Conquest of a Man-Made, Worldwide Human Disease
In the long history of human disease, it has been uncommon to
encounter a completely unique disease. In the 21st century, when this did occur,
the disease was manmade. It is a credit to the hard work of researchers that
they have been able to unravel the mysteries of a complex biologic process in
slightly over one generation. Furthermore, it is remarkable that they have been
able to create the means for prevention of an entire disease. Such is the story
of periprosthetic osteolysis. The four decade saga from the iatrogenic creation
of the disease, to the identification of its pathology, to the unraveling of its
molecular biology, and subsequently to its prevention, is a fascinating report
of medical detective work.
Periprosthetic osteolysis is a unique disease. It had never been
seen prior to the widespread use of total hip arthroplasty. It is the most important
long-term complication of total hip arthroplasty1,2. The osteolysis is
most often secondary to particulate debris generated through wear of ultra high
molecular weight polyethylene (UHMPE) at the articular surface of total hip
replacement. During a forty-four year interval, this unique disease has been
created, identified, explained, and now prevented.
The history of the unraveling and prevention of this world-wide,
unique, never previously encountered, severe disease is a fascinating story of
the integration of surgical innovation, molecular biology and material science.
Not only is periprosthetic osteolysis the single dominant
long-term complication of total hip arthroplasty, it is also the major cause
of acetabular component loosening, necessitating revision of acetabular
components, a major contributor to loosening of femoral components, and the
single most important process behind pathologic fractures of the femur and
pathologic fractures of the acetabulum following total hip arthroplasty.
Recognizing a New Disease
Prior to the widespread adoption of total hip arthroplasty,
osteolysis arising from the prolonged, continuing liberation of micron and
submicron particulate debris within the human body did not exist as a disease
mechanism. As a result, this disease is unique, occurring only during the last
Because of the obscure and unprecedented nature of this disease,
it was 14 years after the first total hip replacement had been done that the
true nature of the disease was effectively identified. In 1976 Willert published
his concept of the migration of the particulate debris into the periprosthetic
effective joint space3,4. That same year we reported 4 cases of
periprosthetic osteolysis5, in which the initial consideration of the
leading diagnostic possibility was metastatic malignancy or myeloma. In all four
cases, sheets of macrophages, without any evidence of malignancy, characterized
The Nature of the Disease
We initially observed in 19836,7 that the so-called
fibrous membrane, which was commonly removed at revision surgery and discarded,
had the capacity to generate PGE-II, and collagenase. This opened the door for
the understanding of the molecular biology of the disease. We also showed that
this fibrous tissue had the capacity to resorb bone when placed on rat calvarias,
and that this capacity could be partially inhibited by NSAIDs.
Subsequently, far more detailed investigations into the synthetic
capacity of the cellular constituents of this membrane have been performed. This
multifaceted elaboration of the molecular biology associated with particulate
periprosthetic disease has been a triumph of the investigative capacity of
orthopaedic surgeons, rheumatologists and molecular biologists, leading to a
substantial understanding of the mechanism of this disease8.
Prevention of Periprosthetic Osteolysis
Since periprosthetic osteolysis is a disease of a prolonged
generation of multiple small particles within the body, the prevention of this
condition hinges on improved articulations. That goal was achieved when innovations
in improving the articular surface were initiated. This happened over four decades
ago with metal on metal articulations9, over three decades ago with
ceramic on ceramic10,11 articulations, and more recently with the advent
of highly crosslinked polyethylenes12-15. All three approaches have
demonstrated that alternate bearing surface combinations are distinctly superior
to the original ultra high molecular weight polyethylene in terms of the prevalence
of osteolysis after total hip arthroplasty.
Superimposed on the excellent long term results of the three
alternate bearing surfaces are the excellent intermediate term clinical results
of the more contemporary versions of each alternate bearing surface. Extrapolation
of this intermediate term data suggests that the use of these three contemporary
alternate bearing surfaces will extensively reduce, and possibly eliminate,
periprosthetic osteolysis in the patient population receiving them.
Thus, over a period of four decades, an entirely new disease
was created as a unanticipated byproduct of the ingenuity of the pioneers who
created total hip arthroplasty. The invention of THA, unwittingly, also created
periprosthetic osteolysis. That devastating complication, subsequently, became
the number one long-term complication of this operation. Through the insightful
investigations of a cadre of clinical and basic researchers, the disease was
first identified, and subsequently more clearly defined as a biologic process.
The use of alternate bearing surfaces now dominates much of total hip arthroplasty.
These events have led to a set of circumstances with a high probability of major
reduction or near elimination of a unique worldwide, never seen before human
disease. In short, this is a fascinating, compelling and important story of the
conquest of a unique worldwide human disease without prior precedent in the entire
William H. Harris, MD, DSc, is Alan Gerry Clinical Professor of Orthopaedic Surgery and Director of Orthopaedic Biomechanics and Biomaterials Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital
Supported by a grant The William H. Harris, MD Foundation
Please address correspondence to:
William H. Harris, M.D.
Director, Orthopaedic Biomechanics and Biomaterials Laboratory
Massachusetts General Hospital
55 Fruit Street, GRB 1126
Boston, MA 02114
(617) 724-0526 (voice)
(617) 726-3883 (fax)
- Harris WH. Osteolysis and particle disease in hip replacement. A review. Acta Orthop Scand. 65: 113-123, 1994
- Harris WH. The problem is osteolysis. J Biomed Mater Res. 31: 19-26, 1996.
- Willert H. Tissue reactions to plastic and metallic wear products of joint endoprostheses. Total Hip Prosthesis, 1976.
- Willert H. Reactions of the articular capsule to wear products of artificial joint prostheses. J Biomed Mater Res. 11: 157-164, 1977.
- Harris WH, Schiller A, Scholler J, Freiberg R and Scott R.: Extensive localized bone resorption in the femur following total hip replacement. J Bone Joint Surg 58A: 612-618, 1976.
- Goldring S, Schiller A, Roelke M, Rourke C, O'Neil D, Harris WH. The synovial-like membrane at the bone-cement interface in loose total hip replacements and its proposed role in bone lysis. J Bone Joint Surg. 65A: 575-584, 1983.
- Goldring S, Jasty M, Roelke M, Rourke C, Bringhurst F, Harris WH. Formation of a synovial-like membrane at the bone-cement interface. Its role in bone resorption and implant loosening after total hip replacement. Arthritis and Rheumatism. 29: 836-842, 1986.
- Archibeck MJ, Jacobs JJ, Roebuck KA, Glant TT: The basic science of periprosthetic osteolysis. Instructional Course Lectures. 50: 185-195, 2001
- Amstutz HC, Campbell P, McKellop H, Schmalzreid TP, Gillespie WJ, et al. Metal on metal total hip replacement workshop consensus document. Clin Orthop S297- 303, 1996.
- Hamadouche M and Sedel L. Review Article Ceramics in Orthopaedics. J Bone Joint Surg (Br). 82-B: 1095-1099, 2000.
- Hamadouche M, Boutink P, Daussance J, Bolander ME, Sedel L. Alumina-on- alumina total hip arthroplasty. J. Bone Joint Surg., 84(A):69-77, 2002.
- Grobbelaar CJ, Weger FA, Spirakis A, Du Plessis TA, Cappaert G, Cakic JN. Clinical Experience with Gamma Irradiation-Crosslinked Polyethylene - A 14 to 20 Year Follow-up Report. South African Bone and Joint Surg. Xl: 140-147, 1999.
- du Plessis TA, Grobbelaar CJ, Marais F. The Improvement of Polyethylene Prostheses through Radiation Crosslinking. Radiat. Phys. Chem. 9: 647-652, 1977.
- Oonishi H and Takayama Y. The Low Wear of Cross-Linked Polyethylene Socket in total Hip Prostheses. Encyclopedic Handbook of Biomaterials and Bioengineering Part A: Materials. 2: 1852-1867, 1995.
- Wroblewski BM. Low-friction arthroplasty of the hip using alumina ceramic and cross-linked polyethylene. A ten-year follow-up report. J Bone Joint Surg (Br) 81B(1): 54- 5, 1999.