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The clutter in my parents'
kitchen sometimes gives me clues about their health that I don't get
through more direct means. When either of them gets
sick, for instance, the counter usually reserved for the occasional baked
good becomes a jumble of medicine bottles. The gradual disappearance of
the little vials reveals when they are on the mend. But none of my parents'
past bouts with illness prepared me for the appearance last month of a
small cardboard box. A label identified the contents as hypodermic
needles. "I've been meaning to
talk to you about that," my mother said casually, once she sensed
that it wasn't cookies I was staring at. "It's not what you
think." Neither she nor my dad,
she assured me, had developed diabetes or become insulin-dependent. That
was a relief. The bad news was that a recent bone mineral density scan
revealed that my mother's spine was disintegrating rapidly. My mother, now 75, had
been diagnosed with osteoporosis five years earlier. By then she had
already lost more than an inch in height and had begun to develop a slight
rounding in her shoulders -- often a precursor to a dowager's hump.
Following his diagnosis, her doctor put her on a regimen of Evista (raloxifene)
and later Fosamax (alendronate). Both drugs commonly are prescribed to
slow breakdown of bone. What was shocking,
however, was the degree to which the drugs had failed her. In the two
years since her last bone density test, bone mass in her spine had
decreased by nearly 10 percent -- a significant and worrisome change, her
internist warned her. Taking into account her age and the fact that a
hairline fracture had been detected in her upper spine in earlier tests,
she was at alarming risk statistically of developing additional fractures.
After reviewing her latest
scan, her doctor suggested she see a specialist who was beginning to do
work with teriparatide, a genetically engineered hormone approved in 2002
by the Food and Drug Administration (FDA). Made by Eli Lilly and Co. and
marketed under the trade name Forteo, the drug contains a synthetic form
of human parathyroid hormone, the primary regulator of calcium and
phosphate in bones. The drug is indicated for people just like my mom --
postmenopausal women already diagnosed with osteoporosis who are at an
elevated risk of fracture -- as well as for men with the condition. Because Forteo would be
broken down quickly during the digestive process, it can't be taken orally
-- it must be taken by injection in the stomach or thigh. Lilly packages
the drug in pre-loaded pen-like devices, each containing enough medication
for 28 days. The pen regulates each squirt, so patients needn't worry
about getting the dosage wrong. All they need to do is screw in a fresh
needle daily and inject. Those were the needles
sitting on the kitchen counter. What a Blast More than the method of
administration separates Forteo from other osteoporosis drugs. Earlier,
so-called anti-resorptive treatments -- including commonly prescribed
nonhormonal treatments like the bisphosphonates Fosamax and Actonel (alendronate
and risedronate, respectively) and the selective estrogen receptor
modulator, or SERM, Evista (raloxifene) -- work by inhibiting the growth
of bone-eating cells known as osteoclasts. Forteo, in contrast, has been
shown to not only stop the growth of osteoclasts, but to replace the bone
eaten away by osteoporosis by increasing the number and action of
bone-forming cells called osteoblasts. In one randomized,
placebo-controlled study funded by Lilly and published in the New England
Journal of Medicine, researchers reported that daily teriparatide
injections given over an average of 21 months to 1,637 postmenopausal
women with osteoporosis increased bone mineral density of the spine and
reduced the risk of new vertebral fractures by more than 65 percent over
placebo. Forteo's benefits exceeded those reported for other treatments in
similar women, the researchers concluded. Forteo also increased bone
mineral density in men, the study found, though it did not look at
fracture risk reduction in men. A possible added benefit
of teriparatide is that it may build new bone even after a patient stops
taking it, said Robert Lindsay, chief of internal medicine at the Helen
Hayes Hospital in West Haverstraw, N.Y. This tantalizing possibility is
based on observational data collected from more than 1,200 participants in
Lilly's earlier studies. In terms of finding a cure
for osteoporosis, Lindsay said, Forteo "points the way." A Bone to Pick Once it became clear that
the anti-resorptive treatments weren't working for her, my mom was glad to
learn she had an alternative. My mother's mother, who died in 1995 at age
90, was never actually diagnosed with osteoporosis. But she had many of
the classic symptoms as she aged, including a dramatic postmenopausal loss
of height and an increased tendency to fall for no apparent reason. Some
of these falls resulted in painful injuries. Understandably, my mother
didn't want to follow suit. Mom also understood that
the damage being done by osteoporosis likely could extend beyond her
skeleton. If her slump -- now only slight -- became more pronounced, it
could make breathing difficult and exacerbate a preexisting lung
condition. That, in turn, would make it more difficult for her to exercise
-- an important part of osteoporosis management. And while she wasn't
experiencing pain from the condition now, there was a good chance she
might in the future, especially if she developed additional fractures. Under the circumstances,
mom wasn't inclined toward squeamishness. When I asked if she minded
giving herself shots, she responded in her usual upbeat way: "Not
really. I'm very thick-skinned." But I had other concerns, too.
Foremost was the fact that, in rat studies, teriparatide had caused an
increase in the incidence of osteosarcoma, a rare bone cancer. Lilly had
halted all human trials of the drug early once researchers began to notice
the rats were developing tumors. FDA approval in November
2002 came with the proviso that Lilly identify the cancer findings boldly
on packages of Forteo and in physician instructions. These "black box
warnings" are the strongest the FDA can require of drug
manufacturers. The agency also limited its approved use of Forteo to two
years per patient. Lilly, meanwhile, agreed
to restrict advertising of the drug to doctors and to recommend the drug's
use only for patients at high risk for fractures. The company also agreed
to continue studying possible links between osteosarcoma and Forteo. Because of the concern
about cancer risk, the Washington-based consumer watchdog group Public
Citizen placed Forteo on its "worst pills" list in 2003 and is
urging consumers not to use it. This, despite the fact
that Forteo has not been linked to osteosarcoma in humans or primates,
according to the FDA. Neither has an elevated risk of osteosarcoma been
observed in patients who have elevated levels of the naturally occurring
human parathyroid hormone after which Forteo is modeled. "You can't ignore the
rat data," said Larry D. Sasich, a research analyst with Public
Citizen. He criticized the FDA for giving Lilly the green light to market
Forteo before more was known about its risks to humans. He also faulted
the agency for approving the drug for men without knowing if it actually
decreased their fracture risk. The FDA shrugs off the
criticism. "We're always faced with the dilemma that people may not
appreciate the risks," said Eric Coleman of the FDA's Division of
Metabolic and Endocrine Drug Products. "But if we didn't approve [Forteo],
we would have all sorts of people clamoring to take the drug anyway. At
the end of the day, you just don't know if the [rat information] is
relevant. Short of not approving the drug, we did what a responsible
agency would do." Well, maybe. But we
weren't just talking abstractly about risk. This was my mother. I wanted a
second opinion. A Needling Detail It was easy to track down
experts who were knowledgeable about teriparatide and who had published
research about the hormone in prestigious, peer-reviewed journals. But
finding experts without direct financial ties to Lilly was more difficult.
My first three calls,
placed to some of the most prominent osteoporosis researchers in the
country, all reached people linked to Lilly. Endocrinologist Ethel Siris,
a professor of clinical medicine at Chad Deal, head of the
Center for Osteoporosis and Metabolic Bone Disease at the Cleveland
Clinic, offered that some of his research had been sponsored by Lilly. Even my mother's own
doctor, Robert Rosenberg, laboratory director for Arthritis and Rheumatism
Associates, a large, multi-center practice in suburban Maryland, told me
that he serves as one of Lilly's many clinical investigators and as a
consultant. (My mother had given Lindsay, with whom I never
spoke directly but who responded quickly to my questions about Forteo via
e-mail, also had received Lilly funding for his research. He is a former
National Osteoporosis Foundation president. Each of the three I spoke
with answered my many questions about the drug and the relative risks and
benefits for osteoporosis patients. Each echoed Coleman's claim about the
lack of any data to suggest Forteo would cause cancer in humans. Each
described the FDA as acting cautiously and responsibly in approving the
drug. And each said he or she would feel comfortable if their own mothers
took the drug. Still, I wanted
confirmation from someone who had less riding on the drug's -- or its
manufacturer's -- success. Finally I touched base with Sundeep Khosla, a
professor at the To my relief, both agreed
with what the others told me. "Forteo's a great
addition to our treatment of osteoporosis," said Khosla, who also
sits on the Osteoporosis Foundation's governing board. "This is the
first drug that has the potential to reverse bone loss. It improves the
quality of the bone and the architecture of the bone." Rosen, who already has
done extensive research on human parathyroid hormone, also was optimistic
about the drug as a treatment for osteoporosis and described the FDA's
approval of Forteo as "extremely judicious." The rats, he said, were
given doses of teriparatide over the course of their entire lifetime.
That, he said, represents a significant departure from the short-term
treatments FDA and Lilly are recommending. Under the regimen FDA approved,
he said, "it's highly, highly unlikely that we will see an incidence
of osteosarcoma." Still, he has
reservations. "Is Forteo better than bisphosphonates?" he asked.
"We don't know. Currently, we don't have any head-to-head data." Also, he said he wasn't
convinced that Lilly had arrived at the proper dosage. In research funded
by NIH, he's now studying whether patients would see benefits in weekly
doses, rather than in a daily injection. Compared with patients taking
pills, those taking injectable drugs typically have more difficultly
keeping up with their medication, he said. Reducing For- teo's dosage to
once a week could help ensure patients stick with the program. "This once-weekly
treatment makes sense, but it is just now being tested in the NIH-sponsored
trial," he said. "It might offer the opportunity of getting a
bone-building treatment at one-seventh the cost." Paying the Price And that brings me to
another lingering concern. The average estimated cost
of a year's supply of Forteo comes in at just under $7,600 -- more than 10
times the cost of other osteoporosis treatments. That puts the drug out of
reach, for the moment, of some who might benefit from it. A year and a quarter after
the drug's debut, Lilly estimates that about 45,000 people take it -- a
small fraction of the number who take the less costly anti-resorptive
medications. Fortunately for my parents, the drug is covered by their
insurance under the Federal Employees Health Benefits plan. A month into her Forteo
treatments, my mom says she's gotten good at giving herself shots. She
says they don't hurt and she's not experiencing side effects. But who
knows? She typically hangs tough in the face of illness. Mom's bottom line is she's
glad to have another shot at staving off the disease when other treatments
failed. The biggest problem she has with Forteo so far, she says, is that the box of needles takes up so much space on the kitchen counter. Copyright © 2004
Global Action on Aging |
