Aims. Osteoporosis is characterized by decreased trabecular bone volume, and microarchitectural deterioration in the medullary cavity. Interleukin-19 (IL-19), a member of the IL-10 family, is an anti-inflammatory cytokine produced primarily by macrophages. The aim of our study was to investigate the effect of IL-19 on osteoporosis. Methods. Blood and femoral bone marrow suspension IL-19 levels were first measured in the lipopolysaccharide (LPS)-induced bone loss model. Small interfering RNA (siRNA) was applied to knock down IL-19 for further validation. Thereafter, osteoclast production was stimulated with IL-19 in combination with mouse macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). The effect of IL-19 was subsequently evaluated using tartrate-resistant acid phosphatase (TRAP) staining and quantitative real-time polymerase chain reaction (RT-qPCR). The effect of IL-19 on osteoprotegerin (OPG) was then assessed using in vitro recombinant IL-19 treatment of primary osteoblasts and MLO-Y4 osteoblast cell line. Finally, transient transfection experiments and chromatin immunoprecipitation (ChIP) experiments were used to examine the exact mechanism of action. Results. In the LPS-induced bone loss mouse model, the levels of IL-19 in peripheral blood serum and femoral bone marrow suspension were significantly increased. The in vivo results indicated that global IL-19 deletion had no significant effect on RANKL content in the serum and bone marrow, but could increase the content of OPG in serum and femoral bone marrow, suggesting that IL-19 inhibits OPG expression in bone marrow mesenchymal stem cells (BMSCs) and thus increases bone resorption. Conclusion. IL-19 promotes bone resorption by suppressing OPG expression in BMSCs in a LPS-induced bone loss mouse model, which highlights the potential benefits and side effects of IL-19 for future clinical applications. Cite this article: Bone Joint Res 2023;12(11):691–701

Bone defects are frequently observed in anterior shoulder instability. Over the last decade, knowledge of the association of bone loss with increased failure rates of soft-tissue repair has shifted the surgical management of chronic shoulder instability. On the glenoid side, there is no controversy about the critical glenoid bone loss being 20%. However, poor outcomes have been described even with a subcritical glenoid bone defect as low as 13.5%. On the humeral side, the Hill-Sachs lesion should be evaluated concomitantly with the glenoid defect as the two sides of the same bipolar lesion which interact in the instability process, as described by the glenoid track concept. We advocate adding remplissage to every Bankart repair in patients with a Hill-Sachs lesion, regardless of the glenoid bone loss. When critical or subcritical glenoid bone loss occurs in active patients (> 15%) or bipolar off-track lesions, we should consider anterior glenoid bone reconstructions. The techniques have evolved significantly over the last two decades, moving from open procedures to arthroscopic, and from screw fixation to metal-free fixation. The new arthroscopic techniques of glenoid bone reconstruction procedures allow precise positioning of the graft, identification, and treatment of concomitant injuries with low morbidity and faster recovery. Given the problems associated with bone resorption and metal hardware protrusion, the new metal-free techniques for Latarjet or free bone block procedures seem a good solution to avoid these complications, although no long-term data are yet available. Cite this article: Bone Joint J 2024;106-B(10):1100–1110

Aims. To investigate the effects of senescent osteocytes on bone homeostasis in the progress of age-related osteoporosis and explore the underlying mechanism. Methods. In a series of in vitro experiments, we used tert-Butyl hydroperoxide (TBHP) to induce senescence of MLO-Y4 cells successfully, and collected conditioned medium (CM) and senescent MLO-Y4 cell-derived exosomes, which were then applied to MC3T3-E1 cells, separately, to evaluate their effects on osteogenic differentiation. Furthermore, we identified differentially expressed microRNAs (miRNAs) between exosomes from senescent and normal MLO-Y4 cells by high-throughput RNA sequencing. Based on the key miRNAs that were discovered, the underlying mechanism by which senescent osteocytes regulate osteogenic differentiation was explored. Lastly, in the in vivo experiments, the effects of senescent MLO-Y4 cell-derived exosomes on age-related bone loss were evaluated in male SAMP6 mice, which excluded the effects of oestrogen, and the underlying mechanism was confirmed. Results. The CM and exosomes collected from senescent MLO-Y4 cells inhibited osteogenic differentiation of MC3T3-E1 cells. RNA sequencing detected significantly lower expression of miR-494-3p in senescent MLO-Y4 cell-derived exosomes compared with normal exosomes. The upregulation of exosomal miR-494-3p by miRNA mimics attenuated the effects of senescent MLO-Y4 cell-derived exosomes on osteogenic differentiation. Luciferase reporter assay demonstrated that miR-494-3p targeted phosphatase and tensin homolog (PTEN), which is a negative regulator of the phosphoinositide 3-kinase (PI3K)/AKT pathway. Overexpression of PTEN or inhibition of the PI3K/AKT pathway blocked the functions of exosomal miR-494-3p. In SAMP6 mice, senescent MLO-Y4 cell-derived exosomes accelerated bone loss, which was rescued by upregulation of exosomal miR-494-3p. Conclusion. Reduced expression of miR-494-3p in senescent osteocyte-derived exosomes inhibits osteogenic differentiation and accelerates age-related bone loss via PTEN/PI3K/AKT pathway. Cite this article: Bone Joint Res 2024;13(2):52–65

Aims. Periprosthetic joint infection (PJI) occurs in approximately 1% to 2% of total knee arthroplasties (TKA) presenting multiple challenges, such as difficulty in diagnosis, technical complexity, and financial costs. Two-stage exchange is the gold standard for treating PJI but emerging evidence suggests 'two-in-one' single-stage revision as an alternative, delivering comparable outcomes, reduced morbidity, and cost-effectiveness. This study investigates five-year results of modified single-stage revision for treatment of PJI following TKA with bone loss. Methods. Patients were identified from prospective data on all TKA patients with PJI following the primary procedure. Inclusion criteria were: revision for PJI with bone loss requiring reconstruction, and a minimum five years’ follow-up. Patients were followed up for recurrent infection and assessment of function. Tools used to assess function were Oxford Knee Score (OKS) and American Knee Society Score (AKSS). Results. A total of 24 patients were included with a mean age of 72.7 years (SD 7.6), mean BMI of 33.3 kg/m. 2. (SD 5.7), and median ASA grade of 2 (interquartile range 2 to 4). Mean time from primary to revision was 3.0 years (10 months to 8.3 years). At revision, six patients had discharging sinus and three patients had negative cultures from tissue samples or aspirates. Two patients developed recurrence of infection: one was treated successfully with antibiotic suppression and one underwent debridement, antibiotics, and implant retention. Mean AKSS scores at two years showed significant improvement from baseline (27.1 (SD 10.2 ) vs 80.3 (SD 14.8); p < 0.001). There was no significant change in mean AKSS scores between two and five years (80.3 (SD 14.8 ) vs 74.1 (SD 19.8); p = 0.109). Five-year OKS scores were not significantly different compared to two-year scores (36.17 (SD 3.7) vs 33.0 (SD 8.5); p = 0.081). Conclusion. ‘Two-in-one’ single-stage revision is effective for treating PJI following TKA with bone loss, providing patients with sustained improvements in outcomes and infection clearance up to five years post-procedure. Cite this article: Bone Jt Open 2022;3(2):107–113

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. Methods. Disease course, histopathological features of arthritis, and micro-CT (µCT) bone analysis of local and systemic bone loss were assessed in 15-week-old IL1-/-IL6-/-hTNFtg in comparison to IL1-/-hTNFtg, IL6-/-hTNFtg, and hTNFtg mice. µCT bone analysis of single deficient and wild-type mice was also performed. Results. Combined deficiency of IL-1/IL-6 markedly ameliorated TNF-mediated arthritis and bilateral sacroiliitis, but without additive benefits compared to single IL-1 deficiency. This finding confirms the important role of IL-1 and the marginal role of IL-6 in TNF-driven pathways of local joint damage, but questions the efficacy of potential combinatorial therapies of IL-1 and IL-6 in treatment of RA. In contrast, combined deficiency of IL-1/IL-6 led to an additive protective effect on TNF-driven systemic bone loss compared to single IL-1 and IL-6 deficiency. This finding clearly indicates a common contribution of both IL-1 and IL-6 in TNF-driven systemic bone loss, and points to a discrepancy of cytokine dependency in local and systemic TNF-driven mechanisms of inflammatory arthritis. Conclusion. Combinatorial treatments in RA might provide different benefits to inflammatory local arthritis and systemic comorbidities. Cite this article: Bone Joint Res 2022;11(7):484–493

Contemporary acetabular reconstruction in major acetabular bone loss often involves the use of porous metal augments, a cup-cage construct or custom implant. The aims of this study were: To determine the reproducibility of a reconstruction algorithm in major acetabular bone loss. To determine the subsequent success of reconstruction performed in terms of re-operation, all-cause revision and Oxford Hip Score (OHS) and to further define the indications for custom implants in major acetabular bone loss. Consecutive series of Paprosky Type III defects treated according to a reconstruction algorithm. IIIA defects were planned to use a superior augment and hemispherical cup. IIIB defects were planned to receive either augment and cup, cup-cage or custom implant. 105 procedures in cohort 100 patients (5 bilateral) with mean age 73 years (42–94). IIIA defects (50 cases) − 72.0% (95%CI 57.6–82.1) required a porous metal augment the remainder treated with a hemispherical cup alone. IIIB defects (55 cases) 71.7% (95%CI 57.6–82.1) required either augments or cup-cage. 20 patients required a hemispherical cup alone and 6 patients received a custom-made implant. Mean follow up of 7.6 years. 6 re-revisions were required (4 PJI, 2 peri-prosthetic fractures & 1 recurrent instability) with overall survivorship of 94.3% (95% CI 97.4–88.1) for all cause revision. Single event dislocations occurred in 3 other patients so overall dislocation rate 3.8%. Mean pre-op OHS 13.8 and mean follow-up OHS 29.8. Custom implants were used in: Mega-defects where AP diameter >80mm, complex discontinuity and massive bone loss in a small pelvis (i.e., unable to perform cup-cage). A reconstruction algorithm can >70% successfully predict revision construct which thereafter is durable with a low risk of re-operation. Jumbo cup utilized <1/3 of cases when morphology allowed. The use of custom implants has been well defined in this series and accounts for <5% of cases

Aims. Glenoid bone loss is a significant problem in the management of shoulder instability. The threshold at which the bone loss is considered “critical” requiring bony reconstruction has steadily dropped and is now approximately 15%. This necessitates accurate measurement in order that the correct operation is performed. CT scanning is the most commonly used modality and there are a number of techniques described to measure the bone loss however few have been validated. The aim of this study was to assess the accuracy of the most commonly used techniques for measuring glenoid bone loss on CT. Methods. Anatomically accurate models with known glenoid diameter and degree of bone loss were used to determine the mathematical and statistical accuracy of six of the most commonly described techniques (relative diameter, linear ipsilateral circle of best fit (COBF), linear contralateral COBF, Pico, Sugaya, and circle line methods). The models were prepared at 13.8%, 17.6%, and 22.9% bone loss. Sequential CT scans were taken and randomized. Blinded reviewers made repeated measurements using the different techniques with a threshold for theoretical bone grafting set at 15%. Results. At 13.8%, only the Pico technique measured under the threshold. At 17.6% and 22.9% bone loss all techniques measured above the threshold. The Pico technique was 97.1% accurate, but had a high false-negative rate and poor sensitivity underestimating the need for grafting. The Sugaya technique had 100% specificity but 25% of the measurements were incorrectly above the threshold. A contralateral COBF underestimates the area by 16% and the diameter by 5 to 7%. Conclusion. No one method stands out as being truly accurate and clinicians need to be aware of the limitations of their chosen technique. They are not interchangeable, and caution must be used when reading the literature as comparisons are not reliable. Cite this article: Bone Jt Open 2023;4(7):478–489

Concepts in glenoid tracking and treatment strategies of glenoid bone loss are well established. Initial observations in our practice in Singapore showed few patients with major bone loss requiring glenoid reconstructions. This led us to investigate the incidence of and the extent of bone loss in our patients with shoulder instability. Our study revealed bony Bankart lesions were seen in 46% of our patients but glenoid bone loss measured only 6–10% of the glenoid surface. In the same study we found that arthroscopic labral repair with capsular plication and Mason-Ellen suturing (Hybrid technique) was sufficient to stabilise patients with bipolar bone defects and minor glenoid bone loss. This led us to develop the concept of minor bone loss and a new algorithm. Our algorithm and strategies to deal with major bone loss will also be discussed, and techniques & outcomes of Arthroscopic Bony Bankart repair, Arthroscopic Glenoid Reconstruction and Arthroscopic Remplissage procedures will be shown

Extensive and severe bone loss of the femur may be a result of a failed total hip arthroplasty (THA) or total knee arthroplasty (TKA) with multiple revision surgeries which may be caused by factors such as infection, periprosthetic fracture or osteolysis. The aim of this study was to assess outcomes of using the “Push-Through Total Femoral Prosthesis” (PTTF) for revision of a total hip replacement with extreme bone loss. Fourteen patients who had extensive bone defects of the femur due to failed THR's and were treated with PTTF between 2012 and 2020 were included in this study. Primary functional outcomes were assessed using Harris Hip Score (HHS), Toronto Extremity Salvage Score (TESS) and Musculoskeletal Tumor Society (MSTS) scores. Range of motion, complications, and ambulatory status were also recorded to assess secondary outcomes. Two of 14 patients underwent surgery with PTTF for both knee and hip arthroplasty revision. The mean time between index surgery and PTTF was 15 years (3 to 32 yrs.). Acetabular components were revised in six of 14 patients. After a mean follow-up of 5.9 years, hip dislocations occurred in 3 patients. All dislocated hips were in patients with retained non-constrained acetabular bearings. Patient satisfaction was high (MSTS: 67%, HHS: 61.2%, TESS 64.6%) despite a high re-operation rate and minor postoperative problems. PTTF is a unique alternative that may be considered for a failed THA revision procedure in patients with an extreme femoral bone defect. Patients are able to ambulate pain free relatively well. Routine usage of constrained liners should be considered to avoid hip dislocation which was our main problem following the procedure

Aims. This study aimed to examine the effects of tumour necrosis factor-alpha (TNF-α) on osteoblasts in metal wear-induced bone loss. Methods. TNF-α immunoexpression was examined in periprosthetic tissues of patients with failed metal-on-metal hip arthroplasties and also in myeloid MM6 cells after treatment with cobalt ions. Viability and function of human osteoblast-like SaOs-2 cells treated with recombinant TNF-α were studied by immunofluorescence, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay, western blotting, and enzyme-linked immunosorbent assay (ELISA). Results. Macrophages, lymphocytes, and endothelial cells displayed strong TNF-α immunoexpression in periprosthetic tissues containing metal wear debris. Colocalization of TNF-α with the macrophage marker CD68 and the pan-T cell marker CD3 confirmed TNF-α expression in these cells. Cobalt-treated MM6 cells secreted more TNF-α than control cells, reflecting the role of metal wear products in activating the TNF-α pathway in the myeloid cells. While TNF-α did not alter the immunoexpression of the TNF-receptor 1 (TNF-R1) in SaOs-2 cells, it increased the release of the soluble TNF-receptor 1 (sTNF-R1). There was also evidence for TNF-α-induced apoptosis. TNF-α further elicited the expression of the endoplasmic reticulum stress markers inositol-requiring enzyme (IRE)-1α, binding-immunoglobulin protein (BiP), and endoplasmic oxidoreductin1 (Ero1)-Lα. In addition, TNF-α decreased pro-collagen I α 1 secretion without diminishing its synthesis. TNF-α also induced an inflammatory response in SaOs-2 cells, as evidenced by the release of reactive oxygen and nitrogen species and the proinflammatory cytokine vascular endothelial growth factor. Conclusion. The results suggest a novel osteoblastic mechanism, which could be mediated by TNF-α and may be involved in metal wear debris-induced periprosthetic bone loss. Cite this article: Bone Joint Res 2020;9(11):827–839

Rates of prosthetic joint infection in megaprostheses are high. The application of silver ion coating to implants serves as a deterrent to infection and biofilm formation. A retrospective review was performed of all silver-coated MUTARS endoprosthetic reconstructions (SC-EPR) by a single Orthopaedic Oncology Surgeon. We examined the rate of component revision due to infection and the rate of infection successfully treated with antibiotic therapy. We reviewed overall revision rates, sub-categorised into the Henderson groupings for endoprosthesis modes of failure (Type 1 soft tissue failure, Type 2 aseptic loosening, Type 3 Structural failure, Type 4 Infection, Type 5 tumour progression). 283 silver-coated MUTARS endoprosthetic reconstructions were performed for 229 patients from October 2012 to July 2022. The average age at time of surgery was 58.9 years and 53% of our cohort were males. 154 (71.3%) patients underwent SC-EPR for oncological reconstruction and 32 (14.8%) for reconstruction for bone loss following prosthetic joint infection(s). Proximal femur SC-EPR (82) and distal femur (90) were the most common procedures. This cohort had an overall revision rate of 21.2% (60/283 cases). Component revisions were most commonly due to Type 4 infection (19 cases), Type 2 aseptic loosening/culture negative disease (15 cases), and Type 1 dislocation/soft tissue (12 cases). Component revision rate for infection was 6.7% (19 cases). 15 underwent exchange of implants and 4 underwent transfemoral amputation due to recalcitrant infection and failure of soft tissue coverage. This equates to a limb salvage rate of 98.3%. The most common causative organisms remain staphylococcus species (47%) and polymicrobial infections (40%). We expand on the existing literature advocating for the use of silver-coated endoprosthetic reconstructions. We provide insights from the vast experience of a single surgeon when addressing patients with oncological and bone loss-related complex reconstruction problems

Management of severe bone loss in total knee arthroplasty presents a formidable challenge. This situation may arise in neglected primary knee arthroplasty with large deformities and attritional bone loss, in revision situations where osteolysis and loosening have caused large areas of bone loss and in tumor situations. Another area of large bone loss is frequently seen in periprosthetic fractures. Trabecular metal (TM) with its dodecahedron configuration and modulus of elasticity between cortical and cancellous bone offers an excellent bail out option in the management of these very difficult situations. Severe bone loss in the distal femur and proximal tibia lend themselves to receiving the TM cones. The host bone surfaces need to be prepared to receive these cones using a high speed burr. The cones acts as a filler with an interference fit through which the stemmed implant can be introduced and cemented. All areas of bone void is filled with morselised cancellous bone fragments. We present our experience of 64 TM cones (28 femoral, 36 tibial cones) over a 10-year period and our results and outcomes for the same. We have had to revise only one patient for recurrence of the tumor for which the cone was implanted in the first place. We also describe our technique of using two stacked cones for massive distal femoral bone loss and its outcomes. We found excellent osteointegration and new host bone formation around the TM construct. The purported role of possible resistance to infection in situations using the TM cones is also discussed. In summary we believe that the use of the TM cones offers an excellent alternative to massive allografts, custom and/or tumor implants in the management of massive bone loss situations

In the setting of traumatic elbow injuries involving coronoid fractures, the relative size of the coronoid fragment has been shown to relate to the stability of the joint. Currently, the challenge lies in accurately classifying the amount of bone loss in coronoid fractures. In comminuted fractures, bone loss is difficult to measure with plain radiographs or computed tomography. The purpose of this study is to describe a novel radiographic measure, the Coronoid Opening Angle (COA), on lateral elbow radiographs. We demonstrate the relationship of the COA to coronoid height and describe how this measure can be used to estimate bone loss and potentially predict elbow instability following coronoid fracture. Radiographs were drawn from a regional database in a consecutive fashion. Candidate radiographs were excluded on the basis of radiographic evidence of degenerative changes, previous surgery or injury, bony deformity, and inadequate lateral view of the elbow. The COA was measured as the angle between the long axis of the ulna at the level of the trochlear notch, and the tip of coronoid, from a common origin at the posterior cortex of the olecranon. Images were reviewed by a fellowship trained upper extremity surgeon, an upper extremity fellow, and a junior resident. Normal COA, coronoid height, and calculated COA at varying amounts of bone loss were calculated by three reviewers. A sensitivity analysis was performed to determine how the COA can most effectively predict bone loss at varying coronoid heights. Intraclass correlation coefficient (ICC) was calculated for 39 subjects. Seventy-two subjects were included for analysis (M=40, F=32). The normal coronoid opening angle is 33.19 degrees [32.2 – 34.2]. Coronoid height is 18.8 mm [18.1 – 19.6]. Extrapolating this baseline data, the COA at 20%, 33%, and 50% of coronoid bone loss was calculated to be 27.5, 23.5, and 18 degrees, respectively. ICC was found to be 0.90 or higher. Cutoff values were determined to maximize the sensitivity of the COA. A cutoff value of 21 degrees has a 92% sensitivity in detecting a minimum of 50% bone loss. The COA with similar sensitivity in predicting 20% and 33% bone loss are 32 and 27 degrees. The coronoid opening angle is a novel technique that can be used on a lateral elbow radiograph to predict the minimum coronoid bone loss. This can be used to guide clinical decision making and potentially predict instability. Future research will aim to validate this tool in the clinical setting in predicting instability

Abstract. Approximately 20% of primary and revision Total Knee Arthroplasty (TKA) patients require multiple revisions, which are associated with poor survivorship, with worsening outcomes for subsequent revisions. For revision surgery, either endoprosthetic replacements or metaphyseal sleeves can be used for the repair, however, in cases of severe defects that are deemed “too severe” for reconstruction, endoprosthetic replacement of the affected area is recommended. However, endoprosthetic replacements have been associated with high complication rates (high incidence rates of prosthetic joint infection), while metaphyseal sleeves have a more acceptable complication profile and are therefore preferred. Despite this, no guidance exists as to the maximal limit of bone loss, which is acceptable for the use of metaphyseal sleeves to ensure sufficient axial and rotational stability. Therefore, this study assessed the effect of increasing bone loss on the primary stability of the metaphyseal sleeve in the proximal tibia to determine the maximal bone loss that retains axial and rotational stability comparable to a no defect control. Methods. to determine the pattern of bone loss and the average defect size that corresponds to the clinically defined defect sizes of small, medium and large defects, a series of pre-operative x-rays of patients with who underwent revision TKA were retrospectively analysed. Ten tibiae sawbones were used for the experiment. To prepare the bones, the joint surface was resected the typical resection depth required during a primary TKA (10mm). Each tibia was secured distally in a metal pot with perpendicular screws to ensure rotational and axial fixation to the testing machine. Based on X-ray findings, a fine guide wire was placed 5mm below the cut joint surface in the most medial region of the plateau. Core drills (15mm, 25mm and 35mm) corresponding to small, medium and large defects were passed over the guide wire allowing to act at the centre point, before the bone defect was created. The test was carried out on a control specimen with no defect, and subsequently on a Sawbone with a small, medium or large defect. Sleeves were inserted using the published operative technique, by trained individual using standard instruments supplied by the manufacturers. Standard axial pull-out (0 – 10mm) force and torque (0 – 30°) tests were carried out, recording the force (N) vs. displacement (mm) curves. Results. A circular defect pattern was identified across all defects, with the centre of the defect located 5mm below the medial tibial base plate, and as medial as possible. Unlike with large defects, small and medium sized defects reduced the pull-out force and torque at the bone-implant interface, however, these reductions were not statistically significant when compared to no bony defect. Conclusions. This experimental study demonstrated that up to 35mm radial defects may be an acceptable “critical limit” for bone loss below which metaphyseal sleeve use may still be appropriate. Further clinical assessment may help to confirm the findings of this experimental study. This study is the first in the literature to aim to quantify “critical bone loss” limit in the tibia for revision knee arthroplasty. Declaration of Interest. (a) fully declare any financial or other potential conflict of interest

The amount of bone loss due to implant failure, loosening, or osteolysis can vary greatly and can have a major impact on reconstructive options during revision total knee arthroplasty (TKA). Massive bone loss can threaten ligamentous attachments in the vicinity of the knee and may require use of components with additional constraint to compensate for associated ligamentous instability. Classification of bone defects can be helpful in predicting the complexity of the reconstruction required and in facilitating preoperative planning and implant selection. One very helpful classification of bone loss associated with TKA is the Anderson Orthopaedic Research Institute (AORI) Bone Defect Classification System as it provides the means to compare the location and extent of femoral and tibial bone loss encountered during revision surgery. In general, the higher grade defects (Type IIb or III) on both the femoral and tibial sides are more likely to require stemmed components, and may require the use of either structural graft or large augments to restore support for currently available modular revision components. Custom prostheses were previously utilised for massive defects of this sort, but more recently have been supplanted by revision TKA component systems with or without special metal augments or structural allograft. Options for bone defect management are: 1) Fill with cement; 2) Fill with cement supplemented by screws or K-wires; 3) Morselised bone grafting (for smaller, especially contained cavitary defects); 4) Small segment structural bone graft; 5) Impaction grafting; 6) Porous metal cones or sleeves 7) Massive structural allograft-prosthetic composites; 8) Custom implants. Of these, use of uncemented highly porous metal metaphyseal cones in combination with an initial cemented or partially cemented implant has been shown to provide versatile and highly durable results for a range of bone defects including those previously requiring structural bone graft. The hybrid fixation combination of both cement and cementless fixation of an individual tibial or femoral component has emerged as a frequent and often preferred technique. Initial secure and motionless interfaces are provided by the cemented portions of the construct, while subsequent bone ingrowth to the cementless porous metal portions is the key to long term stable fixation. As bone grows into the porous portions there is off loading and protection of the cemented interfaces from mechanical stresses. While maximizing support on intact host bone has been a longstanding fundamental principle of revision arthroplasty, this is facilitated by the use of metaphyseal cones or sleeves in combination with initial fixation into the adjacent diaphysis. Preoperative planning is facilitated by good quality radiographs, supplemented on occasion by additional imaging such as CT. Fluoroscopically controlled x-ray views may assist in diagnosing the loose implant by better revealing the interface between the implant and bone and can facilitate accurate delineation of the extent of bone deficiency present. Part of the preoperative plan is to ensure adequate range and variety of implant choices and bone graft resources for the planned reconstruction allowing for the potential for unexpected intraoperative findings such as occult fracture through deficient periprosthetic bone. While massive bone loss may compromise ligamentous attachment to bone, in the majority of reconstructions, the degree of revision implant constraint needed for proper balancing and restoration of stability is independent of the bone defect. Thus, some knees with minimal bone deficiency may require increased constraint due to the status of the soft tissues while others involving very large bone defects, especially of the cavitary sort, may be well managed with minimal constraint

Aims. Gap junction intercellular communication (GJIC) in osteocytes is impaired by oxidative stress, which is associated with age-related bone loss. Ageing is accompanied by the accumulation of advanced oxidation protein products (AOPPs). However, it is still unknown whether AOPP accumulation is involved in the impairment of osteocytes’ GJIC. This study aims to investigate the effect of AOPP accumulation on osteocytes’ GJIC in aged male mice and its mechanism. Methods. Changes in AOPP levels, expression of connexin43 (Cx43), osteocyte network, and bone mass were detected in 18-month-old and three-month-old male mice. Cx43 expression, GJIC function, mitochondria membrane potential, reactive oxygen species (ROS) levels, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation were detected in murine osteocyte-like cells (MLOY4 cells) treated with AOPPs. The Cx43 expression, osteocyte network, bone mass, and mechanical properties were detected in three-month-old mice treated with AOPPs for 12 weeks. Results. The AOPP levels were increased in aged mice and correlated with degeneration of osteocyte network, loss of bone mass, and decreased Cx43 expression. AOPP intervention induced NADPH oxidase activation and mitochondrial dysfunction, triggered ROS generation, reduced Cx43 expression, and ultimately impaired osteocytes’ GJIC, which were ameliorated by NADPH oxidase inhibitor apocynin, mitochondria-targeted superoxide dismutase mimetic (mito-TEMPO), and ROS scavenger N-acetyl cysteine. Chronic AOPP loading accelerated the degradation of osteocyte networks and decreased Cx43 expression, resulting in deterioration of bone mass and mechanical properties in vivo. Conclusion. Our study suggests that AOPP accumulation contributes to age-related impairment of GJIC in osteocytes of male mice, which may be part of the pathogenic mechanism responsible for bone loss during ageing. Cite this article: Bone Joint Res 2022;11(7):413–425

Aims. The association of auraptene (AUR), a 7-geranyloxycoumarin, on osteoporosis and its potential pathway was predicted by network pharmacology and confirmed in experimental osteoporotic mice. Methods. The network of AUR was constructed and a potential pathway predicted by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) terms enrichment. Female ovariectomized (OVX) Institute of Cancer Research mice were intraperitoneally injected with 0.01, 0.1, and 1 mM AUR for four weeks. The bone mineral density (BMD) level was measured by dual-energy X-ray absorptiometry. The bone microstructure was determined by histomorphological changes in the femora. In addition, biochemical analysis of the serum and assessment of the messenger RNA (mRNA) levels of osteoclastic markers were performed. Results. In total, 65.93% of the genes of the AUR network matched with osteoporosis-related genes. Osteoclast differentiation was predicted to be a potential pathway of AUR in osteoporosis. Based on the network pharmacology, the BMD and bone mineral content levels were significantly (p < 0.05) increased in the whole body, femur, tibia, and lumbar spine by AUR. AUR normalized the bone microstructure and the serum alkaline phosphatase (ALP), bone-specific alkaline phosphatase (bALP), osteocalcin, and calcium in comparison with the OVX group. In addition, AUR treatment reduced TRAP-positive osteoclasts and receptor activator of nuclear factor kappa-B ligand (RANKL). +. nuclear factor of activated T cells 1 (NFATc1). +. expression in the femoral body. Moreover, the expressions of initiators for osteoclastic resorption and bone matrix degradation were significantly (p < 0.05) regulated by AUR in the lumbar spine of the osteoporotic mice. Conclusion. AUR ameliorated bone loss by downregulating the RANKL/NFATc1 pathway, resulting in improvement of osteoporosis. In conclusion, AUR might be an ameliorative cure that alleviates bone loss in osteoporosis via inhibition of osteoclastic activity. Cite this article: Bone Joint Res 2022;11(5):304–316

Aims. Recurrent dislocation is both a cause and consequence of glenoid bone loss, and the extent of the bony defect is an indicator guiding operative intervention. Literature suggests that loss greater than 25% requires glenoid reconstruction. Measuring bone loss is controversial; studies use different methods to determine this, with no clear evidence of reproducibility. A systematic review was performed to identify existing CT-based methods of quantifying glenoid bone loss and establish their reliability and reproducibility. Methods. A Preferred Reporting Items for Systematic reviews and Meta-Analyses-compliant systematic review of conventional and grey literature was performed. Results. A total of 25 studies were initially eligible. Following screening, nine papers were included for review. Main themes identified compared 2D and 3D imaging, as well as linear- compared with area-based techniques. Heterogenous data were acquired, and therefore no meta-analysis was performed. Conclusion. No ideal CT-based method is demonstrated in the current literature, however evidence suggests that surface area methods are more reproducible and lead to fewer over-estimations of bone loss, provided the views used are standardized. A prospective imaging trial is required to provide a more definitive answer to this research question. Cite this article: Bone Jt Open 2022;3(2):114–122

The management of bone loss in revision total knee replacement (TKA) remains a challenge. To accomplish the goals of revision TKA, the surgeon needs to choose the appropriate implant design to “fix the problem,” achieve proper component placement and alignment, and obtain robust short- and long-term fixation. Proper identification and classification of the extent of bone loss and deformity will aid in preoperative planning. Extensive bone loss may be due to progressive osteolysis (a mechanism of failure), or as a result of intraoperative component removal. The Anderson Orthopaedic Research Institute (AORI) is a useful classification system that individually describes femoral and tibial defects by the appearance, severity, and location of bone defects. This system provides a guideline to treatment and enables preoperative planning on radiographs. In Type 1 defects, femoral and tibial defects are characterised by minor contained deficiencies at the bone-implant interface. Metaphyseal bone is intact and the integrity of the joint line is not compromised. In this scenario, the best reconstruction option is to increase the thickness of bone resection and to fill the defect with cancellous bone graft or cement. Type 2 defects are characterised by deficient metaphyseal bone involving one or more femoral condyle(s) or tibial plateau(s). The peripheral rim of cortical bone may be intact or partially compromised, and the joint line is abnormal. Reconstruction options for a Type 2A defect include impaction bone grafting, cement, or more commonly, prosthetic augmentation (e.g. sleeves, augments or wedges). In Type 2B defects, metaphyseal bone of both femoral condyles or both tibial plateaus is deficient. The peripheral rim of cortical bone may be intact or partially compromised, and the joint line is abnormal. Options for a Type 2B defect include impaction grafting, bulk structural allograft, prosthetic augmentation, metaphyseal sleeves (in some cases), or metaphyseal cones. Finally, in the presence of a Type 3 deficiency, both metaphyseal and cortical bone is deficient and there is partial or complete disruption of the collateral ligament attachments. In this case, the most commonly used reconstruction options include hinged implants or megaprostheses with or without bulk structural allograft, prosthetic augmentation, and/or metaphyseal/diaphyseal sleeves or cones. Today, we are fortunate to have a wide variety of options available to aid in reconstruction of a revision TKA with massive bone loss. Historically, use of cement, bone grafting, or use of a tumor-type or hinged implant were considered the main options for reconstruction. The development and adoption of highly porous sleeves and cones has given the surgeon a new and potentially more durable option for reconstruction of previously difficult to treat defects. Using radiographs and computed tomography, surgeons are able to preoperatively classify bone loss and anticipate a reconstruction plan based upon the classification; however, it is always important to have several back-up options on hand during revision surgery in the event bone loss is worse than expected