Contrary to popular belief, bone is not a lifeless structure, but is living, growing tissue. Throughout life, a dynamic process called "remodeling" occurs in which old bone is removed (resorption) and new bone is laid down (formation). During the resorption phase, bone removing cells (called osteoclasts) carve cavities into the surface of the bone, while in the formation phase, bone forming cells (called osteotlasts) fill in the cavities with new bone until the bone surface is restore~. Beginning in childhood and continuing throughout early adulthood, bone formation normally occurs faster than bone removal, so that bones become larger, heavier, and denser. In the early to mid-thirties, bone removal overtakes bone replacement leading to a net loss of bone tissue. With osteoporosis, bone formation is inadequate, or bone removal is excessive, or both abnormalities occur. Osteoporosis leads to fragile bones which break easily.

Risk Factors for Osteoporosis

There are a number of risk factors that can increase your likelihood of developing osteoporosis. These risk factors include being female, having a small frame, a family history of the disease, advanced age, early menopause, a diet low in calcium, a sedentary lifestyle, smoking, and excessive us of alcohol.

A significant and often overlooked risk factor is the use of certain medications that have side effects which can damage bone and lead to osteoporosis. One class of drugs that has particularly damaging effects on the skeleton are glucocorticoids. Additionally, excessive doses of thyroid hormones, anticonvulsants, antacids containing aluminum, gonadotropin releasing hormones
used for the treatment of endometriosis, and certain other prescription drugs have been shown to cause bone loss. For many people, these are life-saving or life-enhancing drugs, and their use may be the only way to achieve a better quality of life. That's why it's important to discuss the use of these medications with your physician, and not stop or alter your medication dose on your own.

What are Glucocorticoids?

Glucocorticoids, also called corticosteroids or simply steroids `, are a group of hormones produced by the ~ adrenal glands, which are located above the kidneys. In normal amounts, glucocorticoids play an important role in the regulation of blood sugar levels, retention of salt and water, and in metabolism and growth. They also inhibit the body's immune system and act to suppress allergic reactions. Excessive production of glucocorticoids occurs in a condition called Cushing's syndrome or Cushing's disease. This disease causes a number of symptoms; one of the most serious of these is accelerated bone loss which leads osteoporosis a fractures. Cushing's disease was originally so rare that glucose ticoid-induced osteoporosis did not represent a significant public health problem. However, this changed in the late 1940's when synthetic glucocorticoids were introduced as potent anti-inflammatory 2 and immunosuppressive medications (See Table 1 for a list of the commonly-used glucocorticoid medications). These drugs are widely used for the treatment of a number of disorders, such as rheumatoid arthritis, osteoarthritis, asthma, and lupus erythematosus (see Table 2 for a more complete listing of these disorders). Glucocorticoid are effective in the management of these diseases and improve the patient's quality of life. However, since osteoporosis
is a potential side effect of the use of these drugs, bone health must be carefully monitored during treatment with glucocorticoids.

Table 1: Generic Names of Various Forms of Glucocorticoids

*That Are Available in Commonly Prescribed Medications*

Cortisone

cortisone acetate

Hydrocortisone

hydrocortisone acetate

hydrocortisone sodium phosphate

hydrocortisone sodium succinate

Prednisone

Prednisolone

prednisolone acetate

prednisolone sodium phosphate

prednisolone terbutate

Triamcinolone

triamcinolone acetonide

triamcinolone diacetate

triamcinolone hexacetonide

Methylprednisolone

methylprednisolone acetate

methylprednisolone sodium succinate

Dexamethasone

dexamethasone acetate

dexameehasone sodium phosphate

Betamethasone

betamethasone acetate

betamethasone sodium phosphate

Flunisolide

Beclomethasone Dipropionate

This list is not all-inclusive. If you think you may be taking a medication that contains glucocorticoids, ask your physician or pharmacist.

Glucocorticoid-Induced Osteoporosis

Abnormally high levels of glucocorticoids interfere with the bone remodeling process and calcium regulation in a number of different ways. Glucocorticoids decrease the amount of calcium absorbed from food and increase the loss of calcium in the urine. This leads to the overproduction of the parathyroid hormone, which works to maintain the level of calcium in the blood by removing calcium from bone. Glucocorticoids also exert a direct effect on the cells responsible for bone maintenance, stimulating the osteoclasts and inhibiting the osteoblasts. Furthermore, the production of estrogen in women and testosterone in men is reduced by glucocorticoids, another factor which may contribute to bone loss.

2 Non-steroidalanti-inflammatory medications, .such as aspirin and ibuprofen, do not have a negative effect on bone.

As a result of these multiple effects, glucocorticoids can inhibit skeletal growth and development in children and can result in rapid and severe bone loss in adults. The degree of bone loss is such that, if taken in high doses, glucocorticoids can cause fractures in less than a year. The bones in the spine, the ribs, and the wrist are most susceptible to the effects of glucocorticoids.

Glucocorticoids are administered in a number of different ways: orally, with tablets or pills, or by injections into the joints (e.g.,
for arthritis); by inhaler (e.g., for asthma); as creams (e.g., for skin diseases); as drops (e.g., for eye diseases); or, less commonly, by intravenous injection (e.g., for multiple sclerosis or after organ transplantation). Prolonged oral administration is likely to cause the most bone loss, although excessive use by other routes can also damage bone.

Bone loss increases with the dose and the duration of the steroid treatment. The adverse effects of steroids on the skeleton can occur even with intermittent use of these drugs. Therefore, it is important that your physician prescribe the lowest dose possible to control your symptoms. When your condition improves, steroids should be discontinued, although this usually has to be done gradually to avoid relapse or symptoms due to steroid withdrawal. If glucocorticoid use cannot be discontinued, it may be possible to switch from an orally administered drug to a less harmful route of administration.

Other Drugs That Can Cause Osteoporosis

Although glucocorticoids are the most commonly used drugs that can cause osteoporosis, there are a number of other medications that can adversely affect bone. Not all of the drugs in each category have side effects that result in bone. loss, so your physician may be able to prescribe alternatives that are less harmful to bone.

Thyroid Hormones

Sufficient levels of thyroid hormones are necessary to insure normal skeletal development; excessive amounts, however, can cause bone removal to exceed bone formation, resulting in a net decrease in bone mass. Excess thyroid hormones can result from overproduction by the thyroid gland, from excessive thy
roid hormone replacement therapy for hypothyroidism, or from thyroid hormone administration as suppressive therapy for thyroid nodules.

In order to assure that the dose of thyroid hormones is not too high, a new sensitive thyroid stimulating hormone (TSH) blood test can be performed. It is important to have the sensitive TSH test annually to assure that the amount of medication you are taking is correct for you. Thyroid hormones, like all prescription drugs, should only /be used under the supervision of a physician.

Phenytoin and Barbiturate Anticonvulsants

These drugs are used mainly to prevent seizures (e.g., due to epilepsy and head injuries), and are also used to treat certain cardiac irregularities. Although early reports suggested that these drugs could cause osteomalacia, a softening of the bones, currently it is believed that they are more likely to lead to osteoporosis. In some cases, your physician may be able to replace the phenytoin or barbiturate with another drug that would be less likely to cause osteoporosis.

Aluminum-Containing Antacids

Antacids are used for the treatment of gastrointestinal discomfort. Some antacids contain aluminum while others do not. Ingestion of large amounts of aluminum-containing antacids may lead to deposits of aluminum in bone thus preventing the normal deposition of calcium, and resulting in osteomalacia. Usually this is a problem in individuals with poor kidney function and for those undergoing dialysis. These antacids are available as over-the-counter medications which do not require a prescription. Since excessive amounts of aluminum can be harm
ful, it is important that the doses of these drugs not exceed the amount suggested by your physician. If the dose you are taking does not control your symptoms, ask your physician to suggest another therapy; you should not increase the dose of these antacids by yourself.

Methotrexate

Methotrexate is widely used to treat a variety of cancers, immune disorders, and resistant arthritic conditions such as psoriatic arthritis. It can cause bone loss because of the toxic effects on bone forming cells. Methotrexate may also alter kidney function, resulting in increased calcium loss in the urine.

Cyclosporine A

Cyclosporine A is an immunosuppressive drug used in organ transplantation (kidney, liver, heart, bone marrow) and for the treatment of some diseases of the immune system. Recent reports suggest that there may be bone loss during long-term use of cyclosporine A. The situation is complicated because cyclosporine A is frequently used in combination with glucocorticoids which, as mentioned earlier, can also cause osteoporosis.

Gonadotropin Releasing Hormone Analogues

The long-term use of gonadotropin releasing hormone (GnRH) analogues for the treatment of endometriosis has been associated with bone loss. This is especially a problem if your bone mass is low at the onset of therapy. Although GnRH analog treatment can cause loss of bone, if you are only treat' for a short time you may be able to regain the lost bone after treatment has stopped.

Heparin

Osteoporosis has been reported in a few patients treated long term with high doses of heparin to prevent blood clotting. It is not a common treatment. The cause of heparin-induced osteoporosis is not fully understood at this time but it is thought that heparin may increase the rate of bone breakdown and impair bone formation. The more common blood thinners, including aspirin, have not been shown to have an adverse effect on bone health in adults.

Cholestyramine

Used to control blood cholesterol levels, cholestyramine decreases the absorption of vitamin D and may lead to reduction~ calcium absorption.

Medications and Falls

Preventing falls is important at any age, but it is especially important for those who have osteoporosis because the bones are more fragile and likely to break. Each year, about one-third of individuals 65 years of age or older will fall and some will be disabled by the broken bones that can follow Falls can result from diminished vision, hearing, muscle strength, coordination, and reflexes, and from diseases and medications that affect balance.

In many cases, a fall can be precipitated by medications, such as sedatives, muscle relaxants, and blood pressure drugs that can cause dizziness, light headedness, or loss of balance. When two or more medications are used in combination, tines side effects may be aggravated. As a precaution, talk to your physician or pharmacist about the side effects of the prescription and over-the-counter drugs that you are taking and ask body is made
in the skin upon exposure to sunlight. Therefore, supplements are particularly important in people who are house bound and get little exposure to sunlight. These individuals should take a daily supplement containing at least 400, hut not more than 800 International Units of vitamin D. Higher doses of vitamin D are sometimes recommended for patients with glucocorticoid-induced osteoporosis or patients taking anticonvulsant drugs, but this treatment must be carefully monitored to be certain that there is no excess calcium in the blood or urine since this can lead to a variety of complications. Talk to your doctor about taking a multivitamin.

• Engage in regular physical activity.

Physical activity and exercise can help build and maintain strong bones. Unfortunately, many of the diseases for which glucocorticoids and other medications are prescribed tend to limit the patient's ability to exercise. However, when taking these drugs, every effort should be made to begin and maintain a regular program of weight-bearing exercise. Before increasing your activity level you should consult your physician.

• Don't smoke.

Smoking can contribute to bone loss and increase the risk of developing osteoporosis in men and women. It is not clear what components of smoking are the cause of this risk, but nicotine may be the culprit. In women, smoking decreases circulating levels of estrogen and causes early menopause. The possibility of developing osteoporosis is one more reason not to smoke.

• If you drink, do so in moderation.