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. 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

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

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. 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

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

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

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

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

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

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 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

In osteoporosis treatment, current interventions, including pharmaceutical treatments and exercise protocols, suffer from challenges of guaranteed efficacy for patients and poor patient compliance. Moreover, bone loss continues to be a complicating factor for conditions such as spinal cord injury, prescribed bed-rest, and space flight. A low-cost treatment modality could improve patient compliance. Electrical stimulation has been shown to improve bone mass in animal models of disuse, but there have been no studies of the effects of electrical stimulation on bone in the context of bone loss under hormone deficiency such as in post-menopausal osteoporosis. The purpose of this study was to explore the effects of electrical stimulation on changes in bone mass in the ovariectomized rat model of post-menopausal osteoporosis. All animal protocols were approved by the institutional Animal Research Ethics Board. We developed a custom electrical stimulation device capable of delivering a constant current, 15 Hz sinusoidal signal. We used 30 female Sprague Dawley rats (12–13 weeks old). Half (n=15) were ovariectomized (OVX), and half (n=15) underwent sham OVX surgery (SHAM). Three of each OVX and SHAM animals were sacrificed at baseline. The remaining 24 rats were separated into four equal groups (n=6 per group): OVX electrical stimulation (OVX-stim), OVX no stimulation (OVX-no stim), SHAM electrical stimulation (SHAM-stim), and SHAM no stimulation (SHAM-no stim). While anaesthetized, stimulation groups received transdermal electrical stimulation to the right knee through bilateral skin-mounted electrodes (10 × 10 mm) with electrode gel. The left knee served as a non-stimulated contralateral control. The no-stimulation groups had electrodes placed on the right knee, but not connected. Rats underwent the stim/no-stim procedure for one hour per day for six weeks. Rats were sacrificed (CO2) after six weeks. Femurs and tibias were scanned by microCT focussed on the proximal tibia and distal femur. MicroCT data were analyzed for trabecular bone measures of bone volume fraction (BV/TV), thickness (Tb.Th), and anisotropy, and cortical bone cross-sectional area and second moment of area. Femurs and tibias from OVX rats had significantly less trabecular bone than SHAM (femur BV/TV = −74.1%, tibia BV/TV = −77.6%). In the distal femur of OVX-stim rats, BV/TV was significantly greater in the stimulated right (11.4%, p < 0 .05) than the non-stimulated contralateral (left). BV/TV in the OVX-stim right femur also tended to be greater than that in the OVX-no-stim right femur, but the difference was not significant (17.7%, p=0.22). There were no differences between stim and no-stim groups for tibial trabecular measures, or cortical bone measures in either the femur or the tibia. This study presents novel findings that electrical stimulation can partially mitigate bone loss in the OVX rat femur, a model of human post-menopausal bone loss. Further work is needed to explore why there was a differential response of the tibial and femoral bone, and to better understand how bone cells respond to electrical stimulation. The long-term goal of this work is to determine if electrical stimulation could be used as a complementary modality for preventing post-menopausal bone loss

The aim of this study was to determine if the extent of the glenoid and humeral bone loss affects the rate of recurrent instability and the functional outcome following the Latarjet procedure. 161 patients underwent open Latarjet procedure during the period 2006–2015 (Mean age 30.0 years, 150t (93.2%) Male, 118 (73.3%) primary procedure). Functional outcome was measured using the Western Ontario Shoulder Instability Index (WOSI) and Quick Disabilities of the Arm, Shoulder and Hand (QuickDash) score at a mean of 4.7 years post-operatively. All patients underwent computed tomographic (CT) imaging pre-operatively. Using three-dimensional reconstruction, the glenoid bone loss, Hill-Sachs lesion and ‘Glenoid Track’ status was recorded. Radiographically-confirmed redislocation was rare (1.2%), but 18.5% (n=23/124) reported ongoing subjective shoulder instability. Fifty-two shoulders (32.3%) were classified as “Off-Track”. The median Quick DASH and WOSI scores were 2.27 (IQR 9.09; range 0–70.45) and 272.0 (IQR 546.5; range 0–2003), respectively. There were no significant differences observed between overall Quick DASH scores or WOSI scores for either On-Track or Off-Track groups (p=0.7 and 0.73, respectively). Subjective instability was not influenced by the degree of glenoid bone loss (p=0.82), the overall size of the Hill-Sachs lesion (p=0.80), or the presence of an ‘Off-Track’ lesion (p=0.84). Functional outcome and recurrent instability following the Latarjet procedure do not appear to be influenced by the extent of glenohumeral bone loss prior to surgery

Abstract. Objectives. Osteoporosis of the pelvis and femur is diagnosed in a high proportion of lower-limb amputees which carries an increased fracture risk and subsequently serious implications on mobility, physical dependency and morbidity. Through the development of biofidelic musculoskeletal and finite element (FE) models, we aim to determine the effect of lower-limb amputation on long-term bone remodelling in the hip and to understand the potential underpinning mechanisms for bone degradation in the younger amputee population. Methods. Our models are patient specific and anatomically accurate. Geometries are derived from MRI-scans of one bilateral, above-knee, amputee and one body-matched control subject. Musculoskeletal modelling enables comparison of muscle and joint reaction-forces throughout gait. This provides the loading scenario implemented in FE. FE modelling demonstrates the effect of loading on the amputated limb via a prosthetic socket by comparing bone mechanical stimulation in amputee and control cases. Results. Musculoskeletal modelling shows that the bilateral amputee has 25% higher peak hip-reaction force than controls but a 54% lower peak knee-reaction force. Compensation for missing muscles and joints cause large-scale changes to the muscle loading patterns of the residual limb. FE analysis shows a 32% reduction in bone stimulation within the proximal femur and an 81% reduction in the distal femoral shaft when compared to the healthy control. A shielding effect from weight-bearing through a prosthetic socket was observed that may offset any increases in joint and muscle loading at the amputated hip. Conclusions. Bone loss in the young amputee population could be driven by unloading osteopenia where altered joint and muscle loads cause altered mechanical stimulus in the femur. Over many cycles of remodelling, a net bone loss occurs. Importantly, this suggests that the issue is preventable, or even reversible, with the implementation of targeted loading regimes or changes to the design of the prosthetic socket. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

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 pre-operative 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) Large prosthetic augments (cones); 7) Massive structural allograft-prosthetic composites (APC); 8) Custom implants. Maximizing support on intact host bone is a fundamental principle to successful reconstruction and frequently requires extending fixation to the adjacent diaphysis. Pre-operative 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 pre-operative 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 intra-operative findings such as occult fracture through deficient periprosthetic bone. Reconstruction of bone deficiency following removal of the failed implant is largely dictated by the location and extent of bone loss and the quality of bone that remains. While massive bone loss may compromise ligamentous attachment to bone, in the majority of reconstructions the degree of 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. Highly porous metal augments designed to reestablish metaphyseal support and function in the manner of a prosthetic structural graft have been introduced or are under development by several manufacturers. Published reports of short term experiences have been encouraging for both the tibial side and for femoral augmentation. It remains to be seen whether these implants will provide the desired longer term durability

Glucocorticoid excess is shown to deteriorate bone tissue integrity, increasing the risk of osteoporosis. Marrow adipogenesis at cost of osteogenesis is a prominent feature of this osteoporosis condition. Epigenetic pathway histone deacetylase (HDAC)-mediated histone acetylation regulates osteogenic activity and bone mass. This study is aimed to figure out what role of acetylated histone reader bromodomain-containing protein 4 (BRD4) did play in glucocorticoid-induced osteoporosis. Bone-marrow mesenchymal stem cells were incubated in osteogenic medium with or without 1 μM dexamethasone. Mineralized matrix and adipocyte formation were probed using von Kossa and Nile Red O staining, respectively. Osteogenic and adipogenic marker expression were quantified using RT-PCR. The binding of acetylated histone to promoter of transcription factors were detected using chromatin immunoprecipitation-PCR. Bone mineral density and microstructure in osteoporotic bone were quantified with microCT system. Glucocorticoid repressed osteogenic transcription factor Runx2 expression and mineralized matrix formation along with a low level of acetylated lysine 9 at histone 3 (H3K9ac), whereas BRD4 signaling and adipocytic formation were increased in cell cultures. BRD4 knockdown reversed the H3K9ac enrichment in Runx2 promoter and osteogenesis, but downregulated adipogenic differentiation. Silencing BRD4 attenuated H3K9ac occupancy in forkhead box P1 (Foxp1) relevant to lipid metabolism upon glucocorticoid stress. Foxp1 interference downregulated adipogenic activities of glucocorticoid-treated cells. In vivo, treatment with BRD4 inhibitor JQ-1 compromised the glucocorticoid-induced bone mineral density loss, spare trabecular structure, and fatty marrow, as well as improved biomechanical properties of bone tissue. Taken together, BRD4-mediated Foxp1 pathways drive mesenchymal stem cells shifting toward adipocytic cells rather than osteogenic cells to aggravates excessive marrow adipogenesis in the process of glucocorticoid-induced osteoporosis. Pharmacological inhibition of BRD4 signaling protects bone tissue from bone loss and fatty marrow in glucocorticoid-treated mice. This study conveys a new molecular insight into epigenetic regulation of osteogenesis and adipogenesis in osteoporotic skeleton and highlight the remedial effect of BRD4 inhibitor on glucocorticoid-induced bone loss

The management of femoral bone loss is challenging during revision hip arthroplasty. In patients with Paprosky grade IIIB and IV defects, obtaining fixation and rotational stability using traditional surgical constructs is difficult. The use of a custom-made internal proximal femoral replacement prostheses has been proposed as a solution in patients, with severe femoral bone stock loss. However, there is a paucity in the literature on their use and long-term outcomes. We report on the clinical and radiological results of our cohort. We retrospectively reviewed all patients who underwent internal proximal femoral replacement for revision hip arthroplasty between April 1996 and April 2019. All patients had at least 2 years of follow-up time. 160 patients underwent limb salvage at our institution using internal proximal femoral replacement. The mean follow-up was 79.7 months (S.D 41.3). Indications for revision included periprosthetic fractures, aseptic loosening, and deep infection. The mean Oxford hip score increased from 13.8 (0–22) to 31.5 (18–43) (paired t-test, p < 0.001). Kaplan-Meier prosthesis survival analysis with revision as the endpoint was 87% at 5 years. None required revision of the femoral stem. There were four dislocations (5%) and there was failure to eradicate the deep infection in four. This technique allows instant distal fixation, allowing for early mobilisation. Long-term clinical and radiological outcomes are encouraging and the complication rates are acceptable for this patient group