Aims

The aticularis genu (AG) is the least substantial and deepest muscle of the anterior compartment of the thigh and of uncertain significance. The aim of the study was to describe the anatomy of AG in cadaveric specimens, to characterize the relevance of AG in pathological distal femur specimens, and to correlate the anatomy and pathology with preoperative magnetic resonance imaging (MRI) of AG.

Background

Preoperative diagnosis of fracture related infections can be challenging, especially when confirmatory criteria such as sinus tract and purulent discharge are absent. Although serum parameters, such as CRP and white blood cell count (WBC), showed poor accuracy in the literature, they are still often used in clinical practice. The European Bone and Joint Infection Society (EBJIS) defined evidence-based criteria for fracture related infection. Elevated serum inflammatory markers were regarded as suggestive criteria only, as the literature was of limited quality. This study assessed the diagnostic value of the serum parameters CRP, WBC and differential cell count in the diagnosis of fracture related infections defined by the EBJIS-criteria for fracture related infections.

Aim

This study describes the histologic changes seen with a gentamicin-eluting synthetic bone graft substitute (BGS)(1) in managing bone defects after resection of chronic osteomyelitis (cOM).

Aims

The aim of this study was to evaluate the surgical management and outcome of patients with an acral soft-tissue sarcoma of the hand or foot.

Aim

Advocates of Debridement-Antibiotics-and-Implant-Retention (DAIR) in hip peri-prosthetic joint infection (PJI) argue that a procedure not disturbing a sound prosthesis-bone interface is likely to lead to better survival and functional outcome compared to revision. However, no evidence supports this. This case-control study's aims were to compare outcome of DAIRs for infected 1° total hip arthroplasty (THA) with outcomes following 1° THA and 2-stage revisions of infected 1° THAs.

Aim

This study describes and correlates the radiographic and histologic changes which develop in a Gentamicin-eluting synthetic bone graft substitute* in the management of bone defects after resection of chronic osteomyelitis (COM).

Introduction

The burden of peri-prosthetic joint infection (PJI) following hip and knee surgery is increasing. Endoprosthetic replacement (EPR) is an option for management of massive bone loss resulting from infection around failed lower limb implants.

Debridement, antibiotics and implant retention (DAIR) is a surgical option in the treatment of prosthetic joint infection (PJI). It is thought to be most appropriate in the treatment of early (≤6 weeks post-op) PJI. Most studies to-date reporting on DAIRs in hip PJI have been underpowered by reporting on small cohorts (n= <45), or report on registry data with associated biases and limitations. In our, tertiary referral, bone infection unit we consider DAIR to be a suitable option in all cases of PJI with a soundly fixed prosthesis, with early or late presentation, especially in patients who are too elderly or infirm to undergo major surgery.

Aim: To define the 10-year outcome following DAIR in hip PJI and identify factors that influence it.

We retrospectively reviewed all DAIRs performed in our unit between 1997 and 2013 for hip PJI. Only infected cases confirmed by histological and microbiological criteria were included. Data recorded included patient demographics and medical history, type of surgery performed (DAIR or DAIR + exchange of modular components), organism identified and type/duration of antibiotic treatment. Outcome measures included complications, mortality rate, implant survivorship and functional outcome.

121 DAIRs were identified with mean age of 71 years (range: 33–97). 67% followed an index procedure of 1° arthroplasty. 53% included exchange of modular components. 60% of DAIRs were for early onset PJI. Isolated staphylococcus was present in 50% of cases and 25% had polymicrobial infection. At follow-up (mean:7 years, range: 0.3 – 18), 83 patients were alive; 5- and 10- year mortality rates were 15% and 35% respectively. 45% had a complication (persistence of infection: 27%, dislocation: 10%) and 40% required further surgery. Twenty hips have been revised to-date (17%). Performing a DAIR and not exchanging the modular components was associated with an almost 3× risk (risk ratio: 2.9) of subsequent implant failure (p=0.04). 10-yr implant survivorship was 80% (95%CI: 70 – 90%). Improved 10-year implant survivorship was associated with DAIR performed for early PJI (85% Vs 68%, p=0.04). Functional outcome will be discussed.

DAIR is a particularly valuable option in the treatment of hip PJI, especially in the early post-operative period. Whenever possible, exchange of modular implants should be undertaken, however DAIRs are associated with increased morbidity even in early PJI. Factors that predict success of DAIR in late PJI need to be identified.

Introduction

Solid or cystic pseudotumour is a potentially destructive complication of metal on metal (MoM) couples, usually needing revision surgery. However, complete clearance of the pseudotumour is unlikely at times. This prospective case-controlled study reports cases which had recurrence after revision surgery for pseudotumour related to metal on metal hip couples.

Introduction

Our Unit has been treating large volume soft tissue sarcomas involving the sciatic nerve with epineurectomy for over a decade. The aim of this study was to quantify the functional outcome of patients who were known to have sciatic nerve involvement pre-operatively and went on to have nerve preserving surgery utilising a planned marginal excision with epineurectomy.

Besides conventional chondrosarcoma, several rare chondrosarcoma subtypes are described, comprising about 15% of all chondrosarcomas. Clear cell chondrosarcoma (CCS) is a low-grade malignant tumour, often recurring after curettage, and showing overall survival of about 85%. Mesenchymal chondrosarcoma (MCS) is a highly malignant tumour occurring in bone and soft tissue of relatively young patients. The tumour shows differentiated cartilage mixed with undifferentiated small round cells. It often metastasises and shows a 5-year overall survival of 55%. Dedifferentiated chondrosarcoma (DDCS) is a tumour containing a high-grade non-cartilaginous sarcoma (DD), and a usually low-grade malignant cartilage-forming tumour (WD).

The prognosis is poor. The lack of efficacious treatment of these rare tumours emphasises the need to learn more about their characteristics and to unravel potential targets for therapy.

We constructed tissue microarrays (TMAs) with 2mm cores of 45 DDCS (WD and DD), 24 CCS, and 25 MCS, in triplicate.

Using immunohistochemistry, we investigated protein expression of estrogen-signaling molecules, growth plate-signaling molecules, and other molecules which might be potential targets for therapy. In addition, we gathered genomic information using Agilent 44K oligo arrays.

30% of the WD components were positive for Cox-2. Almost all others were negative. For Bcl2, 88% of the small cells and 32% of the cartilage in MCS were positive. In CCS, WD, and DD 48%, 4%, and 12% were positive, respectively. We demonstrated the presence of ESR1 and aromatase protein in the majority of tumours in all subtypes. Using array CGH, we observed similar aberrations in the two components of DDCS, with additional aberrations in the DD.

Celecoxib treatment is not recommended, as most of the tumours are negative for Cox-2. However, the presence of ESR1 and aromatase support a possible effect of anti-estrogen treatment in all subtypes, and application of Bcl2 inhibitors might chemosensitise MCS.

We report the case of an 82-year-old man who underwent fasciectomy for a severe Dupuytren’s contracture, during which an ossified lesion was encountered within the contracture and surrounding the neurovascular bundle. The abnormal tissue was removed with difficulty and heterotopic ossification was confirmed histologically. We believe this is the first report of heterotopic ossification in Dupuytren’s disease.

Metal on metal hip resurfacing (MMHR) is a popular procedure for the treatment of osteoarthritis in young patients. Several centres have observed masses, arising from around these devices, we call these inflammatory pseudotumours. They are locally invasive and may cause massive soft tissue destruction. The aim of this study was to determine the incidence and risk factors for pseudotumours that are serious enough to require revision surgery.

In out unit, 1,419 MMHRs were performed between June 1999 and November 2008. All revisions were identified, including all cases revised for pseudotumour. Pseudotumour diagnosis was made by histological examination of samples from revision. A Kaplan-Meier survival analysis was performed, Cox regression analysis was used to estimate the independent effects of different factors.

The revision rate for pseudotumour increased with time and was 4% (95% CI: 2.2% to 5.8%) at eight years. Female gender was a strong risk factor: at eight years the revision rate for pseudotumours in men was 0.5% (95% CI 0% to 1.1%), in women over 40 it was 6% (95% CI 2.3% to 10.1%) and in women under 40 it was 25% (95% CI 7.3% to 42.9%) (p< 0.001). Other factors associated with an increase in revision rate were, small components (p=0.003) and dysplasia (p=0.019), whereas implant type was not (p=0.156).

We recommend that resurfacings are undertaken with caution in women, especially those younger than 40 years of age, but they remain a good option in men. Further work is required to understand the patho-aetiology of pseudotumours so that this severe complication can be avoided.

Introduction: Symptomatic abnormal soft-tissue masses relating to the hip joint, such as those described as pseudotumours, are being increasingly reported following metal-on-metal hip resurfacing arthroplasty (MoMHRA). These were found to be locally destructive, requiring revision surgery in a high proportion (75%) of patients. Lymphocyte infiltrations seen in pseudotumours were similar to aseptic lymphocyte vascular associated lesion (ALVAL), which is thought to represent a T-lymphocyte-mediated delayed type hypersensitivity. Therefore, a delayed hypersensitivity reaction to nickel (Ni), chromium (Cr) or cobalt (Co) has been suggested to play a role in pseudotumour aetiology. In patients with bilateral MoMHRA who presented with symptoms on one side, subsequent scans have demonstrated pseudotumours both on the symptomatic and asymptomatic side. Thus, there are concerns that there may be an appreciable number of asymptomatic pseudotumours that surgeons are unaware of and these may eventually become symptomatic.

Aim: The aims of this study were:

to determine the prevalence of asymptomatic pseudotumours after MoMHRA; and

Methods: A total of 201 MoMHRA implanted hips in 158 patients (97 male, 61 female) with a mean age of 56 years (range 33–73 years) were evaluated. The mean follow-up was 61 months (range 13–88 months). Resurfacing devices implanted included 128 Birmingham Hip Resurfacing, 66 Conserve Plus and seven ReCap. The control groups included additional 20 patients, 10 male and 10 female (a mean age 68 years, range 57–80 years) with metal-on-polyethylene total hip arthroplasty and a further 22 age-matched patients (a mean age 55 years) without any metal implants. Ultrasound was used as the initial imaging modality and MRI was used to assess the extent of the identified masses. Patients with a soft-tissue mass had ultrasound-guided aspiration or core biopsy performed. Venous blood samples were collected in all patients for serum cobalt and chromium ion levels analysis using Inductively-Coupled Plasma Mass Spectrometer and lymphocyte transformation tests (LTT). The Oxford Hip Score (OHS) was used to measure the functional outcomes of patients. Acetabular component abduction angle was measured from standardised anteroposterior pelvis radiographs.

Results: Prevalence – Pseudotumours were found in 7 patients (6 female and 1 male). The overall prevalence of asymptomatic pseudotumours was 4%, with a relatively very high (30%) prevalence in females with bilateral implants. Histological examinations showed extensive necrosis of connective tissue, in which there were scattered aggregates of metal particles and a diffuse lymphocyte infiltrate.

Metal Ion Levels – The presence of pseudotumour was associated with significantly higher median serum cobalt levels (9.2mg/L vs. 1.9mg/L, p< 0.001), chromium levels (12.0mg/L vs. 2.1mg/L, p< 0.001), hip aspirate cobalt levels (1182 mg/L vs. 86.2mg/L, p=0.003), and aspirate chromium levels (883mg/L vs. 114.8mg/ L, p=0.006), as well as with inferior functional scores (OHS 41 vs. 47 p< 0.001). There was no significant difference in acetabular cup inclination angle (p=0.51). Lymphocyte Reactivity: A higher incidence and level of enhanced lymphocyte reactivity to Ni (p=0.001), but not to Co or Cr (the principal elements in the CoCr alloy used in metal-on-metal hip resurfacing implants), was found in patients with MoMHRA compared to the patients without MoM implants. However, lymphocyte reactivity to Co, Cr and Ni did not significantly differ in patients with pseudotumours compared to those patients without pseudotumours.

Conclusion: The prevalence of asymptomatic pseudotumours in females was high, especially in females with bilateral MoMHRA implants (30%). The patients with ‘asymptomatic’ pseudotumours were in fact mildly symptomatic. Lymphocyte reactivity to Co, Cr and Ni did not differ in patients with pseudotumour compared to those patients without pseudotumours, suggesting that systemic hypersensitivity type IV reactions, mediated by lymphocyte reactivity to these metals, is not the dominant mechanism in pathogenesis of the soft tissue pseudotumours. Furthermore, pseudotumours were not detected in those patients who had normal levels of cobalt and chromium ions. This suggests that pseudotumours do not occur if MoM articulations are well functioning. Therefore, pseudotumours are likely to be a biological consequence of the large amount of metal debris generated in vivo due to excessive wear.

Introduction: Hoffa’s fat pad (HFP) of the knee is affected by a variety of tumours and tumour-like conditions. HFP can be affected by diffuse or solitary, focal disease. Solitary tumours are relatively uncommon but with widespread uptake of Magnetic Resonance Imaging Scans (MRI) an increasing number of Hoffa’s fat pad tumours (HFP) are being recognized.

Methods: This paper reports a consecutive series of 20 cases of solitary symptomatic HFP tumours referred to Oxford bone and soft tissue tumour service between 1999 and 2008. The commonest presenting symptom was anterior knee pain. All patients underwent open excision after diagnostic magnetic resonance imaging (MRI).

Results: Histology revealed varied diagnoses with the commonest being pigmented villonodular synovitis (PVNS) and ganglia. American Knee Society scores improved from 76 pre-operatively to 96 post-operatively with an improvement in functional scores from 92 to 100. In one patient, MRI identified the cause of hypo-phosphataemic osteomalacia as an HFP phosphaturic mesenchyma tumour despite the lack of local symptoms.

Discussion In conclusion the majority of solitary HFP tumours are benign and may be either cystic or solid. MRI and plain radiographs are the imaging of choice. The definitive treatment of both cystic and solid tumours should be selective arthrotomy and excision biopsy. Arthroscopic resection is not advised, as complete excision is not always possible. None of the 20 patients in this series had a malignant tumour but this has been reported in the literature. Calcification on plain radiographs may indicate a malignant lesion. All patients in our series reported substantial improvement in symptoms following open tumour resection.

Tribological studies of hip arthroplasty suggest that larger diameter metal-on-metal (MOM) articulations would produce less wear than smaller diameter articulations. Other advantages using these large femoral heads implants include better stability with lower dislocation rates and improved range of motion. The aim of the present study was to compare chromium (Cr), cobalt (Co) and titanium (Ti) ion concentrations up to 1-year after implantation of different large diameter MOM total hip arthroplasty (THA).

Methods: Cr, Co and Ti concentrations were measured using a high resolution mass spectrometer (HR-ICP-MS) by an independent laboratory in 110 patients, randomized to receive a large metal-on-metal articulation unce-mented Ti THA from one of the following companies: Zimmer, Smith & Nephew, Biomet or Depuy. Samples of whole blood were collected pre-operatively, and postoperatively at six months and one year.

Summary of Results: At 6 months, whole blood cobalt levels were: (table removed)

Statistical group comparison revealed significant difference for Cr (p=0.006), Co (p=0.047) and Ti (p=< 0.001). With Biomet implants presenting the best results for Cr and Co and Zimmer the highest Ti level.

Discussion: Different implant factors may influence measured metal ion level in whole blood: articular surface wear and implant passive corrosion. Bearing wear may be related to its diameter, quality of the surface finish, component sphericity, radial clearance, manufacturing process (forged vs cast metal) and metal carbon content. Biomet articulation seems to present the best factors selection. Passive corrosion of exposed metallic surfaces is represented by the elevated Ti levels found in all tested systems (Ti was not part of the bearing surfaces). The plasma sprayed acetabular component surface of the Zimmer’s component seems to be responsible for the significant difference in Ti versus the other implants.

Inflammatory changes in synovial tissues occur commonly in knee osteoarthritis (OA) and are termed “inflammatory OA”. The pathogenic significance of this inflammatory OA is uncertain. It is also not known whether inflammatory changes in the synovial membrane are reflected in the synovial fluid (SF) and whether the SF contains a similar inflammatory cell infiltrate.

This study examined 34 cases of knee joint OA and cytologically and immunohistochemically characterised inflammatory cells in the synovial membrane and SF. Specimens of SF and synovial membrane were taken at the time of knee arthroplasty.

All cases of inflammatory OA synovium contained (CD68+) macrophages; several cases also contained a scattered, focally heavy (CD3+) lymphocytic infiltrate and occasional lymphoid aggregates. Inflammatory changes in OA SF reflected this cell composition with numerous CD68+ macrophages and CD3+ lymphocytes being noted in inflammatory OA cases. The SF volume was greater (> 5ml) in cases of inflammatory OA. Non-inflammatory OA knee joints contained very few inflammatory cells, which were mainly macrophages, in both the synovial membrane and SF.

Our findings indicate that inflammatory changes in the synovial membrane of OA knee joints are reflected in the SF and that the volume of SF is commonly increased in cases of inflammatory OA. Both macrophages and lymphocytes in the inflammatory infiltrate of knee joint SF may contribute to joint destruction in OA by providing mononuclear phagocyte osteoclast precursors and the production of inflammatory cytokines and growth factors that promote osteoclastogenesis.

In conclusion, the cytology of SF and synovitic membrane are similar in inflammatory OA. With knee effusions of greater than 5mls and inflammatory synovitic membrane consideration of total knee arthoplasty in the presence of single compartment disease should be considered because of the risk of further joint destruction.

The infrapatellar (Hoffa’s) fat pad can be affected by a variety of tumours and tumour-like conditions which can occasionally present a diagnostic and therapeutic challenge to the treating surgeon. The fat pad can be affected by diffuse or solitary disease. Solitary tumours are relatively uncommon but with widespread uptake of Magnetic Resonance Imaging Scans (MRI) an increasing number of Hoffa’s fat pad tumours (HFP) are being recognized.

Between 1999 and 2008, 20 patients with HFP pathology referred to Oxford bone and soft tissue tumour service underwent resection and histological examination. Clinical records, imaging and histological findings were reviewed. Histology showed eight different diagnoses with Pigmented Villonodular Synovitis (PVNS) and ganglia being the most common pathology.

In one patient, MRI identified the cause of hypophosphataemic osteomalacia as an HFP phosphaturic mesen-chyma tumour despite the lack of local symptoms.

In conclusion, the majority of solitary HFP tumours are benign and maybe cystic or solid. MRI and plain radiographs are the imaging of choice. Cystic tumours maybe aspirated but the definitive treatment of both cystic and solid tumours should be open arthrotomy and excision biopsy. Arthroscopic resection is not advised, as complete excision is not always possible. None of the 20 patients in this series had a malignant tumour but this has been reported in the literature. Calcification on plain radiographs may indicate a malignant lesion. All patients in our series reported substantial improvement in symptoms following open tumour resection.

Introduction: Despite the satisfactory short-term implant survivorship of MoM hip resurfacing arthroplasty, symptomatic abnormal periprosthetic soft-tissue masses relating to the hip joint, ‘pseudotumours’, are being increasingly reported. These were found be locally destructive, requiring revision surgery in 75% of patients. Asymptomatic pseudotumours have not been previously investigated.

Methods: The aims were: (1) to investigate the prevalence of asymptomatic pseudotumours; and (2) to investigate their potential association with the level of metal ions. A total of 160 hips in 123 patients with a mean age 56 years (range 33–73) were evaluated at a mean follow-up of 61 months (range 13–88). Radiographs and OHS were assessed. Patients with a cystic or solid mass detected on the ultrasound/MRI had an aspiration or biopsy performed. Cobalt and chromium levels were analysed using Inductively-Coupled Plasma Spectrometer.

Results: Pseudotumours were found in 6 patients (5F: 1M). In 80% of bilateral cases, it was found in both sides. Histological examination showed extensive necrosis and diffuse lymphocyte infiltration. The presence of pseudotumour was associated with higher serum cobalt (9.2 μg/L vs. 1.9μg/L, p< 0.001) and chromium levels (12.0μg/L vs. 2.1μg/L, p< 0.001); higher hip aspirate cobalt (1182 μg/L vs. 86.2μg/L, p=0.003) and chromium levels (883μg/L vs. 114.8μg/L, p=0.006); and with inferior OHS (23 vs. 14 p=0.08).

Discussion: The prevalence of asymptomatic pseudotumour (5%) was higher than previously reported for the symptomatic pseudotumours (1%). There was a sixfold elevation of serum and a twelve-fold elevation of hip aspirate levels of cobalt and chromium in patients with pseudotumours. This suggests that pseudotumours may be a biological consequence of the large amount of metal debris generated in vivo. The association between pseudotumour and elevated metal ion levels might theoretically be explained by either systemic hypersensitivity responses to metal ions or local cytotoxic effects due to a high level of metal ions.

Introduction: We report on a group of 20 metal-onmetal resurfaced hips (17 patients) presenting with a soft tissue mass associated with various symptoms; these masses we termed pseudotumours.

Methods: All patients underwent plane radiography; CT, MRI and ultrasound investigations were also performed for some patients. Where samples were available histology was performed. Metal ion levels were measured in six patients and one patient had the metal ion levels in the joint fluid measured.

Results: All patients in this series were female. Presentation was variable; the most common symptom was pain or discomfort in the hip region. Other symptoms included spontaneous dislocation, nerve palsy, a noticeable mass or a rash. In all cases a soft tissue mass was present in the region of the hip, this was either solid or cystic. The common histological features were extensive necrosis and lymphocytic infiltration. The blood cobalt and chromium levels varied considerably between the six patients that had these measurements. The median blood chromium level was 3.8 μg/L (range 0.8 to 23 μg/L) and that for cobalt was 11.5 μg/L (range 2.1 to 15 μg/L). The synovial fluid sample taken from a single joint contained much higher metal levels, 701 μg/L for chromium and 329 μg/L for cobalt. Twelve of the 20 cases have so far required revision to a conventional hip replacement.

Discussion: This complication is best imaged with ultrasound, and is not detected by normal xray. We estimate that about 1% of patients develop a pseudotumour in the first five postoperative years. The cause of these pseudotumours is unknown and is probably multifactorial, further work is required to define this; they may be manifestations of a metal sensitivity response. We are concerned that with time the incidence of these pseudo-tumours will increase.

Introduction: Osteoclast-like multinucleated giant cells (MNGCs) are found in a number of soft tissue sarcomas including malignant fibrous histiocytoma and leiomyosarcoma. The nature of these MNGCs is poorly understood and the cellular mechanisms underlying their accumulation in sarcomas is not known.

Methods: We analysed by immunohistochemistry the expression of osteoclast, macrophage and smooth muscle markers by mononuclear and multinucleated cells in two cases of giant cell-rich leiomyosarcoma. We also characterised the role of mononuclear stromal cells and tumour-associated macrophages in the formation of MNGCs by RT-PCR, cell culture studies and immunohistochemistry/histochemistry for macrophage, osteoclast and smooth muscle markers

Results: MNCGs in giant cell-rich leiomyosarcoma expressed an osteoclast-like phenotype, being negative for smooth muscle actin and CD14 but positive for tartrate-resistant acid phophatase (TRAP), CD45, CD68 and vitronectin receptor (VNR). Scattered mononuclear cells expressing an osteoclast-like antigenic phenotype were also noted. An analysis of 25 conventional (non-giant cell-containing) leiomyosarcomas found isolated CD68+ MNGCs in three cases (approximately 12%); all of these cases were Grade-II/III leiomyosarcomas in which there was a prominent tumour-associated macrophage (TAM) infiltrate. Leiomyosarcoma TAMs isolated from two cases of conventional leiomyosarcoma and cultured in the presence of the osteoclastogenic factors RANKL and M-CSF differentiated into TRAP+/VNR+ MNGCs that were capable of lacunar resorption. RT-PCR studies showed that cultured leiomyosarcoma mononuclear stromal cells expressed RANKL, OPG and TRAIL.

Discussion: These findings show that the MNGCs which are found in leiomyosarcomas are osteoclast-like in nature and that these MNGCs are formed from TAMs by a RANKL dependent mechanism which involves an interaction with RANKL-expressing mononuclear stromal cells. A similar mechanism is likely to account for MNGC accumulation in other soft tissue sarcomas.

We report on a group of 20 metal-on-metal resurfaced hips (17 patients) presenting with a soft tissue mass associated with various symptoms. We describe these masses as pseudotumours.

All patients underwent plain radiography and fuller investigation with CT, MRI and ultrasound. Where samples were available, histology was performed. All patients in this series were female. Presentation was variable; the most common symptom was pain or discomfort in the hip region. Other symptoms included spontaneous dislocation, nerve palsy, an enlarging mass or a rash. The common histological features were extensive necrosis and lymphocytic infiltration. Fourteen of the 20 cases (70%) have so far required revision to a conventional hip replacement and their symptoms have either settled completely or improved substantially since the revision surgery. Two of the three bilateral cases have asymptomatic pseudotumours on the opposite side.

We estimate that about 1% of patients develop a pseudotumour in the first five postoperative years after a hip resurfacing. The cause of these pseudotumours is unknown and is probably multi-factorial, further work is required to define this; they may be manifestations of a metal sensitivity response. We are concerned that with time the incidence of these pseudotumours will increase.

Introduction: We report on a group of 20 metal-on-metal resurfaced hips (17 patients) presenting with a soft tissue mass associated with various symptoms; these masses we termed pseudotumours. All patients underwent plane radiography; CT, MRI and ultrasound investigations were also performed for some patients. Where samples were available histology was performed.

Methods: All patients in this series were female. Presentation was variable; the most common symptom was pain or discomfort in the hip region. Other symptoms included spontaneous dislocation, nerve palsy, a noticeable mass or a rash. The common histological features were extensive necrosis and lymphocytic infiltration. Fourteen of the 20 cases (70%) have so far required revision to a conventional hip replacement and their symptoms have either settled completely or improved substantially since the revision surgery. Two of the three bilateral cases have asymptomatic pseudotumours on the opposite side.

Conclusions: We estimate that about 1% of patients develop a pseudotumour in the first five postoperative years after a hip resurfacing. The cause of these pseudotumours is unknown and is probably multi-factorial, further work is required to define this; they may be manifestations of a metal sensitivity response. We are concerned that with time the incidence of these pseudotumours will increase.

We report 17 patients (20 hips) in whom metal-on-metal resurfacing had been performed and who presented with various symptoms and a soft-tissue mass which we termed a pseudotumour. Each patient underwent plain radiography and in some, CT, MRI and ultrasonography were also performed. In addition, histological examination of available samples was undertaken.

All the patients were women and their presentation was variable. The most common symptom was discomfort in the region of the hip. Other symptoms included spontaneous dislocation, nerve palsy, a noticeable mass or a rash. The common histological features were extensive necrosis and lymphocytic infiltration. To date, 13 of the 20 hips have required revision to a conventional hip replacement. Two are awaiting revision.

We estimate that approximately 1% of patients who have a metal-on-metal resurfacing develop a pseudotumour within five years. The cause is unknown and is probably multifactorial. There may be a toxic reaction to an excess of particulate metal wear debris or a hypersensitivity reaction to a normal amount of metal debris. We are concerned that with time the incidence of these pseudotumours may increase. Further investigation is required to define their cause.

The aim of this study was to observe cellular and vascular changes in different stages of full thickness rotator cuff tear.

Biopsies of the Supraspinatus tendon in 40 patients with chronic rotator cuff tears undergoing surgery were analysed using histological and contempary immunocytochemical techniques. Sections were stained with primary antibodies against PCNA (Proliferating cell nuclear antigen), CD34 (QBEnd 10), CD45 (Leucocyte Common Antigen), CD68, D2-40 (Lymphatic Endothelial Marker) and Mast Cell Tryptase. A histological analysis was performed with Mayer’s Haemotoxylin and Eosin, Congo Red and Toluidine Blue.

The reparative response and inflammatory component (figure 1) of the tissue was seen to diminish as the rotator cuff tear size increased. This was evidenced by increasing degeneration and oedema, reducing fibroblast proliferation, reduced thickening of the synovial membrane and reducing vascularity. Macrophage, other leucocyte and mast cell numbers also reduced as tear size increased. Large and massive tears revealed a higher degree of chondroid metaplasia and amyloid deposition when compared to smaller sized tears. There was no association with the patient’s age or duration of symptoms.

Small sized rotator cuff tears retain the greatest potential to heal and have a significant inflammatory component. Tissue from large and massive tears is of such a degenerate nature that it may never heal and this is probably a significant cause of re-rupture after surgical repair in this group. Selection of patients for reconstructive surgery should take into account the composition and healing potential of tendon tissue and its relationship to tear size in chronic tears of the rotator cuff.

Antero-medial osteoarthritis of the knee displays a well recognised pattern of cartilage damage on the medial tibial plateau. Anteriorly there is a full thickness cartilage defect, with transition to a partial thickness defect, becoming full thickness in the posterior third of the plateau. The retained posterior cartilage is macroscopically normal, but no previous study has assessed its histo-logical features. This study characterises the histological changes, to examine if antero-medial OA of the knee represents a model of progressive osteoarthritic cartilage damage.

Five unicompartmental resection specimens of patients with idiopathic single compartment antero-medial osteoarthritis were assessed. The samples were stained with H& E and Saffinin-O stains and reviewed using the Mankin system, an established method for scoring osteoarthritic changes in cartilage (range 0 [normal] to 14 [grossly osteoarthritic]) Digital images of the histology were reviewed by two observers to exclude inter and intra observer error. Each specimen was assessed at 4 interval points (A,B,C,D) along the A-P axis starting from the most posterior aspect of the exposed bone to the area of macroscopically normal cartilage. Three repeat measurements were taken from the macroscopically normal region (D1,D2,D3). The scores were compared to historical age matched controls of non-osteoarthritic cartilage, where a Mankin grade of < 3 suggests normal cartilage.

From anterior to posterior the H& E staining showed a consistent decrease in structural integrity and cellularity of the cartilage, matched by a qualitative decrease in GAG content (Saffinin-O staining). Mean Mankin scores showed a progressive decrease in score; A = 14.0 (95% CI 0), B = 5.8 (95%CI 2.4), C = 4.4 (95%CI 2.5), D = 1.0 (95%CI 0.9) {p=0.04 ANOVA}. Repeated measurements at the macroscopically normal area showed the Mankin grade was maintained; D1= 1.0 (95%CI 0.9), D2 = 0.6 (95%CI 0.5), D3 = 0.6 (95%CI 0.6).

The results show that the retained posterior cartilage in antero-medial arthritis has a consistently normal Mankin grade. We suggest the defect represents a model of progressive cartilage damage from near normal (posterior) to the grossly osteoarthritic state (anterior).

The aim of this study was to observe the macroscopic and microscopic appearance of the Coracoacromial ligament and Subacromial bursa during Subacromial decompression and correlate it with the outcome at 3 months. Twenty patients with Subacromial Impingement without Rotator Cuff tear and five patients with large/massive irreparable Rotator Cuff tears who underwent a Subacromial Decompression. Patients with other shoulder pathology were excluded. Patients completed an Oxford Shoulder Score pre-operatively and their injection history was noted. At operation the shape of the acromion was noted. The macroscopic appearance of the CA ligament and the Subacromial bursa was classified as normal, mild/moderate and severe. Biopsies of the Subacromial bursa and CA ligament were taken and were analysed using histological and contempory immunocytochemical techniques. A histological analysis was performed using Mayer’s Haemotoxylin and Eosin, Toluidine Blue and Congo Red. Sections were stained with primary antibodies against PCNA (Proliferating cell nuclear antigen), Mast Cell Tryptase, CD3 (T-cell), CD20 (B cell), CD 34 (QBEnd 10), CD45 (Leucocyte Common Antigen), CD68 and D2–40 (Lymphatic Endothelial Marker). Post operatively the patients completed an Oxford Shoulder Score at 3 months. All the patients demonstrated an improvement in their Oxford Shoulder Score. The histological analysis demonstrated thickening of the synovial membrane and increased vascularity within the bursa and ligament. Increased numbers of inflammatory cells were present within the ligament and bursa of patients with impingement compared with massive rotator cuff tears. There was a relationship between outcome and the appearance of the bursa and ligament.

Purpose of study: We report the results of a prospective case series of 10 patients who developed tumour-like masses following resurfacing arthroplasty

Method: Ten subjects were referred to the tumour service at the Nuffield Orthopaedic Centre with symptomatic masses around the hip, all had previously received a resurfacing arthroplasty.

We report the clinical, radiographic and histologic features of these cases.

Results: MRI and ultrasound scanning was preformed, which demonstrated masses with solid and cystic components.

Biopsy was performed and subsequent histological examination revealed a profound plasma-cell lymphocytic response associated with metal wear debris.

There were no infections in this series.

Three subjects required revision surgery.

Conclusion: Over 50,000 resurfacing arthroplasties have been implanted worldwide over the past ten years. Although the early clinical results are encouraging little is known about the long term consequences of large head metal on metal bearing surfaces. Despite this, these devices are being widely marketed and are often implanted in younger patients. Resurfacing arthroplasties are associated with high serum and urine metal ion concentrations, metal particles have also been shown to migrate along the lymphatic system. In addition, there is now evidence that high local metal ion concentrations can induce haempoietic cancers.

This study suggests that resurfacing arthoplasty can also induce a local hypersensitivity reaction in response to metal wear debris. It therefore raises new concerns regarding the long-term safety of this procedure.

A prospective study was carried out to determine if recognised histological features seen at surgery could help predict those rotator cuff tendon repairs which re-ruptured. 40 rotator cuff tendon edge specimens from 40 patients’ shoulders were analysed histologically following routine mini-open rotator cuff repair. 32/40 underwent Ultrasonography, at a mean time of 35 months post-operatively, to determine repair integrity. The histological features seen at surgery were then compared to the repair integrity of the tendon from which it had been taken. Rotator cuff repairs that remained intact demonstrated a greater reparative response, in terms of increased fibrobast cellularity, cell proliferation and a thickened synovial membrane, than those repairs which reruptured. Larger tears which remained intact showed a higher degree of vasacularity and a significant inflammatory component than those that re-ruptured. Good tissue quality at the time of surgery allows the repair the best chance of remaining intact despite the size of the lesion. Routine histological analysis of the tissue biopsy, preformed in the post-operatively, can now aid the clinician in terms of early management and repair prognosis.

Aim of Study: Assess clinical outcome and function of planned marginal excision of low grade liposarcoma of the forearm.

Material and Methods: Between 1997 and 2005 15 of 27 soft tissue sarcomas of the forearm were liposarcoma.

13 presented in the extensor compartment and 2 flexor compartment at the level of the distal radius. All presented with a painless mass. 5 patients with neurological symptoms. 4 involving the post interosseus nerve and 1 radial nerve. MRI was the diagnostic imaging technique of choice, 2 had biopsies where there was atypical imaging features.

Treatment and Results: All treated by planned marginal excision in view of proximity of neurovascular structures. The majority of tumours of the extensor compartment of the forearm were either involving or abutting the post interosseus nerve or neurovascular conduit.

All underwent planned marginal excision preserving juxtaposed peripheral nerve. There were no radial, spiral or PIN nerve palsies. One patient presented with PIN palsy had partial resolution of symptoms and function. I wound infection

Conclusion: Low grade lipoma-like liposarcomas have low metastatic potential. In the forearm a wide margin would mean ablation of critical neurological structures and planned marginal excision results in good function and to date no evidence of local recurrence at 2–9 year follow up.

Osteomyelitis commonly causes bone destruction and is most frequently due to infection by Staphylococcus aureus. S. aureus is known to secrete a number of surface-associated proteins which are extremely potent stimulators of bone resorption in the mouse calvarial assay system. The precise cellular and humoral mechanisms whereby this stimulatory effect is mediated, in particular whether osteoclast formation or activity is directly promoted by these factors, have not been determined by this study. Surface-associated material (SAM)(0.001ug/ml)obtained from 24 hour cultures of S. aureus was added to cultures of mouse and human osteoclast precursors (RAW 264.7 cells and human peripheral blood mononuclear cells respectively). These cultures were incubated in the presence and absence of receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage colony stimulating factor (M-CSF). It was found that independent of RANKL, SAM was capable of inducing osteoclast formation in cultures of RAW cells and human monocytes. This was evidenced by the generation of tartrate-resistant acid phosphatase-positive multinucleated cells, which formed lacunar resorption pits when these cells were cultured on dentine slices. In cultures where M-CSF, RANKL and SAM were added, osteoclast formation was increased, but did not exceed the osteoclast formation in cultures with M-CSF and RANKL. These findings indicate that S. aureus produces a soluble factor which can promote osteoclast formation. Identification of this factor may help to develop therapeutic strategies for treating bone destruction due to Staphylococcal osteomyelitis.

Introduction: Osseous metastases from melanoma are relatively common (7% of cases), and occur most often in the axial skeleton. Bone destruction in skeletal metastases of solid tumours is due to stimulation of osteoclast formation and bone resorption. Osteoclasts are formed by the fusion of marrow-derived mononuclear phagocyte precursors which express RANK (receptor activator of nuclear factor κB) which interacts with RANKL expressed by osteoblasts/bone stromal cells in the presence of macrophage colony-stimulating factor (M-CSF). Osteoclast formation by a RANKL-independent, tumour necrosis factor α (TNFα)-induced mechanism has also been reported. Tumour-associated macrophages (TAMs) are present in both primary and secondary tumours and TAMs are known to be capable of osteoclast differentiation. Our aim in this study was to determine the role of TAMs and the humoral mechanisms of osteolysis associated with melanoma metastases.

Materials and Method: In this study we isolated TAMs from extraskeletal primary melanomas and lymph node metastases. TAMs were cultured for up to 21 days in the presence and absence of M-CSF and RANKL or TNF. In a separate experiment, conditioned medium was extracted from the melanoma cell line, SK-Mel-29, and cultured with human peripheral blood mononuclear cells in the presence of M-CSF.

Results: TAM-osteoclast differentiation, as evidenced by the expression of tartrate-resistant acid phosphatase, vitronectin receptor and lacunar resorption pit formation, occurred by both RANKL-dependent and RANKL-independent mechanisms. Osteoclast formation induced by RANKL-independent mechanism was not abolished by the addition of osteoprotegerin or RANK:Fc, decoy receptors for RANK. Conditioned medium from SK-Mel-29 could support osteoclast differentiation in the absence of RANKL. This effect was not abolished by antibodies to RANKL, TNFα, TGFβ, IL-8 or gp130.

Discussion: These results indicate that melanoma TAMs are capable of differentiation into osteoclasts and that both RANKL-dependent and RANKL-independent (TNFα) mechanisms are involved. Melanoma tumour cells also secrete a soluble factor that supports osteoclastogenesis.

Conclusion: Inhibitors of osteoclast formation targeting TAM-osteoclast differentiation and osteoclast activity and identification of the osteoclastogenic factor produced by melanoma cells may have a therapeutic potential in controlling tumour osteolysis.

We are presenting the outcome of a young adult with extensive epithelioid hemangioendothelioma of the femur treated with wide excision and vascularised fibular graft.

An 18-year-old builder was referred with an aggressive primary bone tumor of the right femur. Initial staging showed no evidence of distant disease but tumor confined to a 26.5cm diaphyseal segment of the femoral shaft. The patient’s pre-operative Oxford knee score was 28 and the AKSS scores were 74 (observational) and 65 (functional). True cut open biopsy confirmed low grade angiosarcoma. The patient underwent a wide excision of the lesion through a lateral approach leaving a generous cuff of bone and muscle tissue around the tumor. Clear resection margins were assessed intraoperatively. Histologically, the tumor was found to be epithelioid hemangioendothelioma. The 29.5cm defect was filled with a vascularised bone graft of the ipsilateral fibula. The graft was secured with a 22-hole DCS bridging plate and screws at both ends. Intraoperative knee range of motion was from 0 to 125 degrees without recurvatum and graft movement.

The patient had an unremarkable recovery. At the latest follow-up, one year after his operation, the patient had made an excellent functional recovery with non-symptomatic full weight bearing and had also returned to his work as a builder. He demonstrated a knee range of motion of 0 to 115 with a slight genu varum. The patient’s post-operative Oxford knee score was 40 and the AKSS scores were 70 (observational) and 90 (functional). Radiographs showed excellent union at the distal aspect of the graft and a healing stress fracture of the fibula graft at the proximal aspect.

Vascularized fibular graft with plating is a safe reconstruction limb salvage option for defects of long bones after tumor resection.

Purpose: To quantify the functional outcome of patients who were known to have sciatic nerve involvement pre-operatively and went on to have nerve preserving surgery utilising a planned marginal excision with epineurectomy.

Materials and Methods: Ten patients with large volume posterior thigh soft tissue sarcoma with known sciatic nerve involvement were reviewed between 1997 and 2004. Nine underwent surgery with extended epineurectomy of the sciatic nerve and planned marginal excision.

All patients underwent staging and follow up at Sarcoma Clinic with functional assessment and TESS evaluation.

Results: There were seven low and two high grade posterior thigh tumours of which nine were liposarcoma and 1 haemangiopericytoma. Two were recurrent and eight primary. There were five men and five women with a mean age of 77.

Nine patients underwent planned marginal excision. Sciatic nerve involvement was 13–30cm in eight cases and in one case the sciatic nerve was abutting the tumour throughout its length. There was soft tissue reconstruction in three cases using fascial adductor or gracilis graft for sciatic nerve cover and one with superficial femoral nerve and vein resection requiring ipsilateral saphenous reconstruction. The remainder underwent direct primary reconstruction.

Four patients underwent radiotherapy 46–60 Gy.

There was no local recurrence of disease within 14 – 96m follow-up. There was one patient with post radiation wound breakdown that resolved.

Three patients have died of unrelated causes. To date there has been no evidence of local recurrence of disease at FU.

Conclusion: Planned marginal excision of low grade large volume posterior thigh sarcomas with extensive sciatic nerve involvement can be successfully treated with preservation of the sciatic nerve without significant morbidity and resultant good limb function.

Aim: To review our series of mid foot sarcomas with regard to excision of tumour, tolerance of radiotherapy and preservation of function.

Methods and results: We identified 6 patients with mid foot sarcomas treated in our unit. Synovial sarcoma was the commonest diagnosis. All the patients had stage 1 disease with no evidence of pulmonary metastases at presentation. Patients judged to have resectable tumour but preserving sufficient foot to be functional were spared amputation. They had excision of the sarcoma and immediate reconstruction using fascio-cutaneous free flaps. Complete excision was achieved in all cases. One flap was lost and repeated. In all patients, subsequent radiotherapy was well tolerated without significant complications. All patients remain disease free. All patients have returned to pre-operative functioning including walking and jogging. All except one have returned to work.

Conclusion: Patients and feet treated by wide local excision of mid foot sarcomas and reconstructed by free fascio-cutaneous flaps tolerate post-operative radio-therapy well, and return to near normal function.

Between 1972 and 2002 74 patients were treated under the combined care of the orthopaedic oncology service and lymphoma clinic with primary bone lymphoma. We reviewed the seventeen cases affecting the upper limb (23%). Of the seventeen patients nine remain alive. Assessment of the patient’s clinical presentation, histopathological definition, treatment and function outcome was made. The nine survivors were assessed clinically and with the Oxford shoulder score and the Toronto extremity salvage score.

Average time from first presentation to diagnosis was 7 months. All seventeen were diagnosed as a B –cell non-Hodgkin’s lymphoma, fifteen cases were high grade and two cases were low grade. The scapula was involved in six, humerus eight and clavicle three cases. Seven patients sustained pathological fractures three of which were at presentation; of these two were treated surgically. Eight patients have subsequently died of their disease. Functional outcome in surviving patients after medical treatment was very good with average TESS score of 79% (52%–99%) and OSS of 27 (12–52).

The presentation of lymphoma of the shoulder girdle may mimic benign shoulder conditions and lead to a delay in radiological and histopathological diagnosis. Pathological fracture is a common presentation and complication of treatment, however these fractures have a high chance of healing with medical treatment alone. Although shoulder stiffness remains a problem following medical treatment, overall upper limb function is good. There is little evidence that these patients require surgery in the short to medium term.

Purpose: Bone destruction occurs due to the growth of primary malignant bone tumours (sarcomas) that are often not amendable to surgery. Bone resorption is carried out by osteoclasts which are formed from cells of the mononuclear phagocyte system. Primary malignant bone tumours contain tumour-associated macrophages (TAMs) in addition to neoplastic cells. The aim of the study was to determine the cellular and humoral conditions required for TAM-osteoclast differentiation and to assess the affect of an anti-osteolytic agent on osteoclastic bone resorption.

Methods: TAMs were isolated form bone and soft tissue sarcoma by collagenase digestion and cultured in the presence of RANKL and M-CSF on coverslips and dentine slices for up to 21 days. The extent of osteoclast formation and resorption was determined by expression of osteoclast markers (TRAP, VNR, cathepsin K) in cell cultures on coverslips and the extent of lacunar resorption in cell cultures on dentine slices.

Results: Osteoclast formation occurred only when RANKL and M-CSF were added to the TAM cultures. This resulted in the formation of numerous mononuclear multinucleated cells which were strongly TRAP, VNR and cathepsin K positive. In cell cultures on dentine slices, it was noted that these cells were capable of extensive lacunar resorption with formation of multiple large lacunar resorption pits. The addition of the bisphosphonate zoledronate to the cell cultures resulted in inhibition of osteoclast formation and complete absence of lacunar resorption.

Conclusion: These findings indicate that sarcoma-associated macrophages are capable of differentiating into osteoclasts and that both RANKL and M-CSF are required for this to occur. This process is likely to contribute to tumour osteolysis associated with the growth of sarcomas in bone. Further assessment of the use of inhibitors of osteoclast formation/resorption, is also indicated by our results.

Aims: To determine the pathological changes in the femur following resurfacing hip arthroplasty and identify possible causes of early failure. Methods: Bone samples from 8 femoral heads at several levels were examined histologically following removal of cemented femoral head surface replacement following aseptic early failure: 4 neck fractures (no history of fall), 3 persistent severe pain and 1 cup loosening. Intra-operatively no obvious macroscopic causes of failure (including notching the neck) were noted. In all patients, the initial diagnosis had been osteoarthritis. None had known risk factors for osteonecrosis. Results: In the patients who had recent fracture, the bony changes were suggestive of relatively longstanding osteonecrosis with degenerative, necrotic and þbrotic changes in the bone marrow and loss of osteocyte nuclei in the trabeculae. There was appositional new bone formation at the surface of the necrotic bone trabeculae. The changes were consistent with osteonecrosis of more than 2 weeks duration and probably preceded the fracture in all cases. In the patients who underwent revision for non-fracture, some osteonecrosis was seen, but this was a lot less than when a fracture had occurred. Conclusion: Osteonecrosis of the femoral head is seen following resurfacing hip arthroplasty and may be a predisposing factor in patients who subsequently fracture.

Giant Cell Tumour of the Tendon Sheath is a benign tumour of synovial origin most frequently affecting the upper limb. Up to 11% exhibit radiographic evidence of cortical erosion and intra-osseous expansion. In the upper limb recurrence rates of between 10–50% following excision have been reported. However, GCT-TS is rarely described in the foot and ankle and its behaviour is ill understood.

17 cases of this rarely described tumour in the foot and ankle are presented, describing their clinical presentation, histopathology, treatment and outcome.

Analysis of all cases of histopathologically proven GCT-TS of the foot and ankle from the Oxford Tumour Registry, was conducted between the periods of January 1984 to December 1999.

22 cases were identified of which 17 cases had adequate records to allow analysis of patient demographics, duration of symptoms, preoperative investigations, presumed diagnosis, precise site of origin, post operative complications and recurrence rates

The mean age of presentation was 28 (8–53). 10 cases were female and 7 male. 76% cases occurred in the foot, all of which arose adjacent to the phalanges or heads of the metatarsals. 14% occurred in relation to the ankle or sub-talar joint.

82% presented with a painless swelling. The duration of symptoms ranged from 6 months to 8 years. Only one patient complained of sensory symptoms.

Pre-operative investigations included radiographs in 64% with 3 cases having an additional MRI scan. The MRI scans of GCT-TS have characteristic changes on T1 and T2 images. The presumed preoperative diagnosis was incorrect in 82%.

36% of radiographs taken showed changes including cortical erosion and speckled calcification.

A local excision was performed in 15 cases, an amputation in one and a wide local excision in one case only. There have been no recurrences during the follow up period of between 1–12 years.

GCT-TS of foot and ankle is rare and is commonly misdiagnosed. Despite only a local excision being performed in more than 80% of this series there were no recurrences.

Plain radiographs may show cortical erosion or speckled calcification in up to 36% and MRI is helpful in further defining the anatomy of the lesion, allowing planned excision and reducing the risk of recurrence.

Aseptic loosening is generally associated with the presence of wear particle-associated macrophages in the pseudomembrane commonly formed around failed prosthetic implants. The extent of the macrophage response evoked by the wear particles has been shown to correlate with the amount of periprosthetic osteolysis. Numerous studies have shown that wear particle-associated macrophages contribute to osteolysis by (i) releasing inflammatory cytokines and/or (ii) differentiating into bone resorbing osteoclasts. Although macrophages and macrophage polykaryons are the main inflammatory cells found in periprosthetic tissues, numerous fibroblasts are also present in the connective tissue pseudomembrane. The recently identified molecule, RANKL has been shown to play a central role in the osteoclast formation and bone resorption observed in aseptic loosening. We have shown that arthroplasty macrophages, which express RANK, the receptor for RANKL, are capable of osteoclast differentiation; this process is inhibited by osteoprotegerin (OPG), the soluble decoy receptor for RANKL. As fibroblasts are known to express RANKL, the aim of the present study was to determine whether fibroblasts isolated from periprosthetic tissues could induce the generation of bone resorbing osteoclasts that would contribute to the osteolysis commonly seen in the periprosthetic loosening.

Fibroblast-like cells were isolated from pseudomembrane from patients (n=5) undergoing hip revision due to aseptic loosening, by routine collagenase enzyme digestion. The isolated cells were seeded in flasks for 2–4 weeks before being passaged for a further 3–4 times. Generated fibroblast-like cells (10⁴) were then co-cultured with 5x10⁵ normal human peripheral blood monocytes (n=5) on glass coverslips and dentine slices in the presence of (i) no added factors, (ii) macrophage colony stimulating factor (M-CSF) and (iii) M-CSF plus OPG. All cultures were maintained for 1,17 and 21 days. The extent of osteoclast differentiation was then determined by the expression of specific osteoclast markers including tartrate-resistant acid phosphatase (TRAP) and vitronectin receptor (VNR) and evidence of lacunar resorption.

In the absence M-CSF, no osteoclast formation was noted in 24 hours, 17 or 21 days in fibroblast/monocyte cultures. However, in the presence of M-CSF alone, large numbers of TRAP⁺ and VNR⁺ multinucleated cells capable of lacunar resorption were noted in these co-cultures. The addition of OPG, which is known to inhibit RANKL-mediated osteoclast formation, significantly reduced the extent of osteoclast formation and lacunar resorption in these co-cultures.

These results indicate that one means whereby peri-prosthetic osteolysis may occur is by fibroblasts in the arthroplasty pseudomembrane inducing macrophage-osteoclast differentiation. Fibroblasts express RANKL and interact with arthroplasty macrophages, which express RANK and function as osteoclast precursors. These findings indicate that suppression of osteoclast formation by OPG may be a possible form of therapy for reducing prosthetic loosening.

In rheumatoid arthritis (RA) and other arthritic disorders e.g. gout, there is destruction of articular cartilage and juxta-articular bone. Osteoclasts are specialised multinucleated cells (MNCs) that carry out bone resorption. It has previously been shown that circulating monocytes and synovial macrophages in RA can be stimulated to differentiate into functional osteoclasts in the presence of RANKL and M-CSF. The aim of this study was to determine whether the mononuclear cells present in synovial fluid of RA patients are capable of differentiating into functional osteoclasts in the presence of osteogenic factors.

Mononuclear cells were isolated from the synovial fluid obtained from patients with Ra, osteoarthritis (OA) gout and joint trauma. The cells were seeded onto dentine slices and coverslips and cultured for up to 21 days in the presence/absence of RANKL (30ng/ml) and M-CSF (25ng/ml). Cells cultured on coverslips for 24h, 14 and 21 days were assessed for the expression of the monocyte-macrophage antigen CD14 that is known to be expressed by osteoclasts, and the osteoclast associated markers; tartrate-resistant acid phosphatase (TRAP) and vitronectin receptor (VNR). After 21 days, dentine slices were assessed for evidence of osteoclastic lacunar resorption.

After 24 h culture on coverslips mononuclear cells isolated from the synovial fluid of all the above joint conditions were largely CD14+, and entirely negative for TRAP and VNR. After 14 days culture, in the presence of RANKL and M-CSF these synovial fluid macrophages were stimulated to form multinucleated osteoclasts which were TRAP+ and VNR+ and capable of forming resorption pits on dentine slices. In the absence of either RANKL or M-CSF osteoclast formation did not occur.

The osteogenic factors RANKL and M-CSF have been shown to be present in the synovial fluid of patients with RA, OA, gout and joint trauma. Results from this study demonstrate that CD14+ mononuclear cells (macrophages) in the synovial fluid of patients with the above conditions have the capacity to differentiate into functional multinucleated osteoclasts in the presence of RANKL and M-CSF. These findings show that one cellular mechanisms whereby bone erosions many occur in arthritic disorders is through increased osteoclast formation of synovial fluid macrophages; this process requires RANKL and m-CSF, both of which are produced by inflammatory cells e.g. T Cells found in the synovial fluid and the arthritic synovial membrane.

Mast cells (MC), the tissue-based effector cells in allergic diseases, have many functions. Within bone tissue, they have been linked with new blood vessel formation and marrow fibrosis and it has been proposed that they are capable of promoting osteoclastic bone resorption. MC numbers are known to increase in a number of osteolytic conditions e.g. osteoporosis, hyperparathyroidism and periodontitis. In fracture callus, too, large numbers of MC are present, especially during the onset of remodelling where it is believed they may be responsible for osteoclast recruitment and/or differentiation. The aim of this study was to look for further evidence of mast cell (MC) involvement in pathological bone resorption. MC activity was assessed in tissue sections of osteolytic conditions including Paget’s disease of bone, rheumatoid arthritis and fibrous dysplasia together with several benign and malignant bone tumours. MCs were identified by toluidine blue staining and by immunostaining with a commercial antibody against MC tryptase.

Extensive infiltration of mast cells was observed in fibrous dysplasia, rheumatoid arthritis and Paget’s disease of bone and mast cell accumulation was seen at the bone resorbing margin of a number of enlarging bone tumours including osteosarcoma, giant cell tumour of bone, osteoma and osteoid osteoma.

MCs, along with other inflammatory cells, are known to accumulate at the margins of soft tissue tumours where they are thought to promote tumour growth. The current findings are consistent with a similar role for mast cells in the primary bone tumours examined. In each of the conditions studied, an additional role for MC may be that of promoting bone lysis. MC are known to contain numerous factors including TNF-alpha and IL-1, which are potent stimulators of osteoclast formation and activity.

It is concluded that MCs may contribute to the fibrosis, angiogenesis and increased bone resorption seen in certain metabolic bone diseases. MC activity may also be an important factor contributing to the lysis that occurs in numerous other pathological situations including at the margins of aggressive primary bone tumours and skeletal metastases, leading to the expansion of these lesions.

We analysed the histological findings in 1146 osteoarthritic femoral heads which would have been considered suitable for bone-bank donation to determine whether pathological lesions, other than osteoarthritis, were present. We found that 91 femoral heads (8%) showed evidence of disease. The most common conditions noted were chondrocalcinosis (63 cases), avascular necrosis (13), osteomas (6) and malignant tumours (one case of low-grade chondrosarcoma and two of well-differentiated lymphocytic lymphoma). There were two with metabolic bone disease (Paget’s disease and hyperparathyroid bone disease) and four with inflammatory (rheumatoid-like) arthritis. Our findings indicate that occult pathological conditions are common and it is recommended that histological examination of this regularly used source of bone allograft should be included as part of the screening protocol for bone-bank collection.

The clinical features, investigation, treatment and outcome of two adults with fibrogenesis imperfecta ossium are described. In this rare acquired disorder of bone, normal lamellar collagen is replaced by structurally unsound collagen-deficient tissue, which leads to extreme bone fragility and ununited fractures. Transmission microscopy and SEM showed striking ultrastructural changes in bone structure and mineralisation. Both patients had monoclonal IgG paraproteins in the plasma and one excreted monoclonal lambda light chains in the urine. No abnormal plasma cells were found in the bone marrow and there was no evidence of amyloid deposition in the tissues. In both patients initial treatment with 1 alpha-hydroxycholecalciferol appeared to be ineffective, but in one, repeated courses of melphalan and corticosteroids over three years together with 1 alpha-hydroxycholecalciferol produced striking clinical and histological improvement. The findings in these and other patients strongly suggest that paraproteinaemia is an integral feature of fibrogenesis imperfecta ossium, and this needs further investigation.

We assessed the efficacy of intraoperative frozen-section histology in detecting infection in failed arthroplasties in 106 hips and knees. We found inflammatory changes consistent with infection (an average of one or more neutrophil polymorphs or plasma cells per high-power field in several samples) in 18 cases; there was a significant growth on bacterial culture in 20 cases. Compared with the bacterial cultures, the frozen sections provided two false-negative results and three false-positive results (sensitivity, 90%; specificity, 96%; and accuracy, 95%). The positive predictive value was 88%, the negative value, 98%. These results support the inclusion of intra-operative frozen-section histology in any protocol for revision arthroplasty for loose components.

Macrophages and their fused products are commonly found at the polymethylmethacrylate cement-bone interface, but it is not known if they contribute directly to the osteolysis associated with loosening of the cemented prosthesis. We isolated mononuclear phagocytes from granulomas formed by subcutaneous implantation of polymethylmethacrylate into mice and incubated them on bone slices in which they formed resorption lacunae after co-culture for seven to 14 days with both marrow stromal cells and osteoblast-like cells (in the presence of 1 alpha,25-dihydroxyvitamin D3 and dexamethasone). Increased numbers of tartrate-resistant acid phosphatase-positive mononuclear and multinucleated cells formed in these cultures. Both in the presence and absence of stromal cells, macrophages produced extensive superficial roughening of the bone surface. Polymethylmethacrylate-induced macrophages are thus capable of low-grade surface and high-grade lacunar osteolysis, the latter requiring the presence of specific hormonal and stromal cell elements. These two forms of bone resorption could account for the pathogenesis and clinical patterns associated with loosening of the cemented prosthesis.

The role of inflammatory cells in aseptic loosening and failure of cemented joint replacements is unclear. Inflammatory cells from the revision joint capsule of four failed hip arthroplasties were examined to determine their nature and resorptive capacity. The capsules contained numerous macrophages and abundant foreign-body macrophage polykaryons, distinguished from osteoclasts by their antigenic phenotype and lack of response to calcitonin. When cultured on cortical bone slices in vitro, both macrophages and macrophage polykaryons produced small resorption pits and were associated with areas of superficial resorption of the bone surface. These results indicate that foreign-body induced macrophages and macrophage polykaryons are capable of a type of low-grade bone resorption which may be of pathogenic significance in the loosening of cemented joint prosthetic components.