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

Aims. Osteoporosis can determine surgical strategy for total hip arthroplasty (THA), and perioperative fracture risk. The aims of this study were to use hip CT to measure femoral bone mineral density (BMD) using CT X-ray absorptiometry (CTXA), determine if systematic evaluation of preoperative femoral BMD with CTXA would improve identification of osteopenia and osteoporosis compared with available preoperative dual-energy X-ray absorptiometry (DXA) analysis, and determine if improved recognition of low BMD would affect the use of cemented stem fixation. Methods. Retrospective chart review of a single-surgeon database identified 78 patients with CTXA performed prior to robotic-assisted THA (raTHA) (Group 1). Group 1 was age- and sex-matched to 78 raTHAs that had a preoperative hip CT but did not have CTXA analysis (Group 2). Clinical demographics, femoral fixation method, CTXA, and DXA data were recorded. Demographic data were similar for both groups. Results. Preoperative femoral BMD was available for 100% of Group 1 patients (CTXA) and 43.6% of Group 2 patients (DXA). CTXA analysis for all Group 1 patients preoperatively identified 13 osteopenic and eight osteoporotic patients for whom there were no available preoperative DXA data. Cemented stem fixation was used with higher frequency in Group 1 versus Group 2 (28.2% vs 14.3%, respectively; p = 0.030), and in all cases where osteoporosis was diagnosed, irrespective of technique (DXA or CTXA). Conclusion. Preoperative hip CT scans which are routinely obtained prior to raTHA can determine bone health, and thus guide femoral fixation strategy. Systematic preoperative evaluation with CTXA resulted in increased recognition of osteopenia and osteoporosis, and contributed to increased use of cemented femoral fixation compared with routine clinical care; in this small study, however, it did not impact short-term periprosthetic fracture risk. Cite this article: Bone Joint J 2023;105-B(3):254–260

Aims. The aims of this study were to determine the success of a reconstruction algorithm used in major acetabular bone loss, and to further define the indications for custom-made implants in major acetabular bone loss. Methods. We reviewed a consecutive series of Paprosky type III acetabular defects treated according to a reconstruction algorithm. IIIA defects were planned to use a superior augment and hemispherical acetabular component. IIIB defects were planned to receive either a hemispherical acetabular component plus augments, a cup-cage reconstruction, or a custom-made implant. We used national digital health records and registry reports to identify any reoperation or re-revision procedure and Oxford Hip Score (OHS) for patient-reported outcomes. Implant survival was determined via Kaplan-Meier analysis. Results. A total of 105 procedures were carried out in 100 patients (five bilateral) with a mean age of 73 years (42 to 94). In the IIIA defects treated, 72.0% (36 of 50) required a porous metal augment; the remaining 14 patients were treated with a hemispherical acetabular component alone. In the IIIB defects, 63.6% (35 of 55) underwent reconstruction as planned with 20 patients who actually required a hemispherical acetabular component alone. At mean follow-up of 7.6 years, survival was 94.3% (95% confidence interval 97.4 to 88.1) for all-cause revision and the overall dislocation rate was 3.8% (4 of 105). There was no difference observed in survival between type IIIA and type IIIB defects and whether a hemispherical implant alone was used for the reconstruction or not. The mean gain in OHS was 16 points. Custom-made implants were only used in six cases, in patients with either a mega-defect in which the anteroposterior diameter > 80 mm, complex pelvic discontinuity, and massive bone loss in a small pelvis. Conclusion. Our findings suggest that a reconstruction algorithm can provide a successful approach to reconstruction in major acetabular bone loss. The use of custom implants has been defined in this series and accounts for < 5% of cases. Cite this article: Bone Joint J 2024;106-B(5 Supple B):47–53

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. Osteoporosis is common in total hip arthroplasty (THA) patients. It plays a substantial factor in the surgery’s outcome, and previous studies have revealed that pharmacological treatment for osteoporosis influences implant survival rate. The purpose of this study was to examine the prevalence of and treatment rates for osteoporosis prior to THA, and to explore differences in osteoporosis-related biomarkers between patients treated and untreated for osteoporosis. Methods. This single-centre retrospective study included 398 hip joints of patients who underwent THA. Using medical records, we examined preoperative bone mineral density measures of the hip and lumbar spine using dual energy X-ray absorptiometry (DXA) scans and the medications used to treat osteoporosis at the time of admission. We also assessed the following osteoporosis-related biomarkers: tartrate-resistant acid phosphatase 5b (TRACP-5b); total procollagen type 1 amino-terminal propeptide (total P1NP); intact parathyroid hormone; and homocysteine. Results. The prevalence of DXA-proven hip osteoporosis (T-score ≤ -2.5) among THA patients was 8.8% (35 of 398). The spinal osteoporosis prevalence rate was 4.5% (18 of 398), and 244 patients (61.3%; 244 of 398) had osteopenia (-2.5 < T-score ≤ -1) or osteoporosis of either the hip or spine. The rate of pharmacological osteoporosis treatment was 22.1% (88 of 398). TRACP-5b was significantly lower in the osteoporosis-treated group than in the untreated group (p < 0.001). Conclusion. Osteoporosis is common in patients undergoing THA, but the diagnosis and treatment for osteoporosis were insufficient. The lower TRACP-5b levels in the osteoporosis-treated group — that is, osteoclast suppression — may contribute to the reduction of the postoperative revision rate after THA. Cite this article: Bone Joint Res 2022;11(12):873–880

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. 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

The advent of modular porous metal augments has ushered in a new form of treatment for acetabular bone loss. The function of an augment can be seen as reducing the size of a defect or reconstituting the anterosuperior/posteroinferior columns and/or allowing supplementary fixation. Depending on the function of the augment, the surgeon can decide on the sequence of introduction of the hemispherical shell, before or after the augment. Augments should always, however, be used with cement to form a unit with the acetabular component. Given their versatility, augments also allow the use of a hemispherical shell in a position that restores the centre of rotation and biomechanics of the hip. Progressive shedding or the appearance of metal debris is a particular finding with augments and, with other radiological signs of failure, should be recognized on serial radiographs. Mid- to long-term outcomes in studies reporting the use of augments with hemispherical shells in revision total hip arthroplasty have shown rates of survival of > 90%. However, a higher risk of failure has been reported when augments have been used for patients with chronic pelvic discontinuity. Cite this article: Bone Joint J 2024;106-B(4):312–318

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

The results of the treatment of 31 open femoral fractures (29 patients) with significant bone loss in a single trauma unit were reviewed. A protocol of early soft-tissue and bony debridement was followed by skeletal stabilisation using a locked intramedullary nail or a dynamic condylar plate for diaphyseal and metaphyseal fractures respectively. Soft-tissue closure was obtained within 48 hours then followed, if required, by elective bone grafting with or without exchange nailing. The mean time to union was 51 weeks (20 to 156). The time to union and functional outcome were largely dependent upon the location and extent of the bone loss. It was achieved more rapidly in fractures with wedge defects than in those with segmental bone loss. Fractures with metaphyseal defects healed more rapidly than those of comparable size in the diaphysis. Complications were more common in fractures with greater bone loss, and included stiffness of the knee, malunion and limb-length discrepancy. Based on our findings, we have produced an algorithm for the treatment of these injuries. We conclude that satisfactory results can be achieved in most femoral fractures with bone loss using initial debridement and skeletal stabilisation to maintain length, with further procedures as required

Aims. Severe acetabular bone loss and pelvic discontinuity (PD) present particular challenges in revision total hip arthroplasty. To deal with such complex situations, cup-cage reconstruction has emerged as an option for treating this situation. We aimed to examine our success in using this technique for these anatomical problems. Patients and Methods. We undertook a retrospective, single-centre series of 35 hips in 34 patients (seven male, 27 female) treated with a cup-cage construct using a trabecular metal shell in conjunction with a titanium cage, for severe acetabular bone loss between 2011 and 2015. The mean age at the time of surgery was 70 years (42 to 85) and all patients had an acetabular defect graded as Paprosky Type 2C through to 3B, with 24 hips (69%) having PD. The mean follow-up was 47 months (25 to 84). Results. The cumulative five-year survivorship of the implant with revision for any cause was 89% (95% confidence interval (CI) 72 to 96) with eight hips at risk. No revision was required for aseptic loosening; however, one patient with one hip (3%) required removal of the ischial flange of the cage due to sciatic nerve irritation. Two patients (6%; two hips) suffered from hip dislocation, whereas one patient (one hip) required revision surgery with cement fixation of a dual-mobility acetababular component into a well-fixed cup-cage construct. Two patients (6%; two hips) developed periprosthetic infection. One patient was successfully controlled with a two-stage revision surgery, while the other patient underwent excision arthroplasty due to severe medical comorbidities. For the whole series, the Harris Hip Score significantly improved from a mean of 30 (15 to 51) preoperatively to 71 (40 to 89) at the latest follow-up (p < 0.001). Conclusion. Our findings suggest that cup-cage reconstruction is a viable option for major segmental bone defects involving the posterior column and PD. It allows adequate restoration of the acetabulum centre with generally good stability and satisfactory postoperative function. Instability and infection remain drawbacks in these challenging revision cases. Cite this article: Bone Joint J 2018;100-B:1442–48

The treatment of bone loss in revision total knee arthroplasty has evolved over the past decade. While the management of small to moderate sized defects has demonstrated good results with a variety of traditional techniques (cement and screws, small metal augments, impaction bone grafting or modular stems), the treatment of severe defects continues to be problematic. The use of a structural allograft has declined in recent years due to an increased failure rate with long-term follow-up and with the introduction of highly porous metal augments that emphasise biological metaphyseal fixation. Recently published mid-term results on the use of tantalum cones in patients with severe bone loss has reaffirmed the success of this treatment strategy. . Cite this article: Bone Joint J 2016;98-B(1 Suppl A):120–4

Aims. Loss or absence of proximal femoral bone in revision total hip arthroplasty (THA) remains a significant challenge. While the main indication for the use of proximal femoral replacements (PFRs) is in the treatment of malignant disease, they have a valuable role in revision THA for loosening, fracture and infection in patients with bone loss. Our aim was to determine the clinical outcomes, implant survivorship, and complications of PFRs used in revision THA for indications other than malignancy. Patients and Methods. A retrospective review of 44 patients who underwent revision THA using a PFR between 2000 and 2013 was undertaken. Their mean age was 79 years (53 to 97); 31 (70%) were women. The bone loss was classified as Paprosky IIIB or IV in all patients. The mean follow-up was six years (2 to 12), at which time 22 patients had died and five were lost to follow-up. Results. The mean Harris Hip Score improved from 42.8 (25.9 to 82.9) pre-operatively to 68.5 (21.0 to 87.7) post-operatively (p = 0.0009). A total of two PFRs had been revised, one for periprosthetic infection eight years post-operatively and one for aseptic loosening six years post-operatively. The Kaplan-Meier survivorship free of any revision or removal of an implant was 86% at five years and 66% years at ten years. A total of 12 patients (27%) had a complication including six with a dislocation. Conclusion. PFRs provide a useful salvage option for patients, particularly the elderly with massive proximal femoral bone loss who require revision THA, with significant clinical improvement. While the survivorship of the implant is good at five years, dislocation continues to be the most common complication. The judicious use of larger femoral heads, dual-mobility constructs, or constrained liners may help to minimise the risk of dislocation. Cite this article: Bone Joint J 2017;99-B:325–9

The management of bone loss in revision replacement of the knee remains a challenge despite an array of options available to the surgeon. Bone loss may occur as a result of the original disease, the design of the prosthesis, the mechanism of failure or technical error at initial surgery. The aim of revision surgery is to relieve pain and improve function while addressing the mechanism of failure in order to reconstruct a stable platform with transfer of load to the host bone. Methods of reconstruction include the use of cement, modular metal augmentation of prostheses, custom-made, tumour-type or hinged implants and bone grafting. The published results of the surgical techniques are summarised and a guide for the management of bone defects in revision surgery of the knee is presented

Aims

The Exeter short stem was designed for patients with Dorr type A femora and short-term results are promising. The aim of this study was to evaluate the minimum five-year stem migration pattern of Exeter short stems in comparison with Exeter standard stems.

If a surgeon is faced with altered lesser trochanter anatomy when revising the femoral component in revision total hip replacement, a peri-prosthetic fracture, or Paprosky type IIIb or type IV femoral bone loss, a modular tapered stem offers the advantages of accurately controlling femoral version and length. The splines of the taper allow rotational control, and improve the fit in femoral canals with diaphyseal bone loss. In general, two centimetres of diaphyseal contact is all that is needed to gain stability with modular tapered stems. By allowing the proximal body trial to rotate on a well-fixed distal segment during trial reduction, appropriate anteversion can be obtained in order to improve intra-operative stability, and decrease the dislocation risk. However, modular stems should not be used for all femoral revisions, as implant fracture and corrosion at modular junctions can still occur. Cite this article: Bone Joint J 2013;95-B, Supple A:95–7

In this retrospective study we evaluated the method of acute shortening and distraction osteogenesis for the treatment of tibial nonunion with bone loss in 17 patients with a mean age of 36 years (10 to 58). The mean bone loss was 5.6 cm (3 to 10). In infected cases, we performed the treatment in two stages. The mean follow-up time was 43.5 months (24 to 96). The mean time in external fixation was 8.0 months (4 to 13) and the mean external fixator index was 1.4 months/cm (1.1 to 1.8). There was no recurrence of infection. The bone evaluation results were excellent in 16 patients and good in one, while functional results were excellent in 15 and good in two. The complication rate was 1.2 per patient. We conclude that acute shortening and distraction osteogenesis is a safe, reliable and successful method for the treatment of tibial nonunion with bone loss, with a shorter period of treatment and lower rate of complication