Bone death strikes steroid users without warning.

Excerpts from Internet bulletin board, September/October 1996:

Jennifer: I am on prednisone and sometimes

have terrible joint pain. I have found that BenGay

really helps.

Barbara: Have you been tested for AVN?

Avascular necrosis is one of the side effects of

steroid therapy. Basically, it means bone death.

If you have severe joint pain and

have had intravenous pred, I encourage

you to see an orthopedic doctor.

You may be able to forestall permanent

disability.

Dave: I'm new on the Net and saw

your message. My wife had both hips

replaced after short-term oral prednisone

and Medrol use. Not IV. Have

you heard about other short-term

oral pred AVN cases?

Michael: I've heard of cases from

oral, short-term usage.

Barbara: I was on pred after having

a colectomy, a total of six months.

I had a bone graft on my right knee

last June, and we will try the left next

summer. Since I'm only 33, knee replacement

surgery isn't really an Option.

They wear out after five years

and can only be redone so many

times. I try to post regularly on the

Net about AVN. So many people are

misinformed about it--both doctors

and patients.

A lot of people have learned the hard way that powerful corticosteroids prescribed by doctors can cause irreversible bone damage. In fact, experts now estimate that about 25 percent of the 500,000 hip replacement surgeries performed annually in the United States are the result of prescriptive corticosteroid use.

As Bruce Usher and Richard Friedman of the Medical University of South Carolina have noted, "In the era of modem medicine, rapid advances in diagnosis and treatment have allowed physicians to combat a variety of diseases thought to be untreatable. In the process, new disease entities have been created, such as steroid-induced osteonecrosis of bone." (Bruce W Usher & Richard J. Friedman, Steroid-Induced Osteonecrosis of the Humeral Head, 18 Orthopedics 47 (1995).)

Corticosteroids are often prescribed in association with surgery. Transplant patients, for example, depend on steroids to overcome the immune system's natural rejection of foreign tissue. The drugs also suppress the symptoms of wide range of serious diseases, such as asthma, rheumatoid arthritis, and other connective tissue disorders.

Unfortunately, as millions of viewers of the Oprah Winfrey Show learned last year, these "wonder drugs" have also found their way into prescribed treatments for relatively minor complaints--for example, sinusitis, eczema, and flu symptoms.

Typically, people who seek treatment for these complaints are not warned by doctors about the remote possibility of their contracting AVN. In many instances, patients do not even know they are being injected with steroids. And drug manufacturers' package inserts do not specifically warn about the risk of contracting AVN as a result of short-term steroid therapy.

But patients do contract the disease, and many of them lose their hips. Following are excerpts from the January 5, 1996, Oprah show:

Winfrey: Steve is about to have an operation

to replace the bones in his hips. In April

1994, Steve went to see his doctor because he

couldn't shake a cold and was given a prescription

for prednisone....

Steve Frary: I'm in pain all the day long, really.

It starts when I get out of bed in the

morning.... If I turn my legs the wrong way,

then it's stabbing pain .... You walk the way it

hurts the least.

Winfrey: Steve says he was never warned

about any side effects to the drug.

Frary: I always believed, like, you know, the

doctor's going to tell you what you

should know. I mean, if there's, if

something was dangerous, I would

assume they would tell you: "You

know, this is a real dangerous drug

and you really shouldn't take it It's

only for serious things." But they

gave it to me for a cough. That's the

kicker.

Frary is suing his physician and the drug manufacturer. (Frary v. Upjohn, No. 97-1277 (Mass., Suffolk County Super. Ct. filed Mar. 11, 1997).) Lead attorney is Frederic Halstrom of Boston.

Attorney Linda Robinson of La Jolla, California, who is co-counsel in a number of steroid-induced AVN cases around the country, said, "We've known for years that long-term steroid use can cause osteoporosis and other bone diseases. But there are two new areas of concern: Reported medical research shows that even short-term, low-dose steroid use can cause AVN. In addition, combining a prescription for steroids with one for antibiotics--a very common practice--is known to potentially double the strength of the steroid."

The first trial of a lawsuit demanding compensation from a drug manufacturer for failing to warn of the crippling effects of short-term, low-dose corticosteroids administered in combination with antibiotics opened June 18 in San Diego. (Paccione v. Augusta, No. 690132 (Cal., San Diego County Super. Ct. filed July 3, 1995).)

Philip Paccione, a senior vice president of an investment firm in Rancho Santa Fe, went to his doctor in June 1993 for treatment of a sinus problem. He was given injections of Aristocort and Decadron, both steroids. He was also prescribed oral methyl-prednisolone, a steroid, and the antibiotic erythromycin. Several months later, he was diagnosed with AVN, which required total replacement of one of his hips and will soon require the replacement of the other one.

Robinson points out that information about the multiplier effect of mixing methyl-prednisolone and erythromycin has been available for more than a decade. (C. F. LaForce et al., 72 J. Allergy & Clinical Immunology 34 (1983); Thomas M. Ludden, 10 Clinical Pharmacokinetics 63, 66 (1985).)

"The interaction of the two drugs completely skews the dosage recommendations made by doctors," said Robinson. "In other words, if the doctor says to take two aspirins and you are taking a drug that doubles their potency, then what you're really taking is four aspirins."

Commonly used oral steroids include betamethasone (brand name Celestone), cortisone, dexamethasone (Dalalone, Decadron, Dexacen, Dexone), hydrocortisone (Cortef, Hydrocortone), methylprednisolone (Medrol, Medralone), prednisolone (Predalone, Predcor, Predicort), prednisone (Orasone, Deltasone), and triamcinolone (Aristocort, Cenocort, Kenalog, Trilog, Trilone).

Steroids can attack a person's bones in two ways:

* Steroids combine with calcium in food, making it difficult for blood to absorb calcium. The body corrects its blood calcium deficiency by drawing calcium from bones, leaving them fragile.

* Steroids also inhibit the growth of new bone cells. Like everything else alive, bone is not an inert substance. Cells are constantly dying and being replaced by others. Inhibiting new cell growth allows the process of deterioration to overtake the process of renewal, and the bone dies.

Ironically, many of the tragic consequences of steroid use might have been avoided if patients had been either fully warned or advised how to offset their risks. According to guidelines published recently by the American College of Rheumatology, people on steroid therapy should consume at least 1,500 milligrams of calcium and international units of vitamin D every day, either through diet or supplements, to offset the likelihood of bone deterioration. (Jane E. Brody, Personal Health: Learning to Prevent Osteoporosis in Those Who Must Take Steroid Drugs, N.Y. Times, Jan. 29, 1997, at B10.) Taking supplements later does not replace bone loss.

Antibiotics increase the potency of steroids by slowing their rate of elimination from the body. According to Paul Watkins, director of the General Clinical Research Center at the University of Michigan, a specific enzyme--of which there is a finite amount in the liver of the human body--metabolizes both methylprednisolone and erythromycin.

"If two or more drugs metabolized by the [same] enzyme are taken or administered concurrently, they can compete for the available enzyme," said Watkins. "The result of this competition, which is known as a drug/drug interaction, is ... the drug remains in the body longer and at greater levels than normal." The increased exposure increases the risk of adverse effects.

"According to the law, a manufacturer is strictly liable if it fails to adequately warn of any adverse reactions it knew or should have known," said Robinson. "Strictly liable means it's not necessary to prove negligence or intent Moreover, a manufacturer of drugs has a duty to keep current with medical research related to any drug it puts into commerce. That duty extends to manufacturers of generic drugs."

Pharmacists may also have a duty to warn patients about the dangers of steroid use. Dr. James O'Donnell writes in a recent issue of Pharmacy Practice, "Considering the significant risk factors involved with corticosteroid administration, pharmacists have a serious responsibility to monitor the use of these drugs. As part of this, pharmacists may even need to be involved in a determination whether the drugs should be used at all." (James O'Donnell, Corticosteroid Misadventures, 9 J. Pharmacy Prac. 202,213 (1996).)

Part of the problem is that many patients experience no adverse symptoms from steroid therapy for years. The average interval between onset of steroid therapy and the appearance of hip pain is 33 months. Just as the drugs mask the painful symptoms of a wide range of diseases, they also mask symptoms of their own effects. Patients often have no clue that they are in trouble until their bones painfully begin to disintegrate.

O'Donnell pointed out that the Food and Drug Administration's Drug Experience Reports include numerous examples of irreversible damage to hips and shoulders from six- or seven-day steroid therapies. "Aseptic necrosis can no longer be viewed as a problem that is limited to patients who are receiving long-term, high-dose regimens, he said.

In addition to Frary and Paccione, lawsuits against doctors and drug manufacturers for inappropriate prescription of steroids for minor complaints and for failure to warn about the interaction of steroids with antibiotics have been filed in Ohio, Pennsylvania, and West Virginia. Other cases are being prepared in Florida, Illinois, Indiana, and South Carolina.

Robinson said, "It is one thing to risk irreversible bone damage when your life is at stake and you have no alternative, but it is something else to take that risk for the treatment of headaches and persistent coughs. Drug companies must be held accountable for not adequately warning people about these serious risks. And physicians must be held accountable for misprescribing or overprescribing these potent drugs."