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Three developments that could change how you treat osteoporosis
From the January ACP-ASIM Observer, copyright © 2003 by the
American College of Physicians-American Society of Internal Medicine.
Non-drug therapies in the battle against
osteoporosis
The role testing plays in osteoporosis treatment
By Jason van Steenburgh
For physicians who treat osteoporosis, the news over the last six
months
could potentially change the way they practice.
The first announcement came last July, when the Women's Health
Initiative
released new data highlighting the risks of hormone replacement therapy.
That bombshell frightened patients, leading some to question treatments
that
were helping stave off osteoporosis.
The issue of when and how to treat osteoporosis was further
complicated
last fall when the U.S. Preventive Services Task Force urged physicians
to
begin screening some women for the condition starting at age 60, rather
than
65. While researchers say earlier screening will save lives, the
guidelines
raise questions about what drugs younger seniors should receive for
osteoporosis. (The guidelines are
online.)
 Finally,
in November 2002, the FDA gave its long-awaited approval to a new
osteoporosis drug, teriparatide. Instead of merely slowing bone loss,
experts say the new drug actually accelerates bone growth.
What do these developments mean for you, and should they change your
approach to treating osteoporosis? To answer those questions, we talked
to
physicians who specialize in osteoporosis treatments and have followed
these
developments closely.
HRT's role in prevention
Here's the news that gave physicians the most headaches: Researchers
presented new trial findings stating that women taking hormones face an
increased risk of breast cancer, stroke and coronary events. The data
were
so alarming that researchers halted the trial and urged physicians to
avoid
using HRT in women who are at risk for or have family histories of those
conditions.
Because the announcement generated so much controversy, experts say
that
many patient advocates and physicians may have overlooked vital
information
about HRT's role in preventing osteoporosis. According to data from the
now-halted trial, hormones reduced hip fracture rates by 34%, a finding
that
supported previous data.
While some patients may want to stop hormone therapy, Robert R.
Recker,
MACP, director of the Osteoporosis Research Center at Creighton
University
in Omaha, Neb., said that menopausal patients who have risk factors for
osteoporosis but not for coronary events or breast cancer remain ideal
HRT
candidates.
He recalled one recent patient who was conflicted about using HRT, but
who nonetheless decided to begin using hormones. While the 52-year-old
woman
had a family history of osteoporosis and hot flashes, she had no family
history or other risk factors for breast cancer or coronary events.
"We talked about the options," Dr. Recker said, "and
she chose HRT. The
plan is for her to stay on it to treat her menopausal symptoms and then
to
go to another drug like a bisphosphonate if the HRT doesn't prevent her
from
losing bone."
He added that he and the patient together decided that in the absence
of
severe bone loss, they would give HRT a chance to prevent the development
of
osteoporosis before moving to other therapies.
Dr. Recker said that HRT is a good option for women who are going
through
menopause and have low bone-density measures. (For more on testing for
bone
density, see "The role testing plays in
osteoporosis
treatment.") Patients with low bone density are especially good
candidates for HRT if they have other risk factors for osteoporosis such
as
smoking or a family history of the condition, he said.
Dr. Recker said he doesn't push patients to stay on HRT if they have
serious reservations about the drugs' side effects, but he encourages
them
to examine data from the Women's Health Initiative before forgoing
hormone
therapy. The study found that compared to a control group, 10,000 women
taking hormone therapy for one year would experience seven more coronary
heart disease events, eight more strokes, eight more pulmonary embolisms
and
eight more cases of invasive breast cancer each year.
When it came to colorectal cancer and hip fractures, however, the news
was much better. Researchers found that for every 10,000 women taking HRT
for a year, six fewer women developed colorectal cancers and five fewer
developed hip fractures.
Perhaps even more importantly, Dr. Recker said, the study found HRT
significantly reduced hip fracture rates in a population that had a low
risk
for hip fractures. He predicted that when HRT is studied in a population
at
high risk for fractures, researchers will find even stronger evidence for
using hormones to prevent osteoporosis.
(For more on balancing the risks and benefits of HRT, see "Weighing
the risks of hormone therapy" in the September ACP-ASIM
Observer.)
If patients want to discontinue hormone therapy but tests indicate
they
have significant bone loss, switch them to a new treatment as soon as
possible.
If hormone therapy had been preventing bone loss in these patients,
that
benefit will be lost rapidly, explained Robert L. Meckelnburg, FACP, a
solo
practitioner in Newark, Del., who specializes in osteoporosis.
"After a year
or two off estrogens, women drop back to where they were before they went
on
hormones," he said.
SERMs and bisphosphonates
Not everyone supports using HRT to prevent osteoporosis. Joel S.
Finkelstein, MD, an endocrinologist at Massachusetts General Hospital in
Boston who has researched osteoporosis treatments, said he uses HRT only
to
prevent osteoporosis in patients who have menopausal symptoms and can't
tolerate bisphosphonates or selective estrogen receptor modulators
(SERMs),
the two main options for osteoporosis treatment.
"If their primary reason for being on HRT is osteoporosis, there
are
better and safer drugs," he explained. In addition, he said that no
data
associate either of these drugs with increased risks of coronary events
or
cancer.
As soon as HRT is failing to prevent bone loss, you should switch to
an
alternate treatment. Bisphosphonates and raloxifene (the only FDA-
approved
SERM) are the top choices to treat moderate to severe cases of
osteoporosis.
Even if your patients with moderate to severe osteoporosis decide to
stick with HRT, experts say you should consider an additional first-line
treatment.
How do you choose between bisphosphonates and SERMs? Experts say that
two
factors-age and the location of bone loss-are critical in choosing a
treatment strategy. Because different drugs decrease fracture rates in
different parts of the skeleton, testing the hip and spine will probably
determine which drug therapy to use.
- Bisphosphonates. Most physicians turn to bisphosphonates as
their first treatment choice because of the drugs' demonstrated ability
to
reduce hip fractures, a common fracture site in elderly women.
The
drugs
are recommended for a patient who has broken a limb, men and women in
their late 60s or older, or anyone with severe bone loss. Often, women
go
on both bisphosphonates and HRT. (Studies show that this combination
therapy is more effective than either treatment alone.)
A major downside of bisphosphonates is their tendency to cause
gastrointestinal problems including heartburn and ulcers. Some of those
effects can be minimized if a patient takes the medication with eight
ounces of water, then sits upright for 30 minutes. For some patients,
however, the adverse GI effects can be intolerable.
Although newer bisphosphonates have shown greater efficacy,
Charlotte
A. Harris, FACP, director of the Rush Osteoporosis Treatment Center in
Chicago, said she sometimes uses etidronate, an older bisphosphonate
that
is not FDA-approved as an osteoporosis treatment. "A patient who
has GI
intolerance to the more modern ones can sometimes tolerate it,"
she said.
"You go on it for two weeks, then take 10 weeks off."
Another note of caution about bisphosphonates: When patients
discontinue the drugs, the bone-preserving effect is slowly lost. Some
studies have suggested that the effect lasts in proportion to how long
the
patient used the drug.
A study published in the Dec. 3, 2002, Annals of Internal
Medicine
showed that patients who discontinued using the bisphosphonate
alendronate
had 11.2% lower bone mineral density after two years than those who
continued with the treatment.
There is also a theoretical concern that long-term bisphosphonate
use
could be detrimental. Although there has been no evidence of long-term
side effects, the drugs have been on the market for less than 10 years,
and some researchers are concerned that evidence shows the drugs can
accumulate in the bone.
"For a middle-aged patient on bisphosphonates who will live
another
three decades or more, we don't know what that will do," said Dr.
Recker
from Creighton. He also warned that there are concerns that
bisphosphonates may inhibit bones' responsiveness to anabolic agents
like
teriparatide.
- SERMs. For younger patients who are more likely to have
brittle
spines than brittle hips, raloxifene, which has been shown to increase
spinal bone density, is the drug of choice. Raloxifene is also easier
on
patients' digestive systems than bisphosphonates.
Another reason to
start patients on raloxifene? It can help prevent breast cancer and may
reduce cholesterol.
Keep in mind, however, that women taking HRT for menopausal symptoms
should avoid raloxifene if they suffer from hot flashes, as the drug
actually exacerbates the condition.
New treatment for severe cases
If your patients have severe osteoporosis, you have a new option:
teriparatide. Late last year, the FDA approved the drug, an injectable
agent
based on a parathyroid hormone that will be sold under the brand name
Forteo.
The drug has shown remarkable efficacy in increasing bone density and
reducing fractures. While other anti-resorptive agents stop bone from
being
lost, teriparatide actually stimulates new bone growth, said
Massachusetts
General's Dr. Finkelstein. He said he plans to use it in the most severe
osteoporosis cases, especially patients who have had fractures.
Teriparatide can be taken for up to 24 months to help patients grow
new
bone. After that period, experts recommend reverting to standard
anti-resorptive drugs like bisphosphonates and raloxifene to maintain
those
gains.
The major hurdle for physicians prescribing teriparatide will be
convincing patients that their problem is severe enough to warrant daily
injections. "It is a burdensome therapy in terms of expense and
convenience," Dr. Harris said. "It will probably be used
primarily in
patients on bisphosphonates who are still breaking bones."
Because teriparatide has shown an anabolic effect in both sexes, Dr.
Recker thinks he may eventually offer the drug to up to half of his
osteoporosis patients. He predicted that many, however, will probably
choose
a medication that they can take orally.
Other options
Finally, there are some other drugs you have at your disposal.
- Nasal calcitonin-salmon. One of the first approved
treatments
for osteoporosis is nasal calcitonin-salmon (Miacalcin). Dr.
Meckelnburg
said he occasionally uses it in combination with either bisphosphonates
or
raloxifene, mostly for its narcotic effect on acute fracture
pain.
Dr.
Finkelstein from Massachusetts General, however, said if the drug went
before the FDA today for approval, it would probably be turned down.
"It's
extremely ineffective," he said. "I almost never use it, only
when
everything else has been tried."
Dr. Recker said he doesn't prescribe calcitonin-salmon because it
can
lead to problems with rhinitis. Because rhinitis causes patients to
lose
their sense of smell, it interferes with appetite, which can prevent
osteoporotic patients from eating enough foods rich in calcium and
vitamin
D.
- Intravenous zoledronic acid. Intravenous zoledronic acid, a
bisphosphonate, has been shown to be effective, and many physicians use
it
as an off-label treatment for osteoporosis. It will be at least five
years
until it is FDA-approved as an osteoporosis treatment.
A study
published
in the Feb. 28, 2002, New England Journal of Medicine found that
infusions of 0.25 mg, 0.5 mg or 1 mg every three months, 2 mg every six
months, or 4 mg every 12 months had the same effect on bone density as
oral bisphosphonates.
"It's a good option for people who can't handle oral
bisphosphonates,"
said Felicia Cosman, MD, clinical director for the National
Osteoporosis
Foundation.
She said the perfect candidate for the drug has had wrist and spine
fractures and cannot tolerate a once-a-week course of oral
bisphosphonates, even with a proton pump inhibitor, because of severe
ulcer disease and esophagitis.
The treatment's downside? "We have no fracture data yet,"
Dr. Cosman
said.
Most physicians agree that the lack of studies concentrating on
fracture efficacy as well as minimal information on dosage and regimen
make this an option mainly for patients for whom other treatments have
failed.
The information included herein should never be used as a
substitute
for clinical judgment and does not represent an official position of
ACP-ASIM.
Top
Non-drug therapies in the battle against
osteoporosis
Although the list of available drug therapies for osteoporosis is
growing, modifying diet and lifestyle is still an important part of the
equation. Here are some other strategies to improve bone strength:
- Vitamins and minerals. Adequate vitamin D intake is
especially
important for individuals living in northern climates that have reduced
sunlight several months a year and for elderly patients who rarely
spend
time outdoors.
"I use high-dose vitamin D injections, up to 800
mg
daily," said Kendra Schwartz, MD, associate professor of family
medicine
at Wayne State University School of Medicine in Detroit. "Studies
show it
improves bone mineral density in patients from places without a lot of
sunlight."
Proper calcium intake is also vital to the success of anti-
resorptive
agents. Experts point out that although physicians stress the
importance
of calcium intake, they don't make it clear to their patients that
failure
to take enough calcium while using bisphosphonates, SERMs or HRT will
severely limit the drugs' effect on bone loss.
At the same time, taking supplements in the absence of drug
therapies
is also just a start. By themselves, calcium and vitamin D are only
mildly
effective in preventing bone loss.
- Exercise. Patients who exercise regularly—even a little—
avoid
more falls (and fractures) because they have better endurance and
balance.
A study in the Nov. 13, 2002, Journal of the American Medical
Association showed that women who get four hours per week of even
moderate exercise reduce their rate of hip fracture by 41% compared
with
women who are sedentary.
- Hip protectors. Another proven way to avoid fractures? Pad
vulnerable areas so that if a patient falls, the impact is spread out
and
doesn't cause a fracture.
The best way to accomplish this is through
hip
protectors. Studies have shown the devices drastically reduce hip
fractures among compliant patients. The trick, of course, is getting
patients to wear them.
"They are nearly 100% effective against hip fractures,
inexpensive and
very safe," said Robert R. Recker, MACP, director of the
Osteoporosis
Research Center at Creighton University in Omaha, Neb. "Patients
argue
against them because they think they will be big and bulky, but I have
nurses wear them, then ask patients to tell me which nurse has one on.
They can't. People get used to them very quickly."
"Most osteoporosis patients are thin to start with and the hip
protector is very thin, similar to the shin guards that kids wear to
play
soccer," said Felicia Cosman, MD, clinical director for the
National
Osteoporosis Foundation. "The data are very good for the people
who wear
them."
Top
The role testing plays in osteoporosis
treatment
You can use various imaging techniques to measure bone mineral density
(BMD), a factor that is negatively correlated to fracture rates. Where
patients fall on the T-scale—a measure of standard deviations below
average
BMD—should help guide your treatment strategy.
Robert L. Meckelnburg, FACP, a solo practitioner in Newark, Del., who
specializes in osteoporosis, said that all women should have their BMD
tested as soon as menopause begins, even if they are on HRT. He said that
after the first test, he watches patients closely.
Because many women lose bone density even while taking hormones, Dr.
Meckelnburg said, testing allows him to start women on more aggressive
treatment as soon as they drop half of a standard deviation in the first
few
years after menopause. By testing patients early, he isn't seeing them
for
the first time when they are already two or three standard deviations
below
normal.
Felicia Cosman, MD, clinical director of the National Osteoporosis
Foundation, however, argued that while testing all women's bone density
at
menopause would catch some cases of osteoporosis early, the cost of such
widespread screening would not be worth the few cases that were
caught.
Perhaps even more importantly, as you test younger women for bone
loss,
you identify more borderline cases, which raises questions about who to
treat. Dr. Cosman said that T-scores below minus 2, for example, don't
necessarily indicate the need for hormone therapy or other treatment.
"Advocating testing doesn't mean you advocate treatment,"
she said. "I'm
not sure that patients with a BMD between minus 1 and minus 2.5 should be
treated in the absence of fractures because the risk is rather low."
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