Osteoporosis

Description

Causes

Because the patterns of reforming and resorbing bone often vary from patient to patient, experts believe a number of different factors account for this problem. Important chemicals (such as estrogen, parathyroid hormone, and vitamin D) and blood factors that affect cell growth are involved with this process. Changes in levels of any of these factors could play a role in the development of osteoporosis.

The Role of Sex Hormones in Bone Breakdown

Although ordinarily associated with women, sex hormones play a role in osteoporosis in both genders, most likely by controlling the birth and duration of life of both osteoclasts (bone breakers) and osteoblasts (bone builders).

Women and Estrogen. Experts are still puzzled by the rapid decline in bone density after menopause, when a womans ovaries stop producing estrogen. Estrogen comes in several forms:

The uterus is a hollow muscular organ located in the female pelvis between the bladder and rectum. The ovaries produce the eggs that travel through the fallopian tubes. Once the egg has left the ovary it can be fertilized and implant itself in the lining of the uterus. The main function of the uterus is to nourish the developing fetus prior to birth.

• The most potent form of estrogen is estradiol. Estradiol deficiency appears to be a very strong factor in the development of osteoporosis.
• The other important but less powerful estrogens are estrone and estriol. In one study, high levels of estrone were associated with high risk for spinal fracture, but the researchers said these results might have been due to chance.

The ovaries produce most of the estrogen in the body, but it can also be formed in other tissues, such as body fat, skin, and muscle. After menopause, some amounts of estrogen continue to be manufactured in the peripheral body fat. And even though the ovaries have stopped producing estrogens directly, they continue to be a source of the male hormone testosterone, which converts into estradiol.

Estrogen may have an impact on bone density in various ways:

• Estrogens most important effect on osteoporosis appears to be prevention of bone breakdown (resorption). Some research suggests that estrogen may control the life span of osteoclasts, the cells responsible for bone breakdown.
• One study reported that part of estrogens beneficial actions may involve maintaining normal levels of vitamin D, an important nutrient in bone protection.

Men and Androgens and Estrogen. In men, the most important androgen (male hormone) is testosterone, which is produced in the testes. Other androgens are produced in the adrenal glands. Androgens are converted to estrogen in various parts of a mans body, including bone.

Click the icon to see an image of the adrenal glands.

Studies in 2000 and 2001 have suggested that the loss of estrogen as well as testosterone may contribute to bone loss in elderly men. In one study, elderly men were first given a drug that blocked their normal hormones and then were given estrogen and testosterone patches. When the estrogen patch was removed, the bone breakdown process accelerated. When both patches were removed, the number of the bone-building cells (the osteoblasts) decreased. In other words, both hormones appeared to be integral to bone function in men.

Vitamin D and Parathyroid Hormone Imbalances

Low levels of vitamin D and high levels of parathyroid hormone (PTH) have been associated with hip fracture in women after menopause:

• Vitamin D is a vitamin with hormone-like properties. It is essential for the absorption of calcium into the bone and for normal bone growth. Lower levels result in impaired calcium absorption, which in turn causes an increase in PTH.

Click the icon to see an image of the benefits of vitamin D.

Click the icon to see an image of the sources of vitamin D.

• Parathyroid hormone (PTH) is produced by the parathyroid glands. These are four small glands located on the surface of the thyroid gland. They are the most important regulators of calcium levels in the blood. When calcium levels are low, the glands secrete more PTH, which then increases blood calcium levels. High persistent levels of PTH stimulate bone resorption (bone loss).

Click the icon to see an image of the parathyroid glands.

Genetic Factors

A number of studies on family members, including twins, have strongly suggested that genetic factors help determine bone density. Some examples include the following:

• Of particular interest are genetic factors that affect vitamin D, which is a critical nutrient for calcium absorption in the body.
• A 1998 study has introduced another suspect, a genetic mutation that controls production of a type of collagen, a structural protein that is critical in bone formation.
• Many studies are currently looking at abnormalities in genes that may cause deficiencies in estrogen receptors, molecules that help estrogen work on cells. Estrogen is important in maintaining bone density in both men and women.

An interesting 2000 study on mice suggests that the enzyme leptin may play a role in bone build-up and loss. Mice that have genetic mutations causing them to be deficient in leptin (the so-called obesity gene) are not only obese but they also have extremely strong bones. Leptin is a hormone produced in the brain and is associated with thinness in high levels and obesity in low levels. If leptin proves to affect bone density, by implication the brain becomes an important player in osteoporosis.

Causes of Secondary Osteoporosis

Corticosteroids. More than 30 million Americans have disorders that are commonly treated using corticosteroids (also called glucocorticoids or steroids). Oral corticosteroids are known to reduce bone mass in both men and women. Some studies are reporting a higher risk for bone loss in adults who take inhaled steroids regularly. The risk is higher with increasing doses, and is still lower than with oral steroids. (Children on inhaled steroids may have temporary impaired growth, but they do not appear to be at risk for bone loss.)

Other Medications. Anti-epileptic agents increase the risk for bone loss (as does epilepsy itself). Other agents that increase the risk for bone loss include heparin, progestin without estrogen (such as Depo-Provera or other progestin-based contraceptives), and hormonal agents that suppress estrogen (such as gonadotropin-releasing hormone agonists). Diuretics (used to treat high blood pressure) have different effects on osteoporosis depending on the type. Loop diuretics (which block sodium) have been associated with bone loss. Thiazide diuretics, on the other hand, confer protection against fracture during the time they are used.

Predisposing Medical Conditions. Osteoporosis can be secondary to a number of other conditions, including alcoholism, diabetes, hyperthyroidism, epilepsy, chronic liver or kidney disease, celiac disease, scurvy, rheumatoid arthritis, leukemia, cirrhosis, gastrointestinal diseases, vitamin D deficiency, hypogonadism (impaired development of reproductive organs), lymphoma, hyperparathyroidism, and rare genetic disorders, such as Marfans and Ehlers-Danlos syndrome.