New Study Finds Way to Stop Excessive Bone Growth Following Trauma or Surgery
A
recent United States Army study found that excessive bone growth, also
known as heterotopic ossificiation (HO), affects up to 70 percent of
soldiers who are severely wounded during combat. A much smaller
percentage of the civilian population also suffers from HO following
trauma or invasive surgery. The excessive bone forms within muscles and
other tissues causing severe pain, reduced mobility and even local
paralysis if untreated. A new study by Thomas Jefferson University
researchers found a way to prevent HO in animal models by shutting the
process off in its early stages. The study, reported in September’s
Journal of Orthopaedic Research, is expected to lead to clinical trials
and may hopefully provide a new, effective and safe treatment for HO.
“This
is a major breakthrough in HO research,” said Primary Investigator
Maurizio Pacifici, Ph.D, director of Orthopedic Research at Jefferson
Medical College of Thomas Jefferson University. “We are able to largely
prevent formation and progression of HO lesions. We presented our
initial results at a recent U.S. Army Extremity War Injuries Symposium
in Washington D.C. and they were very well-received and have elicited
great hope on the part of military physicians to finally have a way to
stop HO in troops wounded in war zones.”
In
the ongoing study sponsored by the U.S. Army, Jefferson scientists were
able to prevent HO by disrupting a series of cellular changes that are
needed to produce HO. Following a trauma or invasive surgery, the
condition begins when progenitor and stem cells are recruited to the
injured site and give rise to cartilage tissue that then turns to bone.
This multi-step process is regulated by several factors. One of these
factors is a protein in the nucleus of the progenitor cells that is
called the retinoid alpha receptor. This receptor must be turned off
before the progenitor cells can form cartilage tissue. The Jefferson
scientists, using a pharmacological agent, an alpha agonist, kept the
receptors active, stifling the initiation of the disease in its tracks.
“The
agonist we used in this case is an experimental drug that is not on the
market yet, but is being tested in Phase II human trials for another
disease. We tested whether the drug could work to prevent HO, thereby
looking for another application for the drug,” said Pacifici.
HO
treatments for the general population exist now, but are not always
effective and can produce side effects. Low-dose irradiation,
postoperative nonsteroidal anti-inflammatory drugs or a combination of
both are the current routine treatments for HO. When these treatments
fail and patients require surgical removal of HO lesions, some
complications can arise, including instigation of a new round of HO
formation. These treatments are currently not used in wounded soldiers
because they could have additional complications. For example, low-dose
irradiation could reduce the healing capacity of tissues. Since the
alpha agonist should not interfere with these processes, it could prove
to be a suitable treatment without the significant side effects.
Because
current HO treatments cannot be used, HO remains a potentially serious
problem due to the high incidence among military personnel. Also
without treatment, HO can progress and spread becoming much more
serious over time. Hopefully, if clinical trials are done and prove
successful this treatment could be used as a cure for not only HO but
for other HO-related diseases including Fibrodysplasia Ossificans
Progressive (FOP), an inheritable and severe form of HO.
“We aren’t there yet but we are definitely excited,” concluded Pacifici.
Media Only Contact:
Richard Cushman
Thomas Jefferson University Hospital
Phone: (215) 955-6300
Published: 9/23/2009