many of the patients studied:

Study Link - Changes in Bone Turnover Markers and Menstrual Function After Short-term Oral DHEA in Young Women with Anorexia Nervosa.

Quote from the above study:

Bone loss is a serious consequence of anorexia nervosa (AN). Subnormal levels of serum dehydroepiandrosterone (DHEA) are seen in patients with AN and may be causally linked to their low bone density. Short-term DHEA was well-tolerated and appears to normalize bone turnover in young women with [anorexia nervosa].

On a molecular level, DHEA has been shown to stimulate the function of bone-building osteoblasts, even independent of its conversion to androgens (e.g. testosterone) or estrogens:

Study Link - Dehydroepiandrosterone improves murine osteoblast growth and bone tissue morphometry via mitogen-activated protein kinase signaling pathway independent of either androgen receptor or estrogen receptor.

Again, it’s likely that the best results from DHEA will occur with the use of very low doses. Large doses are often used in research studies, but the safety and effectiveness of large doses is unknown. A person’s goal should always be to restore optimal hormonal balance, and large DHEA doses are likely to be counter-productive to these ends. Oral doses of 5 to 10 milligrams per day, or even every other day, can be sufficient to restore youthful DHEA levels without danger of estrogenic effects. Though remarkably safe in such doses, with DHEA, as with all hormonal intervention, the guidance of a knowledgeable health practitioner is advised.

Prolactin and Bone

The anti-cortisol actions of progesterone and DHEA, though important, aren’t the only reasons why these substances offer great promise for the maintenance and building of bone.

Another stress-related hormone which is associated with bone loss is prolactin. As its name implies, prolactin is largely responsible for stimulating lactation after pregnancy. Because of an infant’s high demand for calcium, it has been proposed that prolactin stimulates the breakdown of bone to supply calcium to the fetus directly, and later, to mother’s milk. The high levels of progesterone during pregnancy serve to inhibit lactation by inhibiting the actions of prolactin. After childbirth, it’s the dramatic drop in progesterone which then allows prolactin to stimulate lactation.

In menopause, though lactation doesn’t occur, there also exists a relative deficit of progesterone which allows prolactin to mobilize calcium from the bones excessively. Estrogen, and estrogen-containing drugs have been shown to increase prolactin, and prolactin has been shown to have profoundly negative effects on bone turnover. Those advocating estrogen/HRT therapy or phytoestrogens for menopause and osteoporosis usually forget that these substances often increase prolactin levels:

Study Link - Incidence of hyperprolactinemia during oral contraceptive therapy.

Study Link - Pharmacological causes of hyperprolactinemia.

Quote from the above study:

A long list of other compounds may determine an increase in prolactin levels, including prokinetics, opiates, estrogens, anti-androgens, anti-hypertensive drugs, H2-receptor antagonists, anti-convulsivants and cholinomimetics

Study Link - Dietary genistein exerts estrogenic effects upon the uterus, mammary gland and the hypothalamic/pituitary axis in rats.

Quote from the above study:

Plasma prolactin was significantly greater in ovariectomized rats fed genistein [a phytoestrogen in soy] (750 microg/g) compared with comparable rats not receiving genistein.

Men and women taking antipsychotic medications which are known to elevate prolactin, are at great risk of developing osteoporosis:

Study Link - Effects of long-term prolactin-raising antipsychotic medication on bone mineral density in patients with schizophrenia.

Quote from the above study:

These results suggest that patients with schizophrenia on long-term prolactin-raising antipsychotic medication are at high risk of developing reduced bone mineral density as a consequence of hyperprolactinaemia-induced hypogonadism.

Progesterone, on the other hand, lowers prolactin secretion, possibly by blocking the effects of estrogen on the pituitary:

Study Link - Progesterone negative feedback on prolactin secretion: importance of the brain control and of estradiol.

Quote from the above study:

Since progesterone action on [prolactin] levels in serum is observed only in rats with a normal brain-pituitary relationship and when high levels of estrogens are present, it is postulated that the negative feedback effect of progesterone on [prolactin] release by the pituitary is in part at the level of the brain, blocking the stimulatory effect of estrogen on [prolactin] secretion.

Knowing that progesterone deficiency is more directly related with bone loss than estrogen deficiency, and knowing that natural progesterone is a remarkably safe substance which combats the bone-destroying actions of both cortisol and prolactin, it’s reasonable to expect progesterone therapy to support bone health in a physiologically sound way. Some studies have shown that progesterone can indeed act to stimulate the production of new bone via its stimulatory action on osteoblasts (the cells which build bone).

Study Link - Progesterone as a bone-trophic hormone.

Quote from the above study:

Progesterone appears to act directly on bone by engaging an osteoblast receptor or indirectly through competition for a glucocorticoid osteoblast receptor. Progesterone seems to promote bone formation and/or increase bone turnover.

Though the research is far from conclusive, many women have experienced success in increasing their bone mass using preparations containing natural progesterone and/or DHEA. It’s important to note that natural progesterone (the same molecule as our body produces) is very different biologically than the synthetic progestins used to balance estrogen in pharmaceutical HRT preparations. In limited contexts, progestins may have some progesterone-like effects, but the molecular manipulation of these chemicals (used to make them patentable, more profitable drugs) also inhibits their metabolism in our body’s sensitive hormonal cascade. As such, in many situations, synthetic progestins can impart effects which are the exact opposite of natural progesterone.

To be continued in the next Integrated Supplements Newsletter…