Disease expands through marriage of marketing and machines

By Susan Kelleher · Seattle Times staff reporter
http://seattletimes.nwsource.com/html/health/sick3.html

After the FDA approved Fosamax for treating post-menopausal
osteoporosis, the drug's maker, Merck & Co., launched a marketing
campaign that seemed to target younger, healthier women.

Every day in clinics and doctors' offices across the country, healthy
middle-age women slide their wrists into portable X-ray machines that
calculate bone density.

If they get a low enough density score, they walk out with a
prescription that's supposed to prevent a hip fracture late in life by
adding bone tissue now.

But there's a big problem with this familiar exercise, according to
some top osteoporosis experts: Most of these women don't need the drug.
They are wasting money and risking side effects for little benefit.

"If you're a healthy 50-year-old - an average woman going through
menopause - your chances of getting a fracture ... are very low,"
said Dr. Susan Ott, a bone specialist at the University of Washington.
"Yet they are pushing the drug right at that age group."

By targeting women in their 50s, manufacturers of drugs for
osteoporosis have helped transform osteoporosis from an underrecognized
disease in elderly women into what some say is a disease affecting tens
of millions.

Drug companies and advocacy groups accomplished that by:

· Expanding the disease to include a new condition, osteopenia, or
pre-osteoporosis, with boundaries so broad they include more than half
of all women over 50.

· Promoting osteopenia and osteoporosis directly to these younger,
healthier women, telling them they are at risk and should consider
taking bone-strengthening drugs such as Fosamax.

· Shaping the way osteoporosis and osteopenia are defined, with
readings from bone-density machines that the drug industry promoted,
subsidized and helped put in doctors' offices.

All of this was done in the name of prevention. But Dr. Steven
Cummings, one of the world's experts on osteoporosis and the director
of the San Francisco Coordinating Center, a research center, says the
drug companies' push has been driven by marketing as well as medicine.

"The word 'prevention,' which has become so popular, has also created
problems," Cummings said.

"Drug therapy for women with osteopenia does do some good because it
reduces the risk of spine fractures, but women with osteopenia have a
low risk of those fractures. ...

"So taking a drug for osteopenia probably does not improve the quality
of life for women with osteopenia. It does generate huge sales."

For elderly women who suffer fractures, bone drugs such as Fosamax are
life-enhancing: strengthening bone, reducing chances of future breaks.

Osteoporosis: Chronology of drug development and sales

Who has osteoporosis

Change a number, create a patient

Top drug makers

The bone-density X-ray machines promoted by Merck & Co. and other drug
companies also are powerful advances in treating the disease. Doctors
can use them to diagnose those truly at risk and track their recovery.

But, as Cummings points out, the utility of the machines and the drugs
for middle-age women is unproven, unless they've had fractures
previously. Their growing use is another cautionary tale of the
influence of drug companies on the definition and treatment of disease.

Even a former lobbyist for Merck concedes that the company's focus has
been on expanding the market for Fosamax, also known by its chemical
name, alendronate.

"The goal is to make the uses as broad as humanly possible," said Kurt
Furst, who worked for Merck from 1997 to 2000. "Merck would tell you
virtually any woman post-menopausal should go on Fosamax. That's a heck
of a lot of women."

By focusing on women 50 and older, Merck is following what other health
organizations recommend, a company spokesman, Skip Irvine, said.

Experts devise a numerical measurement of bone density - and the
boundaries of a new condition.

A generation ago, doctors diagnosed osteoporosis only "after the fall"
- once an elderly patient broke a hip or developed a "spinal hump."
There were few effective treatments for the crippling, costly
condition.

As women began living longer, frustrated physicians saw more and more
cases. In 1984, the National Institutes of Health (NIH), the federal
medical-research agency, sponsored a conference of bone experts to
discuss possible ways to prevent osteoporosis.

Scientists knew that adding calcium to diets could build bone. What
they did not know: whether adding thickness alone would reduce the
chances of fractures later on.

Bone strength, it would turn out, depended not just on density but on
heredity and "bone quality" - the shape and number of spindly
bone-cell connections inside the bones.

Experts at the conference opted to focus on bone size, the only aspect
of bone health with existing treatments. They recommended that women
consume more calcium. That decision "turned out to be quite a big
industry," said Dr. Lawrence Shulman, a former NIH institute director
who organized the conference.

Sales of calcium supplements skyrocketed. Media interest intensified.
And drug companies, recognizing the market opportunity, began
developing more drugs to increase bone density.

They supported new medical societies focused on osteoporosis and pumped
money to doctors and scientists for research.

Meanwhile, the World Health Organization (WHO), the medical agency of
the United Nations, decided to figure out if health-care systems could
save money by preventing fractures instead of paying to treat them
after they occurred.

The WHO sponsored an osteoporosis conference in Rome in 1992,
partnering with the International Osteoporosis Foundation, a nonprofit
organization with a corporate advisory board that currently consists of
31 drug and medical-equipment companies.

The central issue of the conference was whether osteoporosis could be
identified before a patient broke a bone, not after. That required a
different way of looking at the condition, a definition based on a
numerical measurement of bone density.

But what would the magic number be? Everyone loses bone mass as they
age. How would "normal" be defined, and what would be the threshold for
prescribing drugs?

Experts at the conference, which was sponsored by two large drug
companies and a drug-company foundation, decided that "normal" would be
the bone density of a woman at age 30, roughly the age when bone mass
peaks for most people.

Any difference between a woman being measured and the established
standard would be reported as a "T-score." The T-score of a 70-year-old
would reflect a comparison to a woman 40 years younger.

The next step was even trickier: How far below normal would density
have to fall before it was considered osteoporosis? What T-score would
define the disease?

The researchers turned to an analysis of women in Rochester, Minn.,
that showed about 16 percent of post-menopausal women in that city
would sustain a hip fracture in their lifetime. Looking at years of
bone-density scores, the WHO committee calculated that 16 percent of
post-menopausal women had bone-density readings of -2.5 or worse.

So under the new definition, anyone with a spinal fracture or a -2.5
T-score or worse had osteoporosis, the doctors decided. That score
roughly translates into bones that are 32 percent less dense than those
of the average 30-year-old woman.

The WHO committee went even further. It said scores between -1 and -2.5
were the boundaries of a new condition, "osteopenia," or low bone mass.

In a single conference, one disease - osteoporosis - had been
expanded from an elderly person with a fracture to anyone who had a
-2.5 T-score. And another condition, osteopenia, was created.

An important result: Doctors could bill insurance for the bone-density
test, which insurance typically had not covered.

Not everyone looked favorably on the developments.

Dr. Leo Lutwak, a retired U.S. Food and Drug Administration scientist
who attended the conference, had argued against creating a diagnosis of
osteopenia. He feared that the condition would be used incorrectly to
label patients as having a disease, making it easier to treat them with
new bone drugs.

The National Osteoporosis Foundation, another nonprofit backed by drug
firms, estimates that 10 million Americans now have osteoporosis and
that the disease is "a threat for an estimated 44 million Americans, or
55 percent of people 50 years of age and older."

With osteopenia, what patients had were measurements, not disease, said
Cummings, the University of California expert.

"A lot of people who have an average risk of fracture for their age are
told they have a disease," he said. "The average person doesn't know
how that came to be or what it really means. But what some women worry
what this means is you're at risk of falling apart. You're going to
break everything. Doctors began to believe that's what it means."

In 1995, the FDA approved the much-anticipated Fosamax, which
essentially adds mineral to bone, fossilizing it and making it harder.
The drug's possible side effects include upper gastrointestinal
irritation, ulcers of the esophagus, skin rash, low blood calcium and,
in rare instances, necrosis of the jaw.

Merck launched a marketing juggernaut around bone-density testing.
Marrying machine to medicine, Merck promoted portable bone-measuring
devices that doctors could use in their offices to identify those with
bone loss.

The company also bought the exclusive rights to one company's
bone-testing technology, gave a loan to another company to help develop
a different machine, and financed two other firms in order to increase
the number of machines in doctors' offices.

Merck also created the Bone Measurement Institute, a nonprofit
subsidiary with the goal of increasing the use of density-testing
machines.

The goal wasn't only to sell the drug to the elderly who had
osteoporosis. Merck officials said they were aiming for the 40 million
post-menopausal women in America, according to a Columbia University
Business School study of the company.

"They intended to turn Fosamax into a primary care product in the long
run," the study said.

When Merck started its push in 1995, there were 750 bone-measuring
devices in the United States. By 1999, there were between 8,000 and
10,000, according to Merck.

"The drug companies started to make machines available to doctors'
offices and enter into big agreements to reimburse them for scans,"
said Dr. Andrea LaCroix, senior investigator for the Center for Health
Studies at Group Health Cooperative in Seattle.

"We were all keenly aware of it. If you were in clinical practice, you
could get the machines relatively cheap."

Doctors found themselves pressured to provide the density tests.

"From the marketing point of view, if you're a provider, you're facing
a groundswell of demand for testing," LaCroix said. "We know it's not
doing a lot of good, but we can't deny them because" otherwise the
patients would "go someplace else."

The number of people tested on the machines rose to about 3.5 million a
year, a Merck official said.

The U.S. Food and Drug Administration warned Merck in 1997 to stop
implying that all women develop osteoporosis at menopause.

In its letter, the FDA noted that twice before it had advised the
company about proper wording.

In 2001, the FDA warned Merck that its Fosamax Web site "overstates the
benefits while minimizing the risks associated with the drug."

1997 and 2001 letters [PDF]
"Compare the facts" campaign [PDF]

Merck targeted ads and brochures directly at younger women, telling
them that "menopause is the single most important cause of
osteoporosis."

But the FDA ordered the company to stop using that phrase in its ads.
In a July 1997 letter, the agency told Merck that the claim "overstates
the population eligible for therapy with Fosamax by implying that all
women develop osteoporosis at menopause."

Meanwhile, Merck's lobbyists helped to persuade Congress to pass the
Bone Mass Measurement Act in 1997. It authorized Medicare to reimburse
doctors for performing bone-density tests, opening the door to coverage
by other insurers.

Merck was so successful in marrying its marketing to the measurement
that its Fosamax campaign was adopted by the industry as a
"best-practices" model for other drug companies looking to expand their
markets.

Various machines mean varying results, critics say.

But skepticism quietly took hold in some corners of the medical
community.

"It's a violent storm in a very small puddle," said Dr. Brian Garra, a
professor of radiology at the University of Vermont who chaired a
gathering of experts who talked about scrapping the T-score measure in
1999, even though many of them had long associations with drug
companies making osteoporosis treatments.

They were concerned about the reliability of the measures provided by
so many different machines with varying standards and accuracy. A
person could be measured on different machines and come up with widely
varying T-scores. The small, portable machines that tested density at
the wrist were not as reliable as the large machines known as central
DEXA, studies showed.

The system of diagnosing osteoporosis with T-scores was in danger of
falling apart. The main reasons for keeping it, it seemed, hinged on
the fact that it had become so entrenched in the medical culture.

Merck's Bone Measurement Institute director said as much during a FDA
hearing in May 1999.

"We understand that the T-score is not an ideal measurement, but it
serves many, many valuable purposes," Dr. Lewis Sherwood told the
assembled experts. "Even more importantly, it is embedded so thoroughly
in many processes that are used widely."

Dennis Black, a University of California, San Francisco statistician,
told the panel: "The manufacturers as well as the pharmaceutical
companies have been very successful in promulgating T-scores. So I
think there is a feeling that we can't abandon those T-scores totally."

The experts at the FDA hearing agreed a better way than T-scores was
needed to assess someone's risk for fractures. They also agreed that
women were being prescribed drugs they didn't need.

"If you abandon the one string that people hold onto, there will be
nothing to hold onto, and the disease won't be treated at all," Black
said in an interview. "It's better for people to do the wrong thing or
not optimal thing than to do nothing."

Task force would reduce bone testing, rely on "evidence-based
medicine."

Black and others are trying to move the field toward a measure of
"absolute fracture risk." Instead of just a T-score, a woman would be
told the likelihood, stated as a percent, of breaking her hip in the
next five years, given her age, race and overall health.

For example, for a healthy, white 50-year-old woman with osteopenia,
the risk of a hip fracture over the next five years would be less than
1 percent. Her lifetime risk for a hip fracture would range from 16
percent to 27 percent.

But doctors need to be careful about not scaring patients with new
numbers, Cummings said. "We need to make sure people understand that
risk, not just that they receive another number," he said.

Today, many physicians, scientists and osteoporosis experts are pushing
hard to scale back bone testing.

Many of them embrace what is called "evidence-based medicine." It
relies less on treatment guidelines from expert opinions and more on
empirical studies based on tests, medical data and outcomes from
thousands of patients.

In 2002, a federal committee chaired at the time by Dr. Al Berg, head
of the University of Washington's Department of Family Medicine,
developed recommendations that cut through corporate marketing and
focused instead on evidence for screening.

The committee was part of the U.S. Preventive Services Task Force,
which bars members from having financial ties to drug makers. Its
recommendations are highly regarded in primary care and preventive
medicine.

The committee recommended that bone testing be sharply targeted. Women
65 or older should be tested, as well as those over 60 who weighed less
than 127 pounds and were not taking estrogen replacement. Testing
should be done at the hip with a DEXA machine, the committee said.

The recommendations gave credence to those experts who had become
concerned that millions of women would be exposed to drugs for decades
at great expense and without evidence that the drugs were safe or
effective for them.

Experts also said that some elderly women who need the drugs might not
be getting them.

A recent study of 459 patients above age 60 who got chest X-rays in one
hospital emergency room in Canada showed that one in six had spinal
fractures that indicated osteoporosis.

But in nearly half of those cases, radiologists didn't spot the
fractures or note them in their reports. Only 25 percent of the
patients were treated for osteoporosis, the study showed.

As result, said Ott, the UW bone specialist, women who could have
benefited from drugs such as Fosamax weren't getting treated for the
disease.

"What's happening is these women who need it are still being terribly
ignored," Ott said.

"Meanwhile, the women in the advertising look like they're about 40
years old."

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