Hip, spine and wrist fractures caused by osteoporosis cost $15-30 billion a year in the United States alone. Osteoporosis (skeletal deterioration) is usually associated with postmenopausal women. Estrogen replacement therapy is the most commonly used treatment to date. However, new drugs for osteoporosis will soon hit the market.

Drug companies know a gold mine when they see one. The No. 1 selling drug in America is Premarin, a synthetic estrogen made from the urine of pregnant mares. Calcitonin nasal spray has recently been approved for sale in this country, and Merck & Co. will soon begin a massive marketing campaign for their new osteoporosis drug Fosamax (Alendronate).
How Fosamax works:
Fosamax works differently than estrogen or calcitonin. The drug attaches to bone cells called osteoclasts and inhibits them from breaking down bone. Bone is constantly being built up by osteoblasts and broken down by osteoclasts. Proper skeletal formation depends on a coordinated effort between these two types of cells. The clinical trials with Fosamax show it can improve bone density up to 3%; however, no one knows the long-term effects of incorporating a foreign substance into osteoclasts. The longest trial of the drug was three years.

There are also questions about the long-term effects of interfering with the natural process of bone building and tearing down. Fosamax interferes with bone resorption, yet bone resorption does not necessarily lead to osteoporosis. In a recent study in the Journal Of Nutrition, it was found that dietary soybean caused greater resorption of bone and greater bone density in hormone-deficient (ovariectomized) rats. In another study, there was both greater bone resorption and bone augmentation in men given growth hormone (GH), yet the net effect was increased bone.
Understanding Osteoporosis:
A better understanding of why osteoporosis occurs could lead to safer, cheaper and more natural remedies for the condition, and break the drug companies’ stranglehold over its treatment. Studies published during the last five years are encouraging about the prospect of a more natural approach to the prevention and treatment of osteoporosis. A coherent picture is emerging that gives insight into why osteoporosis occurs, and what can be done about it.

Estrogen is a proven treatment for osteoporosis, yet it has been reported that some women with low estrogen levels do not develop osteoporosis. This puzzle was solved in 1992 by researchers in the United Kingdom, who proved that blood levels of estrogen do not necessarily reflect bone levels of the hormone. Bone, it turns out, manufacturers its own estrogen.

Editor’s note: There is evidence that the female hormone progesterone plays an important role in maintaining strong, healthy bones with advancing age. This evidence was presented in the Jan. ’96 issue of LIFE EXTENSION Magazine. The Foundation offers a progesterone cream that has helped to maintain bone strength in post-menopausal women. (See the Life Extension Buyers Club Order Form in the magazine).
The DHEA connection
Both estrogen and testosterone are made from adrenal steroid hormones. Bone cells have enzymes, which convert these adrenal steroids into estrogen. Dehydroepiandrosterone (DHEA) is one of the steroids produced by the adrenal gland. Researchers have found that DHEA is significantly lower in patients with osteoporosis than those without the disease.

DHEA is converted into a type of estrogen called estrone in bone cells through the action of the enzyme aromatase. Estrone increases the activity of osteoblasts, the cells that build bones. A study in Japan on 120 postmenopausal women clearly demonstrates that there is a positive relationship between DHEA sulfate (DHEAS) and bone mineral density through the DHEA-to-estrone pathway. The ability of DHEA to stimulate bone-building cells through this pathway is dependent on a form of vitamin D called Vitamin D3.
(Note: a recent study confirms that vitamin D3 alone is insufficient to stimulate bone-building cells).
Cytokines, free radicals and aging:
DHEA modulates bone density by affecting osteoclasts as well as osteoblasts. This occurs in the following manner: free radicals are produced by certain pro-inflammatory cytokines. (Cytokines are chemical messengers similar to hormones, which affect immunity). These free radicals then activate osteoclasts, the cells that absorb bone and make it porous.

As people grow older, their levels of pro-inflammatory cytokines increase, which, in turn, increases the production of free radicals. The age-related increases of the proinflammatory cytokines tumor necrosis factor (TNF), interleukin 1 (IL-1) and interleukin 6 (IL-6) have been documented in humans.

A study in Nature clearly shows that TNF inhibits bone collagen and enhances the production of collagenase, the enzyme that breaks it down. IL-1 also elevates levels of collagenase. Both cytokines cause resorption of bone. In addition, IL-1 causes the production of prostaglandins, some of which contribute to bone resorption. The role of IL-6 in human bone resorption is controversial, but evidence indicates it stimulates osteoclasts as well.
Is DHEA the future treatment for osteoporosis?
Many studies suggest that DHEA plays dual roles in the development of osteoporosis. Research shows that DHEA reverses the increase of pro-inflammatory cytokines that occurs naturally with age. When DHEA was given to aged mice, IL-6 went down and immune function went up. When it was given to mice exposed to a bacterial toxin, DHEA blocked the effects of TNF, the cytokine which inhibits bone collagen and causes other toxic effects. DHEA may exert its effect on IL-6 through TNF, since TNF causes the production of IL-6. The effects of DHEA on IL-1 are not available, but IL-1 is very similar to TNF.

While the effects of DHEA on cytokines produced by bone cells is still under investigation, it is reasonable to suspect that its effects will mimic what occurs in immune cells. Human studies are lacking partly because the measurement of cytokines in bone cells in vivo is difficult. Moreover, the processes leading to bone accumulation and resorption are complex, and subject to the slightest variation in experimental conditions. Despite these problems in tracking DHEA’s effect on cytokines in human bone, there is ample evidence that DHEA can modulate bone resorption through its effects on cytokines. If DHEA behaves in bone cells as it does in immune cells, it will stop age-related osteoporosis by inhibiting cytokines like TNF that provoke free radicals and cause bone resorption.

Although osteoporosis is usually associated with postmenopausal women, it is being recognized that it is a problem for men as well. Back pain is frequently the main complaint of men with the condition. A mouse study in the Journal of Clinical Investigation in 1995 showed that testosterone replacement stops bone loss in males, as estrogen replacement does in females. Since DHEA is the precursor to both testosterone and estrogen, all indications are that it will prove to be an important treatment for osteoporosis in both men and women. The Life Extension Buyers Club offers DHEA in 25-mg. capsules.
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