J . C o m p . Path. 1998 Vol. 119, 8 9 - 9 3
SHORT PAPER
Characterization of Wear Debris Associated with Aseptic Loosening of a Canine Hip Prosthesis M.J. Day, S.J. Butterworth*, M. R. Palmerj and C. P. CaseJ Department of Pathology and Microbiology and * Department of Clinical Veterinary Science, University of Bristol, Langford BS18 7DU, ^Department of Geology, University of Bristol, Bristol BS8 IRJ and XDepartment of Histopathology, Bristol Royal Infirmary, Marlborough Street, Bristol BS2 8HW, UK
Suminary A 1 2-month-old Golden Retriever bitch underwent unilateral hip arthroplasty following a diagnosis of coxofemoral osteoarthritis secondary to hip dysplasia. The hip prosthesis underwent aseptic loosening and was removed 6 months after implantation. Synovial biopsies taken at that time revealed scattered foci of granulomatous inflammation associated with intra-cytoplasmic and extracellular particulate material. Electron microscopical analyses demonstrated that this material contained cobalt, chromium, titanium and zirconium, which was probably wear debris from the loosened prosthesis. In human patients with hip arthroplasty, widespread dissemination of wear debris from loosened prostheses occasionally occurs, with an increased prevalence of neoplasia. A similar phenomenon may be predicted to occur with the increasing use of hip arthroplasty in the dog. © 1998 W.B. Saunders C o m p a n y Limited
Hip arthroplasty, a now routine procedure in human orthopaedic surgery, is associated with recognized complications of aseptic loosening of the implant and the generation of particulate wear debris derived from the metallic and polyethylene components of the prostheses. This debris may accumulate locally and induce an inflammatory reaction, dominated by macrophages that phagocytize the particles (Howie, 1990; Witt and Swann, 1991) and release soluble factors that contribute to loosening of the prosthesis (Rogers et ai, 1997). Additionally, recent studies have demonstrated systemic dissemination of metallic wear debris to draining lymph nodes, liver and spleen (Langkamer et ai, 1992), where it may persist and be identified many years after the performance of the hip replacement. The identity of the metals that accumulate at these sites has been determined by electronmicroprobe analysis and atomic absorption spectrometry (Langkamer et ai, 1992). Because hip arthroplasty is now performed regularly in patients under 65 years of age, there may be long-term exposure to these metals, with associated toxic or carcinogenic effects. The development of neoplasia in the vicinity of metal implants is documented in man and animals (Banks et ai, 1975; Sinibaldi et al, 1976; Swan, 1984), and epidemiological studies have shown an increased 0021 9975/98/050089-1-05 $12.00/0
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prevalence of lymphoma and leukaemia after hip replacement (Gillespie et al., 1988; Visuri and Koskenvuo, 1991). Although there is no direct evidence that implants are the cause of these effects, wear debris may act as a co-factor or co-carcinogen in the development of neoplasia. Hip replacement is now widely performed in the dog, most commonly for the treatment of degenerative joint disease secondary to hip dysplasia (Olmstcad et al., 1983). Aseptic loosening of a proportion of prostheses was recently reported and the generation of wear debris suggested (Edwards et al., 1997); this suggestion was based on histological examination of samples of blackened synovium taken from three affected dogs, but the material was not further characterized. As hip replacement is generally performed in relatively young dogs (Massat and Vasseur, 1994), the potential for systemic dissemination of wear debris, and the possible effects of long-term exposure to this material, must be considered. The present report characterizes the nature of particulate material accumulated within the synovium of a dog with a loosened hip prosthesis. A 12-month-old Golden Retriever bitch weighing 44 kg had a history of moderate to severe lameness in the right hindlimb of about 4 months' duration. A diagnosis of coxofemoral osteoarthritis secondary to hip dysplasia was made and the patient was considered suitable for total hip arthroplasty. A BioMedtrix (registered trade name) Canine Modular Total Hip prosthesis was used. Initially, the dog's post-operative progress was good, satisfactory right hindlimb function being regained within 8 weeks. However, a gradual deterioration in limb function became evident at a later date, with associated radiographic evidence of femoral stem loosening. As a result, the prosthesis was removed surgically 6 months after implantation. At the same time, swabs were taken for bacteriological examination, which gave negative results, and biopsies were taken for histopathology. The synovial biopsy consisted of an irregular strip of pale connective tissue (4-0 X 0-25 cm), from which several representative portions were taken. These were processed by routine methods for light microscopy and sections were cut and stained with haematoxylin and eosin (HE); further tissue was prepared for transmission electron microscopy (TEM). Microscopical examination revealed a fibrovascular matrix, with no obvious synoviocyte lining. There were scattered foci of inflammation, characterized by a predominantly macrophage infiltrate, with occasional giant cells. Within these areas were numerous fragments of particulate material; these were of two distinct types, as determined by both light and electron microscopy (Figs 1 and 2). The first type consisted of extracellular, rounded and translucent fragments (approximately 50-100 \iva), which were weakly birefringent under polarized light and electron-lucent by electron microscopy. The second type consisted of irregular, granular to needle-like, black particles that formed extracellular aggregates (5-20 jam) or were present as small, individual particles within macrophage cytoplasm. These appeared as electron-dense particles by electron microscopy. Twenty electron-dense particles dispersed within a sample of the synovium were analysed by electron microprobe (Day et al., 1996). Lack of appropriate standards meant that fully quantitative chemical characterization of the
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Fig. 1.
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(a) Section from affected synovium sliowing macrophages with intracytoplasmic wear debris, including small, dark particles (small arrow; approximately 1-2 )Xm) and larger, translucent fragments (large arrow; approximately 5-20 )Im). H E . x 150. (b) Section from affected synovium containing a large, extracellular portion of translucent material (arrow) and small, dark particles within the cytoplasm of macrophages. H E . X 200.
particles was not possible. Nevertheless, some conclusions could be drawn from the results of the analysis. Fourteen of the particles contained high concentrations of calcium and phosphorus and were assumed to be fragments of bone apatite. Of the remainder, three particles consisted predominantly of
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* . ' '••
Fig. 2.
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Affected synovium, showing scattered extt.u i lliilar .igi^iegciie^ ol electron-dense and -lucent particles. T E M . x 6280.
cobalt and chromium and two consisted of titanium. One particle contained a high concentration of zirconium. The prosthesis used consisted of a titanium stem inserted into the femoral medulla, a femoral head manufactured from a cobalt—chrome alloy, and an acetabular cup made from ultra high molecular weight polyethylene with a circumferential stainless steel wire for identification on imaging examination. The particles containing cobalt, chromium and titanium were therefore assumed to be derived from the prosthesis. The implant was anchored with polymethylmethacrylate bone cement. The electron-lucent material observed within the synovial biopsy had a microscopical appearance consistent with the polyethylene or methylmethacrylate wear particles described in human and canine patients with loosened metal-on-polyethylene (Howie, 1990) or cemented polyethylene prostheses (Mendes g/a/., 1974). The particle containing zirconium was most likely derived from the material used to cement the prosthesis. Analysis of the particulate material within inflamed synovium suggested that it originated from the prosthesis. From studies of human hip arthroplasty patients, we predict that in cases such as the one described the metallic wear debris may be disseminated to lymph nodes and other organs. If so, an
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i n c r e a s e d p r e v a l e n c e of neoplastic disease, p a r t i c u l a r l y of t h e l y m p h o i d system, m a y b e c o m e a p p a r e n t if such dogs are m o n i t o r e d over l o n g p e r i o d s . References Banks, W. C , Morris, E., Herron, M. R. and Green, R, W. (1975). Osteogenic sarcoma associated with internal fracture fixation in two dogs. Journal of the American Veterinary Medical Assocation, 167, 166-167. Day, M. J., Pearson, G. R., Lucke, V. M., Lane, S.J. and Sparks, R. S . J . (1996). Lesions associated with mineral deposition in the lymph node and lung of the dog. Veterinary Pathology, 33, 29-42. Edwards, M. R., Egger, E. L. and Schwartz, P. D. (1997). Aseptic loosening of the femoral implant after cemented total hip arthroplasty in dogs: 11 cases in 10 dogs [1991-1995). Journal of the American Veterinary Medical Association, 211, 580-586. Gillespie, W. L, Frampton, C. M. A., Henderson, R. L and Ryan, P. M. (1988). T h e incidence of cancer following total hip replacement. Journal of Bone and Joint Surgery, 70, 539-542. Howie, D. W. (1990). Tissue response in relation to type of wear particles around failed hip arthroplasties. Journal of Arthroplasty, 5, 337-348. Langkamer, V. G., Case, C. P., Heap, P., Taylor, A., Collins, C , Pearse, M. and Solomon, L. (1992). Systemic distribution of wear debris after hip replacement. Journal of Bone and Joint Surgery, 74, 831-839. Massat, B . J . and Vasseur, P. B. (1994). Clinical and radiographic results of total hip arthroplasty in dogs: 96 cases [1986-1992). Journal of the American Veterinary Medical Association 205 448—454. Mendes, D. G., Walker, P. S., Figarola, F. and Bullough, P. G. (1974). Total surface hip replacement in the dog. Clinical Orthopaedics and Related Research, 100, 256-264. Olmstead, M. L., Hohn, R. B. and Turner, T. M. (1983). A five-year study of 221 total hip replacements in the dog. Journal of the American Veterinary Medical Association, 183, 191-194. Rogers, S. D., Howie, D. W., Graves, S. E., Pearcy, M . J . and Haynes, D. R. (1997). In vitro human monocyte response to wear particles of titanium alloy containing vanadium or niobium. Journal of Bone and Joint Surgery, 79, 311-315. Sinibaldi, K., Rosen, H., Liu, S. K. and DeAngelis, M. (1976). Tumours associated with metallic implants in animals. Clinical Orthopedics, 118, 257-266. Swan, M. (1984). Malignant soft-tissue tumour at the site of a total hip replacement. Journal of Bone and Joint Surgery, 66, 6 2 9 - 6 3 1 . Visuri, T. and Koskenvuo, M. (1991). Cancer risk after McKee-Farrar total hip replacement. Orthopedics, 14, 137-142. Witt, J. D. and Swann, M. (1991). Metal wear and tissue response in failed titanium alloy total hip replacements. Journal of Bone and Joint Surgery, 73, 559-563. Received, January 2Qth, 1 Accepted, March 9th, 1998