Tracing the life cycle of a manmade
MGH surgeon tells 40-year tale of
investigation and innovation into the challenge of hip implant failure
BOSTON - December 21, 2004 - A remarkable story of how a
new disease was inadvertently caused by successful medical treatment,
ultimately understood, and eventually defeated by scientific innovation
is being told a major player in the process. In the December issue
of Clinical Orthopedics and Related Research, William Harris,
MD, DSc, of Massachusetts General Hospital (MGH), describes how
the development of total hip replacement led to an unexpected problem,
erosion of bone adjacent to the implant, and how his team and others
both identified the process underlying that breakdown and helped
to develop new materials that avoid the problem.
"The history of the unraveling and prevention of this worldwide,
unique, severe disease is a fascinating story of the integration
of surgical innovation, molecular biology and material science,"
writes Harris, who is Alan Gerry Clinical Professor of Orthopaedic
Surgery at Harvard Medical School.
Harris was a pioneer in the field of joint replacement, beginning
in the late 1960s. But he and other surgeons gradually observed
that hip implants could loosen starting about 5 years after surgery
and eventually fail completely. There were many theories about the
cause of that loosening, several which focused on the adhesive used
or the possibility of infection.
In 1976 Harris reported that implant failures appeared to be caused
by a biological response at the site of the implant, which resulted
in erosion of the bone. Looking further into the complication, Harris
and colleagues found that, when the metal head of the implant rubbed
against the polyethylene joint socket, small particles of polyethylene
broke off over time. As the immune system reacted against these
foreign particles, eventually it would attack and destroy the bone
tissue, loosening the implant to the point of failure. It turned
out that this complication was an entirely new manmade disease called
periprosthetic osteolysis - a condition spawned inadvertently by
the medical pioneers who, in finding a treatment for debilitating
hip disease, had created a whole new problem.
In the early 1990s, Harris and his team began to focus their attention
on finding a way to decrease the wear and tear of the polyethylene
cushion in the joint, with an ultimate goal of eliminating osteolysis.
The team's initial work involved designing a hip simulator that
could accurately replicate the motions and forces of the human hip
and measure the wear performance of the implant. The MGH group then
turned to a team of polymer chemists from Massachusetts Institute
of Technology (MIT) for help in figuring out just how to make a
polyethylene cushion that would resist wear and erosion through
years of constant motion and weight. They eventually found the solution
by "crosslinking" the polyethylene, which involves using
a high dose of irradiation to bond molecules more tightly together,
producing a much stronger and more durable material. Out of this
MGH-MIT collaboration emerged a highly crosslinked, ultra-high-molecular-weight
The research team improved and refined the material by putting it
through a melting process to eliminate any free radicals that could
cause oxidation and lead to the degradation of the implant material.
The material continued to prove strong and reliable in several studies,
showing virtually no wear even after being subjected to excessive
use and intense abuse. In 1999, the FDA approved highly crosslinked
polyethylene for use in implants, the manufacture of which has been
licensed to Zimmer, Inc. In subsequent years, the compound has continued
to hold up exceptionally well, improving the long-term outlook for
patients and expanding the field of total joint replacement.
"The availability of implants with crosslinked polyetheylene
has made a great deal of difference for patient care," Harris
says. "For example, we used to be reluctant to do total hip
replacements in young people because of the long-term risk of periprosthetic
osteolysis, which led to doing some less satisfactory types of procedures
that only postponed the need for an total hip. While we are still
careful about doing hip replacements in any patients, current evidence
suggests that the incidence of osteolysis is extraordinarily low
with the new implants, making the procedure appropriate for a broader
range of patients."
Peter L. Slavin, MD, MGH president, recently said of this accomplishment,
"The key beneficiaries of this work are patients throughout
the world who, thanks to Dr. Harris and his team, now have the chance
to experience a better quality of life for a much longer time."
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of more than $400 million
and major research centers in AIDS, cardiovascular research, cancer,
cutaneous biology, medical imaging, neurodegenerative disorders,
transplantation biology and photomedicine. In 1994, MGH and Brigham
and Women's Hospital joined to form Partners HealthCare System,
an integrated health care delivery system comprising the two academic
medical centers, specialty and community hospitals, a network of
physician groups, and nonacute and home health services.
Media Contact: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
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