Arthritis: The Disease, the Drugs, and Why Avoid Them
Physicians of the utmost fame
Were called at once; but when they came
They answered, as they took their fees,
"There is no cure for this disease."
—hilaire belloc (1870-1953)
Arthritis disables more people than any other chronic disorder and tops the list of diseases for which older people seek medical treatment. In 1998, the number of afflicted in the United States hit a staggering 43 million—15 percent of the population—up from 35 million in 1985, in part because the population in general is growing older. The market for analgesic painkillers is even more staggering, amounting to about $10 billion annually.1
Sales of Searle's arthritis drug Celebrex rivaled the blockbuster Viagra when it hit the market in early 1999. But the success of this "super aspirin" seems to reflect the widespread desperation of arthritis victims more than the viability of the treatment. Celebrex (discussed later in this chapter) is no more effective than older, cheaper options in reversing joint dysfunction. Its claim to fame is that it suppresses pain with fewer daunting side effects than the older drugs. Conventional medicine still has no safe and proven protocol for reversing arthritis.
DEFINING THE DISEASE
The word arthritis is derived from the Greek arthron for joint and -itis for inflammation. It thus means inflammation of the joint. Inflammation causes swelling, which causes pain by pressing on the nerves. Joint dysfunction that does not involve inflammation is technically called "arthrosis," meaning simply joint disease.
The most common form of arthritis is osteoarthritis, a chronic degenerative disease that is epidemic among the elderly. It afflicts about 21 million people in the United States. According to the Arthritis Foundation, the second leading arthritis-related condition is fibromyalgia, a form of muscular rheumatism that involves joint pain and is believed to afflict 3 to 6 million people. The third most frequent arthritic condition is rheumatoid arthritis, the most intractable and painful form of the disease. It afflicts 2.5 million people.2 Fourth is gout, a gene-linked condition in which excess uric acid accumulates and forms crystals that irritate the joints. Other common forms of arthritis include bursitis, a painful inflammation of the bursae (the fluid-filled sacs that cushion the bones, tendons, and ligaments where they move against each other); and ankylosing spondylitis, an inflammation of the spine and hip joints. Many other conditions also involve an element of inflammatory arthritis, including systemic lupus erythematosus or SLE, a chronic inflammatory disease that strikes connective tissue throughout the body.
THE MECHANICS OF THE DISEASE
Different forms of arthritis have unique features that are discussed in later chapters. All, however, involve a breakdown of joint cartilage faster than the body can repair it. The joint is where the bones meet and are cushioned so they can move without irritating each other. The joint is protected by a capsule consisting of tough fibrous tissue. It covers the synovial membrane, which surrounds the joint and provides a lubricating fluid. Joints are covered with a smooth layer of cartilage that allows for easy sliding and absorbs shock. Arthritis strikes this cartilage, causing it to become swollen, flake, and crack.
When this occurs the body tries to protect itself by layering down extra calcium at the ends of the bone, forming bony spurs inside the joint. These are the bony knobs called Heberden's nodes visible at the ends of the fingers of some arthritis victims. If the node breaks off, it can form a "joint mouse" that moves in the joint space. A joint mouse that has gotten caught between the moving bones can cause serious pain. Friction between the bones also causes heat to build, but the narrowing of the synovial membrane makes blood flow insufficient to carry the heat away. When the joint isn't moving, the synovial membrane gets stiff, leading to "gelling" that makes it even more difficult to move.3
THE PHARMACEUTICAL APPROACH: NSAIDs
The conventional approach to the treatment of arthritis is to suppress joint pain with drugs. Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) relieve pain by blocking the inflammatory process, but this approach comes with a price. A 1998 study in the Journal of the American Medical Association estimated that more than 100,000 deaths now occur annually from legal drugs prescribed and used correctly. That makes pharmaceutical side effects the fourth leading cause of death in the United States, following only heart disease, cancer, and stroke.4 And ulcers and gastrointestinal bleeding caused by NSAIDs are the most common serious adverse reactions of any drugs on the American market. This side effect has become so common and well known that the complex has its own name: "NSAID gastropathy." A recent Stanford study attributed 107,000 hospitalizations and 16,500 deaths yearly to NSAIDs. Taking them increases your likelihood of being hospitalized for gastrointestinal afflictions by a factor of more than six.5
People who take an occasional aspirin for a headache aren't at great risk. The problems come for people who take the drugs daily in relatively high doses over a period of years. Fourteen million arthritics now fall in that category. NSAIDs were developed specifically to treat rheumatoid arthritis, a crippling form of the disease for which side effect risks may be justified; but NSAIDs are now also frequently prescribed for osteoarthritis, a much larger market with a correspondingly greater potential for drug casualties.
Aspirin, the grandfather of anti-inflammatories, has long been the most popular treatment for arthritis. Americans collectively pop more than 80 million aspirin tablets daily. Critics question whether the Food and Drug Administration (FDA) would allow this drug on the over-the-counter market if it were introduced today because of its potentially serious side effects; but it has been around in pill form since 1899 (longer than the FDA itself) and was grandfathered in without testing.
How aspirin works wasn't discovered until more than seventy years after it appeared on the market. The mechanism involves natural substances called prostaglandins, which are released when cells are injured or stimulated. One type, called PGE2, alerts the body to disturbances in normal function by increasing the awareness of pain. Other prostaglandins contribute to the heat and swelling of inflammation and promote the coagulation of blood. Aspirin interferes with the body's biosynthesis of these prostaglandins, thereby suppressing inflammation and the awareness of pain.
The problem is that prostaglandins perform normal body functions that are suppressed along with the inflammatory process. Some prostaglandins help to regulate the flow of blood through the kidneys and the filtration and excretion of sodium and toxins. When aspirin inhibits these functions, the result can be fluid retention and the buildup of nitrogenous wastes in the blood.6 Other prostaglandins have a direct action on stomach cells. They inhibit acid production and prevent acid damage to the lining of the stomach. When these prostaglandins are suppressed, acid can eat holes in the stomach and intestines. This unwanted side effect is the largest single cause of disease and death due to aspirin and other NSAIDs. Aspirin also causes an excretion of vitamin C in the urine that is three times normal; it can cause iron deficiency from blood loss from irritation of the intestinal lining; it prevents blood from clotting; and it blocks the effects of interferon, one of the substances by which the immune system fights off infections and other ills.7
Non-aspirin NSAIDs include ibuprofen (Motrin, Advil), indomethacin (Indocin), naproxen (Naprosyn, Aleve), and piroxicam (Feldene), among other popular options. The non-aspirin NSAIDs were originally thought to have an advantage over aspirin in that they were better tolerated and produced less gastrointestinal distress. But the FDA eventually proclaimed that the safety of one NSAID could not be clearly distinguished from another.8
All NSAIDs, including aspirin, inhibit the synthesis of prostaglandins.9 NSAIDs can also provoke asthma in some people. A British study found that people over sixty who took non-aspirin NSAIDs were three times as likely as nonusers to be hospitalized with bleeding gastric and duodenal ulcers.10 In another study, elderly people who took ibuprofen regularly were found to be four times as likely to die from ulcers and gastrointestinal bleeding as those not taking it.11
Concerns about the side effects of NSAIDs have led the FDA to require new labels that state in part: "Serious gastrointestinal toxicity such as bleeding, ulceration, and perforation can occur at any time, with or without warning symptoms, in patients treated chronically with NSAID therapy." All of the currently available NSAIDs are now thought to have roughly equivalent pain-relieving effects, and all are known to cause stomach damage.12
Acetaminophen (Tylenol and other brands) is an over-the-counter analgesic that is easier on the stomach than NSAIDs; but it doesn't qualify as an anti-inflammatory, because it doesn't reduce inflammation. It therefore isn't much help for arthritics; and while it is easier on the stomach than NSAIDs, it still isn't safe taken over long periods, since it can cause fatal damage to the liver.13
ANTACIDS AND ACID-BLOCKERS
As many as 25 percent of people taking NSAIDs at any given time have evidence of ulcers detectable by clinical testing, but most of these ulcers have no symptoms and will heal on their own. The danger comes when an ulcer forms near a blood vessel or grows too large. It can then cause severe pain and other serious complications. Since in its early stages the ulcer goes unnoticed, a serious stomach bleed can come on suddenly, often requiring transfusions and surgery.14
Many arthritics try to avoid this result by taking antacids or acid-blockers (Tagamet, Zantac, Pepcid AC) preventatively. But a Stanford study reported in 1996 found that this could do more harm than good. The first symptom of an ulcer is usually heartburn. By masking heartburn symptoms, the drugs allow ulcers to get much larger before they are detected. People taking acid-blockers were found to be more than twice as likely to be hospitalized for gastrointestinal complications as those not taking them.15 Acid-blockers also come with their own list of side effects, and one of them is joint and muscle pain. Again, they result largely because the drugs block natural processes.16
Stomach acid has beneficial functions, one of which is to kill bacteria in the stomach. Without the acid, you run the risk of infection by salmonella and other undesirables. Because acidblockers don't cure ulcers but only mask symptoms, they have to be taken for life by ulcer patients. They have been called "annuity medicines" for drug companies, since they can cost several dollars a day.
In an effort to circumvent the ulcer problem, drug manufacturers developed the Cox-2 inhibitors. These are "super aspirins" that block the Cox-2 enzyme that drives inflammation but don't block the Cox-1 enzyme that releases the prostaglandins protecting the stomach. The drugs don't suppress pain or reverse the ravages of the disease any better than older options, but they have fewer side effects than other arthritis drugs.17
At least, that is the claim of their manufacturers. The FDA is not convinced. It approved Searle's Cox-2 inhibitor Celebrex as a good option to relieve arthritis pain but declared there is no proof the drug is easier on patients' stomachs than other drugs. The FDA has required the same warning about side effects as for older painkillers.18 Potential downsides of Celebrex reported in the Proceedings of the National Academy of Sciences include a reduction in beneficial prostaglandins and an increase in the risk of heart attack.19
Despite these drawbacks, in its first three weeks on the market in early 1999 about 142,000 prescriptions were written for Celebrex, making it the second-fastest-selling new drug after the anti-impotence drug Viagra. Over the long run, in fact, Celebrex is expected to fare better than Viagra, since most users take anti-impotence drugs only when the urge strikes them (or when they hope it will). Arthritis victims take arthritis drugs virtually every day; and once they start on one, they are likely to take it for life. In 1998, drug companies sold about $6 billion in brand-name prescription NSAIDs. Sales of Celebrex were projected to reach $1 billion a year later, equivalent to a sixth of the NSAID market.20 Celebrex costs $2.50 to $3.00 per day for the lowest effective dose (200 mg). This is more than three times the cost of a therapeutically equivalent amount of NSAIDs (ibuprofen or naproxen); while glucosamine and chondroitin sulfates, the most popular nutritional remedies, may be had for as little as twenty cents a day.
Merck, the world's largest drug company, sought government approval for its own Cox-2 inhibitor, Vioxx, in the spring of 1999. Merck hoped to persuade the FDA that Vioxx is superior to Celebrex and does not need any warning label about gastrointestinal effects.21 But as with Celebrex, the FDA has not permitted Merck to claim that Vioxx is less damaging to the gastrointestinal tract than traditional NSAIDs such as aspirin. The reviewing committee approved the drug for short-term use but observed that its side effects, including swelling, high blood pressure, and elevated potassium levels, increase with increasing doses, suggesting it might not be safe for use long term. The committee advised against its use for chronic pain and said its use for acute pain should be limited to five days, the longest Merck had studied it for that purpose.22
If the FDA is heeded, Vioxx won't be much help for arthritis sufferers, since they need long-term relief; but the FDA's warnings probably won't halt its use for arthritis pain. The rule is that once a drug has been approved, a doctor may prescribe it for any purpose deemed in his or her professional judgment to be appropriate. Celebrex, its competitor Cox-2 inhibitor, became the number one prescription arthritis medication a year after it got FDA approval.
THE UNDER-APPRECIATED BENEFITS OF INFLAMMATION
Even if the Cox-2 inhibitors are not hazardous to the stomach (a matter that remains in dispute), there is a more fundamental problem with these drugs. All arthritis drugs, including Cox-2 inhibitors, relieve the pain of arthritis merely by suppressing some stage of the inflammatory process, thus relieving pressure on the nerves. They do this by inhibiting the synthesis of prostaglandins that cause dilation of the blood vessels. The problem is that this dilation is necessary to increase the blood flow required for the repair of joint structures.
Studies have shown that suppressing inflammation not only doesn't cure arthritis but actually speeds joint deterioration. Inflammation is a natural process by which the body tries to remove dead or damaged tissue cells and lays down the matrix for new cells to replace the old. It does this by a buildup of body fluids that serves to destroy or wall off toxins and injured tissue and carry immune system cells to the site of damage. When this process is interfered with, the already compromised joint simply deteriorates more rapidly. In the hip, the resulting affliction is called "analgesic hip," a progressive degeneration of the joint caused by the very drugs given to treat joint pain. Cartilage and bone degeneration increases, leading to more hyperplasia (abnormal proliferation of normal cells), more joint capsule scarring, and more pain.23 Animal studies have shown that aspirin, indomethacin, and other NSAIDs promote the rapid breakdown of cartilage.24 All NSAIDs can also cause sodium and water retention, which is thought to trigger changes in deteriorating cartilage.25 And NSAIDs suppress the production of proteoglycans, a type of glycoprotein found in connective tissue. The stiffness and cushioning ability of cartilage is directly correlated with its content of these substances.26
Excerpted from Healing Joint Pain Naturally by Ellen Hodgson Brown. Copyright © 2001 by Ellen Hodgson Brown. Excerpted by permission of Three Rivers Press, a division of Random House, Inc. All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.