Yrjö T. Konttinen, MD, Division of Rheumatic Diseases, Department of Medicine/ Surgical Hospital, Kasarmikatu 11-13, 00013 Helsinki University Central Hospital, Finland; and Department of Anatomy, Institute of Biomedicine, P.O. Box 9 (Siltavuorenpenger 20 A), 00014 University of Helsinki, Finland. Fax: Int-358-9-1918499; E-mail: yrjo.konttinen@helsinki.fi; homepage: http://www.helsinki.fi/science/TULES


Objectives: To analyze the foreign body reaction in aseptic loosening of totally replaced joints.

Background: Aseptic loosening is a major concern as for the long-term outcome of joint replacements. A synovial membrane-like interface membrane (SLIM) develops between the implant/cement-to-bone interface in aseptic loosening. As a result of wear and tear, finite fatigue life and corrosion, foreign material is released into periprosthetic tissues.

Methods: Retrieval analysis of SLIM obtained at revision operations and experimental animal models using: proton induced x-ray emission, polarized microscopy, scanning electron microscopy and microradiography for analysis of foreign bodies/ implants; immunohistochemical single and double staining, immunoelectron microscopy, extraction of proteins and their characterization using biochemical activity assays and immunochemical assays (ELISA and Western blotting), extraction of mRNA and its characterization using RT-PCR, in situ hybridization and in situ RT-PCR. Intervention assays using various amino- and alkyl-bisphosphonates and diamond coated prosthetic devices (coated at van de Graaff acceleration laboratory using pulse arch discharge method).

Results: Retrieval analysis of the removed implants demonstrates loss of implant material. Correspondingly, retrieval analysis of periprosthetic host tissues demonstrates, that foreign bodies, often phagocytozed by the macrophage-like cells in SLIM, are always present in the samples. Phagocytosis of the foreign bodies leads to macrophage activation. Activated macrophages produce various cytokines, which cause recruitment of other cells, in particular of fibroblasts and mast cells. In addition, antigen-driven, oligoclonal T lymphocyte activation may occur in a subset of patients. Interestingly, the periprosthetic tissues are hypovascular. Cellular composition and histopathology of SLIM is compatible with a foreign body type chronic inflammatory response.1 As a result of the foreign body reaction cytokines, able to upregulate osteoclast function and/or inhibit osteoblasts, are produced in excess of those doing the opposite.2 Another important aspect is that the local cells, probably stimulated by foreign bodies, micromovement and soluble cytokines, produce matrix metalloproteinases (MMPs, in particular collagenase-3 and MT-MMPs) and serine proteinases. These proteinases are able to degrade extracellular matrix at neutral pH.3,4 To prevent these inadvertent host foreign body responses, we have done experimental work using diamond coated implants. They are well tolerated by cultured macrophages and by rabbit tissues in bone harvestering chamber and in situ and they have superior biomechanical properties.5,6 It is also possible to inhibit osteoclasts and at the same time inhibit MMPs (indication protected with a patent) using bisphosphonates.7

Conclusion: Intervention with diamond surface coating (preventing the formation of the foreign bodies) and with bisphosphonates (inhibiting osteoclasts and collagenolysis) will help to either accept or reject the working hypothesis on the role of the foreign bodies and an eventual prophylaxis/ therapy for treatment of aseptic loosening.

1) Santavirta S, Konttinen YT, Hoikka V, Eskola A: Immunopathological response to loose cementless acetabular components. J Bone Joint Surg (Br) 73-B:38-42, 1991
2) Konttinen YT, Xu J-W, Pätiälä H, Imai S, Waris V, Li T-F, Goodman SB, Nordsletten L, Santavirta S: Cytokines in aseptic loosening of total hip replacement. Current Orthop 11:40-47, 1997
3) Takagi M, Konttinen YT, Santavirta S, Ida H, Ishii M, Akimoto I, Saotome K: MT1-MMP/MMP-2/TIMP-2 system in loose hip prosthesis. Lab Invest 78:735-742, 1998
4) Hanemaaijer R, Sorsa T, Konttinen YT, Ding Y, Sutinen M, Visser H, van Hinsbergh VWM, Helaakoski T, Kainulainen T, Rönkä H, Tschesche H, Salo T: Matrix metalloproteinase-8 is expressed in rheumatoid synovial fibroblasts and endothelial cells. Regulation by tumor necrosis factor-a and doxycycline. J Biol Chem 272:31504-31509, 1997
5) Nordsletten L, Høgåsen AKM, Konttinen YT, Santavirta S, Aspenberg P, Aasen AO: Human monocytes are stimulated by particles of hydroxyapatite and silicon carbide, but not by diamond. In vitro studies of new prosthesis coatings. Biomaterials 17:1521-1527, 1996
6) Aspenberg P, Anttila A, Konttinen YT, Lappalainen R, Goodman SB, Nordsletten L, Santavirta S: Benign response to particles of diamond and SiC: bone chamber studies of new joint replacement coating materials in rabbits. Biomaterials 17:807-812, 1996
7) Teronen O, Konttinen YT, Lindqvist C, Salo T, Ingman T, Lauhio A, Ding Y, Santavirta S, Valleala H, Sorsa T: Inhibition of matrix metalloproteinase-1 by dichloromethylene bisphosphonate (clodronate). Calcified Tissue Int 61:59-61, 1997