Aims. This study describes the variation in the annual volumes of revision hip arthroplasty (RHA) undertaken by consultant surgeons nationally, and the rate of accrual of RHA and corresponding primary hip arthroplasty (PHA) volume for new consultants entering practice. Methods. National Joint Registry (NJR) data for England, Wales, Northern Ireland, and the Isle of Man were received for 84,816 RHAs and 818,979 PHAs recorded between April 2011 and December 2019. RHA data comprised all revision procedures, including first-time revisions of PHA and any subsequent re-revisions recorded in public and private healthcare organizations. Annual procedure volumes undertaken by the responsible consultant surgeon in the 12 months prior to every index procedure were determined. We identified a cohort of ‘new’ HA consultants who commenced practice from 2012 and describe their rate of accrual of PHA and RHA experience. Results. The median annual consultant RHA volume, averaged across all cases, was 21 (interquartile range (IQR) 11 to 34; range 0 to 181). Of 1,695 consultants submitting RHA cases within the study period, the top 20% of surgeons by annual volume performed 74.2% of total RHA case volume. More than half of all consultants who had ever undertaken a RHA maintained an annual volume of just one or fewer RHA, however, collectively contributed less than 3% of the total RHA case volume. Consultant PHA and RHA volumes were positively correlated. Lower-volume surgeons were more likely to undertake RHA for urgent indications (such as infection) as a proportion of their practice, and to do so on weekends and public holidays. Conclusion. The majority of RHAs were undertaken by higher-volume surgeons. There was considerable variation in RHA volumes by indication, day of the week, and between consultants nationally. The rate of accrual of RHA experience by new consultants is low, and has important implications for establishing an experienced RHA consultant workforce. Cite this article: Bone Joint J 2023;105-B(10):1060–1069

Aims. This study evaluates the association between consultant and hospital volume and the risk of re-revision and 90-day mortality following first-time revision of primary hip arthroplasty for aseptic loosening. Methods. We conducted a cohort study of first-time, single-stage revision hip arthroplasties (RHAs) performed for aseptic loosening and recorded in the National Joint Registry (NJR) data for England, Wales, Northern Ireland, and the Isle of Man between 2003 and 2019. Patient identifiers were used to link records to national mortality data, and to NJR data to identify subsequent re-revision procedures. Multivariable Cox proportional hazard models with restricted cubic splines were used to define associations between volume and outcome. Results. Among 12,961 RHAs there were 513 re-revisions within two years, and 95 deaths within 90 days of surgery. The risk of re-revision was highest for a consultant’s first RHA (hazard ratio (HR) 1.56 (95% CI 1.15 to 2.12)) and remained significantly elevated for their first 24 cases (HR 1.26 (95% CI 1.00 to 1.58)). Annual consultant volumes of five/year were associated with an almost 30% greater risk of re-revision (HR 1.28 (95% CI 1.00 to 1.64)) and 80% greater risk of 90-day mortality (HR 1.81 (95% CI 1.02 to 3.21)) compared to volumes of 20/year. RHAs performed at hospitals which had cumulatively undertaken fewer than 167 RHAs were at up to 70% greater risk of re-revision (HR 1.70 (95% CI 1.12 to 2.59)), and those having undertaken fewer than 307 RHAs were at up to three times greater risk of 90-day mortality (HR 3.05 (95% CI 1.19 to 7.82)). Conclusion. This study found a significantly higher risk of re-revision and early postoperative mortality following first-time single-stage RHA for aseptic loosening when performed by lower-volume consultants and at lower-volume institutions, supporting the move towards the centralization of such cases towards higher-volume units and surgeons. Cite this article: Bone Joint J 2024;106-B(10):1050–1058

Aims. Successful cell therapy in hip osteonecrosis (ON) may help to avoid ON progression or total hip arthroplasty (THA), but the achieved bone regeneration is unclear. The aim of this study was to evaluate amount and location of bone regeneration obtained after surgical injection of expanded autologous mesenchymal stromal cells from the bone marrow (BM-hMSCs). Methods. A total of 20 patients with small and medium-size symptomatic stage II femoral head ON treated with 140 million BM-hMSCs through percutaneous forage in the EudraCT 2012-002010-39 clinical trial were retrospectively evaluated through preoperative and postoperative (three and 12 months) MRI. Then, 3D reconstruction of the original lesion and the observed postoperative residual damage after bone regeneration were analyzed and compared per group based on treatment efficacy. Results. The mean preoperative lesion volume was 18.7% (SD 10.2%) of the femoral head. This reduced to 11.6% (SD 7.5%) after three months (p = 0.015) and 3.7% (SD 3%) after one year (p < 0.001). Bone regeneration in healed cases represented a mean 81.2% (SD 13.8%) of the initial lesion volume at one year. Non-healed cases (n = 1 stage progression; n = 3 THAs) still showed bone regeneration but this did not effectively decrease the ON volume. A lesion size under mean 10% (SD 6%) of the femoral head at three months predicted no ON stage progression at one year. Regeneration in the lateral femoral head (C2 under Japanese Investigation Committee (JCI) classification) and in the central and posterior regions of the head was predominant in cases without ON progression. Conclusion. Bone regeneration was observed in osteonecrotic femoral heads three months after expanded autologous BM-hMSC injection, and the volume and location of regeneration indicated the success of the therapy. Cite this article: Bone Joint Res 2022;11(12):881–889

Aims. The COVID-19 pandemic led to a national suspension of “non-urgent” elective hip and knee arthroplasty. The study aims to measure the effect of the COVID-19 pandemic on total hip arthroplasty (THA) and total knee arthroplasty (TKA) volume in Scotland. Secondary objectives are to measure the success of restarting elective services and model the time required to bridge the gap left by the first period of suspension. Methods. A retrospective observational study using the Scottish Arthroplasty Project dataset. All patients undergoing elective THAs and TKAs during the period 1 January 2008 to 31 December 2020 were included. A negative binomial regression model using historical case-volume and mid-year population estimates was built to project the future case-volume of THA and TKA in Scotland. The median monthly case volume was calculated for the period 2008 to 2019 (baseline) and compared to the actual monthly case volume for 2020. The time taken to eliminate the deficit was calculated based upon the projected monthly workload and with a potential workload between 100% to 120% of baseline. Results. Compared to the period 2008 to 2019, primary TKA and THA volume fell by 61.1% and 53.6%, respectively. Since restarting elective services, Scottish hospitals have achieved approximately 40% to 50% of baseline monthly activity. With no changes in current workload, by 2021 there would be a reduction of 9,180 and 10,170 for THA and TKA, respectively. Conversely, working at 120% baseline monthly output, it would take over four years to eliminate the deficit for both TKA and THA. Conclusion. This national study demonstrates the significant impact that COVID-19 pandemic has had on overall THA and TKA volume. In the six months after resuming elective services, Scottish hospitals averaged less than 50% normal monthly output. Loss of operating capacity will increase treatment delays and likely worsen overall morbidity. Cite this article: Bone Joint Open 2021;2(3):203–210

Aims. Europe has found itself at the epicentre of the COVID-19 pandemic. Naturally, this has placed added strain onto healthcare systems internationally. It was feared that the impact of the COVID-19 pandemic could overrun the Irish healthcare system. As such, the Irish government opted to introduce a national lockdown on the 27 March 2020 in an attempt to stem the flow of admissions to hospitals. Similar lockdowns in the UK and New Zealand have resulted in reduced emergency department presentations and trauma admissions. The aim of this study is to assess the effect of the national lockdown on trauma presentations to a model-3 hospital in Dublin, Ireland. Methods. A retrospective study was conducted. All emergency department presentations between 27 March 2019 to 27 April 2020 and 27 March 2020 to 27 April 2020 were cross-referenced against the National Integrated Medical Imaging System-Picture Archiving Communication System (NIMIS-PACS) radiology system to identify those with radiologically proven skeletal trauma. These patients were grouped according to sex, age, discharge outcome, mechanism of injury, and injury location. Results. A 21% decrease in radiologically proven trauma was observed on comparison with the same time-period last year. Additionally, a 40% reduction in trauma admissions was observed during the COVID-19 lockdown. A 60% reduction in sports-related injuries and road traffic accident-related injuries was noted during the national lockdown. However, a 17% increase was observed in patients sustaining trauma because of domestic accidents. Conclusion. Variation was observed in both the volume and nature of trauma presentations during the COVID-19 lockdown. As would be expected, a reduction was seen in the number of injuries resulting from outdoor activities. Interestingly, increased rates of domestic injuries were seen during this period which could represent an unintended consequence of the prolonged period of lockdown. Cite this article: Bone Joint Open 2020;1-6:261–266

Objectives. Pedicle-lengthening osteotomy is a novel surgery for lumbar spinal stenosis (LSS), which achieves substantial enlargement of the spinal canal by expansion of the bilateral pedicle osteotomy sites. Few studies have evaluated the impact of this new surgery on spinal canal volume (SCV) and neural foramen dimension (NFD) in three different types of LSS patients. Methods. CT scans were performed on 36 LSS patients (12 central canal stenosis (CCS), 12 lateral recess stenosis (LRS), and 12 foraminal stenosis (FS)) at L4-L5, and on 12 normal (control) subjects. Mimics 14.01 workstation was used to reconstruct 3D models of the L4-L5 vertebrae and discs. SCV and NFD were measured after 1 mm, 2 mm, 3 mm, 4 mm, or 5 mm pedicle-lengthening osteotomies at L4 and/or L5. One-way analysis of variance was used to examine between-group differences. Results. In the intact state, SVC and NFD were significantly larger in the control group compared with the LSS groups (P<0.05). After lengthening at L4, the percentage increase in SCV (per millimetre) was LRS>CCS>FS>Control. After lengthening at L5 and L4-L5, the percentage increase in SCV (per millimetre) was LRS>FS>CCS>Control. After lengthening at L4 and L4-L5, the percentage increase in NFD (per millimetre) was FS>CCS>LRS>Control. After lengthening at L5, the percentage increase in NFD (per millimetre) was CCS>LRS>control>FS. Conclusions. LRS patients are the most suitable candidates for treatment with pedicle-lengthening osteotomy. Lengthening L4 pedicles produced larger percentage increases in NFD than lengthening L5 pedicles (p < 0.05). Lengthening L4 pedicles may be the most effective option for relieving foraminal compression in LSS patients. Cite this article: P. Li, L. Qian, W. D. Wu, C. F. Wu, J. Ouyang. Impact of pedicle-lengthening osteotomy on spinal canal volume and neural foramen size in three types of lumbar spinal stenosis. Bone Joint Res 2016;5:239–246. DOI: 10.1302/2046-3758.56.2000469

Aims

Elective orthopaedic services have had to adapt to significant system-wide pressures since the emergence of COVID-19 in December 2019. Length of stay is often recognized as a key marker of quality of care in patients undergoing arthroplasty. Expeditious discharge is key in establishing early rehabilitation and in reducing infection risk, both procedure-related and from COVID-19. The primary aim was to determine the effects of the COVID-19 pandemic length of stay following hip and knee arthroplasty at a high-volume, elective orthopaedic centre.

Aims. The risk of postoperative complications after resection of soft-tissue sarcoma in the medial thigh is higher than in other locations. This study investigated whether a vessel sealing system (VSS) could help reduce the risk of postoperative complications after wide resection of soft-tissue sarcoma in the medial thigh. Methods. Of 285 patients who underwent wide resection for soft-tissue sarcoma between 2014 and 2021 at our institution, 78 patients with tumours in the medial thigh were extracted from our database. Information on clinicopathological characteristics, preoperative treatment, surgical treatment (use of VSS, blood loss volume, operating time), and postoperative course (complications, postoperative haemoglobin changes, total drainage volume, and drainage and hospitalization durations) were obtained from medical records. We statistically compared clinical outcomes between patients whose surgery did or did not use VSS (VSS and non-VSS groups, respectively). Results. There were 24 patients in the VSS group and 54 in the non-VSS group. There were no significant differences between the two groups in terms of clinicopathological background. The total drainage volume in the VSS group was significantly less than that in the non-VSS group (1,176 ml vs 3,114 ml; p = 0.018). Moreover, the drainage and hospitalization durations were significantly shorter in the VSS group compared to the non-VSS group (p = 0.017 and p = 0.024, respectively). Conclusion. Our results suggest that use of VSS can help reduce the risk of postoperative complications after wide resection of soft-tissue sarcoma in the medial thigh. Cite this article: Bone Jt Open 2023;4(6):442–446

Aims. The aim of this study was to describe a quantitative 3D CT method to measure rotator cuff muscle volume, atrophy, and balance in healthy controls and in three pathological shoulder cohorts. Methods. In all, 102 CT scans were included in the analysis: 46 healthy, 21 cuff tear arthropathy (CTA), 18 irreparable rotator cuff tear (IRCT), and 17 primary osteoarthritis (OA). The four rotator cuff muscles were manually segmented and their volume, including intramuscular fat, was calculated. The normalized volume (NV) of each muscle was calculated by dividing muscle volume to the patient’s scapular bone volume. Muscle volume and percentage of muscle atrophy were compared between muscles and between cohorts. Results. Rotator cuff muscle volume was significantly decreased in patients with OA, CTA, and IRCT compared to healthy patients (p < 0.0001). Atrophy was comparable for all muscles between CTA, IRCT, and OA patients, except for the supraspinatus, which was significantly more atrophied in CTA and IRCT (p = 0.002). In healthy shoulders, the anterior cuff represented 45% of the entire cuff, while the posterior cuff represented 40%. A similar partition between anterior and posterior cuff was also found in both CTA and IRCT patients. However, in OA patients, the relative volume of the anterior (42%) and posterior cuff (45%) were similar. Conclusion. This study shows that rotator cuff muscle volume is significantly decreased in patients with OA, CTA, or IRCT compared to healthy patients, but that only minimal differences can be observed between the different pathological groups. This suggests that the influence of rotator cuff muscle volume and atrophy (including intramuscular fat) as an independent factor of outcome may be overestimated. Cite this article: Bone Jt Open 2021;2(7):552–561

Aims. Disorders of bone integrity carry a high global disease burden, frequently requiring intervention, but there is a paucity of methods capable of noninvasive real-time assessment. Here we show that miniaturized handheld near-infrared spectroscopy (NIRS) scans, operated via a smartphone, can assess structural human bone properties in under three seconds. Methods. A hand-held NIR spectrometer was used to scan bone samples from 20 patients and predict: bone volume fraction (BV/TV); and trabecular (Tb) and cortical (Ct) thickness (Th), porosity (Po), and spacing (Sp). Results. NIRS scans on both the inner (trabecular) surface or outer (cortical) surface accurately identified variations in bone collagen, water, mineral, and fat content, which then accurately predicted bone volume fraction (BV/TV, inner R. 2. = 0.91, outer R. 2. = 0.83), thickness (Tb.Th, inner R. 2. = 0.9, outer R. 2. = 0.79), and cortical thickness (Ct.Th, inner and outer both R. 2. = 0.90). NIRS scans also had 100% classification accuracy in grading the quartile of bone thickness and quality. Conclusion. We believe this is a fundamental step forward in creating an instrument capable of intraoperative real-time use. Cite this article: Bone Jt Open 2023;4(4):250–261

Aims. Acridine orange (AO) demonstrates several biological activities. When exposed to low doses of X-ray radiation, AO increases the production of reactive radicals (radiodynamic therapy (AO-RDT)). We elucidated the efficacy of AO-RDT in breast and prostate cancer cell lines, which are likely to develop bone metastases. Methods. We used the mouse osteosarcoma cell line LM8, the human breast cancer cell line MDA-MB-231, and the human prostate cancer cell line PC-3. Cultured cells were exposed to AO and radiation at various concentrations followed by various doses of irradiation. The cell viability was then measured. In vivo, each cell was inoculated subcutaneously into the backs of mice. In the AO-RDT group, AO (1.0 μg) was locally administered subcutaneously around the tumour followed by 5 Gy of irradiation. In the radiation group, 5 Gy of irradiation alone was administered after macroscopic tumour formation. The mice were killed on the 14th day after treatment. The change in tumour volume by AO-RDT was primarily evaluated. Results. The viability of LM8, MDA-MB-231, and PC-3 cells strongly decreased at AO concentration of 1.0 μg/ml and a radiation dose of 5 Gy. In xenograft mouse model, the AO-RDT also showed a strong cytocidal effect on tumour at the backside in osteosarcoma, breast cancer, and prostate cancer. AO-RDT treatment was more effective for tumour control than radiotherapy in breast cancer. Conclusion. AO-RDT was effective in preventing the proliferation of osteosarcoma, breast cancer, and prostate cancer cell lines in vitro. The reduction in tumour volume by AO-RDT was also confirmed in vivo. Cite this article: Bone Joint Res 2022;11(10):715–722

Aims. This study aimed to develop and validate a fully automated system that quantifies proximal femoral bone mineral density (BMD) from CT images. Methods. The study analyzed 978 pairs of hip CT and dual-energy X-ray absorptiometry (DXA) measurements of the proximal femur (DXA-BMD) collected from three institutions. From the CT images, the femur and a calibration phantom were automatically segmented using previously trained deep-learning models. The Hounsfield units of each voxel were converted into density (mg/cm. 3. ). Then, a deep-learning model trained by manual landmark selection of 315 cases was developed to select the landmarks at the proximal femur to rotate the CT volume to the neutral position. Finally, the CT volume of the femur was projected onto the coronal plane, and the areal BMD of the proximal femur (CT-aBMD) was quantified. CT-aBMD correlated to DXA-BMD, and a receiver operating characteristic (ROC) analysis quantified the accuracy in diagnosing osteoporosis. Results. CT-aBMD was successfully measured in 976/978 hips (99.8%). A significant correlation was found between CT-aBMD and DXA-BMD (r = 0.941; p < 0.001). In the ROC analysis, the area under the curve to diagnose osteoporosis was 0.976. The diagnostic sensitivity and specificity were 88.9% and 96%, respectively, with the cutoff set at 0.625 g/cm. 2. . Conclusion. Accurate DXA-BMD measurements and diagnosis of osteoporosis were performed from CT images using the system developed herein. As the models are open-source, clinicians can use the proposed system to screen osteoporosis and determine the surgical strategy for hip surgery. Cite this article: Bone Joint Res 2023;12(9):590–597

Aims. Mechanical stimulation is a key factor in the development and healing of tendon-bone insertion. Treadmill training is an important rehabilitation treatment. This study aims to investigate the benefits of treadmill training initiated on postoperative day 7 for tendon-bone insertion healing. Methods. A tendon-bone insertion injury healing model was established in 92 C57BL/6 male mice. All mice were divided into control and training groups by random digital table method. The control group mice had full free activity in the cage, and the training group mice started the treadmill training on postoperative day 7. The quality of tendon-bone insertion healing was evaluated by histology, immunohistochemistry, reverse transcription quantitative polymerase chain reaction, Western blotting, micro-CT, micro-MRI, open field tests, and CatWalk gait and biomechanical assessments. Results. Our results showed a significantly higher tendon-bone insertion histomorphological score in the training group, and the messenger RNA and protein expression levels of type II collagen (COL2A1), SOX9, and type X collagen (COL10A1) were significantly elevated. Additionally, tendon-bone insertion resulted in less scar hyperplasia after treadmill training, the bone mineral density (BMD) and bone volume/tissue volume (BV/TV) were significantly improved, and the force required to induce failure became stronger in the training group. Functionally, the motor ability, limb stride length, and stride frequency of mice with tendon-bone insertion injuries were significantly improved in the training group compared with the control group. Conclusion. Treadmill training initiated on postoperative day 7 is beneficial to tendon-bone insertion healing, promoting biomechanical strength and motor function. Our findings are expected to guide clinical rehabilitation training programmes. Cite this article: Bone Joint Res 2023;12(5):339–351

Aims. This study investigated the effects of β-caryophyllene (BCP) on protecting bone from vitamin D deficiency in mice fed on a diet either lacking (D-) or containing (D+) vitamin D. Methods. A total of 40 female mice were assigned to four treatment groups (n = 10/group): D+ diet with propylene glycol control, D+ diet with BCP, D-deficient diet with control, and D-deficient diet with BCP. The D+ diet is a commercial basal diet, while the D-deficient diet contains 0.47% calcium, 0.3% phosphorus, and no vitamin D. All the mice were housed in conditions without ultraviolet light. Bone properties were evaluated by X-ray micro-CT. Serum levels of klotho were measured by enzyme-linked immunosorbent assay. Results. Under these conditions, the D-deficient diet enhanced the length of femur and tibia bones (p < 0.050), and increased bone volume (BV; p < 0.010) and trabecular bone volume fraction (BV/TV; p < 0.010) compared to D+ diet. With a diet containing BCP, the mice exhibited higher BV and bone mineral density (BMD; p < 0.050) than control group. The trabecular and cortical bone were also affected by vitamin D and BCP. In addition, inclusion of dietary BCP improved the serum concentrations of klotho (p < 0.050). In mice, klotho regulates the expression level of cannabinoid type 2 receptor (Cnr2) and fibroblast growth factor 23 (Fgf23) through CD300a. In humans, data suggest that klotho is connected to BMD. The expression of klotho is also associated with bone markers. Conclusion. These data indicate that BCP enhances the serum level of klotho, leading to improved bone properties and mineralization in an experimental mouse model. Cite this article: Bone Joint Res 2022;11(8):528–540

Aims. No predictive model has been published to forecast operating time for total knee arthroplasty (TKA). The aims of this study were to design and validate a predictive model to estimate operating time for robotic-assisted TKA based on demographic data, and evaluate the added predictive power of CT scan-based predictors and their impact on the accuracy of the predictive model. Methods. A retrospective study was conducted on 1,061 TKAs performed from January 2016 to December 2019 with an image-based robotic-assisted system. Demographic data included age, sex, height, and weight. The femoral and tibial mechanical axis and the osteophyte volume were calculated from CT scans. These inputs were used to develop a predictive model aimed to predict operating time based on demographic data only, and demographic and 3D patient anatomy data. Results. The key factors for predicting operating time were the surgeon and patient weight, followed by 12 anatomical parameters derived from CT scans. The predictive model based only on demographic data showed that 90% of predictions were within 15 minutes of actual operating time, with 73% within ten minutes. The predictive model including demographic data and CT scans showed that 94% of predictions were within 15 minutes of actual operating time and 88% within ten minutes. Conclusion. The primary factors for predicting robotic-assisted TKA operating time were surgeon, patient weight, and osteophyte volume. This study demonstrates that incorporating 3D patient-specific data can improve operating time predictions models, which may lead to improved operating room planning and efficiency. Cite this article: Bone Jt Open 2022;3(5):383–389

Aims. The management of periprosthetic joint infection (PJI) remains a major challenge in orthopaedic surgery. In this study, we aimed to characterize the local bone microstructure and metabolism in a clinical cohort of patients with chronic PJI. Methods. Periprosthetic femoral trabecular bone specimens were obtained from patients suffering from chronic PJI of the hip and knee (n = 20). Microbiological analysis was performed on preoperative joint aspirates and tissue specimens obtained during revision surgery. Microstructural and cellular bone parameters were analyzed in bone specimens by histomorphometry on undecalcified sections complemented by tartrate-resistant acid phosphatase immunohistochemistry. Data were compared with control specimens obtained during primary arthroplasty (n = 20) and aseptic revision (n = 20). Results. PJI specimens exhibited a higher bone volume, thickened trabeculae, and increased osteoid parameters compared to both control groups, suggesting an accelerated bone turnover with sclerotic microstructure. On the cellular level, osteoblast and osteoclast parameters were markedly increased in the PJI cohort. Furthermore, a positive association between serum (CRP) but not synovial (white blood cell (WBC) count) inflammatory markers and osteoclast indices could be detected. Comparison between different pathogens revealed increased osteoclastic bone resorption parameters without a concomitant increase in osteoblasts in bone specimens from patients with Staphylococcus aureus infection, compared to those with detection of Staphylococcus epidermidis and Cutibacterium spp. Conclusion. This study provides insights into the local bone metabolism in chronic PJI, demonstrating osteosclerosis with high bone turnover. The fact that Staphylococcus aureus was associated with distinctly increased osteoclast indices strongly suggests early surgical treatment to prevent periprosthetic bone alterations. Cite this article: Bone Joint Res 2023;12(10):644–653

Aims. Several artificial bone grafts have been developed but fail to achieve anticipated osteogenesis due to their insufficient neovascularization capacity and periosteum support. This study aimed to develop a vascularized bone-periosteum construct (VBPC) to provide better angiogenesis and osteogenesis for bone regeneration. Methods. A total of 24 male New Zealand white rabbits were divided into four groups according to the experimental materials. Allogenic adipose-derived mesenchymal stem cells (AMSCs) were cultured and seeded evenly in the collagen/chitosan sheet to form cell sheet as periosteum. Simultaneously, allogenic AMSCs were seeded onto alginate beads and were cultured to differentiate to endothelial-like cells to form vascularized bone construct (VBC). The cell sheet was wrapped onto VBC to create a vascularized bone-periosteum construct (VBPC). Four different experimental materials – acellular construct, VBC, non-vascularized bone-periosteum construct, and VBPC – were then implanted in bilateral L4-L5 intertransverse space. At 12 weeks post-surgery, the bone-forming capacities were determined by CT, biomechanical testing, histology, and immunohistochemistry staining analyses. Results. At 12 weeks, the VBPC group significantly increased new bone formation volume compared with the other groups. Biomechanical testing demonstrated higher torque strength in the VBPC group. Notably, the haematoxylin and eosin, Masson’s trichrome, and immunohistochemistry-stained histological results revealed that VBPC promoted neovascularization and new bone formation in the spine fusion areas. Conclusion. The tissue-engineered VBPC showed great capability in promoting angiogenesis and osteogenesis in vivo. It may provide a novel approach to create a superior blood supply and nutritional environment to overcome the deficits of current artificial bone graft substitutes. Cite this article: Bone Joint Res 2023;12(12):722–733

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. This study aimed to demonstrate the promoting effect of elastic fixation on fracture, and further explore its mechanism at the gene and protein expression levels. Methods. A closed tibial fracture model was established using 12 male Japanese white rabbits, and divided into elastic and stiff fixation groups based on different fixation methods. Two weeks after the operation, a radiograph and pathological examination of callus tissue were used to evaluate fracture healing. Then, the differentially expressed proteins (DEPs) were examined in the callus using proteomics. Finally, in vitro cell experiments were conducted to investigate hub proteins involved in this process. Results. Mean callus volume was larger in the elastic fixation group (1,755 mm. 3. (standard error of the mean (SEM) 297)) than in the stiff fixation group (258 mm. 3. (SEM 65)). Pathological observation found that the expression levels of osterix (OSX), collagen, type I, alpha 1 (COL1α1), and alkaline phosphatase (ALP) in the callus of the elastic fixation group were higher than those of the stiff fixation group. The protein sequence of the callus revealed 199 DEPs, 124 of which were highly expressed in the elastic fixation group. In the in vitro study, it was observed that a stress of 200 g led to upregulation of thrombospondin 1 (THBS1) and osteoglycin (OGN) expression in bone marrow mesenchymal stem cells (BMSCs). Additionally, these genes were found to be upregulated during the osteogenic differentiation process of the BMSCs. Conclusion. Elastic fixation can promote fracture healing and osteoblast differentiation in callus, and the ability of elastic fixation to promote osteogenic differentiation of BMSCs may be achieved by upregulating genes such as THBS1 and OGN. Cite this article: Bone Joint Res 2024;13(10):559–572