Michael McClung, M.D., explains a new drug to fight osteoporosis that is
easier to take and just as effective as traditional drugs.
Ivanhoe Broadcast News Transcript with Michael McClung, M.D.,
Endocrinologist, Providence Portland Medical Center, Portland, Oregon,
TOPIC: Injection for Better Bones
What is the name of the new drug for osteoporosis?
Dr. McClung: The new drug is named AMG162.
How is it different than what is on the market already for osteoporosis?
Dr. McClung: AMG162 is a human antibody that is directed against a specific
molecule that is the major regulator of bone loss in people. So the antibody
interferes with the molecule's activity. As a result, activity of bone
dissolving cells slows bone loss and helps preserve bone structure. Its end
effect is similar to other drugs, but the mechanism by which it does that is
different than drugs like Fosamax (alendronate) or Actonel (risedronate). Itís
different in that it specifically inhibits the major regulator of bone
What do they do thatís different?
Dr. McClung: The drugs we have to treat osteoporosis come in two categories.
There are antiresorptive drugs, and that includes most of the drugs that doctors
use like Fosamax, Actonel, calcitonin and estrogen. All of those work by turning
down the activity of bone-dissolving cells. These drugs donít restore the bone,
they donít make bone grow, and they donít restore the abnormal structure that
has occurred in older patients with osteoporosis. Thereís a different category
of drugs, thatís called anabolic or growth-promoting agents. One medicine,
Forteo, is given by daily injection and actually stimulates new bone growth,
increases bone mass, and helps restore some of the disordered architecture. But
most of the drugs that we use are in the anti-resorption category, and AMG162
fits in that same category.
So, basically they stop bone loss rather than promoting new bone growth?
Dr. McClung: Correct.
The anabolic drugs donít target the same protein that weíre talking about
Dr. McClung: Right. So drugs like Fosamax and Actonel are incorporated into
the bone-dissolving cells that interfere with the activity of the cells. The
AMG162 finds the regulator of the cells and is a very powerful and effective way
to turn down the activity in those bone-dissolving cells.
Can you explain what happens to bone as we get older?
Dr. McClung: Bone is a very dynamic tissue that has this marvelous dance of
bone-dissolving cells and bone-forming cells. The bone-dissolving cells are
osteoclast. They break down old bone, and thatís replaced with healthy, new
young bone. Thatís the way we maintain the structure and viability of our
skeleton, so thatís a good process. After menopause in women, and with aging in
both men and women, the activity of the bone-dissolving cells increases and
outstrips the ability of the bone-forming cells to keep up. That results in bone
loss and destruction of bone tissue in what we call osteoporosis. AMG162
decreases the activity of osteoclasts.
What is the biggest advantage to this new drug?
Dr. McClung: I think the advantages fall into two categories. First, all of
the medicines that are currently used have some side effects. Fosamax and
Actonel are perceived to result in stomach upset and irritability in some
patients, and that limits its usefulness. By administering the drug
subcutaneously, or through a shot in the skin, those GI symptoms are avoided.
Maybe more importantly, the ability to administer AMG162 only twice yearly,
provides the opportunity to get away from the difficulty that we have with
people stopping their medication. With osteoporosis medications, itís clear that
fewer than 50 percent of the people who are given the prescription continue
their treatment beyond a year, and thatís not the effective way to treat this
Why do they stop?
Dr. McClung: They stop because of side-effects, the inconvenience of daily
dosing, or they simply forget to take their medicine. Oftentimes, patients
arenít aware of how important it is to continue therapy for a long time to get
the full benefit of treatment. By having a drug that is administered just twice
a year where the patient would come to his doctorís office to have it
administered, at least in principal, it would provide the opportunity to improve
the persistence and compliance with treatment. Lastly, AMG162 works more quickly
than other medicines that we have, like within hours after its administration.
The activity of bone-dissolving cells is substantially reduced, whereas with
drugs like Fosamax and Actonel, it takes a few weeks before the full effect is
seen. For most patients, thatís not a very big issue. For some patients, who are
at really high risk for fracture, to have a drug that works quickly and that can
be administered conveniently, would provide an advantage.
Is there risk of infection at the injection site?
Dr. McClung: In the studies weíve performed, weíve not observed any unusual
side effects with the medication, but that study is small. Much larger studies
are ongoing, and that will be explored further. The injection is into the skin
like an insulin shot, and if done correctly, the probability of having an
infection from injection or side effects from injection is very small.
With traditional drugs, how often to patients take their doses?
Dr. McClung: For Fosamax and Actonel, most people take their medicine once a
week. For other medicines, it has to be taken every day.
What would the cost of the new drug be?
Dr. McClung: Well, itís way too early to know what the manufacturer is going
to do about the pricing of the drug.
Tell me about your study of this new drug's effect on osteopororsis.
Dr. McClung: The study weíve performed was a phase II study that had two
objectives: One was to evaluate various doses or various dosing intervals to
figure out which was the optimal regimen. What we learned was that all of the
doses that were administered from small to large, and whether it was given every
three months or every six months, all of the doses were very effective in
turning down the activity of bone-dissolving cells. The second objective was to
compare the effects we saw with AMG162 with the responses to Fosamax. What we
observed was that in both the spine and the hip, the density changes were at
least as great with AMG162 as were seen with Fosamax. So itís unlikely that any
antiresorptive drug will be very much more effective than our current drugs
which are very effective. The advantages have to do with the dosing regimen,
with the tolerability, and with the speed of onset of action.
What did you see with the bone density measurements in your study?
Dr. McClung: In menopausal women who are not on estrogen, the number of
places in the bone where bone dissolving is actively happening is increased.
When we administer these antiresorptive drugs and turn down the activity of the
cells, many of those cavities that have been dissolved away will fill in over
time, and we can observe that and measure that with our bone density test. So in
the first year of treatment, there is a modest increase of 4 percent to 5
percent in the bone density values in the spine and hip. After that, the values
tend to plateau.
It seems like when you see an increase in bone density, that means youíre
actually building the bone?
Dr. McClung: Not exactly. In post-menopausal women, when the activity of the
osteoclast is increased, there are more cavities, and the cavities that the
bone-dissolving cells dig out are deeper than normal. With treatment, fewer
cavities wind up existing, and the cavities that are there are more shallow. So
the filling in of that space is what we measure as an increase in bone density,
so itís filling in some of the holes of the cavities that were there, but it
doesnít make the structure of the bone get better, and it doesnít stimulate new
Since most women do not know they have osteoporosis until they break a bone,
how do you get them passionate about preventing it?
Dr. McClung: We know that low bone density, or osteoporosis, is a powerful
risk factor for fractures. The whole objective for treatment is to reduce the
likelihood of fractures happening, and the two fractures that are most
devastating to women are spine fractures and hip fractures. Spine fractures
result in height loss, curvature of the back, multiple fractures, and both
physical and psychological disability. Many women, particularly whose mothers or
aunts have had osteoporosis, are aware that this can be a very devastating
clinical problem. When women have their first fracture, they suddenly realize
that they feel old, and the concern of those fractures is what makes many women
interested in knowing if they have osteoporosis and if they are a candidate for
How many women are at risk?
Dr. McClung: All women and men are at risk for osteoporosis because bone
loss happens in all of us with aging. In the United States, there is an
estimated 8 million women who now have osteoporosis and somewhere in the range
of 2 to 3 million men with osteoporosis. Another 20 or 30 million have low bone
density, who are at risk for developing osteoporosis. We now have ways to
identify those people who are at risk, with a combination of measurement of bone
density, which is a very powerful predictor of fracture risk, and other risk
factors that include age and body size. Small people or thin people are more
likely to fracture than heavy people. Those with a family history of fracture
and once somebody has had a fracture are determinants of future fracture risk.
So the combination of bone density and those important clinical risk factors
allow us to identify the specific individuals who are at risk for fracture who
would benefit from treatment.
Who is a potential candidate for AMG162?
Dr. McClung: The person who is a candidate for AMG162 would be a
post-menopausal woman who has osteoporosis, which are generally women in their
late 60s or 70s, whoíve had a bone density test, and who have been found to have
low bone density. Most often, low bone density is found in smaller, rather than
larger women, and in those women who have a family history. So, the poster girl
for AMG162 would be a woman whoís in her late 60s or 70s with a family history,
particularly if sheís had a fracture herself since menopause.
What are the things younger women can do now to prevent osteoporosis from
Dr. McClung: There are maybe three or four things they can do. Probably the
most important is to have chosen your parents well. We inherit how much bone we
make, and thatís the major determinant of who is going to develop osteoporosis.
The other three things are to maintain an adequate and appropriate diet,
especially a diet that is adequate in calcium and vitamin D, or the sunshine
vitamin. Secondly, to maintain a regular program of physical activity. Thatís
important in maintaining both muscle strength and for elderly people, is
important in slowing the rate of bone loss. Lastly, to avoid the lifestyle
factors that are detrimental to bone health, the most important of which is
What are the current recommendations for calcium?
Dr. McClung: The recommendation for calcium in post-menopausal women is a
total daily intake of 1500 milligrams a day. So, that would be one quart of
milk, plus three servings of dairy products a day. Most adults have to take a
supplement to get to that point. More important is vitamin D. The current
recommendation is 400 units a day, which is the amount in a quart of milk or a
multivitamin, up until age 65. If you are over age 65, the recommendation is 600
units a day. Most of us feel those recommendations are actually too low, and
that often older men and women require intakes of up to 1000 units a day to
provide adequate vitamin D. My recommendation is for men and women 65 and older
their intake of vitamin D be in the range of 800 units to 1000 units per day and
then 1500 milligrams of calcium. Itís important to note that 1500 milligrams of
total calcium, so thatís the amount of calcium in oneís diet plus the amount in
the supplement. Weíre not recommending that everybody supplement their diet with
1500 milligrams of calcium. If their calcium intake is high because of dairy
product intake or because they eat soy-based products, then they donít need to
take extra supplements.
Do you think the awareness of osteoporosis is growing? Why do you think it
does not get as much attention as it should?
Dr. McClung: Well, itís not as dramatic as a heart attack, but osteoporosis
does kill people. The mortality following a hip fracture is very high. Even
after having spine fractures, mortality rates are increased. But more
importantly, especially after spine fractures, the disability, the discomfort
and the marked change in lifestyle that happens has had major impact on the
quality of life of men and women. The awareness of osteoporosis in this country
has improved and increased dramatically in the last 20 years. Before 1985, no
one ever knew about osteoporosis. With the activities of the National
Osteoporosis Foundation, of the International Osteoporosis Foundation, and a
whole variety of interested people, the awareness of osteoporosis around the
country has increased substantially. And appropriately, awareness is now
focusing on identifying which women beyond menopause are those at risk. Not
everyone is at high risk, but itís important to identify and find those women at
high risk who would be the perfect candidates for current and new treatments.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not
to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any
medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no
responsibility for the depth or accuracy of physician statements. Procedures or
medicines apply to different people and medical factors; always consult your
physician on medical matters.
If you would like more information, please contact:
Providence Portland Medical Center
4805 NE Glisan
Portland, OR 97213