Aims. Treatment of high-grade limb bone sarcoma that invades a joint requires en bloc extra-articular excision. MRI can demonstrate joint invasion but is frequently inconclusive, and its predictive value is unknown. We evaluated the diagnostic accuracy of direct and indirect radiological signs of intra-articular tumour extension and the performance characteristics of MRI findings of intra-articular tumour extension. Methods. We performed a retrospective case-control study of patients who underwent extra-articular excision for sarcoma of the knee, hip, or shoulder from 1 June 2000 to 1 November 2020. Radiologists blinded to the pathology results evaluated preoperative MRI for three direct signs of joint invasion (capsular disruption, cortical breach, cartilage invasion) and indirect signs (e.g. joint effusion, synovial thickening). The discriminatory ability of MRI to detect intra-articular tumour extension was determined by receiver operating characteristic analysis. Results. Overall, 49 patients underwent extra-articular excision. The area under the curve (AUC) ranged from 0.65 to 0.76 for direct signs of joint invasion, and was 0.83 for all three combined. In all, 26 patients had only one to two direct signs of invasion, representing an equivocal result. In these patients, the AUC was 0.63 for joint effusion and 0.85 for synovial thickening. When direct signs and synovial thickening were combined, the AUC was 0.89. Conclusion. MRI provides excellent discrimination for determining intra-articular tumour extension when multiple direct signs of invasion are present. When MRI results are equivocal, assessment of synovial thickening increases MRI’s discriminatory ability to predict intra-articular joint extension. These results should be interpreted in the context of the study’s limitations. The inclusion of only extra-articular excisions enriched the sample for true positive cases. Direct signs likely varied with tumour histology and location. A larger, prospective study of periarticular bone sarcomas with spatial correlation of histological and radiological findings is needed to validate these results before their adoption in clinical practice. Cite this article: Bone Jt Open 2024;5(10):944–952

Introduction: Arthrodesis of the knee nowadays is used as a salvage procedure, commonly for patients with a failed TKR or in infected trauma cases. We present 4 patients with extensive bone defects following septic sequelae of trauma treated by Arthrodesis of the knee joint.

Materials and Methods: Four patients (avg. 46.5 years; range 37–57 years; three male and one female) with longstanding infected non-union fractures (3 months–2 years) at the knee joint (three Tibial plateau and one distal femur) were treated by initial debridement and removal of dead or infected bone. This led to substantial bone defects (6–12 cm) of the debrided bone at the knee joint. The patients then underwent bone transport with a circular frame to compensate for this bone defect before achieving an Arthrodesis of the knee joint. Three patients also had a free muscle flap for soft tissue coverage before bone transport was begun.

Results: Arthrodesis of the knee was achieved in all patients at an average time of 26 months (20–32 months). None of the patients have any active infection of the limb.

Discussion and Conclusions: Knutson et al (1984) said that massive bone loss may substantially reduce the success rate of Arthrodesis of the knee. Wilde and Stearns (1989) noted decreased fusion rates with greater degrees of bone loss. In our series the bone defects were a sequelae of infective non–union, this further complicates the healing process. However, using circular frame for Bone transport to overcome the defect and to achieve compression at the Arthrodesis site is a useful technique for such challenging cases.

Osteochondral allografts (frozen uncontrolled, or cryo-protected with dimethyl sulfoxide) were transplanted into medial femoral condyles of eighteen sheep. Cores from the ipsilateral graft site served as autografts for the contralateral limb. Analysis of graft and host cancellous bone microarchitecture by μCT at three months post transplant demonstrated no significant differences among the treatment groups. Dramatic bone resorption at the graft–host interface, however, occurred in up to 1/3 of condyles from all treatment groups, including fresh autografts suggesting that factors other than donor source or tissue storage played an important role in the bone incorporation of osteochondral grafts. The purpose of this study was to study the effect of different freezing protocols on periarticular cancellous bone architecture after osteochondral allograft transplantation. There were no significant differences in graft or host cancellous bone architecture among the groups (autografts, frozen allografts, cryopreserved allografts). Dramatic resorption of graft bone in condyles from all treatment groups suggested that factors other than donor source or tissue storage played important roles during incorporation of osteochondral grafts. Graft positioning, graft orientation, and recipient bed necrosis may play significant roles during incorporation of osteochondral graft bone. Osteochondral allografts (10 mm diameter) were transplanted into medial femoral condyles of eighteen skeletally mature Suffolk ewes. Allografts were frozen (–80°C) without cryoprotectant (FROZ) or treated with dimethyl sulfoxide (cryoprotectant) and frozen (–80°C at 1°C · min. −1. ) (CRYO). Osteochondral cores removed from ipsilateral graft sites served as fresh autografts (AUTO) for the contralateral medial femoral condyles. Condyles were harvested at three months and scanned (micro computed tomography –μCT). Three dimensional μCT data of graft and host cancellous bone regions were analyzed for bone volume fraction, trabecular thickness, bone surface–volume ratio, and trabecular anisotropy. No morphological differences were found among treatment groups. Excessive bone resorption of graft and interface precluded analysis of some samples from each group (ALLO — 2/9, CRYO — 3/9, AUTO — 6/18). Dramatic bone loss did not correlate with poor graft orientation, placement, infection, or recipient–bed necrosis, but a combination of these factors may contribute to excessive cancellous bone resorption in osteochondral grafts. Funding: Medical Research Council of Canada, Canadian Institutes of Health Research, No commercial funding. Please contact author for figures and/or diagrams

Introduction and Objective. Heterotopic ossification is the formation of extraskeletal mineralized tissue commonly associated with either trauma or surgery. While several mouse models have been developed to better characterize the pathologic progression of HO, no model currently exists to study HO of the hip, the most common location of acquired HO in patients. Owing to the unique biological mechanisms underpinning the formation of HO in different tissues, we sought to develop a model to study the post-surgical HO of the hip. Materials and Methods. Wild-type mice C57BL/6J mice were used to study the procedure outcomes, while Pdgfra-CreERT2;mT/mG and Scx-GFP reporter animals were used for the lineage tracing experiments (total n=16 animals, male, 12 weeks old). An anterolateral approach to the hip was performed. Briefly, a 2 cm incision was made centered on the great trochanter and directed proximal to the iliac crest and distally over the lateral shaft of the femur. The joint was then reached following the intermuscular plane between the rectus femoris and gluteus medius muscles. After the joint was exposed, the articular cartilage was removed using a micropower drill with a 1.2 mm reamer. The medius gluteus and superficial fascia were then re-approximated with Vicryl 5-0 suture (Ethicon Inc, Somerville, NJ) and skin was then closed with Ethilon 5-0 suture (Ethicon Inc). Live high resolution XR imaging was performed every 2 wks to assess the skeletal tissues (Faxitron Bioptics, Tucson, AZ). The images were then scored using the Brooker classification. Ex-vivo microCT was conducted using a Skyscan 1275 scanner (Bruker-MicroCT, Kontich, Belgium). 3D reconstruction and analysis was performed using Dragonfly (ORS Inc., Montreal, Canada). For the histological analysis of specimens, Hematoxylin and Eosin (H&E), modified Goldner's Trichrome (GMT) stainings were performed. Reporter activity was assessed using fluorescent imaging. Results. Substantial periarticular heterotopic bone was seen in all cases. A periosteal reaction and an initial formation of calcified tissue within the soft tissue was apparent starting from 4 wks after surgery. By XR, progressive bone formation was observed within the periosteum and intermuscular planes during the subsequent 8 weeks. Stage 1 HO was observed in 12.5% of cases, stage 2 in 62.5% of cases, and stage 3 HO in 25% of cases. 3D microCT reconstructions of the treated hip joints demonstrated significant de novo heterotopic bone in several location which phenocopy human disease. Heterotopic bone was observed in an intracapsular location, periosteal location involving the iliac bone and proximal femur, and intermuscular locations. Histological analyses further confirmed these findings. To assess the cells which gave rise to HO in this model, an inducible PDGFRα and constitutive Scx-GFP reporter mice were used. A dramatic increase in mGFP reporter activity was noted PDGFRα within the HO injury site, including in areas of new cartilage and bone formation. Scx-associated reporter activity increased in the soft tissue and periosteal periacetabular areas of injured hips. Conclusions. HO has a diverse set of pathologies, of which joint associated HO after elective surgery is the most common. Here, we present the first mouse model of hip dislocation and acetabular reaming that mimics elements of human periarticular HO. The diverse locations of HO after acetabular reaming (intracapsular, intermuscular and periosteal) suggests the activation of different and specific HO program after surgery. Such a field effect would be consistent with local trauma and inflammation, which is a well-studied contributor to HO genesis. Not surprisingly, joint-associated HO significantly derives from PDGFRα-expressing cells, which has been shown to similarly give rise to intramuscular and intratendinous HO

Aims

The preventive effects of bisphosphonates on articular cartilage in non-arthritic joints are unclear. This study aimed to investigate the effects of oral bisphosphonates on the rate of joint space narrowing in the non-arthritic hip.

Aims

Insufficient treatment response in rheumatoid arthritis (RA) patients requires novel treatment strategies to halt disease progression. The potential benefit of combination of cytokine-inhibitors in RA is still unclear and needs further investigation. To explore the impact of combined deficiency of two major cytokines, namely interleukin (IL)-1 and IL-6, in this study double deficient mice for IL-1αβ and IL-6 were investigated in different tumour necrosis factor (TNF)-driven inflammatory bone disorders, namely peripheral arthritis and sacroiliitis, as well as systemic bone loss.

Septic arthritis induced by Staphylococcus aureus causes a rapid destruction of joint cartilage and periarticular bone. The mechanisms behind this phenomenon are not fully understood. Toll-like receptors (TLRs) are essential in host defense against pathogens by virtue of their capacity to detect microbes and initiate the immune response. TLR2 is seen as the most important receptor for gram-positive bacteria. TLR2 signaling can lead to the activation of NF-kB through myeloid differentiation factor 88 (MyD88) dependent pathway. The purpose of this study was to examine the catabolic role of TLR2 mediated by the NF-kB pathway in human septic arthritic chondrocytes. Septic arthritic (SA) chondrocytes (n=7) and fibroblast-like synoviocytes (n=7) infected by gram-positive bacteria, mainly Staphylococcus aureus, as well as chondrocytes from healthy individuals (n=5) were used for this study. The expression of TLR2 in septic articular cartilage and normal cartilage was analyzed by real time reverse transcription polymerase chain reaction as well western blot analysis. Production of matrix metalloproteinase MMP- 13 and IL-1b was evaluated by enzyme-linked immunosorbent assay. MyD88 protein expression levels and NF-kB activation were evalutated by western blot analysis. Downregulation of TLR2 expression was achieved after transfection with specific siRNA against TLR2 using liposomes. We observed that TLR2 mRNA and protein expression was significantly up-regulated in septic arthritic cartilage. Also MMP-13 and IL-1b production were significantly increased in septic arthritic chondrocytes compared to normal. Blocking TLR2 in septic chondrocytes resulted in significant reduction of MyD88 and NF-kB protein levels as well as reduction in MMP-13 and IL-1b expression. It could be suggested that stimulation of TLRs by microbial components may represent the initial signal promoting a pro-inflammatory environment that will enhance degeneration of articular cartilage and the surrounding synovial cells. Targeting NF-kB signalling pathway through TLR2 gene silencing may be of potential therapeutic value in treatment of joint diseases

Objectives. Tranexamic acid (TXA) is an anti-fibrinolytic medication commonly used to reduce perioperative bleeding. Increasingly, topical administration as an intra-articular injection or perioperative wash is being administered during surgery. Adult soft tissues have a poor regenerative capacity and therefore damage to these tissues can be harmful to the patient. This study investigated the effects of TXA on human periarticular tissues and primary cell cultures using clinically relevant concentrations. Methods. Tendon, synovium, and cartilage obtained from routine orthopaedic surgeries were used for ex vivo and in vitro studies using various concentrations of TXA. The in vitro effect of TXA on primary cultured tenocytes, fibroblast-like synoviocytes, and chondrocytes was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assays, fluorescent microscopy, and multi-protein apoptotic arrays for cell death. Results. There was a significant (p < 0.01) increase in cell death within all tissue explants treated with 100 mg/ml TXA. MTT assays revealed a significant (p < 0.05) decrease in cell viability in all tissues following treatment with 50 mg/ml or 100 mg/ml of TXA within four hours. There was a significant (p < 0.05) increase in cell apoptosis after one hour of exposure to TXA (100 mg/ml) in all tissues. Conclusion. The current study demonstrates that TXA caused significant periarticular tissue toxicity ex vivo and in vitro at commonly used clinical concentrations. Cite this article: M. McLean, K. McCall, I. D. M. Smith, M. Blyth, S. M. Kitson, L. A. N. Crowe, W. J. Leach, B. P. Rooney, S. J. Spencer, M. Mullen, J. L. Campton, I. B. McInnes, M. Akbar, N. L. Millar. Tranexamic acid toxicity in human periarticular tissues. Bone Joint Res 2019;8:11–18. DOI: 10.1302/2046-3758.81.BJR-2018-0181.R1

Osteoarthritis (OA) involves pathology in both articular cartilage and subchondral bone. The osteoprotegerin (OPG)/receptor activator of nuclear factor kappa beta ligand (RANK-L) balance is known to modulate bone turnover. We compared the bony changes in human total knee arthroplasty (TKA) and cadaveric controls. A qualitative increase in subchondral and ligamentous insertional bone mineral density was observed on micro-CT sections of TKA bone compared with cadaveric controls. In-situ hybridization of digoxygenase (DIG)-labelled OPG riboprobes showed selective uptake in osteoblasts but not osteocytes or osteoclasts in TKA bone. Those data suggested that the upregulation of OPG expression by osteoblasts may have precipitated the bony hypertrophy of end-stage OA. Altered joint mechanics produced by periarticular bone remodelling may precede the cartilage changes of osteoarthritis (OA). Recently, receptor activator of nuclear factor kappa beta (RANK), along with its soluble ligand (RANK-L), have been shown to induce both maturation and activation of bone-degrading osteoclasts. Activation of RANK on osteoclast cells by RANK-L is opposed by another soluble factor, osteoprotegerin (OPG). Thus RANK/OPG balance is important in regulating bone turnover. Here, we compared periarticular bone from patients with end-stage OA undergoing total knee arthroplasty (TKA) with those of cadaveric controls. We assessed bony, histological and molecular changes that are important in the pathogenesis of OA. Using in-situ hybridization, we found increased staining of digoxygenase (DIG)-labelled OPG in osteoblasts of TKA bone. A corresponding increase in subchondral and insertional bone was seen on micro-CT (μCT) sections from TKA bone in comparison with cadaveric controls. Those changes were accompanied by marked articular cartilage degeneration on histology. This study is the first of which we are aware that directly assessed the role of OPG in inducing the bony changes seen in human end-stage OA. We used μCT to compare corresponding samples qualitatively from TKA and cadaveric bone. Adjacent sections underwent hybridization of digoxygenase (DIG)-labelled OPG riboprobes to assess gene expression in situ. Finally, samples were stained and analysed for histology. Bony hypertrophy may be a result of overexpression of OPG that occurs as an important feature of OA pathophysiology. Funding: This work was supported by a grant from the Hip Hip Hooray Fund of the Canadian Orthopaedic Research Foundation (CORF) and the Wood Professorship in Joint Injury Research. There was no commercial funding for this research project