Glimmer of Hope that Drug Can Regenerate Some
Cartilage Lost to Osteoarthritis
Forteo (teriparatide) also first to prevent
cartilage loss from osteoarthritis after joint injury (See warning in
sidebar)
Sept. 14, 2009 Millions of senior citizens
suffering from painful osteoarthritis may find a glimmer of hope in a
study presented this weekend that says an existing osteoporosis drug is
the first ever found to prevent cartilage loss from osteoarthritis
following joint injury, and may also regenerate some cartilage that has
been lost to osteoarthritis.
While the study was in mice, the model closely
mimics human osteoarthritis that develops following knee injuries,
according to the study the authors presented to the annual meeting of
the American Society for Bone and Mineral Research in Denver on
Saturday.
Study confirms no two knee joints are alike, finds
that female knees are more vulnerable -Sept. 9, 2009 - This story has
links to more on osteoarthritis reports in the Fitness & Exercise
archives.
Cartilage can become damaged by many kinds of
injury and by mechanical stresses that come with age. Over time, damaged
cartilage deteriorates to cause osteoarthritis (OA), with its attendant
joint inflammation and pain.
Currently available drugs like steroids or
non-steroidal anti-inflammatory agents (e.g. Advil, Aleve) reduce pain
but do not address the loss of cartilage behind the osteoarthritis,
which is projected to afflict more than 50 million Americans by 2020.
Cartilage forms the sponge-like, shock-absorbing
layers that keep the impact of running and jumping and lifting from
grinding bones against each other in joints. The cell type at the heart
of osteoarthritis is the chondrocyte, the cartilage-producing cell
responsible for maintaining the integrity of joint cartilage.
Outside of joints, chondrocytes undergo a normal
maturation process that helps to form bone as part of fracture healing
and bone growth in children. Disease processes and injury, however,
cause chondrocytes in joint surface cartilage to become like those that
help to heal bone elsewhere, but in a place where bone is not supposed
to form. This mistaken maturation contributes to the gradual destruction
of the joint seen in osteoarthritis.
Teriparatide
injection causes osteosarcoma (cancer of the bones) in
laboratory rats.
It is possible that teriparatide injection may
also increase the chances that humans will develop this rare but
serious cancer. Because of this risk, teriparatide injection
should not be used to prevent osteoporosis, to treat mild
osteoporosis, or by people who can take other medications for
osteoporosis.
You should not use
teriparatide injection unless you have osteoporosis and at least
one of the following conditions is met:
...you have already had at least one bone fracture;
...your doctor has determined that you are at high risk of
fractures;
...or you cannot take or do not respond to other medications for
osteoporosis.
Tell your doctor
if you have or have ever had a bone disease such as Paget's
disease, bone cancer or a cancer that has spread to the bone, or
radiation therapy of the bones. Your doctor will order certain
tests to see if teriparatide injection is right for you.
Your doctor or
pharmacist will give you the manufacturer's patient information
sheet (Medication Guide) when you begin treatment with
teriparatide injection and each time you refill your
prescription.
Read the information carefully and ask your doctor
or pharmacist if you have any questions. You can also visit the
Food and Drug Administration (FDA) website (click
here)
or the manufacturer's website to obtain the Medication Guide.
Talk to your
doctor about the risks of using teriparatide injection.
Parathyroid hormone (PTH), known as teriparatide in
drug form, has emerged as a major player in the maintenance and healing
of bone, and the race is on to design new applications for it.
Past studies have established that PTH prevents
chondrocytes from undergoing maturation, and stimulates their
proliferation, preserving larger pools of cartilage cells in the joint.
Signaling molecules like PTH have their effect in
the body by interacting with specifically shaped proteins on the cell
surfaces called receptors. PTH docks into its receptors, like a ship
coming into port, which changes the shape of the dock such that
biochemical signals are sent.
The authors of the current study observed that
chondrocytes within injured and degenerating cartilage have more PTH
type 1 receptors on their surfaces. This makes them especially sensitive
to the PTH signal that prevents harmful chondrocyte maturation into bone
in the joint cartilage. Thus, PTH therapy should increase the cartilage
supply exactly where cartilage loss is causing disease, they say.
"Right now physicians have no way to bring back
cartilage in patients who have lost it to osteoarthritis," said Randy
Rosier, M.D., Ph.D., professor within the Department of Orthopaedics and
Rehabilitation at the University of Rochester Medical Center.
"Our current results, at least in mice, show that
we can inhibit cartilage degeneration and improve the volume of
cartilage in diseased joints. It's remarkable enough that this compound
delays the loss of cartilage, but these results show it also may be able
to restore, at least to some extent, cartilage in already degraded joint
surfaces."
Researchers examined the impact of a daily dose of
Forteo (teriparatide), manufactured by Eli Lilly, and a generic version
of teriparatide made by Sigma on the progress of OA following injury in
study mice.
Experiments established a five-fold increase in PTH
type 1 receptor expression in the articular cartilage of mice with
injury-related osteoarthritis when compared to healthy cartilage. Injury
triggers genetic mechanisms in an attempt to begin repairs, a repair
response that may be responsible for the increase in PTH receptor in the
joint.
This in turn makes damaged cartilage particularly
responsive to PTH.
In the current study, one group of mice with
cartilage and ligament injuries was randomized to receive either saline
as a control, Forteo or generic PTH daily for 12 weeks.
A second group of mice with joint injuries did not
receive treatment until 8 weeks after injury. The delay was an attempt
to determine the effect of treatment once the osteoarthritic process was
already underway and some cartilage lost, a scenario that more closely
mimics clinical reality.
Patients do not visit their physician after an
injury asking the doctor to prevent the onset of osteoarthritis 10 years
in the future, Rosier said. They come in when an old injury and time
have combined to degrade cartilage to the point where function is lost
and pain felt.
Studies revealed that after 12 weeks of Forteo - or
generic PTH treatment, there was approximately 27 percent more joint
cartilage compared to saline-treated mice.
Strikingly, they say, delayed teriparatide
treatment was even more effective in improving the amount of cartilage,
with up to 35 percent more cartilage in Forteo - and PTH-treated groups
than in the saline group, suggesting an ability to regenerate at least
some of the lost cartilage.
With a new use patent application in place, the
team will next seek to confirm the durability of the effect in further
animal studies, and prepare to seek funding from the National Institutes
of Health to begin pilot clinical studies of PTH treatment of
osteoarthritis in humans, possibly in the later half of 2010.
Along with Rosier, the study was led by Erik
Sampson, Todd O'Brien, Di Chen, Susan Bukata, J. Edward Puzas, Regis
O'Keefe and Michael Zuscik within the Department of Orthopaedics and by
Hani Awad in the Department of Biomedical Engineering at the University
of Rochester Medical Center.
The study was funded by the National Institutes of
Health.
"These pre-clinical findings provide strong
proof-of-concept support for the potential use of teriparatide to slow
joint cartilage degeneration in OA patients, and perhaps even reverse
it," Rosier said.
"In the near future, we hope this serves as the
foundation of new treatments that restore function to long injured
joints, perhaps staving off joint replacement surgeries for some years."
Editors Note: Drs. Puzas and Bukata are members of
Eli Lilly's speaker bureau.
Keep up with the latest news for senior citizens, baby
boomers
Sept. 14, 2009 Millions of senior citizens
suffering from painful osteoarthritis may find a glimmer of hope in a
study presented this weekend that says an existing osteoporosis drug is
the first ever found to prevent cartilage loss from osteoarthritis
following joint injury, and may also regenerate some cartilage that has
been lost to osteoarthritis.
