In type-II fractures of the odontoid process, the treatment is either conservative in a halo vest or primary surgical stabilisation. Since nonunion, requiring prolonged immobilisation or late surgery, is common in patients treated in a halo vest, the identification of those in whom this treatment is likely to fail is important.

We reviewed the data of 69 patients with acute type-II fractures of the odontoid process treated in a halo vest. The mean follow-up was 12 months. Conservative treatment was successful, resulting in bony union in 32 (46%) patients. Anterior dislocation, gender and age were unrelated to nonunion. However, nonunion did correlate with a fracture gap (> 1 mm), posterior displacement (> 5 mm), delayed start of treatment (> 4 days) and posterior redisplacement (> 2 mm).

We conclude that patients presenting with these risk factors are unlikely to achieve bony union by treatment in a halo vest. They deserve careful attention during the follow-up period and should also be considered as candidates for primary surgical stabilisation.

In the differentiation of osteoclasts the differentiation factor (RANKL) interacts with the receptor activator of NF-κB (RANK) in a direct cell-to-cell contact between osteoblast and (pre)osteoclast. This is inhibited by soluble osteoprotegerin (OPG). The mRNA levels of both RANKL (p < 0.01) and RANK (p < 0.05) were high in peri-implant tissue and RANKL+ and RANK+ cells were found in such tissue. Double labelling also disclosed soluble RANKL bound to RANK+ cells. We were unable to stimulate fibroblasts to express RANKL in vitro, but monocyte activation with LPS gave a fivefold increase in RANK mRNA levels. In contrast to RANKL and RANK expression in peri-implant tissue, expression of OPG was restricted to vascular endothelium. Endothelial cell OPG mRNA levels were regulated by TNF-α and VEGF, but not by hypoxia. It is concluded that activated cells in the interface tissue overproduce both RANKL and RANK and they can interact without interference by OPG.

We reviewed 110 patients with an unstable fracture of the pelvic ring who had been treated with a trapezoidal external fixator after a mean follow-up of 4.1 years. There were eight open-book (type B1, B3-1) injuries, 62 lateral compression (type B2, B3-2) and 40 rotationally and vertically unstable (type C1-C3) injuries.

The rate of complications was high with loss of reduction in 57%, malunion in 58%, nonunion in 5%, infection at the pin site in 24%, loosening of the pins in 2%, injury to the lateral femoral cutaneous nerve in 2%, and pressure sores in 3%. The external fixator failed to give and maintain a proper reduction in six of the eight open-book injuries, in 20 of the 62 lateral compression injuries, and in 38 of the 40 type-C injuries. Poor functional results were usually associated with failure of reduction and an unsatisfactory radiological appearance. In type-C injuries more than 10 mm of residual vertical displacement of the injury to the posterior pelvic ring was significantly related to poor outcome. In 14 patients in this unsatisfactory group poor functional results were also affected by associated nerve injuries. In lateral compression injuries the degree of displacement of fractures of the pubic rami caused by internal rotation of the hemipelvis was an important prognostic factor.

External fixation may be useful in the acute phase of resuscitation but it is of limited value in the definitive treatment of an unstable type-C injury and in type-B open-book injuries. It is usually unnecessary in minimally displaced lateral compression injuries.

We studied the presence of anabolic growth factors in human herniated intervertebral discs (IVD) using a reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. Messenger RNA (mRNA) was isolated from the nucleus pulposus using oligo (dT)₂₅ superparamagnetic beads and probing with gene-specific primers in RT-PCR.

mRNA coding for TGF-α (3/10), EGF (0/10), TGF-β1 (0/10) and TGF-β3 (2/10) or the EGF receptor (EGF-R; 0/10) and TGF-β type-II receptor (0/10) was found only occasionally. Beta-actin was always present and positive sample controls confirmed the validity of the RT-PCR assay. These RT-PCR findings were confirmed using immunohistochemical staining of EGF and TFG-β, whereas TGF-α protein was always found associated with discocytes.

We conclude that the nucleus pulposus of the herniated IVD is vulnerable to proteolytic degradation and depletion of proteoglycans due to the lack and/or low production of anabolic growth factors/receptors which could increase the local synthesis of the extracellular matrix.

A foreign-body-type host response can contribute to the induction and release of collagenolytic tissue-destructive enzymes of pathogenetic significance. Our aim was to analyse collagenase-3 in two conditions with putative involvement of foreign-body reactions. Synovial membrane-like tissue samples were obtained from cases of aseptic loosening of a total hip replacement (THR) and osteoarthritis (OA).

The reverse transcription polymerase chain reaction (RT-PCR) disclosed that all the samples from patients contained collagenase-3 mRNA compared with only three out of ten control samples. The identity of the RT-PCR amplification product was confirmed by nucleotide sequencing. Immunohistochemical staining showed that collagenase-3 was present in endothelial cells, macrophages and fibroblasts, including those found in the synovial lining. This finding was confirmed by avidin-biotin-peroxidase complex-alkaline phosphatase-anti-alkaline phosphatase double staining and the specificity of the staining by antigen preabsorption using recombinant human collagenase-3.

Collagenase-3 was released into the extracellular space and thus found in the synovial fluid in all patient samples as shown by Western blotting. The similar extent of collagenase-3 expression in aseptic loosening and OA compared with the low expression in control synovial membrane suggests involvement of a similar, foreign-body-based pathogenetic component in both. Comparative analysis of collagenase-3 and of foreign particles indicates that paracrine factors rather than phagocytosis per se are responsible for the induction of collagenase-3.

We suggest that due to its localisation and substrate specificity, collagenase-3 may play a significant pathogenetic role in accelerating tissue destruction in OA and in aseptic loosening of a THR.

Aseptic loosening is a major cause of failure of total hip arthroplasty. The adverse tissue response to prosthetic wear particles, with activation of cytokine and prostanoid production, contributes to bone loss around the implants. We have investigated the possibility that inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) are expressed in macrophages in the pseudomembrane at the bone-implant interface, thereby contributing to the periprosthetic bone resorption.

We also assessed whether peroxynitrite, a nitric oxide (NO)-derived oxidant associated with cellular injury, is generated in the membrane. Enzymatic activity of iNOS was measured using the arginine-citrulline assay technique and prostaglandin E₂ (PGE₂), as an indicator of COX-2 activity, was measured using an enzyme immunoassay.

Cellular immunoreactivity for iNOS, nitrotyrosine (a marker of peroxynitrite-induced cellular injury) and COX-2 was assessed by quantitative peroxidase immunocytochemistry while immunofluorescence methods were used for subsequent co-localisation studies with CD68⁺ macrophages.

The presence of calcium-independent iNOS activity and PGE₂ production was confirmed in the homogenized interface membrane. Immunocytochemistry showed that periprosthetic CD68⁺ wear-debris-laden macrophages were the most prominent cell type immunoreactive for iNOS, nitrotyrosine and COX-2. Other periprosthetic inflammatory and resident cell types were also found to immunolocalise nitrotyrosine thereby suggesting peroxynitrite-induced protein nitrosylation and cellular damage not only in NO-producing CD68⁺ macrophages, but also in their neighbouring cells. These data indicate that both iNOS and COX-2 are expressed by CD68⁺ macrophages in the interface membrane and peroxynitrite-induced cellular damage is evident in such tissue. If high-output NO and peroxynitrite generation were to cause macrophage cell death, this would result in the release of phagocytosed wear debris into the extracellular matrix. A detrimental cycle of events would then be established with further phagocytosis by newly-recruited inflammatory cells and subsequent NO, peroxynitrite and prostanoid synthesis. Since both NO and have been implicated in the induction and PGE₂ maintenance of chronic inflammation with resulting loss of bone, and peroxynitrite in the pathogenesis of disease states, they may be central to the pathogenesis of aseptic loosening.

The membranes surrounding seven loose cementless acetabular implants were shown to contain polyethylene particles, birefringent in polarised light. Three of these implants were made of titanium alloy and the membranes around these contained titanium particles as well. There was no metallosis around the four implants made of chromium-cobalt-steel alloy. Both titanium and polyethylene particles caused migration, adherence and phagocytosis of CD11b-positive, peroxidase-negative macrophages. There were no histological signs of activation of the specific immune response; neither interleukin-2 receptor-positive activated T cells nor PCA-1 plasmablasts/plasma cells were present in the tissues. In cases of simple loosening, resident mesenchymal fibroblast-like cells were active. In aggressive granulomatosis, there were many macrophages and multinucleated giant cells but little fibroblast reaction. The clinical relevance of the findings is that the use of cementless prostheses is not a guarantee against adverse tissue reactions.

The outcome of operations performed on 38 patients for rheumatoid disorders of the cervical spine were analysed 10 or more years later. The mean age of the patients at the time of operation was 56 years (35 to 77); 32 had seropositive disease. The mean duration of the disease was 17 years (four to 36). Twenty-seven patients had painful anterior atlanto-axial subluxation (AAS), nine had subaxial subluxation alone and two had severe cranial subluxation of the odontoid, one also with subaxial subluxation. One patient died from postoperative staphylococcal septicaemia and another 18 died during the follow-up period. Patients with coincident cardiac or other diseases, and those with cranial subluxation of the odontoid of more than 3 mm had an increased mortality. Neither the patients' age nor the magnitude of AAS correlated with mortality. Of the 37 patients with occipitocervical pain, 30 were relieved and all the six patients with tetraparesis were improved. Of the 24 Gallie fusions only 12 were solidly united; patients with long-term cortisone treatment were more likely to develop pseudarthrosis. There was no correlation between clinical outcome and radiological result. Four patients had further operations to treat subluxation which developed below the fused segments.

We describe six patients with aggressive granulomatous lesions around cementless total hip prostheses. Two patients previously had a cemented prosthesis in the same hip. The Lord prosthesis was used in five patients, the PCA in one. Both prostheses were made of chrome-cobalt alloy. Pain on weight-bearing occurred on average 3.2 years after the cementless arthroplasty, and at that time radiography revealed aggressive granulomatosis around the proximal femoral stem and the acetabular component in five of the patients; one had a large solitary granuloma in the proximal femur. Revision was performed on average 4.8 years after the cementless arthroplasty. At that time all granulomas had grown large in size; while waiting for revision operation, two femoral stem components fractured. All the granulomas showed a uniform histopathology, which included histiocytosis; the cause for these lesions was thought to be plastic debris from the acetabular socket.

Cytological analysis of material aspirated from the effusion which occasionally develops around a polyglycolic acid (PGA) osteosynthesis implant showed a predominance of inflammatory monocytes and in particular lymphocytes. In order to discover whether PGA implants are immunologically inert, density gradient-isolated peripheral blood mononuclear cells were cultured in 0.2 ml of 10% delta FCS-RPMI 1640 culture medium supplemented with 10 mg PGA. Phytohaemagglutinin (PHA) lectin, a purified protein derivate of tuberculin (PPD) antigen and culture medium alone were used as positive and negative controls. We studied lymphocyte activation kinetics on days 0, 1, 3 and 5. Major histocompatibility complex locus II antigen (MHC locus II antigen) and interleukin-2 receptor (IL-2R) expression were analysed using the avidin-biotin-peroxidase complex (ABC) method and lymphocyte DNA synthesis by using 3H-thymidine incorporation and beta-scintillation counting. Especially on culture days 0 and 1, lymphocytes and monocytes were seen by light microscopy to be attached to PGA particles. However, our results show no PGA-induced lymphocyte DNA synthesis, but PGA-induced MHC locus II antigen and IL-2R activation marker expression was seen, greater than in negative controls, but less than that seen in PPD antigen driven lymphocyte response. This suggests that PGA is an immunologically inert implant material, but it does seem to induce inflammatory mononuclear cell migration and adhesion, leading to a slight non-specific lymphocyte activation. This activation is lower than that seen in mitogen and antigen-driven lymphocyte responses.

In 16 patients we used uncemented Lord prostheses at revision operations for aggressive granulomatosis after cemented hip arthroplasties; in 12 bone grafts also were used. In 13 hips the granulomatous lesions were multifocal, and in one the acetabular component was involved. There was no evidence of infection in any case: all the patients had normal ESR and CRP levels. The revision operation was performed on average 9.4 years after the primary replacement; the mean age at revision was 64 years. On radiographs, the bone around the prosthesis had consolidated by an average of 16 months. At follow-up, two to six years later (mean 3.5 years) there had been no recurrences, nine patients had an excellent Mayo hip score, five were good and two fair.

We reviewed 19 patients who presented with aggressive granulomatosis around the femoral stem after hip replacement. All had experienced stress pain and had required revision arthroplasty on average 8.8 years after the primary operation. Fifteen patients were men and four were women; none had rheumatoid arthritis. One patient had an uncemented Moore hemiprosthesis; the others all had cemented total hip replacements. When first detected, the granulomatous lesions were multifocal in 13 patients. The first granuloma was in the region of the lesser trochanter in 10, and near the tip of the stem in only two. Speed of growth varied but on average there was doubling of the area on anteroposterior films in 2.2 years (range 6 months to 4.6 years). Aggressive granulomatous lesions in replaced hips are a distinct condition, different from simple loosening or infection; the lesions may grow rapidly, so revision surgery is indicated soon after diagnosis.

We have reviewed six patients with old tuberculosis of the knee treated by total replacement an average of 35 years after the primary infection. Three patients had no antituberculous prophylaxis and three had drugs for two to three weeks before and three weeks after the operation. One patient with a missed primary diagnosis had a relapse of the tuberculous arthritis 18 months after his arthroplasty and was successfully treated with antituberculous drugs for one year. At an average follow-up of 6.3 years all the patients were markedly improved. Old tuberculosis of the knee can be treated successfully with arthroplasty but there is a risk of reactivation of disease and prophylactic drugs are recommended.

We report the results of cementless total joint replacement in 18 patients with old tuberculosis of the hip, performed, on average, 34 years after the onset of infection. Mean follow-up was 3.5 years. Only seven of the patients had antituberculous drugs during or after the operation. Using the Mayo hip score, 15 patients had excellent or good results and two had a fair rating. One patient had the prosthesis removed more than one year postoperatively for late haematogenous staphylococcal infection and had a poor rating. All the patients had relief of hip-related pain. Despite the absence of any reactivation of tuberculosis in our series, we recommend the use of specific prophylaxis.