In a related study also conducted by researchers at Kyushu University in Japan testing bone mineral density and DHEA levels in 120 post-menopausal women aged 51 to 99 years found a definitive link to increased DHEA levels and stronger bones.

Dr. George Redmon

 

The Physiological Interaction of DHEA on Bone Health

 

Over the past decade there has been renewed interest in the rise of specific disorders related to deteriorating musculoskeletal health.  Musculoskeletal disorders like osteoporosis, weak bones, arthritis, and other bone diseases account for more than 50% of all the chronic conditions Americans over the age of fifty are afflicted with.1  In fact, one out of every four Americans suffer from some form of bone and or joint disorder.1  This despite participation in a collaborative effort of many well-known health organizations entitled the National Bone and Joint Decade (March 2002 thru March 2011).  The goal of this coalition of health organizations was to promote and facilitate collaboration that focused on improving bone and joint health through education and research.2  However, disorders related to bone health and bone density are expected to escalate in the next decade and beyond, as a direct result of an increased aging population and inappropriate lifestyle factors.1  While previous studies and education have focused on adequate calcium intake along with vitamin D3 to improve absorption as well as the attributes of exercise and its link to calcium supplantion in bones, numerous studies have also focused on the synergistic or combined effects of other nutrients on bone health.3  Nutrients such as magnesium, vitamin K2, Boron and phosphorus.  However, based on new information about bone health researchers have focused on ways to reduce or circumvent certain physiological processes that disrupt or inhibit bone remodeling, thus accelerating bone deterioration and density.4  For example, researchers at the Clinical Laboratory and Molecular Diagnostics Department of the Coeriatric Hospital in Ancona Italy, found that when the body is under continuous states of chronic low-grade inflammation that this inhibits osteoblast activity (cells responsible for bone formation) which up-regulating osteoclast activity (cells which break down bone).5  According to these researchers there now exists a well-known physiological paradox of immune suppression and the coexistence of increased levels of pro-inflammatory agents called cytokines that have a negative impact on metabolism, bone density and strength.  From all indications, these progressive pathophysiological changes explains the aging mechanisms that foster decline and the body’s struggle to maintain robustness, in the midst of increasing frailty.5  This increased frailty based on new research is found within the bone matrix as a direct result of declining levels of the hormone DHEA during the aging process.5  In this report, I will discuss how dehydroepiandrosterone (DHEA) actually increases bone density in aging individuals by modulating key regulatory activities within the bone matrix.

The DHEA Story

Dehydroepiandrosterone is one of the most abundant hormones found in the human body.  Sometimes referred to as the mother hormone, it regulates the body’s production and modulation of 18 other steroid hormones such as estrogen and testosterone, as well as the stress hormones cortisol and norepinephrine.6  Commonly used as an anti-aging supplement,7  DHEA has been linked to improving immune system function, antioxidant profiles,8  and the destruction of various brain chemicals associated with Alzheimer’s disease and dementia.9  Its use as an anti-cancer,10  anti-atherosclerosis, anti-obesity and anti-diabetic agent11 has been well documented.  There has also been consistent data that has definitively associated declining levels of DHEA with decreased functional limitations, in both men and women and increased rates of mortality.12  As the most abundant hormone in the human body, levels tend to decline at an accelerated rate in the mid thirties.  In fact, by age 65 blood levels drop 10 to 20% of optimal levels.  By age 80, blood levels can drop to less than 5% of youthful levels of that of individuals aged 25 to 35.13 

How DHEA Outsmarts Osteoporosis


In a 2006 study appearing in Clinical Calcium and a related 2006 study in Cellular and Molecular Immunology, researchers described how reduced activity levels of DHEA in aging females in practical terms could be considered a precursor to osteoporosis.  Researchers studying the role of androgens and DHEA in relationship to bone metabolism at the Department of Geriatric Medicine, Kyushu University Japan, found androgen receptor sites in osteoblast, osteoclast and in bone marrow stromal cells.  Androgens or growth agents like DHEA have demonstrated the ability to regulate the expression and activity of many different cytokines and growth factors, while modulating the maintenance and repair activities within the bone matrix.14  These researchers found that post-menopausal women benefit from DHEA as a bone restoration agent via its intracrine mechanism of actions within osteoblast, where DHEA is converted to estrogen through a process referred to as the aromatase activity.14  As a precursor to estrogen, progesterone and testosterone, all of the hormones deter bone loss, as a direct result of their physiological inter-actions with DHEA.  Paradoxically, bone cells convert DHEA into estrone, the form of estrogen that is responsible for accelerating the activity of the osteoblast, the cells which actually make new bone.  The osteoclasts are cells that initiate the destruction of bone.  This action called The Transformation Process, DHEA’s transformation into estrone occurs with the help of vitamin D3.  Vitamin D3, however, needs DHEA to invigorate and strengthen the osteoblast.15  Based on the conclusions from this study, these researchers found a positive correlation between DHEA levels and increased bone density in women over fifty.  The higher a woman’s DHEA levels were at menopause, the greater the density of the bones.16  This study also clarifies how skeletal health is dependent upon the delicate balance between bone formation and bone resorption.  Bone loss is often occurs as a result of an imbalance between these two processes.  While the deterioration of bone, fragility and fractures are associated with many factors such as genetics, environmental, nutritional, and chronic disease, the correlation to hormonal activity is still an important factor to consider especially in aging women.17  In fact by raising DHEA levels in aging men and especially women can reduce the incidences of osteoporotic fractures.18  In a related study also conducted by researchers at Kyushu University in Japan testing bone mineral density and DHEA levels in 120 post-menopausal women aged 51 to 99 years found a definitive link to increased DHEA levels and stronger bones.19  According to data collected by these researchers they also concluded that DHEA’s conversion to estrone (E1) is osteoblast, which is an important factor to maintaining bone mineral density as estrogen levels decline following menopause.19  These researchers had also previously administered DHEA to experimental female rats whose ovaries had been removed (pophorectomy).  While DHEA is also produced in the ovaries, without them, supplemental DHEA still increased the rate of bone density in these animal models.19  Conversely, researchers at the Department of Obstetrics and Gynecology, at Jiaotong University investigating the physiological effects of DHEA on postmenopausal women with osteoporosis, reported that DHEA improved osteoblast or bone building activity substantially.20  Based on their study results, DHEA inhibited the bone resorption or breakdown of bone by osteoclast at blood concentrations of 0.01 microm.  This positive physiological action were even more pronounced at concentration of 0.1 microm.20

DHEA Increases Bone Mineral Density

In a study appearing in the Townsend Letter for Doctors and Patients, seventy women and seventy men aged 60 to 88 in a double-blind placebo controlled study were randomly administered 50 mg/d of DHEA or a placebo for a year.21  Compared to the placebo group the mean bone mineral density increased in the DHEA group by 1% to 0.05% in the hip.  In the femoral shaft bone mineralization increased by 1.2% versus 0.06% in the placebo group.  Similar increases were also seen in BMD in the lumbar spine region of women in this study by 2.2% in the DHEA group as compared to 0.04% in placebo.21  Results of this study indicate that markers of bone resoption appear to be a stronger predictor of future bone loss than markers of bone formation, with the link being stronger in older women as compared to young women.22,23,24

Mounting Problem

Recently researchers at the Division of Adolescent/Young Adult Medicine at Harvard Medical School conducted a randomized double blind study of 15 anorexic young women.  Looking at how well dose ranges of 50 mg, 100 mg and 200 mg a day improved bone mineral density.  These researchers reported that all of the subjects receiving each dose range had dramatic decreases in markers for bone resorption with significant increases in markers related to bone formation.25  These results have far reaching implications on reference to preserving bone health of young women with anorexia nervosa.  These women tend to exhibit subnormal levels of dehydroepiandosterone (DHEA) and estrogen which studies suggest that this link is a direct cause to the bone loss seen in these individuals.26  To assess this proposed above negative mechanisms of action, researchers at the Children’s Hospital in Boston MA compared the effects of a one year course of oral DHEA treatment versus that of conventional hormonal replacement therapy (HRT) in young women with anorexia nervosa.26  In this trial sixty one young women were randomly administered 50 mg/d of DHEA or 20 micrograms of the HRT drug ethinylestradio/0.1 mg levonorgestrel.  Anthropometric or body measurements, nutritional, and exercise data were recorder over a 3-month period.  Bone mineral density and body composition changes were measured every 6 months over the course of one year.  While both therapies in this study significantly decreased bone resorption or breakdown process, hip bone mass density were positively correlated with increases in insulin growth factor (IGF-1) bone formation markers and bone-specific alkaline phosphatase (bone ALP)26 which is an enzyme immunoassay which is used to measure active bone formation.27,28  The increase in IGF-1 associated with DHEA intake is also of great significance here as IGF-1 plays a critical role in bone metabolism.  Higher levels of IGF-1 have what researchers refer to an osteotrophic effect.28  The osteotrophic effect is a term used to describe the relationship between physical exercise and osteoporosis.  While too little exercise serves as a precursor to osteoporosis, moderate exercise reduces the risk of developing this bone disorder.  However, excessive exercise increases the risk of developing osteoporosis, when combined with the absence of menstruation and in cases of anorexia and other eating disorders.29  Researchers speculate that the osteotrophic effect is more pronounced with physical activity during early childhood and adulthood, because growing bone has a greater capacity to add new bone to the skeleton than mature or older bone.  Hence the need to restore and maintain youthful levels of DHEA.29

The IGF-1 Connection

 While a decline of the hormone IGF-1 is seen in aging women and men, it is also seen in young women suffering from anorexia nervosa.30  In the above aforementioned study as compared with hormone replacement therapy, DHEA had clear anabolic or growth effects on the bone matrix as evidenced by the direct correlation between increases in hip dual energy x-ray absorptiometry (DXA) measurements and IGF-1 levels and substantial increases on bone formation markers.31  Furthermore, Mexican researchers cite the fact that a major complication of eating disorders, especially anorexia nervosa is bone mass loss.32  The mechanisms implied in the destruction of bone deterioration are declining estrogen levels, elevated cortisol levels and decreases insulin like growth factors (IGF-1) in these individuals.  According to these investigators, the first line of treatment to recover bone mass in these cases is with nutritional rehabilitation and weight gain, hormonal replacement therapy, combined with an anabolic method that can positively manipulating bone restorative activities within the bone matrix.32

The Cortisol Connection

A mounting body of scientific data suggests that DHEA also improves bone repair and building activities as a direct result of its ability to reduce levels of the stress hormone cortisol.33  Studies have shown that when cortisol levels remain elevated as a result of physical and mental stress, this up-regulates the what stress researchers refer to as the fight or flight response.34  To deal with a perceived stress or as first discovered by Dr. Hans Selye, known as the father of stress research, the body quickly reroutes energy sources and micronutrients involved with bone building activities to muscle tissue.35  Additionally, according to scientists at the Department of Molecular and Clinical Endocrinology at the University of Naples in Italy, they reported that glucocorticoid-induced osteoporosis is one of the most frequent causes of secondary osteoporosis.36  Investigating what effect sex steroids had on reducing the severity of hypercortisolism on bone mineral density (BMD) and the prevalence of vertebral fractures in female patients, these researchers based on data collected from a cross-sectional case-controlled study found that by increasing DHEA levels at any degree of cortisol excess, minimized the negative aspects of vertebrae fractures.  They concluded that the lumbar spine bone mass density is directly related to cortisol-to-DHEA ratio, actually being the best predictors of impending vertebral fractures.36

Suggested Dose: Based on a large body of scientific evidence, 50 mg to 200 mg a day is needed to maintain blood levels of 20-30 nmol/l.  Many physicians check DHEA blood levels and adjust daily dose ranges to maintain levels as cited above. Which exhibit positive affects on maintaining bone health.37

Conclusions

These is now considerable evidence that verifies the efficacy of restoring declining DHEA levels in aging women to enhance bone mineral density.38,39  In fact, based on current data, improvements in bone mineral density in response to DHEA supplementation appears to occur not only as a result of suppression of bone resorption but more importantly stimulation of bone formation.40,41  In practical terms here, DHEA should be considered as a primary adjunct to current supplementation and other modes of osteoporosis prevention programs42 in pre and postmenopausal women over the age of 35.42,44  This consideration should be vigorously discussed with healthcare professional, as DHEA is the only hormone that can both stop bone breakdown, while stimulating bone formation.45

 

 References

 

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