Shared genetic liability between major depressive disorder and osteoarthritis

Aims Deciphering the genetic relationships between major depressive disorder (MDD) and osteoarthritis (OA) may facilitate an understanding of their biological mechanisms, as well as inform more effective treatment regimens. We aim to investigate the mechanisms underlying relationships between MDD and OA in the context of common genetic variations. Methods Linkage disequilibrium score regression was used to test the genetic correlation between MDD and OA. Polygenic analysis was performed to estimate shared genetic variations between the two diseases. Two-sample bidirectional Mendelian randomization analysis was used to investigate causal relationships between MDD and OA. Genomic loci shared between MDD and OA were identified using cross-trait meta-analysis. Fine-mapping of transcriptome-wide associations was used to prioritize putatively causal genes for the two diseases. Results MDD has a significant genetic correlation with OA (rg = 0.29) and the two diseases share a considerable proportion of causal variants. Mendelian randomization analysis indicates that genetic liability to MDD has a causal effect on OA (bxy = 0.24) and genetic liability to OA conferred a causal effect on MDD (bxy = 0.20). Cross-trait meta-analyses identified 29 shared genomic loci between MDD and OA. Together with fine-mapping of transcriptome-wide association signals, our results suggest that Estrogen Receptor 1 ( ESR1), SRY-Box Transcription Factor 5 ( SOX5), and Glutathione Peroxidase 1 ( GPX1) may have therapeutic implications for both MDD and OA. Conclusion The study reveals substantial shared genetic liability between MDD and OA, which may confer risk for one another. Our findings provide a novel insight into phenotypic relationships between MDD and OA. Cite this article: Bone Joint Res 2022;11(1):12–22.

Femoral stem neck geometry determines hip range of motion shape

Aims In computer simulations, the shape of the range of motion (ROM) of a stem with a cylindrical neck design will be a perfect cone. However, many modern stems have rectangular/oval-shaped necks. We hypothesized that the rectangular/oval stem neck will affect the shape of the ROM and the prosthetic impingement. Methods Total hip arthroplasty (THA) motion while standing and sitting was simulated using a MATLAB model (one stem with a cylindrical neck and one stem with a rectangular neck). The primary predictor was the geometry of the neck (cylindrical vs rectangular) and the main outcome was the shape of ROM based on the prosthetic impingement between the neck and the liner. The secondary outcome was the difference in the ROM provided by each neck geometry and the effect of the pelvic tilt on this ROM. Multiple regression was used to analyze the data. Results The stem with a rectangular neck has increased internal and external rotation with a quatrefoil cross-section compared to a cone in a cylindrical neck. Modification of the cup orientation and pelvic tilt affected the direction of projection of the cone or quatrefoil shape. The mean increase in internal rotation with a rectangular neck was 3.4° (0° to 7.9°; p < 0.001); for external rotation, it was 2.8° (0.5° to 7.8°; p < 0.001). Conclusion Our study shows the importance of attention to femoral implant design for the assessment of prosthetic impingement. Any universal mathematical model or computer simulation that ignores each stem’s unique neck geometry will provide inaccurate predictions of prosthetic impingement. Cite this article: Bone Joint Res 2021;10(12):780–789.

Preoperative measures of bone mineral density from digital wrist radiographs

Aims Assessment of bone mineral density (BMD) with dual-energy X-ray absorptiometry (DXA) is a well-established clinical technique, but it is not available in the acute trauma setting. Thus, it cannot provide a preoperative estimation of BMD to help guide the technique of fracture fixation. Alternative methods that have been suggested for assessing BMD include: 1) cortical measures, such as cortical ratios and combined cortical scores; and 2) aluminium grading systems from preoperative digital radiographs. However, limited research has been performed in this area to validate the different methods. The aim of this study was to investigate the evaluation of BMD from digital radiographs by comparing various methods against DXA scanning. Methods A total of 54 patients with distal radial fractures were included in the study. Each underwent posteroanterior (PA) and lateral radiographs of the injured wrist with an aluminium step wedge. Overall 27 patients underwent routine DXA scanning of the hip and lumbar spine, with 13 undergoing additional DXA scanning of the uninjured forearm. Analysis of radiographs was performed on ImageJ and Matlab with calculations of cortical measures, cortical indices, combined cortical scores, and aluminium equivalent grading. Results Cortical measures showed varying correlations with the forearm DXA results (range: Pearson correlation coefficient (r) = 0.343 (p = 0.251) to r = 0.521 (p = 0.068)), with none showing statistically significant correlations. Aluminium equivalent grading showed statistically significant correlations with the forearm DXA of the corresponding region of interest (p < 0.017). Conclusion Cortical measures, cortical indices, and combined cortical scores did not show a statistically significant correlation to forearm DXA measures. Aluminium-equivalent is an easily applicable method for estimation of BMD from digital radiographs in the preoperative setting. Cite this article: Bone Joint Res 2021;10(12):830–839.

3D ultrasound reconstruction of sonographic callus

Aims The aim of this study was to establish a reliable method for producing 3D reconstruction of sonographic callus. Methods A cohort of ten closed tibial shaft fractures managed with intramedullary nailing underwent ultrasound scanning at two, six, and 12 weeks post-surgery. Ultrasound capture was performed using infrared tracking technology to map each image to a 3D lattice. Using echo intensity, semi-automated mapping was performed to produce an anatomical 3D representation of the fracture site. Two reviewers independently performed 3D reconstructions and kappa coefficient was used to determine agreement. A further validation study was undertaken with ten reviewers to estimate the clinical application of this imaging technique using the intraclass correlation coefficient (ICC). Results Nine of the ten patients achieved union at six months. At six weeks, seven patients had bridging callus of ≥ one cortex on the 3D reconstruction and when present all achieved union. Compared to six-week radiographs, no bridging callus was present in any patient. Of the three patients lacking sonographic bridging callus, one went onto a nonunion (77.8% sensitive and 100% specific to predict union). At 12 weeks, nine patients had bridging callus at ≥ one cortex on 3D reconstruction (100%-sensitive and 100%-specific to predict union). Presence of sonographic bridging callus on 3D reconstruction demonstrated excellent reviewer agreement on ICC at 0.87 (95% confidence interval 0.74 to 0.96). Conclusion 3D fracture reconstruction can be created using multiple ultrasound images in order to evaluate the presence of bridging callus. This imaging modality has the potential to enhance the usability and accuracy of identification of early fracture healing. Cite this article: Bone Joint Res 2021;10(12):759–766.

Cortical bone thickness of the distal radius predicts the local bone mineral density

Aims The distal radius is a major site of osteoporotic bone loss resulting in a high risk of fragility fracture. This study evaluated the capability of a cortical index (CI) at the distal radius to predict the local bone mineral density (BMD). Methods A total of 54 human cadaver forearms (ten singles, 22 pairs) (19 to 90 years) were systematically assessed by clinical radiograph (XR), dual-energy X-ray absorptiometry (DXA), CT, as well as high-resolution peripheral quantitative CT (HR-pQCT). Cortical bone thickness (CBT) of the distal radius was measured on XR and CT scans, and two cortical indices mean average (CBTavg) and gauge (CBTg) were determined. These cortical indices were compared to the BMD of the distal radius determined by DXA (areal BMD (aBMD)) and HR-pQCT (volumetric BMD (vBMD)). Pearson correlation coefficient (r) and intraclass correlation coefficient (ICC) were used to compare the results and degree of reliability. Results The CBT could accurately be determined on XRs and highly correlated to those determined on CT scans (r = 0.87 to 0.93). The CBTavg index of the XRs significantly correlated with the BMD measured by DXA (r = 0.78) and HR-pQCT (r = 0.63), as did the CBTg index with the DXA (r = 0.55) and HR-pQCT (r = 0.64) (all p < 0.001). A high correlation of the BMD and CBT was observed between paired specimens (r = 0.79 to 0.96). The intra- and inter-rater reliability was excellent (ICC 0.79 to 0.92). Conclusion The cortical index (CBTavg) at the distal radius shows a close correlation to the local BMD. It thus can serve as an initial screening tool to estimate the local bone quality if quantitative BMD measurements are unavailable, and enhance decision-making in acute settings on fracture management or further osteoporosis screening. Cite this article: Bone Joint Res 2021;10(12):820–829.