Osteoporosis Protocol



Osteoporosis is a debilitating, costly, and difficult-to-treat decline in bone density that occurs primarily in postmenopausal females. It causes a progressive marked reduction in bone mineral density that often results in fractures of a serious nature. Most commonly these are spinal and hip fractures. Osteoporosis is a major public health issue for more than 28 million Americans, 80% of whom are women. It is estimated that in the United States today, 10 million individuals already have osteoporosis, and 18 million more probably have a low bone density, placing them at increased risk for osteoporosis in later years. Half of the women over the age of 50 will have an osteoporosis-related fracture in their lifetime. Although osteoporosis is often thought of as an old person's disease, it can affect younger people who have hormonal difficulties, particularly women with anorexia, bleeding, or menstrual abnormalities in their 20s. Osteoporosis also occurs in men. Osteoporosis is responsible for more than 1.5 million fractures annually, including 300,000 hip fractures, 700,000 vertebral fractures, and 250,000 wrist fractures (Riggs et al. 1995). The estimated cost for osteoporosis and associated fractures is $13.8 billion a year (Iqbal 2000).

Peak bone mass is achieved by both men and women in their 20s and 30s. After that time there begins a period of the net bone loss. With the onset of menopause, women begin an accelerated period of bone loss that may increase by tenfold so that they may lose bone at the rate of 3-6% per year (Christiansen 1994). Osteoclasts, the bone cells that break down bone, are activated by a loss of estrogen and a subsequent elevation of inflammatory factors that stimulate bone resorption (removal of bone from the body with transport to the blood).

Known risk factors for osteoporosis are:

Being female
Thin or small frame
Family history of osteoporosis
Postmenopausal, including surgical menopause (i.e., hysterectomy including ovariectomy)
History of anorexia or bulimia
Prolonged amenorrhea (absence of menstrual periods)
Low calcium diet
Lack of exercise
Cigarette smoking
Excessive alcohol use
Excessive caffeine use

Detection of Osteoporosis

Osteoporosis usually has no symptoms, although loss of height and pain can be involved if there are fractures. An awareness of the potential for osteoporosis from a healthcare provider or media advertising may be the only warning for some women. Osteoporosis is detected either by inadvertent fracture, which is too late, or by regular bone density measurements in a period of increased risk.

Standard testing for bone loss will measure levels of deoxypyridinoline (Dpd), a cross-link of type 1 collagen that provides tensile strength to the collagen matrix of bone. Dpd is released into the circulation during bone resorption and is excreted unmetabolized into urine. Because Dpd levels are not affected by diet or physical exercise, urinary Dpd concentrations reflect the true rate of bone turnover. The following reference ranges show normal bone resorption rates determined after laboratory testing:

Normal Range
(nmol Dpd/mmol creatinine)
Women 2.3-7.4
Men 2.3-5.4

Levels of Dpd above the normal reference range are consistent with bone loss. The name of this simple blood test that measures bone loss is "Pyrilinks-D."

All postmenopausal women, particularly in the early years after cessation of menses, should have bone density studies--preferably the quantitative computed tomography (QCT) test. These bone density tests should be performed about every 1-2 years in the first 5 years after menopause. At this point, any significant bone loss should be treated to prevent further loss. The bone densities of patients are compared to a standard 35-year-old population of the same gender, and osteoporosis is defined as a patient with a spinal bone density 2.5 or greater standard deviations (SD) from the mean of that population. This is called the T-score. There is an exponential increase in fractures with decreasing bone mineral density. For every 1 SD decrease in bone mass, there is a twofold increase in risk of fracture.

Once detected, there are a number of treatments available, both alternative and standard. However, the most significant "treatment" is prevention and awareness of the possibility of osteoporosis. The likelihood of osteoporosis occurring can be reduced significantly by following these general guidelines:

Stay active. Back extension exercises are particularly important as are weight-bearing exercises.
Eat a diet that is high in calcium and other important trace minerals (including magnesium) and low in phosphorus (see Vitamin/Mineral Treatments and Bone Loss).
Reduce caffeine and alcohol and eliminate cigarette smoking.
Balance hormones.

Postmenopausal Osteoporosis
Osteoporosis is a metabolic disease affecting the skeleton which causes a reduction in the amount of bone tissue. Bones are weakened as these tissues are resorbed or taken up by local cells. At the core, trabecular bone becomes less dense. On the perimeter, cortical bones lose thickness. Osteoporosis increases the bones' susceptibility to fracture because of thinner bone tissue at the perimeter and more porous bone tissue at the core. Type I, Postmenopausal Osteoporosis, usually occurs in women following menopause. Type II, or Age-Related Osteoporosis, afflicts both women and men aged 70 or older.
Postmenopausal osteoporosis usually occurs in women several years after menopause. At this time, women's ovaries produce less estrogen (a female sex hormone). In the absence of estrogen, bone resorption increases, dropping overall bone mass below the maintenance density level and risking fracture. (Anatomical Chart Company 2002®, Lippincott Williams & Wilkins)
Bone Formation & Restoration
Bone is composed of 30% organic and 70% mineral substances. The organic portion is called osteoid and acts as the matrix or framework for the mineral part. Osteoid is produced by bone cells called osteoblasts. The mineral part consists of calcium and other valuable minerals and hardens upon the osteoid matrix. Osteoclasts are large bones which reshape mature bone by resorbing the mineral and organic components. Bone formation and resorption are normal, continuous processes.
In osteoporosis, there is an overall decrease in bone mass because resorption by osteoclasts exceeds bone formation. Osteoblasts continue to produce bone, but not to the same extent that it is being resorbed.

During the last two decades, a number of valuable treatments for osteoporosis have become available and are reviewed in this protocol. It is important to note that most treatments, at best, provide minimal increases in bone density. The most significant treatment is still prevention of bone loss, particularly for postmenopausal women. Primary prevention, before there is any actual bone loss, can probably be accomplished at first with only diet, supplementation, and exercise changes as described below.

Secondary prevention, when there has been some loss but the goal is to prevent further reduction or to increase bone density, will most likely require hormonal replacement therapy. Much of this is discussed in the Female Hormone Replacement Therapy protocol, particularly with regard to progesterone and estrogen and to concerns about estrogen side effects. Below we discuss various interventions that can be used.

Osteoporosis and Hormone Metabolism

Estrogens and Progesterones
Estrogen Receptor Modulators
Soy Products
Bone Loss
Other Hormones

Estrogens and Progesterones
The primary cause of osteoporosis is hormonal imbalances that interfere with the bone-forming cells. The osteoblasts are specialized bone cells that function to pull calcium, magnesium, and phosphorus from the blood in order to build bone mass. Osteoblasts require the hormone progesterone to maintain youthful bone-forming capability during and after menopause. Young women with amenorrhea (absence of menstrual cycle), short luteal phases, or other ovulation disturbances show an increased bone density when given synthetic progesterone (medroxyprogesterone) (Prior 1990; Prior et al. 1994). Studies have also demonstrated increased bone mass and decreased fracture rate with synthetic estrogen therapy (Zarcone et al. 1997; Castelo-Branco 1998). As a result, there have been huge advertising campaigns promoting the use of Premarin, a synthetic estrogen derived from horse urine, as a treatment for osteoporosis.

However, estrogen therapy has significant risks that include an increased risk of uterine and breast cancer. It used to be thought that if synthetic progesterone were given with synthetic estrogen in a cyclical fashion that the increase in cancer risk from estrogen alone would be diminished. However, the well-known Nurses' Health Study, conducted at Harvard Medical School, reported that women had a 23-67% increase in their risk of breast cancer while using estrogen alone or estrogen and a synthetic progestin. This study showed that the carcinogenic risk of estrogen-progestin replacement therapy became most pronounced when it was used for 10 or more years (Colditz et al. 2000).

However, data from the Breast Cancer Detection Demonstration Project suggest that relative risk is increased by 20% even after 4 years of use compared to no hormone treatment and that surprisingly there was a 40% increased risk of breast cancer using both estrogen and progestin combined, compared to only 20% increase for estrogen alone. (Schairer et al. 2000). This latter finding goes against theoretical beliefs and prior research that combining estrogen with progesterone would mitigate against an increased risk due to the "anti-proliferative" effect of progestin. Other side effects of estrogens include vaginal bleeding, breast tissue tenderness, and deep vein thrombosis.

Because of the worrisome side effects of estrogen replacement, alternative physicians have recommended the use of progesterone in a natural form and the use of other forms of estrogen rather than estradiol, both of which can be compounded by pharmacists into creams that bypass the liver. Dr. John Lee, working in California, demonstrated an increased bone density in women using progesterone cream. Since natural progesterone cannot be patented, there is little economic incentive to conduct the kind of extensive clinical trials that have been done with FDA-approved progestin drugs. Dr. Lee has studied the clinical outcomes and found them positive, however. For those contemplating hormone therapy, there are reasonable alternatives provided that bone density is followed closely. If bone densities are increasing or remaining the same on natural estrogen or progesterone regimes, then this is a reasonable course to follow. Women often find that natural progesterone and estrogens are easier to take. Natural progesterone and estrogen certainly have less impact on the liver, especially if absorbed through the skin.

Natural progesterone may be obtained in several different forms. The safest route of progesterone administration is via a topically applied cream that absorbs directly through the skin and into fat cells. It is important to apply natural progesterone cream to different parts of the body (face, breasts, abdomen, and thighs) so the fat cells under the skin in any one particular area required to assimilate the hormone into the body are not oversaturated. The topical application of progesterone enables it to enter the body without first going through the digestive system. If progesterone were to be taken orally, it would have to first pass through the liver, which degrades and excretes much of the hormone into the bile. Natural progesterone is available in topically applied creams that contain between 900-1400 mg of natural progesterone per 2-oz jar.

In using progesterone cream, pre- and postmenopausal women should start with 1/4-1/2 tsp a day. Those with severe osteoporosis should use 1/2 teaspoon morning and night for the first jar, followed by 1/4 tsp a day for the second jar onward. Premenopausal women who have premenstrual syndrome (PMS) may consider taking 1/8-1/4 tsp of progesterone on days 15-26 of their menstrual cycle.

It is advisable for women to ask their doctors to measure blood or saliva levels of the various hormones to best individualize the correct dosage, although natural progesterone has been safely used by millions of women by individually adjusting the dose to reflect alleviation of PMS or menopausal symptoms. In other words, if hot flashes, night sweats, headache, and depression are alleviated by using 1/4 tsp of natural progesterone cream daily, then a woman may be able to safely stay at that dose. While it is prudent to consider progesterone blood or saliva testing, the safety of natural progesterone is such that a pregnant woman will naturally secrete large amounts of progesterone without encountering toxicity. In an ideal setting, hormonal blood or saliva testing would be done routinely, but since most pre- and postmenopausal women produce very little progesterone, these women have historically safely self-administered topical progesterone cream according to how well it corrects their menopausal symptoms. With the advent of lower-cost saliva and blood testing, it should be possible for more women to target their ideal progesterone level. While relief of postmenopausal symptoms is possible, the actual effect must be measured by QCT bone density testing to see if there is a positive effect on osteoporosis.

Selective Estrogen Receptor Modulators [SERMS]
More recently other hormonal treatments have been developed that include selective estrogen receptor modulators or SERMS. Raloxifene (Evista) was the first member of this family of drugs, which have now been shown to have a positive effect on a woman's bone density (Fontana et al. 2001). Raloxifene is related to tamoxifen (Nolvadex), which has been used to treat breast cancer for many years. These drugs selectively bind to estrogen receptors, and it is the selectivity of these drugs that has set them apart from other synthetic hormones. Thus, raloxifene will bind to estrogen receptors in bone osteoclasts thereby decreasing the resorption of calcium into the blood.

Studies have found significant increases in bone density with raloxifene and subsequent drugs of this type. They are not without risk and should not be taken by people with liver disease, nor will they help with postmenopausal hot flashes. Currently, raloxifene is the only SERM with FDA approval for postmenopausal osteoporosis. Lasofoxifene, a newer and more potent SERM, is currently undergoing clinical trials in postmenopausal women. Similar to raloxifene, lasofoxifene does not appear to stimulate uterine tissue, a negative effect associated with other SERMs. The drug is presently in Stage III FDA review and possibly may launch in 2002 or 2003.

Osteoporosis Protocol Pg (1) (2) (3)

These statements have not been evaluated by the FDA. These products are not intended to diagnose, treat, cure, or prevent any disease