Here’s a drug marketing plan that is dazzling in its brilliant effectiveness. I’m thinking of including it in any future PR workshops I do on marketing communications. It’s a plan to sell pills to treat something called osteopenia, a condition that only recently started to be thought of as a problem that even needs treatment.

It’s a plan to convince consumers and their physicians that these pills should be in the medicine cabinets of millions of women worldwide.

But more broadly, it’s a plan to change the definition of what a disease is, and the role that drug companies can play in that change. 

Until the mid-1990s, only a handful of people had even heard of osteopenia.  It is defined as a slight thinning of the bones that occurs naturally as women get older, and typically does not result in bone breaks.

But drug giant Merck wanted to sell a whole lot more of its drug Fosamax, prescribed to treat those already diagnosed with osteoporosis, a disease (mostly seen in the elderly) that can cause bones to become more porous and to break more easily. It was particularly important at that time, because Merck’s patent protection on the drug was due to expire, thus opening the door to cheaper generics and plummeting profits.

In order to pitch Fosamax by linking the benign condition of osteopenia with osteoporosis, Merck would need a marketing plan, and a hotshot to work the plan.

So Merck hired super-sales guy Jeremy Allen to help position Fosamax as a ‘cure’ for the new ‘disease’ of osteopenia.

To convince large numbers of middle-aged women that they needed to take Fosamax to prevent the old age bone fractures of osteoporosis, Merck first needed to convince women to get their bones scanned so they could be diagnosed with osteopenia.  How to do this?  Existing bone scanning systems were expensive, cumbersome and hard to come by. Here was Jeremy Allen’s brilliant marketing plan in a nutshell:

• create an institution, a non-profit entity whose mission was not just to sell our drugs, but to serve the public good – and name this the Bone Measurement Institute
• set up our own factory to manufacture small, portable peripheral scanning machines to measure bone density in the heel, wrist or forearm – and make them affordable enough for individual doctors and clinics to purchase
• make the scanning test results simple and graphic: green means normal, red means osteoporosis and yellow means this new ‘disease’ of osteopenia
• use our new Bone Measurement Institute to lobby governments to pass legislation allowing medical insurance plans to pay for these new bone scans
• pay other organizations to lobby government, too
• produce a new low-dose version of Fosamax designed specifically for those diagnosed with the new ‘disease’ of osteopenia
• create Direct To Consumer TV ads urging women to get their bone density tested because they might need to take Fosamax to treat their osteopenia and thus prevent osteoporosis

And it worked.

Annual bone density screening rates in North America increased by 263% from 2002 to 2007.  By 2007, the number of people on Fosamax had increased by 153%.

But how did this non-disease osteopenia get invented in the first place?

According to a National Public Radio report, it seems that one day back in 1992, a bunch of bone doctors were sitting around at a meeting in Italy chatting about osteoporosis, and — more or less off the cuff —  came up with the term osteopenia to describe bone density that was somewhere between perfectly normal and very early osteoporosis.

The chairman of the meeting, Dr. John Kanis, of the World Health Organization’s Collaborating Centre for Metabolic Bone Diseases, told NPR that they created this bone density sub-category mostly because they thought it might be useful for public health researchers who like clear categories for their studies.

“We never imagined that people would come to think of osteopenia as a disease in itself to be treated.”

Meanwhile, studies in women were showing that while Fosamax and similar drugs could reduce spinal fractures in those who are already diagnosed with osteoporosis, the drugs were not as likely to prevent hip fractures, the type of bone fractures that are significantly more common and dangerous, especially in elderly women in their late 70s and 80s. About 25% of people who experience a hip fracture end up in a nursing home, 50% never again reach their functional capacity, and 25% of patients over 65 years of age with a hip fracture die in the first year after the incident.

According to Dr. H. Gilbert Welch‘s book Over-diagnosed: Making People Sick in the Pursuit of Health, here are the overall numbers for treatment of decreased bone density:

• Winners (drug treatment saved them from a fracture): 5%
• Treated for naught (had a fracture anyway, despite treatment): 44%
• Losers (treated, but never would have had a fracture without treatment): 51%

Even more alarming, Dr. Susan Ott of the University of Washington worries that taking osteoporosis medications longterm — over five years or more — might actually make bones brittle.  In a 2004 letter published in the Annals of Internal Medicine, Dr. Ott wrote:

“Many people believe that these drugs are ‘bone builders,’ but the evidence shows they are actually bone hardeners.”

Other researchers also suggested that many years of using Fosamax (or other drugs like Procter & Gamble’s Actonel in a class called bisphosphonates) could eventually cause more bone fractures.   *See NEWS UPDATE below.

Or could it? Not surprisingly, drug manufacturers of bisphosphonates are fighting back ferociously.  A Merck-funded review paper published recently in the New England Journal of Medicine concludes emphatically:

“The occurrence of fracture of the subtrochantericor diaphyseal femur was very rare, even among women who had been treated with bisphosphonates for as long as 10 years.”

Sounds promising for Big Pharma. But if you look very, very closely, the article’s fine print confesses:

“The review was underpowered for definitive conclusions.”

You might justifiably ask why any medical journal would stoop to publishing a meaningless scientific paper that the paper’s own authors admit lacks any “definitive conclusions”. Even more troubling than a journal article that was itself bought and paid for by Merck, is the conflict of interest disclosure list at the bottom of this NEJM article.

It reads like a Who’s Who of Big Pharma.

Of the 12 study authors listed in the NEJM article, at least three are full-time employees of Merck or Novartis. Each one of the others admit owning equity interests in or receiving cash, travel expenses, or “consulting and lecture fees” from Merck, Novartis,Amgen, Roche Nycomed, Procter & Gamble, AstraZeneca, GlaxoSmithKline,Medtronics, Nastech, Nestle, Fonterra Brands, OnoPharma, Osteologix, Pfizer, Eli Lilly, Sanofi-Aventis, Tethys, Unilever,Unipath, Inverness Medical, Ortho Clinical Diagnostics, OSIProsidion, or Takeda.

Why is the New England Journal of Medicine or any other credible medical journal accepting for publication articles submitted by paid employees of pharmaceutical companies?

Here in my own province of British Columbia, the Medical Services Commission of BC slapped a moratorium on public funding of bone mineral density (BMD) testing in new health care facilities throughout the province back in May of 1996, according to Dr. Ken Bassett.

A senior medical consultant at the University of British Columbia’s Centre for Health Services and Policy Research, Dr. Bassett’s research focuses on the systematic review of drug therapy and drug funding policy.

His paper called On Trying to Stop the Measurement of Bone Density to Sell Drugs (ISBN 0-88865-240-2) was presented at the 12th Annual Health Policy Conference held in Vancouver, B.C. in November 1999.

This moratorium effectively stopped the diffusion of BMD technology in our publicly-funded facilities in the province for three years. The moratorium occurred because a medical consultant with the provincial government’s Ministry of Health took a stand based on the best available scientific evidence at the time. As this consultant explained:

“I was convinced that there was no scientific evidence that bone mineral density testing led to improved patient outcome. In my opinion, we had better things to spend our money on.”

But by late 1999, says Dr. Bassett, this medical consultant had left the Ministry of Health; his contract had not been renewed. The BMD moratorium ended. And in 1999, the number of publicly funded facilities with BMD-testing capability in our province doubled. Commercial interests are promoting BMD testing in most large and medium-sized communities in the province.

Dr. Bassett explains why this promotion is such a concern:

“Bone mineral density has not been linked to any improvement in health outcome.

“Women are being tested at age 50 and, based on those results, are being asked to take medications to prevent fractures predicted to occur 20-30 years later.”

He adds that the ‘osteoporosis disease management model’ favoured by several large drug and device manufacturers is a masterfully crafted means to promote the medical management of bones and ‘bone health’ across a lifespan:

“It brings together bone mineral density measurements with specific drug therapy designed to alter those measurements. The ultimate goal is to create a direct relationship between BMD measurement and drug prescription. Since the early 1990s, the osteoporosis disease management model has been vigorously promoted for all women at or beyond menopause.”

Dr. Bassett warns that this model draws attention away from problems of diet, exercise, lifestyle, and poverty and toward a specific, measurable, alterable component of bone structure.

Not only is it alterable, but pharmaceutical products exist for the job, although, conveniently, the fact that weight-bearing exercise could also alter BMD, as well as conferring other life-course benefits, is conveniently ignored. In their absence, it seems a virtual certainty that the pressure for BMD testing facilities would not have developed, says Dr. Bassett.

Also in my own province, independent researchers (read: not taking money from drug companies) at Vancouver’s Therapeutics Initiative at the University of British Columbia concluded:

“In the short-term, bisphosphonates show some effectiveness in preventing vertebral fractures demonstrated by x-ray.

“The efficacy with regard to preventing hip fractures is uncertain; for primary prevention, hip fractures are not reduced and for secondary prevention, the effect is of small magnitude and of questionable clinical relevance.

“In the long-term, there is an increased risk of atypical fractures affecting the femur. In addition, one cohort study suggests the incidence of hip fractures could be increased instead of reduced. Clarification of the long-term effects of bisphosphonates is therefore necessary and suspension of the use of these drugs for osteoporosis should be considered.”

Even Consumer Reports has raised the alarm with their online warning called Popular Osteoporosis Drugs Come with Mounting Concerns:

“Research has found that bisphosphonates offer only modest benefits in building bone and preventing fractures. And all pose risks. Growing evidence has now linked the drugs to a long list of worrisome side effects.

“Those concerns have recently taken on added urgency as many doctors have started prescribing bisphosphonates not just for people with outright osteoporosis but also for those with osteopenia or pre-osteoporosis, even though it’s less clear that the drugs are effective for this less serious but more common condition. 

“People who are told that they have osteopenia only need to take non-drug steps to strengthen their bones and prevent falls.”

Apparently, our bones are constantly being remodeled, breaking down old bone and growing newer, healthier bone. This process gives our bones the ability to grow, and also heal after injuries. Bisphosphonates, however, slow this turnover. By stopping the resorption of the old bone, the drug could prevent its replacement by new bone, thus making the bone more brittle and prone to fracture – ironically, the very outcome the drugs are prescribed to prevent.

With so many unknowns, cautious doctors are reluctant to prescribe bisphosphonates to women in their 50s. Until there is proof that these drugs are effective at preventing a hip fracture 20 years in the future, this seems like a safe decision, because hip fractures are not likely to occur before the age of 70.

University of Toronto researcher Dr. Angela Cheung agrees, reporting in the May 2004 issue of the Canadian Medical Association Journal:

“We do not recommend using drug therapy for the primary prevention of osteoporosis, especially in young postmenopausal women. More than 45% of postmenopausal women have so-called ‘osteopenia’. The fracture risk for these women is very low.”

Dr. Ott adds that there are in fact no longterm studies that have looked at what actually happens to women diagnosed with the non-disease osteopenia who start taking Fosamax in their 50s and continue treatment longterm in the hopes of preventing old age bone fractures. And none are planned.

In the U.K., experts at the National Osteoporosis Society – which describe osteoporosis as the “fright factor equivalent of breast cancer” – do not recommend preventive drug therapy or supplements either. According to Sarah Leyland of the NOS:

“There is currently no conclusive evidence that supplements taken at menopause when bone density naturally begins to decrease will reduce the risk of osteoporosis in later life.”

What the NOS does recommend for all women is:

• eat a healthy, balanced diet to help build and maintain strong bones
• eat a calcium-rich, low-salt diet with plenty of fruits and veggies
• do regular weight-bearing exercises like running, walking, tennis, aerobics
• keep fit and active in later life to prevent falls and fractures
• avoid excessive amounts of cola drinks, caffeine, alcohol and salt which can affect the way calcium is absorbed or excreted by the body.
• don’t let your body weight get too low (I’m working on this goal!)
• quit smoking, which has detrimental effects on bone health

But bone researcher Dr. Steve Cummings of the California Pacific Medical Center Research Institute claims that at a certain point, just seeing the word “osteopenia” on a bone density scan’s report had a profound effect on both women and their doctors. Dr. Cummings explained the phenomenon in an NPR interview:

“Bone density scanning becomes increasingly available. And women start wanting it, and they hear their friends have had a measurement of bone density, and their friend was told that they have osteopenia, and they want to know if they have that condition, too. And then their friend starts getting treated with Fosamax or some other drug, and they want to know if they should be treated, too.”

Until drugs like Fosamax began to emerge, the standard osteoporosis treatments were calcium, vitamin D, weight-bearing exercise and hormonal treatments, though ultimately hormonal treatments proved problematic.

After Women’s Health Initiative researchers found that estrogen posed more risks than benefits in the treatment of osteoporosis, sales of Fosamax shot up by 32%.  Low calcium and vitamin D intake had also been associated with increased risk for fractures, but in the WHI Calcium and Vitamin D (CaD) trial, middle-aged CaD recipients showed higher bone densities but similar numbers of hip fractures. Only women who were older than 60 saw a 21% decreased risk for hip fracture compared with placebo.

Since osteoporosis is a serious problem that affects millions of older people, mostly women, the potential market for Fosamax to treat osteoporosis was large, but the potential market for Fosamax to prevent osteoporosis was enormous.

By 2008, when Fosamax lost its patent protection, annual sales of the drug had topped $3.2 billion.  Merck by then had other big problems to contend with, such as their 2004 forced withdrawal of the deadly arthritis painkiller Vioxx, once a $2.5 billion-a-year blockbuster for them, as well as the ensuing $4.85 billion Vioxx lawsuit settlement following the deaths of over 60,000 Vioxx users.

Reports in the Journal of the American Medical Association during the Vioxx lawsuits revealed that in 16 of 20 published medical journal articles that reported on original Vioxx clinical trials, a Merck employee was designated as the author of the manuscript. But an outside academic scientist was listed as the lead author by the time the study was published.

Back to Fosamax: initial rave reviews of the drug seem far less compelling now, particularly in light of 2006 reports linking use of the drug to a possible serious side effect called osteonecrosis of the jaw (ONJ) in women taking Fosamax.*

For example, in 2002, Merck controlled virtually everything about a famous Annals of Internal Medicine paper praising the use of Fosamax. Dr. Susan Greenspan, director of the Beth Israel Deaconess Osteoporosis Prevention and Treatment Center at the time, claimed to be the lead author of this paper – or at least, her name appears in the journal as author.

But as it turns out, Merck revealed to the Los Angeles Times in April of that year that the drug company:

• paid for the recruitment and participation of all 327 clinical trial subjects described in this journal article
• collected the data from 25 separate facilities
• handled “coordinating the early phases of the study”
• provided “expertise in study conduct”
• retained control and ownership of the research itself

The year before Greenspan’s paper was published in 2001, Fosamax sales barely reached $1 billion. By the following year after the paper’s publication, the drug saw sales of $2.7 billion.

In 2003, a newcomer GlaxoSmithKline drug called Boniva (or Bonviva in Europe) was approved for the treatment of osteoporosis – but claims only to be useful for reducing fractures of the spine – again, a far less dangerous form of bone break in osteoporotic women.  Boniva is administered monthly as a pill, or every three months intravenously.

Both Boniva and Fosamax, however, take two years to show any evidence of spinal fracture decrease, according to their own studies.

Funny, Sally Fields doesn’t mention that in her Direct To Consumer advertising . . .

Meanwhile, if you’ve been diagnosed with osteoarthritis (which unlike osteopenia is indeed a real condition), here’s a non-drug therapy that the American College of Rheumatology recommends in this report called Fight Arthritis With Exercise in the Journal of Musculoskeletal Medicine:

“Persons who have arthritis often avoid exercise for fear of pain or injury or not wanting to make a lifestyle change, but those who do exercise have less pain, more energy, improved sleep, and better function.

“Patients with arthritis, particularly osteoarthritis, are encouraged to increase their physical activity. Exercise may have a positive effect in reducing pain that is related to arthritis and other rheumatologic diseases.

“In addition, remaining physically active may help patients reduce other health risks, including type 2 diabetes mellitus and cardiovascular disease.”

Read or listen to the entire NPR story.

NEWS UPDATE: June 25, 2010

Merck Ordered To Pay $8 Million in Fosamax Case

June 25, 2010 (Reuters) – A U.S. jury on Friday awarded $8 million in compensatory damages to a Florida woman who sued Merck & Co. alleging the company’s osteoporosis drug Fosamax damaged her jaw.

Shirley Boles, 71, of Walton Beach, Florida, sued Merck in 2006, claiming she suffered dental and jaw problems because she took Fosamax from 1997 to 2006. Boles’s attorney Tim O’Brien said in a statement:

“Today’s verdict is just the first step, but it’s important because the jury found that Merck defectively designed the drug.”

There are currently 1,280 plaintiff groups involving almost 900 U.S. lawsuits by patients who claim Fosamax caused the condition known as osteonecrosis of the jaw, or death of jawbone tissue.

See also:

• The Myth of Osteoporosis: Blowing The Whistle On the “Epidemic”
• There’s A Pill For That!
• Merck Paying Off 3,100 Families For Heart Attack/Stroke Deaths Linked to Vioxx Painkilling Drug
• Are You a ‘Health-Seeker’ – or a ‘Disease-Seeker’? from my other site, Heart Sisters
• NEWS UPDATE on increased risk of atypical leg fractures in women taking bisphosphonates for five years or longer:  February 22, 2011, Journal of the American Medical Association: Bisphosphonate Use and the Risk of Femoral Shaft Fractures in Older Women
• NEWS UPDATE on atypical leg fractures linked to bisphosphonates: October 14, 2010: FDA issues warning on bisphosphonates
• ABC News video called Osteoporosis Drug Blamed For Leg Breaks

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