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. The aim of this study was to perform a systematic review of the evidence for the use of intraoperative cell salvage in patients undergoing revision hip arthroplasty, and specifically to analyze the available data in order to quantify any associated reduction in the use of allogenic blood transfusion, and the volume which is used. Methods. An electronic search of MEDLINE (PubMed), Embase, Scopus, and the Cochrane Library was completed from the date of their inception to 24 February 2022, using a search strategy and protocol created in conjunction with the PRISMA statement. Inclusion criteria were patients aged > 18 years who underwent revision hip arthroplasty when cell salvage was used. Studies in which pre-donated red blood cells were used were excluded. A meta-analysis was also performed using a random effects model with significance set at p = 0.05. Results. Of the 283 studies which were identified, 11 were included in the systematic review, and nine in the meta-analysis. There was a significant difference (p < 0.001) in the proportion of patients requiring allogenic transfusion between groups, with an odds ratio of 0.331 (95% confidence interval (CI) 0.165 to 0.663) associated with the use of cell salvage. For a total of 561 patients undergoing revision hip arthroplasty who were treated with cell salvage, 247 (44.0%) required allogenic transfusion compared with 418 of 643 patients (65.0%) who were treated without cell salvage. For those treated with cell salvage, the mean volume of allogenic blood which was required was 1.95 units (390 ml) per patient (0.7 to 4.5 units), compared with 3.25 units (650 ml) per patient (1.2 to 7.0 units) in those treated without cell salvage. The mean difference of -1.91 units (95% CI -4.0 to 0.2) in the meta-analysis was also significant (p = 0.003). Conclusion. We found a a significant reduction in the need for allogenic blood transfusion when cell salvage was used in patients undergoing revision hip arthroplasty, supporting its routine use in these patients. Further research is required to determine whether this effect is associated with types of revision arthroplasty of differing complexity. Cite this article: Bone Joint J 2023;105-B(10):1038–1044

Aims. This study aims to determine the rate of and risk factors for total knee arthroplasty (TKA) after operative management of tibial plateau fractures (TPFs) in older adults. Methods. This is a retrospective cohort study of 182 displaced TPFs in 180 patients aged ≥ 60 years, over a 12-year period with a minimum follow-up of one year. The mean age was 70.7 years (SD 7.7; 60 to 89), and 139/180 patients (77.2%) were female. Radiological assessment consisted of fracture classification; pre-existing knee osteoarthritis (OA); reduction quality; loss of reduction; and post-traumatic OA. Fracture depression was measured on CT, and the volume of defect estimated as half an oblate spheroid. Operative management, complications, reoperations, and mortality were recorded. Results. Nearly half of the fractures were Schatzker II AO B3.1 fractures (n = 85; 47%). Radiological knee OA was present at fracture in 59/182 TPFs (32.6%). Primary management was fixation in 174 (95.6%) and acute TKA in eight (4.4%). A total of 13 patients underwent late TKA (7.5%), most often within two years. By five years, 21/182 12% (95% confidence interval (CI) 6.0 to 16.7) had required TKA. Larger volume defects of greater depth on CT (median 15.9 mm vs 9.4 mm; p < 0.001) were significantly associated with TKA requirement. CT-measured joint depression of > 12.8 mm was associated with TKA requirement (area under the curve (AUC) 0.766; p = 0.001). Severe joint depression of > 15.5 mm (hazard ratio (HR) 6.15 (95% CI 2.60 to 14.55); p < 0.001) and pre-existing knee OA (HR 2.70 (95% CI 1.14 to 6.37); p = 0.024) were independently associated with TKA requirement. Where patients with severe joint depression of > 15.5 mm were managed with fixation, 11/25 ultimately required TKA. Conclusion. Overall, 12% of patients aged ≥ 60 years underwent TKA within five years of TPF. Severe joint depression and pre-existing knee arthritis were independent risk factors for both post-traumatic OA and TKA. These features should be investigated as potential indications for acute TKA in older adults with TPFs. Cite this article: Bone Joint J 2024;106-B(1):28–37

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