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Posts Tagged ‘osteoporosis’

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Bone drugs’ adverse effect found to be very rare

Posted by medconsumers on May 28, 2010

Remember those scary reports of spontaneous thighbone fractures that occurred in some women who were taking fracture-prevention drugs like Fosamax? The bone breaks for no apparent reason. (In one memorable case, a woman said her thighbone broke while standing in a stalled subway train that lurched suddenly.) Such fractures are described as very rare (0.03%), according to a new analysis of the data generated by three large trials. These are the same clinical trials that proved bone drugs like Fosamax and Zometa are more effective than no treatment (placebo) in reducing hip fracture—the most serious complication of osteoporosis. Now the results of these trials were searched solely for the rate of spontaneous thighbone fracture.

It’s a relief to know that this is “a very rare” side effect of osteoporosis drugs. But looking at these trial results again reminds me that their hip fracture prevention benefit is also pretty rare. The first to win FDA approval was Fosamax (generic name: alendronate), produced by Merck. After three years, only 1% fewer drug-treated women suffered a hip fracture, compared to untreated women. The drugs’ effectiveness looks much better when the company-sponsored researchers throw in fractures in other sites—spine, wrist, and forearm. In one osteoporosis research sleight of hand that’s always bothered me, it is common to count a reduction in spinal fractures that are symptomless and can be seen only on X-ray.

But I digress. Back to the spontaneous thighbone fractures and how we now know they are very rare. The three major trials that provided the data for this conclusion had a combined total of 14,195 women randomly assigned to take either a placebo or a bone drug (Fosamax in two trials, Zometa in one). Keep in mind that most of what are called hip fractures are actually breaks in the “neck” of the femur, or thighbone, where it meets the pelvis in the ball and socket joint.

So here’s final count: Of the 284 women who had hip or femur fractures, only 10 had what’s called atypical thighbone fractures. It’s interesting to note how few hip or femur fractures—atypical or not—occurred, considering that the 14,195 study participants were considered to be at high risk for fracture and between the ages of 65 and 80 years when they entered the study. Could it be that this isn’t the biggest health threat we face in old age? Or could it be that the study participants weren’t followed long enough?

This analysis appeared in The New England Journal of Medicine and was funded by Merk and Novartis (maker of Zometa). How long can people safely take this drug is not answered by this analysis. It’s a question that lingers over all bone drugs called bisphosphonates (other brand names: Boniva, Actonel, Reclast). The authors of this analysis conclude that the risk of spontanous thighbone fracture remains rare “even among women treated with bisphosphonates for as long as ten years.” Buried deep in this paper, however, is the fact that few women were followed this long. The majority were followed only three to four years. Women on long-term bisphosphonate therapy are advised to report thighbone pain immediately to their doctors as this was the telling symptom that preceded a spontaneous fracture.

For more information
To determine whether you can benefit from Fosamax or any other bisphophonate drug, see this chart from the Cochrane Collaboration, which is based on the results of the above-mentioned three clinical trials. You will see that women who have been diagnosed with low bone density or who have broken bones in their spines are more likely to benefit than those whose bone density is near normal (osteopenia) or who do not have spinal fractures. click here

Visit the Web site of Susan Ott, MD, an expert in bone physiology at the University of Washington, Seattle. Everything from osteoporosis prevention to summaries of the latest bisphosphonate studies.

For background on how osteoporosis became a much-feared disease, read this 2009 article for the American Journal of Nursing, The Marketing of Osteoporosis.

Osteonecrosis of the jaw, another rare side effect of bisphosphonate drugs, was not addressed in the new analysis. For more information, click here.

Maryann Napoli, Center for Medical Consumers(c)

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Posted in Drugs, Pain, Scans and X-rays, Women's Health, osteoporosis | Tagged: , , , , , , , , , | Comments Off

Osteoporosis drugs

Posted by medconsumers on March 22, 2010

Older women have long been encouraged to have their bone density measured periodically. And many who followed the advice have walked away with a prescription for Fosamax. Not surprisingly, the promotion of bone density testing has been spearheaded by Merck, maker of Fosamax, which is widely prescribed to women with bone loss. A decade after Fosamax became available in 1995 medical journals began reporting an apparently rare side effect. Spontaneous fractures of the thighbone called atypical subtrochanteric femur fractures occurred in women who had taken Fosamax for more than six years. All the drugs in the same class, known as bisphosphonates (Actonel, Fosamax, Boniva, Reclast), were under suspicion of causing this unusual fracture. In June 2008, the Food and Drug Administration requested patient data from all companies that make bisphosphonate drugs. The FDA has finished its review and recently posted this conclusion on its Web site:

“At this point, the data that FDA has reviewed have not shown a clear connection between bisphosphonate use and a risk of atypical subtrochanteric femur fractures. FDA is working closely with outside experts, including members of the recently convened American Society of Bone and Mineral Research Subtrochanteric Femoral Fracture Task Force, to gather additional information that may provide more insight into this issue.” Click here for entire FDA posting.

Another Fosamax Adverse Effect?

A possible connection between bisphosphonates and another rare side effect called osteonecrosis of the jaw will be tested in court, according to recent ruling. A federal judge refused to dismiss 40 lawsuits against the Novartis Corp, maker of bisphosphonates Aredia and Zometa. Novartis is accused of failure to warn patients that these drugs can cause destruction of the jawbone, primarily in people with advanced cancer given one of these drugs intravenously. Osteonecrosis of the jaw appears to be associated with certain dental procedures. When case reports of this injury first appeared in a medical journal over five years ago, these untreatable injuries were thought to be confined solely to cancer patients given high doses of a bisphosphonate intravenously. In time, however, similar injuries were reported in long-term users of oral bisphosphonates. Read “Osteonecrosis of the jaw—more common than previously thought.”

More information
Bisphosphonate drugs are better at improving bone density than they are at reducing the chances of having a hip fracture in old age. For more, read my 2009 article for the American Journal of Nursing called “The marketing of osteoporosis—how a risk factor became a disease.”

Maryann Napoli, Center for Medical Consumers©

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Prevent falls with vitamin D3

Posted by medconsumers on September 23, 2009

For decades, osteoporosis prevention meant drugs, estrogen, and calcium supplements—all of which we now know are better at increasing bone density than actually reducing hip fractures. Some osteoporosis researchers have taken a different approach: concentrate on ways to prevent elderly people from falling which can, in turn, prevent other injuries as well as hip fractures. This school of thought just got a major boost from the pooled results of eight clinical trials that found high doses of vitamin D3 supplements can cut the chances of falling by up to 26%. Unexpectedly, calcium supplements did not seem to be important to this benefit. Most impressive, the analysis indicates that muscle weakness is reversible in elderly people.

Muscle weakness has long been known to be a key risk factor for falls, and vitamin D is known to improve muscle strength. But there were lingering questions regarding the best type of vitamin D and the appropriate dose for the prevention of falls. They are answered by a new meta-analysis of eight trials, published early this month in the online version of the British Medical Journal. An international team headed by H.A. Bischoff-Ferrari, University of Zurich, Switzerland, identified eight trials in which women and men, age 65 years and older, had been randomly assigned to take either a placebo or some form of vitamin D in doses ranging from 200 to 1,000 International Units (IU) a day, with or without calcium. Trials lasted from 9 to 36 months.

No fall reduction benefit was found in the people who had been taking vitamin D in doses less than 700 IU daily. When the researchers singled out the trials with the highest quality for fall assessment (i.e., five of the eight trials), the best results were shown in the trials that involved high doses of vitamin D3 (cholecalciferol). “38% of individuals treated with 700-1000 IU vitamin D3 had at least one fall versus 50% of individuals in the control group taking calcium or placebo,” explained Dr. Bischoff-Ferrari in an e-mail. This benefit showed up within two to five months of the initiation of treatment.

Dr. Bischoff-Ferrari and colleagues did not rule out the possibility that vitamin D doses higher than 1,000 IU daily could be even more effective. No high-quality randomized trials have explored this possibility. The new findings support the vitamin researchers in the U.S. who, for years, have been calling for an increase in the recommended daily allowance, which is 200 to 600 IU.

And what about that no-effect finding for calcium? This will come as a surprise to older women who have long been told to take at least 1200 mg calcium daily to avoid osteoporosis. Dr. Bischoff explained, “Vitamin D increases the uptake of calcium. If one has more vitamin D, [the] calcium uptake is more efficient and less calcium may be sufficient. That does not mean that we do not need calcium — calcium is important for bone — but it means that when we get sufficient vitamin D, we may lower the recommendations for calcium intake. In clinical practice this may offer the opportunity to recommend vitamin D supplementation in combination with a ‘bone healthy diet’ covering calcium needs by milk products and vegetables rich in calcium. This is possible if the target intake of calcium is 700 mg of calcium per day rather than [current recommendation of] 1000 to 1500 mg per day.” Dr. Bischoff-Ferrari backed up these assertions with two recently published research papers that came with her e-mailed responses.

More information:
People fall for a variety of reasons, including over-sedation with prescription drugs. For more about this and the minimal efficacy of Fosamax and other bone drugs, see our 2008 article entitled, “Osteoporosis: many drugs prescribed, not so many hip fractures avoided.” and our 2005 article entitled,”Vitamin D defiency—cause of many ailments.”

Maryann Napoli,Center for Medical Consumers(c)

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The Marketing of Osteoporosis

Posted by medconsumers on May 19, 2009

How a risk factor (bone loss) became a disease (osteoporosis) by Maryann Napoli. American Journal of Nursing. For PDF version, go to “article tools” at top right.

Posted in Drug ads, Drugs, Scans and X-rays, Screening, Women's Health, osteoporosis | Tagged: , , , , , | Comments Off

Fosamax-Induced Osteonecrosis of the Jaw More Common Than Previously Thought

Posted by medconsumers on March 1, 2009

Dentists have been in the forefront of identifying a severe complication of Fosamax, the osteoporosis drug widely prescribed to prevent fractures. The January issue of the Journal of the American Dental Association published a study describing a significant risk of osteonecrosis of the jaw from even oral use of Fosamax. Until this small study of 208 dental patients was published, jaw osteonecrosis was thought to be rare and limited to people with cancer who received large doses of Fosamax intravenously to treat bone metastases.

Dental School Patients Studied

In this study conducted at the University of Southern California School of Dentistry, 4% of the dental patients taking oral Fosamax had osteonecrosis of the jaw. All had suffered dental trauma—either a tooth extraction or ill-fitting dentures that resulted in jawbone exposure; all were women, average age 73 years, who had been taking the drug for 12 months or longer. Osteonecrosis is defined as “the presence of exposed bone in the mouth, which fails to heal after appropriate intervention over a period of six or eight weeks.”

Parish P. Sedghizadeh, DDS, and colleagues at the USC School of Dentistry found no cases of osteonecrosis of the jaw among their 4,384 dental patients not taking Fosamax who underwent tooth extraction. Fosamax was the first and most aggressively promoted of all drugs in a class called bisphosphonates, which also includes Actonel, Boniva, Aredia, Zometa and Bonefos.

4% Risk is Not Rare

Sedghizadeh and colleagues say their findings contradict Merck’s claim that jaw osteonecrosis is a rare side effect of its drug. “We have been told that the risk with oral bisphosphates is negligible, but 4% is not negligible,” said Dr. Sedghizadeh. (The benefit of Fosamax could also be described as rare because the drug reduces the risk of hip fracture from 2% to 1%, as demonstrated in premarketing trials.) Prior to receiving FDA approval, Fosamax was tested in trials that lasted only three to five years. Ever since this drug first came on the market in 1996, the unanswered question has been: How long can people safely take Fosamax—or any one of other bisphosphonates, which are known to suppress bone turnover.

Drugs Have a Long Half-Life

This warning came from the USC Dental School research team: Bisphosphonates have half-lives of ten years or more, and people taking the drug orally may ultimately reach the same high dose level as that given intravenously to treat bone metastases in cancer patients. Sedghizadeh and colleagues also explained that because bisphosphonates stay in the bone for a long time, the risk of osteonecrosis remains even after people go off the drugs. The half-life of a drug describes how long it takes for half of it to be eliminated from the bloodstream.

The USC study is not the last word on the frequency of osteonecrosis of the jaw in people taking bisphosphonates. A much larger study is needed; ideally, one that takes place in many dental schools. Researchers at other institutions are trying to determine the prevalence of osteonecrosis of the jaw in cancer patients treated with bisphosphonates for cancer metastases. In the journal Bone, Dr. I.R. Reid, University of Auckland, estimated that it is 5% among people with myeloma, breast cancer or prostate cancer.

What to do

Thirteen years after Fosamax was launched, severe adverse effects have been showing up that may not be as rare as the public has been led to believe. Last year, the FDA reported that all bisphosphonates carry the risk of severe and sometimes incapacitating musculoskeletal pain. And case reports in several medical journals describe an unusual type of severe fracture of the femur associated with bisphosphonate use. In 2007 an increase in serious cases of atrial fibrillation was reported in people given the relatively new once-a-year bisphosphonate injection for fracture prevention (Zometa).

Osteonecrosis Treatments

As for osteoporosis of the jaw, more information is needed about how to prevent and treat it successfully—if that’s possible. Sedghizadeh and colleagues at USC Dental School did not have too much to offer on this topic. They advise unnamed alternate treatment options be considered for “nonnecessary extractions;” reducing the amount of the bacteria with a chlorhexidine rinse for those who must undergo a procedure; and daily antibiotics for those with denture trauma. For the exposed bone that fails to heal, the researchers name a procedure called “mucosal coverage.”

University of New Zealand’s Dr. Reid put it more succinctly “Management focuses on prevention, treatment of infection and cessation of bisphosphonate. The role of surgery is unclear.”

For more information: Read my 2008 article about Fosamax and this 2008 article about Evista. For an overview of how the definition of osteoporosis was expanded by the pharmaceutical industry: read “The marketing of osteoporosis: how a risk factor became a disease,” which appeared in the April 2009 issue of the American Journal of Nursing.

Maryann Napoli, Center for Medical Consumers©

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Osteoporsis Drug: New Adverse Effects

Posted by medconsumers on August 1, 2008

More Bad News About Fosamax

An unusual type of severe fracture has been reported in people taking Fosamax for more than five years. Ironically, this drug is widely prescribed to prevent fractures in people with bone loss. The new finding came from a series of case reports published in the May/June Journal of Orthopaedic Trauma.

The fractures occurred in the femur, which is the large thighbone that connects to the hip. They are particularly alarming because of the unusual pattern described by many of the people whose cases were reported. Their thighbones had ached inexplicably for months or weeks and then broke spontaneously while walking or standing. Nineteen of the 20 people in the case series had been taking Fosamax for an average of nearly seven years.

These are not the first reports of what is called atypical low-energy fractures after long-term Fosamax (generic name: alendronate) therapy. In 2005, the Journal of Clinical Endocrinology & Metabolism published case reports of nine women who sustained spontaneous non-spinal fractures while on Fosamax, six of whom showed either delayed healing or no healing for three months to two years. And last year, the Journal of Bone and Joint Surgery reported that nine Fosamax-treated women in Singapore showed the same early warning signs prior to a spontaneous fracture.

These adverse effects are not unexpected. Ever since Fosamax first came on the market over a decade ago, some osteoporosis researchers have periodically expressed safety concerns about prolonged usage, mostly in letters to medical journals. The drug improves bone density, but it does so by suppressing the bone remodeling process by which microscopic parts of old bone are constantly being dissolved and new bone is added.

Here’s how bone physiologist Susan Ott, MD, describes Fosamax’s effect on this process, “The bisphosphonates get deposited in the bone and will accumulate for years. It is possible that many years of continuous medicine would make bone more brittle or impair the ability to repair damage. Bisphosphonates do reduce fractures and improve measurements of bone strength for the first five years in both animal studies and in women who have osteoporosis. After five years, the fracture rates are as high in the women who keep taking alendronate as in the women who quit (see http://courses.washington.edu/bonephys).”

Although Fosamax advertising has focused women and doctors on the importance of bone density, bone strength is now regarded by osteoporosis researchers as more important to fracture prevention (see HealthFacts, April 2008).

Atypical low-energy fractures did not appear in the clinical trials required of Merck, maker of Fosamax, for FDA approval because these trials lasted only three to five years. Although these fractures are considered to be a rare side effect at this time, some osteoporosis experts are now advising against taking the drug beyond five years.

The published case reports all involved Fosamax, which is one of a drug class called bisphosphonates. Others in the class include: Actonel, Boniva, Aredia and Didronel. That all the case reports are confined to Fosamax may be explained by the fact that Fosamax was the first bisphosphonate to be aggressively marketed for the treatment of osteoporosis, and many more women worldwide have been taking this particular bone drug and for a longer time.

It’s reasonable to assume that the spontaneous fracture risk is associated with prolonged use of any bisphosphonate until research proves otherwise. Read this March 15, 2010 notice from FDA, stating that the agency has reviewed the relevant data and “found no clear connection between bisphosphonate use and a risk of atyical subtrochanteric femur fractures.” Also, read this 2009 updates on this topic “Osteonecrosis of the jaw—more common than previously thought” and this article written for the American Journal of Nursing “The Marketing of Osteoporosis–How a risk factor became a disease.”

Maryann Napoli, Center for Medical Consumers ©

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Women-in-Towels Evista Ad Critiqued

Posted by medconsumers on July 1, 2008

The women in Eli Lilly’s new ad campaign are attractive, healthy-looking and wearing nothing but towels. “Cut two risks with Evista. The only agent indicated to treat osteoporosis and reduce the risk for invasive breast cancer.”

That two-for-one claim for Evista makes it different from other drugs taken by symptom-free people. Studies showed that the harm related to each disease drops a percentage point or two in those who took Evista, compared to those who did not. The drug is better than a placebo (or it would not get FDA approval), but not much better. This is a recurring theme in Center for Medical Consumers articles because it’s a recurring theme in many drug trials. And often the small risk of a serious adverse reaction to the drug equals that small chance of benefit.

Evista (generic name: raloxifene) has been on the market since 1997 as an osteoporosis drug. It produces a 2%-3% increase in bone density; reduces the rate of vertebral (spinal) fractures; but does not prevent the most serious type of fracture (hip). Vertebral fractures can cause pain and a dowager’s hump in advanced age, but many are symptomless. The studies did not last long enough for Lilly to make claims regarding prevention of a dowager’s hump or loss of height.
Breast Cancer “Risk Reduction”

Last year Lilly received FDA approval to promote Evista as a drug that can “reduce the risk of invasive breast cancer.” This careful wording from the Evista ads is important. Lilly cannot claim its drug prevents breast cancer because the disease can take anywhere from 8 to 17 years to develop. There were, in fact, fewer breast cancers diagnosed in the women taking Evista, compared to those taking placebos. But the trials didn’t last long enough to determine whether the drug prevents breast cancer or simply delays its onset. In Evista trials that lasted up to eight years—breast cancer was diagnosed in 2.5% of the women taking a placebo and 1% of the women taking Evista.

The other claim for Evista is based on the fact that the women in the studies already had osteoporosis (bone loss). One way bone drug companies can inflate the benefit of their product is to count symptomless vertebral fractures that can be detected only on x-ray. (In other words, the women are unaware of them.) At the start of the Evista trial about half the women had painful vertebral fractures and the other half had “fractures diagnosed radiographically.” After four years, things looked better for Lilly when results for all women were combined, but less impressive when women with painful fractures were singled out. In the latter group, only about 1% fewer Evista-treated women had new painful vertebral fractures than the women taking placebos.

Thus far serious adverse reactions to Evista include deep vein thrombosis, pulmonary embolism, retinol vein thrombosis and an increased risk of fatal stroke. (See boxed warning of the FDA-approved label). Separately, each is classified as rare, which, according to FDA standards, describes any drug reaction that occurs in less than 2% of study participants. Collectively, though, these potentially fatal adverse reactions could reach 1-2% which comes close to the percentage of women who benefited from Evista in the FDA-required clinical trials.

And lastly, the visual message conveyed by the women-in-towels ad is misleading. Most of the women look to be in their fifties. At the start of the Evista trials, however, most participants were over age 65 years, a time of life when vertebral fractures are far more likely to occur.

Maryann Napoli, Center for Medical Consumers ©
July 2008

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Osteoporosis: Many Drugs Prescribed, Not So Many Hip Fractures Avoided

Posted by medconsumers on April 1, 2008

Fracture prevention is focused on bone density, but other factors like bone quality and muscle strength are also important, according to a recent commentary by two Toronto physicians for the Journal of the American Medical Association. They advocate a broader view of osteoporosis prevention but first, here is an historical context for this disease that has become a major health concern for women.

Osteoporosis was unknown to the public until the 1980s. The disease used to be diagnosed in the elderly only after a “fragility fracture” had occurred. But a new definition, based on bone mineral density, was established in 1993 at a World Health Organization meeting of osteoporosis researchers. Soon bone scans became a must for all women over age 50.

In 1995, the first non-hormonal drug to prevent osteoporotic fractures—Fosamax—came on the market. Its manufacturer, Merck, sponsored an aggressive ad campaign initially aimed at doctors, featuring a woman who looked no more than 45 and this message: “Don’t wait for a fracture.” Merck’s ads aimed at women simply told them to “ask your doctor whether a bone density test is right for you.” Chances are high that widespread use of bone scans would identify many women as having bone loss. The first step toward a drug prescription.

Many middle-aged women who had never had a fracture were put on Fosamax. It is unlikely that they were told that the drug had been tested only in elderly women who already had a fracture, and the results were unimpressive. After three years, hip fractures occurred in 1% of those on Fosamax, compared with 2% of those on a placebo. (A 50% reduction in hip fracture!” screamed some of the ads.) In time, another “condition” called osteopenia, or pre-osteoporosis, was created by drug makers. By then, other drug companies had introduced their own Fosamax knockoffs like Actonel, Boniva, Reclast, Zometa, etc. All are in the same drug class called bisphosphonates.

Drug prescribing is clearly tied in with bone mineral testing, but the now-popular scanning technique known by the acronym DEXA is not good at predicting which women in their early 50s will have a hip fracture at age 80 years, when it would most likely occur. This was the conclusion of a 1998 report from the British Columbia Office for Health Technology Assessment. The report was ignored in the U.S. where Merck was financing the installation of DEXA machines in doctors’ offices.

In 2005, The Seattle Times published an investigative series of medical articles. The in-depth report on the selling of osteoporosis revealed that two multi-national pharmaceutical giants had financed that 1993 World Health Organization meeting. (Ostensibly, the meeting was about a multi-country study of the prevalence of osteoporosis.) The pharmaceutical funding of this WHO meeting sheds new light on the revised definition of osteoporosis. What had been simply a risk factor (bone loss) became a disease (osteoporosis) at that meeting, where an arbitrary definition of bone loss was also created. Overnight, the number of potential customers for bone drugs had been expanded greatly.

The story of Fosamax and its knockoffs perfectly illustrates how the pharmaceutical industry starts creating a market for a new drug years before it is approved. First industry must sell you fear of a disease, then comes the drug to “prevent” its most serious consequences.

Today, the guidelines for bone density measurement recommend testing not begin before age 60, but now there’s a bigger problem Researchers have known, at least since 2000, that bone strength or bone quality are better predictors of hip fracture than bone density. In 2001, the National Institutes of Health redefined osteoporosis as a combination of bone mineral density and bone quality. But here’s the rub: There is no test for bone quality or bone strength.

In their recent commentary for the Journal of the American Medical Association, the Toronto physicians, Angela M. Cheung, MD, and Allan S. Detsky, MD, said that bone density and bone quality are just two of many factors to be taken into consideration for fracture prevention—in addition to the usual advice about calcium intake, vitamin D, exercise, smoking cessation and reducing alcohol intake. They call for more research into the reasons why elderly people fall, such as oversedation with prescription drugs, orthostatic hypotension (low blood pressure upon standing), impaired gait or balance, poor eyesight and hearing, arthritis, etc. They also want more attention given to tai chi exercises to improve balance and muscle strength. Research for fracture prevention should move beyond the realm of endocrinologists and rheumatologists to include neurologists, physiatrists, physiotherapists, engineers and muscle activation therapists.

Where can someone with osteoporosis find an engineer or a muscle activation therapist? “At an osteoporosis center based at an academic medical center,” answered Dr. Cheung in a telephone interview. “We have much to learn from these folks, and we need to engage in a dialogue with them to help people reduce their fracture risk.” Dr. Cheung, who is at the University Health Network and Mount Sinai Hospital in Toronto, was asked why she still sees a role for bisphosphonates when the trials cited in her commentary had such negative findings. [“...in two well-designed randomized controlled trials in which high-risk elderly people without fracture but low bone mineral density, treatment with bisphosphonates did not decrease the risk of hip fractures.”] “These drugs are not just for hip fractures, but for overall fractures,” she answered, citing the example of her patients who have difficulty eating because the rib cage has collapsed due to spinal fractures. She also praised a 2007 study by Black and colleagues, which showed that hip fracture can be reduced with a more potent bisphosphonate given intravenously to participants, aged 70 to 90 years. [Note: This study showed only a 1% difference between the drug-treated and the placebo groups in terms of hip fracture reduction.]

Unfortunately, the current TV ads for this intravenous once-a-year bisphosphonate drug are conveying the same misleading message shown in the early ads for Fosamax. They feature a thin, fit 60ish woman—far younger than those who participated in the clinical trial.

Maryann Napoli, Center for Medical Consumers ©
April 2008


FDA Alert about Osteoporosis Drugs

The FDA posted an alert on its Web site, “…highlighting the possibility of severe and sometimes incapacitating bone, joint, and/or muscle (musculoskeletal) pain in patients taking bisphosphonates. Although severe musculoskeletal pain is included in the prescribing information for all bisphosphonates, the association between bisphosphonates and severe musculoskeletal pain may be overlooked by healthcare professionals, delaying diagnosis, prolonging pain and/or impairment, and necessitating the use of analgesics.”

Bisphosphonates are a popular class of drugs prescribed to reduce the risk of fractures from osteoporosis. The alert applies to all drugs in this class, including Fosamax, Boniva, Actonel, Aredia and Didronel. The FDA reports, “The severe musculoskeletal pain may occur within days, months, or years after starting a bisphosphonate. Some patients have reported complete relief of symptoms after discontinuing the bisphosphonate, whereas others have reported slow or incomplete resolution.”

WWW.FDA.gov/medwatch/safety, 1/7/08

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Drug Advertising Critique

Posted by medconsumers on January 1, 2007

Bone Loss Drug Ads: Half-Truth in Advertising

The print ad for Actonel, a drug to “help fight fracture,” features a fiftyish white woman next to the headline: “How many women over 50 will break a bone due to osteoporosis? A)1 in 2000, B) 1 in 200, C) 1 in 20, D) 1 in 2 Answer: D) 1 in 2.”

The source for the “1 in 2 correct answer,” listed after the quiz, is the 2004 Report of the Surgeon General on Bone Health and Osteoporosis. Here is how the Report actually put it: “Four out of every 10 white women age 50 or older in the United States will experience a hip, spine, or wrist fracture sometime during the remainder of their lives.” (Only white women were studied for fracture risk.)

The ad implies that the 1 in 2 fracture odds start at age 50. It does not explain this is the lifetime risk of having any fracture for women who live to be 90. But it is hip fracture that is the most serious consequence of osteoporosis, and osteoporosis-related hip fractures before the age of 70 are rare. In fact, a 70-year-old white woman with a total hip score of -2* has only a 5% risk of having a hip fracture in the next ten years. And an 80 year-old woman with bone density at her hip that is average for her age has a 9.7% risk of a hip fracture in the next decade.

But these statistics, which come from the excellent Web site of bone physiologist Susan Ott, MD, aren’t scary enough to appear in an ad for a bone drug. Dr. Ott acknowledges that bisphosphonates, the drug class to which Actonel, Fosamax, and Boniva belong, are widely prescribed to women under 65, but says she is reluctant to give them to women this young.

Dr. Ott, associate professor of medicine at University of Washington, would rather restrict bisphosphonates to those under 65 with severe osteoporosis—that is, a history of non-traumatic fracture—and those who take prednisone. She advises her patients to stop taking bisphosphonates after five years because of “long-term safety issues. Dr. Ott’s Web site is http://courses.washington.edu/bonephys

*Test result indicates bone loss, but not osteoporosis, which is -2.5 standard deviations below the young adult mean.

Gardasil Vaccine Ads Aimed at Teens

The first thing you notice about the Gardasil TV ads, featuring teen-age girls engage in various athletic activities, is that there is no mention of the fact that the Gardasil vaccine is for the prevention of a sexually transmitted disease.

One version of these ads, which features mothers and daughters, was found to be cleverly manipulative by a New York Times reporter, Claire Dederer. The ad shows cool, self-reliant girls involved in cool, self-reliant physical activities with the repeat message: I want to be one less woman who will battle cancer.

“The mothers appear about halfway through [the ad] and they’ve got the bad news,” writes Dederer. “In loving tones they break it to their daughters: ‘Gardasil may not fully protect everyone,’ they say. Tenderly they list the side effects. This is an ingenious ploy: the cool girls want to be ‘one less’; the moms are the ones putting on the brakes. Having mothers voice the downside of Gardasil reinforces the message that if you get this vaccination, you’re the rebellious, independent thinker: ‘forget the side effects. Forget Mom. I’m getting vaccinated.’”

Maryann Napoli, Center for Medical Consumers ©
January 2007

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Reduce Risk of Breast Cancer

Posted by medconsumers on May 1, 2006

Drugs to Reduce Breast Cancer Risk: Is It Worth It?

Initial results from a government-sponsored study indicate that the osteoporosis drug raloxifene (brand name: Evista) may protect against breast cancer. The study compared it against an older anti-breast cancer drug, tamoxifen (brand name: Nolvadex), and found both are equally good at reducing the chances of developing breast cancer. Some media reports of this study were overly enthusiastic about its finding.

The study is yet to be published and therefore has not been peer-reviewed. If the results hold up, Eli Lilly, maker of raloxifene, will be able to apply to the FDA for permission to promote raloxifene as a breast cancer preventive. Expect an overheated advertising campaign by Lilly touting raloxifene as a “two-for”—a drug that will save women from osteoporosis AND breast cancer.

Raloxifene has been on the market since 1997. It is good at increasing bone density; completely ineffective at reducing the most serious type of fracture (hip); and minimally effective in reducing spinal fractures. Spinal fractures can cause pain and a dowager’s hump in advanced age, but many are entirely symptomless. Tamoxifen has been on the market since 1972. First as an adjunctive treatment for breast cancer and more recently (1998) as a preventive drug for healthy but high-risk women. It never took off for the latter purpose because, according to one report, many doctors were uneasy about prescribing a cancer drug to healthy women every day for five years.

Both raloxifene and tamoxifen are what is called selective estrogen receptor modulators, or SERMs, which means that they protect the breast from estrogen’s cancer-causing potential but preserve estrogen’s protective effect on the bones. This is why SERMS were initially promoted as designer estrogens.

The National Cancer Institute sponsored the new study that compared the two drugs called the STAR trial, short for Study of Tamoxifen and Raloxifene, and the initial results were posted last month on its Web site (www.cancer.gov see initial results STAR). The STAR trial included postmenopausal women at high risk for breast cancer who had been randomly assigned to take one or the other drug. The NCI hailed both drugs as having reduced the incidence of breast cancer by 50%, which was uncritically picked up by most of the media.

Here’s what the NCI should have explained: Of the 9,700-plus women in each drug group, about 165 got breast cancer. This translates to 1.7%; whereas, 3.4% would be expected to develop breast cancer had they not taken a drug. (Hence the 50% reduction in breast cancer incidence.) Another way of saying the same thing is: 98.3% of high-risk women will not get cancer if they take raloxifene or tamoxifen; whereas, if they take no drug, 96.6% of women will not get cancer. Obviously, much more research is needed to determine who is at high risk for breast cancer.

If you are thinking of taking raloxifene every day for five years, consider the following:

It is premature to call raloxifene and tamoxifen preventive drugs. The STAR lasted only four years and breast cancer can take from 12 to 17 years to develop. Therefore, it is not known whether these drugs prevent breast cancer or merely delay its onset. The Tamoxifen Breast Cancer Prevention Trial lasted nearly five years.

The media reports of STAR emphasized fewer adverse reactions for raloxifene. However the 29% fewer blood clots and 36% fewer uterine cancers are not considered to be statistically significant because these conditions are rare. (Findings could have occurred by chance.) However, the finding of fewer cataracts in the raloxifene users is statistically significant. There were fewer cases of noninvasive breast cancer (e.g., ductal carcinoma in site, which does not always become life-threatening if left undetected.) in the women taking tamoxifen. [Note: When the STAR results were reported at a June meeting of the American Society of Clinical Oncology and published simultaneously online in the Journal of the American Medical Association, there was no overall difference between the two drugs in the study participants’ self-reported side effects—with some exceptions. Hot flashes, vaginal bleeding, bladder control problems were more common in women on tamoxifen. And pain during sexual intercourse and joint pain were more common in those on raloxifene.]

Raloxifene’s spinal fracture reduction benefit is small. Three-year results of a major trial showed spinal fractures in 10.1% of the women on placebos; in 6.6% of women on 60-mg/daily of raloxifene; and in 5.4% for women on 120 mg/daily of raloxifene.

Less is known about the long-term effects of raloxifene than is known about tamoxifen. It took more than 25 years of tamoxifen use before a rare life-threatening adverse effect (endometrial sarcoma) became apparent.

Maryann Napoli, Center for Medical Consumers ©May 2006

For another perspective on this study, see Breast Cancer Action’s Newsletter

http://www.bcaction.org/Pages/SearchablePages/2006Newsletters/Newsletter092A.html

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