Aims

The aim of this study was to evaluate the diagnostic value of preoperative serum CRP, white blood cell count (WBC), percentage of neutrophils (%N), and neutrophil to lymphocyte ratio (NLR) when using the fracture-related infection (FRI) consensus definition.

Aims

The aim of this study was to determine the diagnostic utility of histological analysis in spinal biopsies for spondylodiscitis (SD).

Aims

This study aimed to investigate the role of quantitative histological analysis in the diagnosis of fracture-related infection (FRI).

Aim

The aim was to investigate the value of quantitative histological analysis in the diagnosis of fracture-related infection (FRI).

Pathological assessment of periprosthetic tissues is important, not only for diagnosis, but also for understanding the pathobiology of implant failure. The host response to wear particle deposition in periprosthetic tissues is characterised by cell and tissue injury, and a reparative and inflammatory response in which there is an innate and adaptive immune response to the material components of implant wear. Physical and chemical characteristics of implant wear influence the nature of the response in periprosthetic tissues and account for the development of particular complications that lead to implant failure, such as osteolysis which leads to aseptic loosening, and soft-tissue necrosis/inflammation, which can result in pseudotumour formation. The innate response involves phagocytosis of implant-derived wear particles by macrophages; this is determined by pattern recognition receptors and results in expression of cytokines, chemokines and growth factors promoting inflammation and osteoclastogenesis; phagocytosed particles can also be cytotoxic and cause cell and tissue necrosis. The adaptive immune response to wear debris is characterised by the presence of lymphoid cells and most likely occurs as a result of a cell-mediated hypersensitivity reaction to cell and tissue components altered by interaction with the material components of particulate wear, particularly metal ions released from cobalt-chrome wear particles.

Cite this article: Professor N. A. Athanasou. The pathobiology and pathology of aseptic implant failure. Bone Joint Res 2016;5:162–168. DOI: 10.1302/2046-3758.55.BJR-2016-0086.

The aim of this study was to review the early outcome of the Femoro-Patella Vialla (FPV) joint replacement. A total of 48 consecutive FPVs were implanted between December 2007 and June 2011. Case-note analysis was performed to evaluate the indications, operative histology, operative findings, post-operative complications and reasons for revision. The mean age of the patients was 63.3 years (48.2 to 81.0) and the mean follow-up was 25.0 months (6.1 to 48.9). Revision was performed in seven (14.6%) at a mean of 21.7 months, and there was one re-revision. Persistent pain was observed in three further patients who remain unrevised. The reasons for revision were pain due to progressive tibiofemoral disease in five, inflammatory arthritis in one, and patellar fracture following trauma in one. No failures were related to the implant or the technique. Trochlear dysplasia was associated with a significantly lower rate of revision (5.9% vs 35.7%, p = 0.017) and a lower incidence of revision or persistent pain (11.8% vs 42.9%, p = 0.045).

Focal patellofemoral osteoarthritis secondary to trochlear dysplasia should be considered the best indication for patellofemoral replacement. Standardised radiological imaging, with MRI to exclude overt tibiofemoral disease should be part of the pre-operative assessment, especially for the non-dysplastic knee.

Cite this article: Bone Joint J 2013;95-B:793–7.

Giant cell tumours (GCT) of the synovium and tendon sheath can be classified into two forms: localised (giant cell tumour of the tendon sheath, or nodular tenosynovitis) and diffuse (diffuse-type giant cell tumour or pigmented villonodular synovitis). The former principally affects the small joints. It presents as a solitary slow-growing tumour with a characteristic appearance on MRI and is treated by surgical excision. There is a significant risk of multiple recurrences with aggressive diffuse disease. A multidisciplinary approach with dedicated MRI, histological assessment and planned surgery with either adjuvant radiotherapy or systemic targeted therapy is required to improve outcomes in recurrent and refractory diffuse-type GCT.

Although arthroscopic synovectomy through several portals has been advocated as an alternative to arthrotomy, there is a significant risk of inadequate excision and recurrence, particularly in the posterior compartment of the knee. For local disease partial arthroscopic synovectomy may be sufficient, at the risk of recurrence. For both local and diffuse intra-articular disease open surgery is advised for recurrent disease. Marginal excision with focal disease will suffice, not dissimilar to the treatment of GCT of tendon sheath. For recurrent and extra-articular soft-tissue disease adjuvant therapy, including intra-articular radioactive colloid or moderate-dose external beam radiotherapy, should be considered.

Introduction: Giant cell tumour of bone (GCTB) is an expansile osteolytic tumour of bone which contains numerous osteoclast-like giant cells. GCTB is a locally aggressive tumour which can cause extensive bone destruction that can be difficult to control surgically, up to 35% of cases recurring after simple curettage. Bisphosphonates are anti-resorptive agents that have proved effective in the treatment of a number of osteolytic conditions.

Methods: This study reports results from four European centres where bisphosphonates are being used to treat problematic GCTBs. Details of treatment with bisphosphonates of 25 cases of primary, recurrent and metastatic GCTBs was assessed clinically and radiologically.

Results: Most primary/recurrent tumours did not exhibit progressive enlargement and, in some cases, both primary and metastatic GCTBs showed a degree of radiological improvement following treatment. Some patients also noted relief of pain following treatment. In a few cases, no apparent treatment effect was noted and there was disease progression. Several inoperable large spinal/pelvic GCTBs remained stable in size following treatment.

Discussion: Our findings provide preliminary evidence for the use of bisphosphonates to inhibit the progressive osteolysis associated with GCTB. These agents had a beneficial clinical and/or radiological effect in most cases. This study reports results from four European centres and highlights the fact that these centres are all employing different clinical indications and different regimes of bisphosphonate treatment. Bisphosphonates have significant side effects and indications for treatment and standardisation of drug type and dosage regimes (and measurement of agreed outcome measures to determine treatment efficacy) should be established for the use of these agents to control GCTB tumour growth and osteolysis.

Giant cell tumour of bone (GCTB) is an expansile osteolytic tumour of bone which contains numerous osteoclast-like giant cells. GCTB is a locally aggressive tumour which can cause extensive bone destruction that can be difficult to control surgically, up to 35% of cases recurring after simple curettage. Bisphosphonates are anti-resorptive agents that have proved effective in the treatment of a number of osteolytic conditions.

In keeping with its known effect on osteoclasts, we found that the aminobisphosphonate zoledronate abolished in vitro lacunar resorption in cultures of osteoclasts isolated from GCTB. The effect of zoledronate and other bisphosphonates on 15 cases of recurrent primary GCTB, four of which had metastasised to the lung, was assessed clinically. Most recurrent tumours did not exhibit progressive enlargement and, in some cases, both primary and metastatic GCTBs showed a degree of radiological improvement following treatment However, tumours did not diminish in size and, in some cases, no apparent treatment effect was noted.

Our findings provide in vitro evidence for the use of bisphosphonates to inhibit the progressive osteolysis associated with GCTB. In vivo, these agents produced a degree of clinical and radiological improvement in some cases. This study reports results from three European centres where bisphosphonates are being used to treat recurrent GCTB and highlights the fact that these centres are all employing different clinical indications and different regimes of bisphosphonate treatment. Bisphosphonates have significant side effects and indications for treatment and standardisation of drug type and dosage regimes (and measurement of agreed outcome measures to determine treatment efficacy) should be established before these agents are included as part of a treatment protocol to control GCTB tumour growth and osteolysis.

Giant cell tumour of bone (GCTB) is a primary tumour of bone characterised by a proliferation of mononuclear stromal cells and infiltrating macrophages and osteoclast-like giant cells. GCTB has a variable and unpredictable course and can produce metastatic lesions, mostly in the lungs, in up to 3% of cases. Whether these represent tumour implants rather than true neoplastic secondaries is uncertain. In this study, we analysed morphological and immunophenotypic features of primary GCTBs which metastasised to the lung as well as the metastatic lesions themselves in order to determine if these would provide a clue as to the mechanism of lung metastasis in GCTB.

17 cases of primary GCTB which metastasised to the lung and the lung metastases in these cases were obtained from IOR, Bologna. Morphologically, primary tumours showed variable features, often containing both giant cell-rich and mononuclear stromal cell-rich areas. Mononuclear cells showed frequent mitotic activity and a degree of nuclear pleomorphism; none of the tumours showed cytological features of malignancy. The tumours were highly vascular and frequently contained dilated thin-walled blood vessels and large areas of haemorrhage. GCTB lung metastases were generally small and contained osteoclast-like giant cells and mononuclear stromal cells which showed typical mitotic activity; cytologically, the metastatic tumours were relatively bland and showed little nuclear pleomorphism. Expression of HLA-DR (an allele of which has been associated with a more aggressive GCTB phenotype) and smooth muscle actin (SMA) was noted in stromal cells in primary and secondary GCTBs; frequently, the same pattern of SMA expression was seen in both primary and secondary lesions. Osteoclasts were vitronectin receptor+, CD14-HLA-DR- in both primary and secondary GCTBs.

Our findings indicate that mononuclear stromal cells in lung metastases of GCTB often recapitulate the immunophenotype of the primary tumours from which they derive. Taken with the morphological finding that many primary GCTBs are highly vascular and contain areas of haemorrhage, it is possible that the lung “secondaries” of GCTB more likely represent tumour implants than true neoplastic metastases.

The cause of fracture of the femoral neck after hip resurfacing is poorly understood. In order to evaluate the role of avascular necrosis we compared 19 femoral heads retrieved at revision for fracture of the femoral neck and 13 retrieved for other reasons.

We developed a new technique of assessing avascular necrosis in the femoral head by determining the percentage of empty osteocyte lacunae present. Femoral heads retrieved as controls at total hip replacement for osteoarthritis and avascular necrosis had 9% (sd 4; n = 13) and 85% (sd 5; n = 10, p < 0.001) empty lacunae, respectively.

In the fracture group the percentage of empty lacunae was 71% (sd 22); in the other group it was 21% (sd 13). The differences between the groups were highly significant (p < 0.001).

We conclude that fracture after resurfacing of the hip is associated with a significantly greater percentage of empty osteocyte lacunae within the trabecular bone. This indicates established avascular necrosis and suggests that damage to the blood supply at the time of surgery is a potent risk factor for fracture of the femoral neck after hip resurfacing.

We assessed the predictive value of the macroscopic and detailed microscopic appearance of the coracoacromial ligament, subacromial bursa and rotator-cuff tendon in 20 patients undergoing subacromial decompression for impingement in the absence of full-thickness tears of the rotator cuff. Histologically, all specimens had features of degenerative change and oedema in the extracellular matrix. Inflammatory cells were seen, but there was no evidence of chronic inflammation. However, the outcome was not related to cell counts.

At three months the mean Oxford shoulder score had improved from 29.2 (20 to 40) to 39.4 (28 to 48) (p < 0.0001) and at six months to 45.5 (36 to 48) (p < 0.0001). At six months, although all patients had improved, the seven patients with a hooked acromion had done so to a less extent than those with a flat or curved acromion judged by their mean Oxford shoulder scores of 43.5 and 46.5 respectively (p = 0.046). All five patients with partial-thickness tears were within this group and demonstrated less improvement than the patients with no tear (mean Oxford shoulder scores 43.2 and 46.4, respectively, p = 0.04). These findings imply that in the presence of a partial-thickness tear subacromial decompression may require additional specific treatment to the rotator cuff if the outcome is to be improved further.

Cellular mechanisms that account for tumour osteolysis associated with Ewing’s sarcoma are uncertain. Osteoclasts are marrow-derived multinucleated cells that effect tumour osteolysis. Osteoclasts are known to form from macrophages by both receptor activator for nuclear factor κB ligand (RANKL)-dependent and RANKL-independent mechanisms. In this study our aim has been to determine whether tumour-associated macrophages (TAMs) isolated from Ewing’s sarcoma are capable of differentiating into osteoclasts and to characterise the cellular and humoral mechanisms whereby this occurs. TAMs were isolated from two Ewing’s sarcomas and cultured on both coverslips and dentine slices for up to 21 days with soluble RANKL and human macrophage colony stimulating factor (M-CSF). Osteoclast formation from TAMs (CD14+) was evidenced by the formation of tartrate–resistant acid phosphatase and vitronectin receptor-positive multinucleated cells which were capable of carrying out lacunar resorption. This osteoclast formation and resorption was inhibited by the addition of the bisphosphonate, zoledronate. Osteoclast formation was also seen when Ewing’s sarcoma-derived TAMs were cultured with TNF α in the presence of M-CSF. We also found that TC71 Ewing’s sarcoma cells were capable of independently stimulating osteoclast formation through the release of a soluble factor. These results indicate that TAMs in Ewing’s sarcoma are capable of osteoclast differentiation by both RANKL-dependent and RANKL-independent mechanisms and that Ewing’s sarcoma cells produce an osteoclastogenic factor. The role bisphosphonates may play in inhibiting osteoclast formation and osteolysis in Ewing’s sarcoma merits further investigation.

We treated 22 patients with a diagnosis of primary frozen shoulder resistant to conservative treatment by manipulation under anaesthetic and arthroscopic release of the rotator interval, at a mean time from onset of 15 months (3 to 36). Biopsies were taken from this site and histological and immunocytochemical analysis was performed to identify the types of cell present. The tissue was characterised by the presence of fibroblasts, proliferating fibroblasts and chronic inflammatory cells. The infiltrate of chronic inflammatory cells was predominantly made up of mast cells, with T cells, B cells and macrophages also present.

The pathology of frozen shoulder includes a chronic inflammatory response with fibroblastic proliferation which may be immunomodulated.

Aim: To describe the clinical, radiological and pathological features of this rare subtype of osteoblastoma diagnosed pre-operatively and treated by excision.

Conclusion: Toxic osteoblastoma is a benign bone forming tumour that presents with systemic symptoms of fever, anorexia and weight loss.

It has a characteristic radiographic appearance with marked periostitis in the involved bone mimicking osteosarcoma and associated focal abnormality in juxtaposed skeletal sites.

With the help of two previously reported cases from the literature of aggressive bone forming tumours in children who presented with marked anorexia and cachexia diagnosed as osteomyelitis and osteosarcoma and treated by ablative surgery this tumour was correctly diagnosed with planned subtotal scapulectomy and reconstruction enabling a good functional result. The systemic symptoms fully resolved following surgery with return of appetite and weight gain.

We have studied cellular and vascular changes in different stages of full thickness tears of the rotator cuff. We examined biopsies from the supraspinatus tendon in 40 patients with chronic rotator cuff tears who were undergoing surgery and compared them with biopsies from four uninjured subscapularis tendons. Morphological and immunocytochemical methods using monoclonal antibodies directed against leucocytes, macrophages, mast cells, proliferative and vascular markers were used.

Histological changes indicative of repair and inflammation were most evident in small sized rotator cuff tears with increased fibroblast cellularity and intimal hyperplasia, together with increased expression of leucocyte and vascular markers. These reparative and inflammatory changes diminished as the size of the rotator cuff tear increased. Marked oedema and degeneration was seen in large and massive tears, which more often showed chondroid metaplasia and amyloid deposition. There was no association between the age of the patient and the duration of symptoms. In contrast, large and massive tears showed no increase in the number of inflammatory cells and blood vessels.

Small sized rotator cuff tears retained the greatest potential to heal, showing increased fibroblast cellularity, blood vessel proliferation and the presence of a significant inflammatory component. Tissue from large and massive tears is of such a degenerative nature that it may be a significant cause of re-rupture after surgical repair and could make healing improbable in this group.

We present the histological findings of bone retrieved from beneath the femoral components of failed metal-on-metal hip resurfacing arthroplasties. Of a total of 377 patients who underwent resurfacing arthroplasty, 13 required revision; for fracture of the femoral neck in eight, loosening of a component in three and for other reasons in two. None of these cases had shown histological evidence of osteonecrosis in the femoral bone at the time of the initial implantation.

Bone from the remnant of the femoral head showed changes of osteonecrosis in all but one case at revision. In two cases of fracture which occurred within a week of implantation, the changes were compatible with early necrosis of the edge of the fracture. In the remaining six fractures, there were changes of established osteonecrosis. In all but one of the non-fracture cases, patchy osteonecrosis was seen.

We conclude that histological evidence of osteonecrosis is a common finding in failed resurfaced hips. Given that osteonecrosis is extensive in resurfaced femoral heads which fail by fracture, it is likely to play a role in the causation of these fractures.

Giant-cell tumour of the tendon sheath (GCT-TS) is a benign solitary tumour which usually arises in the limbs. It occurs most often in the hand where local recurrence after excision has been reported in up to 45% of cases. It is less common in the foot where the biological behaviour and risk of local recurrence have not been defined. We have studied 17 cases of GCT-TS of the foot and ankle in which treatment was by excision. Fifteen presented as a solitary, painless, slow-growing soft-tissue swelling. One lesion was associated with sensory deficit of a digital nerve and one with pain on walking. Thirteen cases originated from the periarticular tendon-sheath complex of the small joints of the toes and four from the capsule or long tendons of the ankle. A correct preoperative diagnosis was made in only three cases. MRI proved to be the most useful preoperative investigation as GCT-TS has a characteristic appearance which allows planned local excision to be carried out. None of the patients with histologically confirmed GCT-TS required further surgery. There was no local recurrence in 15 patients who were available for follow-up at a mean of 85 months.

The cellular mechanisms which account for the formation of osteoclasts and bone resorption associated with enlarging benign and malignant mesenchymal tumours of bone are uncertain. Osteoclasts are marrow-derived, multinucleated, bone-resorbing cells which express a macrophage phenotype. We have determined whether tumour-associated macrophages (TAMs) isolated from benign and malignant mesenchymal tumours are capable of differentiating into osteoclasts. Macrophages were cultured on both coverslips and dentine slices for up to 21 days with UMR 106 osteoblastic cells in the presence of 1,25 dihydroxyvitamin D₃ (1,25(OH)₂D₃) and human macrophage colony-stimulating factor (M-CSF) or, in the absence of UMR 106 cells, with M-CSF and RANK ligand.

In all tumours, the formation of osteoclasts from CD14-positive macrophages was shown by the formation of tartrate-resistant-acid-phosphatase and vitronectin-receptor-positive multinucleated cells which were capable of carrying out lacunar resorption. These results indicate that the tumour osteolysis associated with the growth of mesenchymal tumours in bone is likely to be due in part to the differentiation of mononuclear phagocyte osteoclast precursors which are present in the TAM population of these lesions.

Age-related localised deposition of amyloid in connective tissue has been found in degenerative articular and periarticular tissue. Biopsies of the supraspinatus tendon of 28 patients undergoing repair of the rotator cuff were analysed histologically for the presence of localised deposition of amyloid. There was a long history of impingement in 20 patients, and eight patients had suffered an acute traumatic tear with no preceding symptoms. Localised deposition of amyloid identified by Congo Red staining was detected in 16 samples (57%). Amyloid was present in 14 (70%) of the degenerative tears, but in only two (25%) of the acute tears. Immunohistochemical staining showed that the amyloid deposits were positive for P component, but negative for κ and λ light chains, prealbumin, and β2 microglobulin. Critical electrolyte staining revealed highly-sulphated glycosaminoglycans at sites of deposition of amyloid. The presence of localised deposition of amyloid in tears of the rotator cuff is likely to represent irreversible structural changes. These findings support the theory that impingement and tears are due to intrinsic degenerative changes within the tendons of the rotator cuff.