The ageing population and an increase in both the incidence and prevalence of cancer pose a healthcare challenge, some of which is borne by the orthopaedic community in the form of osteoporotic fractures and metastatic bone disease. In recent years there has been an increasing understanding of the pathways involved in bone metabolism relevant to osteoporosis and metastases in bone. Newer therapies may aid the management of these problems. One group of drugs, the antibody mediated anti-resorptive therapies (AMARTs) use antibodies to block bone resorption pathways. This review seeks to present a synopsis of the guidelines, pharmacology and potential pathophysiology of AMARTs and other new anti-resorptive drugs. . We evaluate the literature relating to AMARTs and new anti-resorptives with special attention on those approved for use in clinical practice. Denosumab, a monoclonal antibody against Receptor Activator for Nuclear Factor Kappa-B Ligand. It is the first AMART approved by the National Institute for Health and Clinical Excellence and the US Food and Drug Administration. Other novel anti-resorptives awaiting approval for clinical use include Odanacatib. Denosumab is indicated for the treatment of osteoporosis and prevention of the complications of bone metastases. Recent evidence suggests, however, that denosumab may have an adverse event profile similar to bisphosphonates, including atypical femoral fractures. It is, therefore, essential that orthopaedic surgeons are conversant with these medications and their safe usage. . Take home message: Denosumab has important orthopaedic indications and has been shown to significantly reduce patient morbidity in osteoporosis and metastatic bone disease. Cite this article: Bone Joint J 2016;98-B:160–5

Immunoscintigraphy using radioisotope-labelled monoclonal antibody prepared against osteosarcoma 791T cells was used to detect a primary osteosarcoma. The eight-centimetre tumour was detected using rectilinear scintigraphy of 131I-labelled antibodies. Image enhancement was achieved by subtraction of blood-pool radioactivity labelled with technetium-99m. The ratio of tumour to non-tumour uptake of radioactivity (5:1) suggested that antibody targeting of therapeutic agents is feasible

Aims. It is increasingly appreciated that coordinated regulation of angiogenesis and osteogenesis is needed for bone formation. How this regulation is achieved during peri-implant bone healing, such as osseointegration, is largely unclear. This study examined the relationship between angiogenesis and osteogenesis in a unique model of osseointegration of a mouse tibial implant by pharmacologically blocking the vascular endothelial growth factor (VEGF) pathway. Materials and Methods. An implant was inserted into the right tibia of 16-week-old female C57BL/6 mice (n = 38). Mice received anti-VEGF receptor-1 (VEGFR-1) antibody (25 mg/kg) and VEGF receptor-2 (VEGFR-2) antibody (25 mg/kg; n = 19) or an isotype control antibody (n = 19). Flow cytometric (n = 4/group) and immunofluorescent (n = 3/group) analyses were performed at two weeks post-implantation to detect the distribution and density of CD31. hi. EMCN. hi. endothelium. RNA sequencing analysis was performed using sorted CD31. hi. EMCN. hi. endothelial cells (n = 2/group). Osteoblast lineage cells expressing osterix (OSX) and osteopontin (OPN) were also detected with immunofluorescence. Mechanical pull-out testing (n = 12/group) was used at four weeks post-implantation to determine the strength of the bone-implant interface. After pull-out testing, the tissue attached to the implant surface was harvested. Whole mount immunofluorescent staining of OSX and OPN was performed to determine the amount of osteoblast lineage cells. Results. Flow cytometry revealed that anti-VEGFR treatment decreased CD31. hi. EMCN. hi. vascular endothelium in the peri-implant bone versus controls at two weeks post-implantation. This was confirmed by the decrease of CD31 and endomucin (EMCN) double-positive cells detected with immunofluorescence. In addition, treated mice had more OPN-positive cells in both peri-implant bone and tissue on the implant surface at two weeks and four weeks, respectively. More OSX-positive cells were present in peri-implant bone at two weeks. More importantly, anti-VEGFR treatment decreased the maximum load of pull-out testing compared with the control. Conclusion. VEGF pathway controls the coupling of angiogenesis and osteogenesis in orthopaedic implant osseointegration by affecting the formation of CD31. hi. EMCN. hi. endothelium. Cite this article: Bone Joint J 2019;101-B(7 Supple C):108–114

1. A hypothesis outlining an auto-immune mechanism for antibody production against autogenous nucleus pulposus is presented. 2. Auto-antibodies to autogenous nucleus pulposus have been experimentally produced in rabbits. 3. These antibodies are cell-bound within lymphoid cells and are greatest in primary lymph nodes. This antibody is demonstrated by a positive pyronin reaction. 4. Lymphoid cells fixed in Carnoy's fluid and stained for pyronins also show a distinct natural yellow fluorescence. This fluorescence occurs only in the cytoplasm of those cells which are pyronin-positive and presumably producing antibody. 5. The lymph node phase of the reaction is greatest at four days and is sustained for three weeks. A secondary generalised lymph node response occurs in all lymph nodes at six weeks

1. An immunological examination of the sera of thirty rabbits which had received primary and secondary homografts of cancellous bone into a subcutaneous site did not reveal the presence of circulating precipitins, haemagglutinins or passive haemagglutinins. These findings are consistent with the observations of Bonfiglio and his colleagues (1955). 2. Electrophoretic examination of the serum of four rabbits receiving primary and secondary homografts of bone into an intramuscular site did not reveal any change in the serum protein fractions. 3. A search for auto-antibodies produced by primary and secondary autografts of cancellous bone was unsuccessful in fifteen rabbits. 4. The multiple injections of saline extracts of bone into four rabbits did not evoke the production of demonstrable circulating antibodies, results which are in accord with the findings of Bonfiglio and colleagues (1955) and Curtiss and colleagues (1959). 5. For the first time the production of classical antibodies in response to injections of extracts of heterologous bone has been recorded. The repeated injections of a saline extract of rabbit bone intraperitoneally into ten mice produced demonstrable precipitins and passive haemagglutinins both to protein and polysaccharide fractions present in the bone extracts. 6. Knowledge concerning the production of humoral antibodies to transplants and extracts of bone has been reviewed

Aims

Bacterial infection activates neutrophils to release neutrophil extracellular traps (NETs) in bacterial biofilms of periprosthetic joint infections (PJIs). The aim of this study was to evaluate the increase in NET activation and release (NETosis) and haemostasis markers in the plasma of patients with PJI, to evaluate whether such plasma induces the activation of neutrophils, to ascertain whether increased NETosis is also mediated by reduced DNaseI activity, to explore novel therapeutic interventions for NETosis in PJI in vitro, and to evaluate the potential diagnostic use of these markers.

Aims

Low-grade central osteosarcoma (LGCOS), a rare type of osteosarcoma, often has misleading radiological and pathological features that overlap with those of other bone tumours, thereby complicating diagnosis and treatment. We aimed to analyze the clinical, radiological, and pathological features of patients with LGCOS, with a focus on diagnosis, treatment, and outcomes.

Aims. Tissue responses to debris formed by abrasion of polymethylmethacrylate (PMMA) spacers at two-stage revision arthroplasty for prosthetic joint infection are not well described. We hypothesised that PMMA debris induces immunomodulation in periprosthetic tissues. Patients and Methods. Samples of tissue were taken during 35 two-stage revision arthroplasties (nine total hip and 26 total knee arthroplasties) in patients whose mean age was 67 years (44 to 85). Fourier transform infrared microscopy was used to confirm the presence of PMMA particles. Histomorphometry was performed using Sudan Red and Haematoxylin-Eosin staining. CD-68, CD-20, CD-11(c), CD-3 and IL-17 antibodies were used to immunophenotype the inflammatory cells. All slides were scored semi-quantitatively using the modified Willert scoring system. Results. The mean CD-68 scores did not show any significant change during the six weeks between the stages. Perivascular and diffuse scores showed significant difference in CD-3, CD-20, CD-11(c) and IL-17. At the time of re-implantation, a shift in the pattern of the expression of dendritic cells towards a perivascular arrangement and towards the periphery of PMMA particles was observed. Positive microbiological cultures were found at the time of re-implantation in three patients. Five further revisions were required for other reasons. Conclusion. Our results represent a biological reaction of the synovial tissues to spacers with a less diffuse expression of dendritic cells and an increased expression of perivascular lymphocytes. The use of spacers in two-stage revision for infection probably induces an immunomodulation of synovial tissues. Cite this article: Bone Joint J 2016;98-B:1062–8

The aim of this study was to investigate the occurrence of tissue hypoxia and apoptosis at different stages of tendinopathy and tears of the rotator cuff. We studied tissue from 24 patients with eight graded stages of either impingement (mild, moderate and severe) or tears of the rotator cuff (partial, small, medium, large and massive) and three controls. Biopsies were analysed using three immunohistochemical techniques, namely antibodies against HIF-1α (a transcription factor produced in a hypoxic environment), BNip3 (a HIF-1α regulated pro-apoptotic protein) and TUNEL (detecting DNA fragmentation in apoptosis). The HIF-1α expression was greatest in mild impingement and in partial, small, medium and large tears. BNip3 expression increased significantly in partial, small, medium and large tears but was reduced in massive tears. Apoptosis was increased in small, medium, large and massive tears but not in partial tears. These findings reveal evidence of hypoxic damage throughout the spectrum of pathology of the rotator cuff which may contribute to loss of cells by apoptosis. This provides a novel insight into the causes of degeneration of the rotator cuff and highlights possible options for treatment

1. The management of fractures in five patients with haemophilia is described: two patients had antibodies to antihaemophilic globulin. 2. The principles of management of injured haemophilia patients are described, as are the special problems in patients with antibodies to AHG. 3. Stability of the fragments must be achieved to prevent the hazards of displacement of the fracture, recurrent bleeding and pseudotumour formation which may threaten viability of the limb. 4. Stabilisation of potentially unstable fractures can be achieved at the onset by internal fixation. Plaster casts should be reserved for stable fractures or fractures occurring in young children

Seven out of 22 children with monarticular juvenile rheumatoid arthritis (MJRA) developed involvement of other joints between six months and three and a half years from the onset. In the other 15 patients the disease has remained monarticular for between one and 16 years (mean six years). Chronic iridocyclitis was seen in three of the five boys, two with antinuclear antibodies. Children with MJRA and antinuclear antibodies should have periodic ophthalmic assessment. Synovial biopsy was of value primarily in excluding other cases of arthritis, but there was only limited correlation between the histological findings and the subsequent course of the disease

1. Eight cases of monarticular brucellar arthritis in children are described. They have been followed up from between one and six years and all are now fully active and clinically normal. 2. The history was usually short, with limp, swelling of the joint and pain as the presenting symptoms. Constitutional disturbance was slight in all cases. 3. Diagnosis was confirmed by high concurrent serum agglutinin titres which were not found in control children of the same age from the same areas. Mercaptoethanol resistant antibody (IgG) and complement fixing antibodies were also demonstrated in the sera of four cases. One child had a positive blood culture. 4. The condition responded rapidly to rest and splintage and, to date, recovery seems to have been complete

In vitro studies on isolated bone cells were undertaken to investigate the presence of transplantation (histocompatibility) antigens. Bone cells were cultured with allogeneic lymphocytes and exposed to cytotoxic sera containing antibodies against transplantation antigens, to determine their antigenic profile. Preliminary results suggest that bone cells may not express lymphocyte stimulating antigens in an active form, at least after the isolation procedure performed. On the other hand, bone cells were killed by cytotoxic antibodies in a specific way, providing evidence for the presence of serologically defined (SD) transplantation antigens on the cell surface. Additional studies with absorbed sera suggest "sharing" of histocompatibility antigens between bone cells and lymphocytes. The relevance of the surface antigens of bone cells to clinical fields such as bone allotransplantation, susceptibility to various orthopaedic diseases and skeletal sarcomata is discussed

1. The humoral immune response of rats against sheep iliac bone grafts has been examined. 2. Fresh, marrow-containing grafts elicited a brisk and sustained antibody response. Attempts to wash out the marrow were not uniformly successful in removing cellular antigens from the grafts. 3. Decalcifying and freezing bone grafts at —20 degrees Celsius do not impair immunogenicity to any significant extent. Immunogenicity was found to be reduced in grafts subjected to freeze-drying. 4. Deproteinised Oswestry bone grafts and Kiel grafts gave rise to antibody production in a few recipients, and in the case of the former this response did not occur until after six or seven weeks from grafting. 5. The highest degree of osteogenesis in composite bone xenograft-autografts was found by Salama and colleagues (1973) to occur in Oswestry bone grafts. It is suggested that osteogenesis in xenografts may be impaired by an immune response

Periprosthetic joint infection (PJI) remains an extremely challenging complication. We have focused on this issue more over the last decade than previously, but there are still many unanswered questions. We now have a workable definition that everyone should align to, but we need to continue to focus on identifying the organisms involved. Surgical strategies are evolving and care is becoming more patient-centred. There are some good studies under way. There are, however, still numerous problems to resolve, and the challenge of PJI remains a major one for the orthopaedic community. This annotation provides some up-to-date thoughts about where we are, and the way forward. There is still scope for plenty of research in this area.

Cite this article: Bone Joint J 2022;104-B(11):1193–1195.

Aims

We performed a systematic literature review to define features of patients, treatment, and biological behaviour of multicentric giant cell tumour (GCT) of bone.

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

A rat model of lumbar root constriction with an additional sympathectomy in some animals was used to assess whether the sympathetic nerves influenced radicular pain. Behavioural tests were undertaken before and after the operation. On the 28th post-operative day, both dorsal root ganglia and the spinal roots of L4 and L5 were removed, frozen and sectioned on a cryostat (8 μm to 10 μm). Immunostaining was then performed with antibodies to tyrosine hydroxylase (TH) according to the Avidin Biotin Complex method. In order to quantify the presence of sympathetic nerve fibres, we counted TH-immunoreactive fibres in the dorsal root ganglia using a light microscope equipped with a micrometer graticule (10 x 10 squares, 500 mm x 500 mm). We counted the squares of the graticule which contained TH-immunoreactive fibres for each of five randomly-selected sections of the dorsal root ganglia. The root constriction group showed mechanical allodynia and thermal hyperalgesia. In this group, TH-immunoreactive fibres were abundant in the ipsilateral dorsal root ganglia at L5 and L4 compared with the opposite side. In the sympathectomy group, mechanical hypersensitivity was attenuated significantly. We consider that the sympathetic nervous system plays an important role in the generation of radicular pain

Periprosthetic joint infection (PJI) is a difficult complication requiring a comprehensive eradication protocol. Cure rates have essentially stalled in the last two decades, using methods of antimicrobial cement joint spacers and parenteral antimicrobial agents. Functional spacers with higher-dose antimicrobial-loaded cement and antimicrobial-loaded calcium sulphate beads have emphasized local antimicrobial delivery on the premise that high-dose local antimicrobial delivery will enhance eradication. However, with increasing antimicrobial pressures, microbiota have responded with adaptive mechanisms beyond traditional antimicrobial resistance genes. In this review we describe adaptive resistance mechanisms that are relevant to the treatment of PJI. Some mechanisms are well known, but others are new. The objective of this review is to inform clinicians of the known adaptive resistance mechanisms of microbes relevant to PJI. We also discuss the implications of these adaptive mechanisms in the future treatment of PJI.

Cite this article: Bone Joint J 2022;104-B(5):575–580.

Aims

Aseptic loosening is a leading cause of uncemented arthroplasty failure, often accompanied by fibrotic tissue at the bone-implant interface. A biological target, neutrophil extracellular traps (NETs), was investigated as a crucial connection between the innate immune system’s response to injury, fibrotic tissue development, and proper bone healing. Prevalence of NETs in peri-implant fibrotic tissue from aseptic loosening patients was assessed. A murine model of osseointegration failure was used to test the hypothesis that inhibition (through Pad4^-/- mice that display defects in peptidyl arginine deiminase 4 (PAD4), an essential protein required for NETs) or resolution (via DNase 1 treatment, an enzyme that degrades the cytotoxic DNA matrix) of NETs can prevent osseointegration failure and formation of peri-implant fibrotic tissue.

Aims

The modified Glasgow Prognostic Score (mGPS) uses preoperative CRP and albumin to calculate a score from 0 to 2 (2 being associated with poor outcomes). mGPS is validated in multiple carcinomas. To date, its use in soft-tissue sarcoma (STS) is limited, with only small cohorts reporting that increased mGPS scores correlates with decreased survival in STS patients.

Aims

The primary aim was to assess the rate of postoperative COVID-19 following hip and knee arthroplasty performed in March 2020 in the UK. The secondary aims were to assess whether there were clinical factors associated with COVID-19 status, the mortality rate of patients with COVID-19, and the rate of potential COVID-19 in patients not presenting to healthcare services.

Aims

We aimed to describe the epidemiological, biological, and bacteriological characteristics of osteoarticular infections (OAIs) caused by Kingella kingae.

Total elbow replacement can be a valuable option for the treatment of the elbow in haemophilia where there are associated arthropathic changes. We describe the outcome of seven elbow replacements in five consecutive patients with severe haemophilia A (native factor levels < 1%) at a mean of 42 months (25 to 65) after operation. All the patients had excellent relief of pain and improvement in function. One failure was due to infection in an immunocompromised patient with both HIV and Hepatitis C antibodies who was on anti-retroviral chemotherapy. The implant was revised at 30 months in a one-stage procedure and showed no evidence of loosening or infection 35 months later

We investigated the rates of expression of bone morphogenetic protein-2 (BMP-2) in 29 adult patients with high-grade malignant fibrous histiocytoma of soft tissue, using the BMP-2-specific monoclonal antibody, AbH3b2/17, and found that they ranged from 1.9% to 78.9%. The survival at five years of the groups expressing high (≥30%) and low (< 30%) levels of BMP-2 was 85.7% and 36.3%, respectively. Multivariable analysis showed that only BMP-2 had prognostic significance for continuous disease-free survival and for overall survival (p < 0.05). Our findings indicate that over-expression of BMP-2 in malignant fibrous histiocytoma of soft tissue is the most reliable prognostic indicator of the parameters assessed

The growth plates of the femoral head of Japanese white rabbits aged 5, 10, 15 and 20 weeks were stained for apoptotic and proliferating chondrocytes using the TUNEL and PCNA antibody staining techniques. Both TUNEL- and PCNA-positive chondrocytes were detected in all of the specimens. The positive ratios of both stainings were calculated for the whole plate and for the resting, proliferating and hypertrophic zones. The highest ratios in both stainings occurred in the hypertrophic zone in all age groups. With growth, the TUNEL-positive ratio increased whereas the proliferating ratio decreased. We suggest that the increase in chondrocytic death by apoptosis and the decrease in cell proliferation potential led to closure of the growth plate

Tissues from five patients who underwent revision operations for failed total hip replacements were found to contain large quantities of particulate titanium. In four cases this metal must have come from titanium alloy screws used to fix the acetabular component; in the fifth case it may also have originated from a titanium alloy femoral head. Monoclonal antibody labelling showed abundant macrophages and T-lymphocytes, in the absence of B-lymphocytes, suggesting sensitisation to titanium. Skin patch testing with dilute solutions of titanium salts gave negative results in all five patients. However, two of them had a positive skin test to a titanium-containing ointment

Aims

Local recurrence remains a challenging and common problem following curettage and joint-sparing surgery for giant cell tumour of bone (GCTB). We previously reported a 15% local recurrence rate at a median follow-up of 30 months in 20 patients with high-risk GCTB treated with neoadjuvant Denosumab. The aim of this study was to determine if this initial favourable outcome following the use of Denosumab was maintained with longer follow-up.

1. A comparative study has been made of the major transplantation antigens present on the chondrocyte isolated from articular cartilage of the sheep and lymphocytes from the cartilage donors. 2. It has been shown that the chondrocyte possesses antigens of the major histocompatibility system in common with the lymphocyte. 3. In order to demonstrate the similarity between the antigen structure of the chondrocyte and the lymphocyte it was necessary to treat cartilage cells with papain after isolation in order to remove the matrix more completely. Failure to do this led to an apparent deficit of antigens on the chondrocyte. 4. It was found that lysis of cells by antibodies was slower when chondrocytes were the target cells than when lymphocytes were used. It is concluded that this is due to a protective role of remaining cartilage matrix

We studied 16 club feet and 27 normal feet from spontaneously aborted human fetuses in the second trimester of gestation and measured the length of the spring ligament, and the declination angle and size of the talus. We also studied the cellular characteristics of the spring ligament and the immunohistochemical features of the medial ankle ligaments using monoclonal antibodies against type-III collagen, desmin, vimentin, and smooth muscle actin. Histomorphometric results indicated that the talar deformity was not the primary lesion. Histological and immunohistochemical findings showed that the cells and collagen fibres of the medial ankle ligaments of club feet appeared to be the site of the earliest changes, in that they had lost their spatial orientation and had contracted. In severe club feet before the third trimester of gestation, myofibroblast-like cells seemed to create a disorder of the ligaments resembling fibromatosis. This led to contraction and resulted in typical club-foot deformity

Of 935 consecutive patients referred with shoulder pain, 50 fitted the criteria for primary frozen shoulder. Twelve patients who failed to improve after conservative treatment and manipulation had excision of the coracohumeral ligament and the rotator interval of the capsule. The specimens were examined histologically, using special stains for collagen. Immunocytochemistry was performed with monoclonal antibodies against leucocyte common antigen (LCA, CD45) and a macrophage/synovial antigen (PGMI, CD68) to assess the inflammatory component, and vimentin and smooth-muscle actin to evaluate fibroblasts and myofibroblasts. Our histological and immunocytochemical findings show that the pathological process is active fibroblastic proliferation, accompanied by some transformation to a smooth muscle phenotype (myofibroblasts). The fibroblasts lay down collagen which appears as a thick nodular band or fleshy mass. These appearances are very similar to those in Dupuytren's disease of the hand, with no inflammation and no synovial involvement. The contracture acts as a check-rein against external rotation, causing loss of both active and passive movement

Bone loss around replacement prostheses may be related to the activation of mononuclear phagocytes (MNP) by prosthetic wear particles. We investigated how osteoblast-like cells were regulated by human MNP stimulated by particles of prosthetic material. Particles of titanium-6-aluminium-4-vanadium (TiAlV) stimulated MNP to release interleukin (IL)-1β, tumour necrosis factor (TNF)α, IL-6 and prostaglandin E. 2. (PGE. 2. ). All these mediators are implicated in regulating bone metabolism. Particle-activated MNP inhibited bone cell proliferation and stimulated release of IL-6 and PGE. 2. The number of cells expressing alkaline phosphatase, a marker associated with mature osteo-blastic cells, was reduced. Experiments with blocking antibodies showed that TNFα was responsible for the reduction in proliferation and the numbers of cells expressing alkaline phosphatase. By contrast, IL-1β stimulated cell proliferation and differentiation. Both IL-1β and TNFα stimulated IL-6 and PGE. 2. release from the osteoblast-like cells. Our results suggest that particle-activated mono-nuclear phagocytes can induce a change in the balance between bone formation and resorption by a number of mechanisms

We investigated the lymphocyte-mediated immune response to polymethylmethacrylate bone cement in 26 patients who had revision surgery for aseptic loosening of cemented total hip arthroplasties, at a mean time of seven years after the first replacement. We studied eight patients with cemented total hip arthroplasties which were not loose as controls. Patch tests to polymethylmethacrylate bone cement were positive in 13 patients with loosening, and these patients had higher lymphoblast transformation values against polymethylmethacrylate bone cement patients with a negative skin reaction (p < 0.01) or those in the control group (p < 0.001). Specific monoclonal antibodies were used to assess the percentage of certain cells of the immune system according to their cluster of differentiation (CD). There was a higher number of total T and B lymphocytes (CD2 and CD22) and interleukin-2 receptor-positive lymphocytes (activated cells, CD25) in patients with loose prostheses. More CD25 lymphocytes were found in patients with positive patch tests. The activation of the lymphocyte-mediated immune response was not related to the presence or absence of aggressive granulomatous lesions at the cement-bone interface

The role of three genetically distinct collagen types in the formation of endochondral bone and in calcification and resorption of cartilage has been assessed. Using antibodies specific to types I, II and III collagen we have demonstrated in the embryonic chick tibia that endochondral bone formation began with deposition of type III collagen in lacunae of hypertropic chondrocytes by invading bone-marrow-derived cells. This was followed by the deposition of type I collagen, which is the collagenous constituent of endochondral osteoid. At later stages of development endochondral osteoid was found in the epiphysial growth plate in apparently intact lacunae of hypertrophic chondrocytes; this indicated that the latter might contribute to the synthesis of osteoid type I collagen. Immuno-histological staining for collagen types, and von Kossa staining for calcium phosphate on parallel sections, demonstrated that type I and type II collagen matrices were substrates for calcification. Endochondral bone (with type I collagen) was found on scaffolding of both uncalcified and calcified cartilage (with type II collagen), indicating that calcification of endochondral osteoid and of the underlying cartilage occurred independentyl. Spicules of endochondral cancellous bone of a four-week-old chick contained a core of calcified type II collagen

We studied the cellular response to physeal distraction in the growth plates of skeletally immature rabbits. We used a new method of labelling and detection of proliferating cells with bromodeoxyuridine (BUdR) and an anti-BUdR antibody. The application of an external fixator but no distraction force produced no changes in the growth plates. After five days of distraction at a maximum force of 20 N, the growth plate became thicker, mainly because of an increase in the number of hypertrophic chondrocytes, but there was no evidence of increased cell proliferation. Recent fractures were seen at the junction of growth plate and metaphysis but the increase in bone length was insignificant. After ten days of distraction at the same maximum force, the chondrocyte columns had become disorganised and cell proliferation was significantly decreased. There was an increase in bone length due to distraction of the fracture gap. In this model, physeal distraction did not stimulate cell proliferation, but actually inhibited it. The apparent increase in growth-plate thickness produced by distraction is not due to increased cell production, but results from inhibition of endochondral ossification and the consequent accumulation of hypertrophic chondrocytes. Any growth after distraction depends on the ability of growth-plate chondrocytes to divide. The decrease in proliferative activity which we found after ten days of distraction suggests the need for caution in the use of such procedures in young children

Caveolae, specialised regions of the cell membrane which have been detected in a wide range of mammalian cells, have not been described in bone cells. They are plasmalemmal invaginations, 50 to 100 nm in size, characterised by the presence of the structural protein, caveolin, which exists as three subtypes. Caveolin-1 and caveolin-2 are expressed in a wide range of cell types whereas caveolin-3 is thought to be a muscle-specific subtype. There is little information on the precise function of caveolae, but it has been proposed that they play an important role in signal transduction. As the principal bone-producing cell, the osteoblast has been widely studied in an effort to understand the signalling pathways by which it responds to extracellular stimuli. Our aim in this study was to identify caveolae and their structural protein caveolin in normal human osteoblasts, and to determine which subtypes of caveolin were present. Confocal microscopy showed staining which was associated with the plasma membrane. Transmission electron microscopy revealed the presence of membrane invaginations of 50 to 100 nm, consistent with the appearance of caveolae. Finally, we isolated protein from these osteoblasts, and performed Western blotting using anti-caveolin primary antibodies. This revealed the presence of caveolin-1 and -2, while caveolin-3 was absent. The identification of these structures and their associated protein may provide a significant contribution to our further understanding of signal transduction pathways in osteoblasts

We studied the vascular pattern of human posterior tibial tendons by injection techniques and immunohistochemically using antibodies against laminin. The intravascular volume of the posterior tibial tendon was determined using a new method of injection of a solution of . 99m. Tc and gelatin ink into the lower legs of cadavers. Three segments of 1 cm length from different regions of the human posterior tibial tendon were measured using a gamma well counter. The main blood supply arises from the posterior tibial artery. Blood vessels enter the paratenon of the posterior tibial tendon via a mesotenon from the posterior aspect. From the paratenon, the blood vessels penetrate the posterior tibial tendon and anastomose with a longitudinally orientated intratendinous network. The number of vessels in the substance of the tendon is consistently less than that in the surrounding paratenon. The distribution of blood vessels within the posterior tibial tendon is not homogeneous. In the retromalleolar region the intravascular volume was significantly reduced with a mean value of 15 μl/g of tendon tissue. There was no significant difference between the mean intravascular volumes of the proximal and distal areas (distal, 27.7 μl/g tendon tissue; proximal, 30 μl/g tendon tissue). The immunohistochemical investigation showed that there was no immunostaining for laminin in the anterior part of the tendon in the region where it passes behind the medial malleolus. This region is avascular. The most frequent site of rupture of the posterior tibial tendon is in the region behind the medial malleolus. A potential endogenous risk factor may be the limited healing potential of avascular tissue

Aims

Tenosynovial giant cell tumour (TGCT) is one of the most common soft-tissue tumours of the foot and ankle and can behave in a locally aggressive manner. Tumour control can be difficult, despite the various methods of treatment available. Since treatment guidelines are lacking, the aim of this study was to review the multidisciplinary management by presenting the largest series of TGCT of the foot and ankle to date from two specialized sarcoma centres.

A protocol of treatment for acute haematogenous osteomyelitis has been evaluated in 75 children. Intravenous cloxacillin and benzylpenicillin were given in hospital until the child had improved after which oral antibodies and immobilisation were continued at home for a total of six weeks. Oral cloxacillin was used most frequently as Staphylococcus aureus was the major pathogen. Simple drainage of subperiosteal pus was carried out in the 17 children with clinical evidence of an abscess. Ninety-two per cent of the 55 children with acute osteomyelitis diagnosed early were cured by a single course of antibiotics without an operation and with less than one week in hospital. Only 25 per cent of the 12 children with late-diagnosed acute osteomyelitis were cured with a single course of antibiotics and an operation. A longer period in hospital, a prolonged course of antibiotics, and secondary operations were required to cure the other children. Seven (88 per cent) of the eight neonates and infants with acute osteomyelitis were cured with a single course of antibiotics and an operation with only one to two weeks spent in hospital. The remaining infant was cured with a further course of antibiotics. The overall cure rate with a single course of treatment was 83 per cent, and the remaining children were cured with further treatment. More children would be cured with a single course of antibiotics and immobilisation without the need for surgical intervention if treated was started within one or two days of the onset of the illness rather than after four to five days when the disease is more advanced with the formation of and abscess

1. The effects of the insertion of pieces of fresh cancellous bone into the subcutaneous tissues of the ear upon lymph nodes and spleens have been investigated in seventy rabbits. 2. The main immunological response is found to occur in the first regional nodes draining the sites of insertion of homografts of bone, which show a considerable increase in weight compared with nodes draining autografts of bone. 3. An increased number of large and medium lymphoid cells occurs principally in the first regional node of the homografted animals, as Scothorne and McGregor (1955) observed using skin as the homografted tissue. 4. The large and medium lymphoid cell response is found in both the cortex and the medulla of the lymph nodes. In the cortex a sectoral distribution of the cellular response is observed and the name reactive cortex is given to these sectors. Evidence is presented to show that the sectoral pattern of reactivity is probably determined by the localised entry into the node of iso-antigens through lymphatic vessels draining the bed of the graft. 5. We have made a quantitative analysis of the large and medium lymphoid cell response in the reactive parts of the diffuse lymphoid tissue of the cortex. The mean maximal large and medium lymphoid cell response occurs five days after the insertion of bone homografts. 6. The origin and fate of the large and medium lymphoid cells and their role in the production of antibodies is reviewed in the light of recent work. 7. A correlation is made between the maximal production of large and medium lymphoid cells in the first regional lymph node, the invasion of the graft bed with small lymphocytes and the inhibition of new bone formation in the homografts

We obtained intervertebral discs with cartilage endplates and underlying cancellous bone at operation from patients with degenerative disc disease and then used immunohistochemical techniques to localise the nerves and nerve endings in the specimens. We used antibodies for the ubiquitous neuronal protein gene product 9.5 (PGP 9.5). Immunoreactivity to neuropeptide Y was used to identify autonomic nerves and calcitonin gene-related peptide (CGRP) and substance P to identify sensory nerves. Blood vessels were identified by immunoreactivity with platelet-endothelial cell-adhesion molecule (CD31; PECAM). In a control group with no known history of chronic back pain, nerve fibres immunoreactive to PGP 9.5 and neuropeptide Y were most closely related to blood vessels, with occasional substance P and CGRP immunoreactivity. In patients with severe back pain and markedly reduced disc height, proliferation of blood vessels and accompanying nerve fibres was observed in the endplate region and underlying vertebral bodies. Many of these nerves were immunoreactive to substance P or CGRP, and in addition, substance P- and CGRP-immunoreactive nociceptors were seen unrelated to blood vessels. Quantification by image analysis showed a marked increase in CGRP-containing sensory nerve fibres compared with normal control subjects. We speculate that a chemotactic response to products of disc breakdown is responsible for the proliferation of vascularity and CGRP-containing sensory nerves found in the endplate region and vertebral body adjacent to degenerate discs. The neuropeptides substance P and CGRP have potent vasodilatory as well as pain-transmitting effects. The increase in sensory nerve endings suggests increase in blood flow, perhaps as an attempt to augment the nutrition of the degenerate disc. The increase in the density of sensory nerves, and the presence of endplate cartilage defects, strongly suggest that the endplates and vertebral bodies are sources of pain; this may explain the severe pain on movement experienced by some patients with degenerative disc disease

1. A primary subacute type of staphylococcal osteomyelitis has been described. It is the commonest form of osteomyelitis seen in East Africa, and the incidence appears to be increasing in Great Britain. 2. A review of the literature indicates that this is not a new disease but that in the past there has been some confusion in terminology. 3. The causative organism is a coagulase positive staphylococcus, but in a few instances a coagulase negative one has been isolated. The staphylococcus is thought to be of reduced virulence and in East Africa it is likely that the population has acquired an increased resistance to the staphylococcus. 4. Two radiologically distinct groups are recognised, depending on whether a bone abscess is present or not. In the first group there are two types of localised abscesses: the familiar Brodie's lesion and the less well recognised large bone abscess that occurs in the metaphysis of a long bone. While the pathology of the two types is similar, the radiological features are quite distinct. The lesions in the second group are characterised by extensive diaphysial changes, with or without metaphysial involvement, and an obvious abscess cannot usually be demonstrated. 5. The main clinical features are the long history, often weeks or months, before diagnosis; insignificant or absent general reaction to the infection and minimum physical signs. 6. Vertebral body osteomyelitis in adults is included because it generally presents as a subacute infection; the difficulties in distinguishing it from a tuberculous infection are outlined. 7. The most useful diagnostic aids are the staphylococcal antibody titres (especially in vertebral infections) and the erythrocyte sedimentation rate. A limited surgical exposure is usually required if the causative organism is to be isolated and empirical antibiotic therapy is to be avoided. The total and differential white blood count are so often normal in these patients that they are considered to be of no diagnostic value. 8. Curettage and local antibiotics together will cure the localised bone abscess. Other lesions may be effectively treated by systemic antibiotics alone, but in the later stages removal of sequestra and infected granulation tissue may be necessary. In this instance it is essential to make a planned incision and to cut a window in the bone large enough to expose the whole of the lesion; primary suture of the wound is advocated

Aims

The risk to patients and healthcare workers of resuming elective orthopaedic surgery following the peak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been difficult to quantify. This has prompted governing bodies to adopt a cautious approach that may be impractical and financially unsustainable. The lack of evidence has made it impossible for surgeons to give patients an informed perspective of the consequences of elective surgery in the presence of SARS-CoV-2. This study aims to determine, for the UK population, the probability of a patient being admitted with an undetected SARS-CoV-2 infection and their resulting risk of death; taking into consideration the current disease prevalence, reverse transcription-polymerase chain reaction (RT-PCR) testing, and preassessment pathway.

Aims

There is a lack of evidence about the risk factors for local recurrence of a giant cell tumour (GCT) of the sacrum treated with nerve-sparing surgery, probably because of the rarity of the disease. This study aimed to answer two questions: first, what is the rate of local recurrence of sacral GCT treated with nerve-sparing surgery and second, what are the risk factors for its local recurrence?

Aims

Prosthetic joint infection (PJI) remains a major clinical challenge. Neutrophil CD64 index, Fc-gamma receptor 1 (FcγR1), plays an important role in mediating inflammation of bacterial infections and therefore could be a valuable biomarker for PJI. The aim of this study is to compare the neutrophil CD64 index in synovial and blood diagnostic ability with the standard clinical tests for discrimination PJI and aseptic implant failure.

The transition from shutdown of elective orthopaedic services to the resumption of pre-COVID-19 activity presents many challenges. These include concerns about patient safety, staff safety, and the viability of health economies. Careful planning is necessary to allow patients to benefit from orthopaedic care in a safe and sustainable manner.

Cite this article: Bone Joint J 2020;102-B(7):807–810.

Aims

Tibiotalocalcaneal (TTC) fusion is used to treat a variety of conditions affecting the ankle and subtalar joint, including osteoarthritis (OA), Charcot arthropathy, avascular necrosis (AVN) of the talus, failed total ankle arthroplasty, and severe deformity. The prevalence of postoperative complications remains high due to the complexity of hindfoot disease seen in these patients. The aim of this study was to analyze the relationship between preoperative conditions and postoperative complications in order to predict the outcome following primary TTC fusion.

Aims

To investigate the benefits of denosumab in combination with nerve-sparing surgery for treatment of sacral giant cell tumours (GCTs).

Aims

The purpose of this study was to clarify the clinical behaviour, prognosis, and optimum treatment of dedifferentiated low-grade osteosarcoma (DLOS) diagnosed based on molecular pathology.

Aims

HIV predisposes patients to opportunistic infections. However, with the establishment of Highly Active Anti-Retroviral Therapy (HAART), patients’ CD4 counts are maintained, as is a near normal life expectancy. This study aimed to establish the impact of HIV on the bacteriology of spondylodiscitis in a region in which tuberculosis (TB) is endemic, and to identify factors that might distinguish between them.