In this study, we aimed to investigate the causal associations of brain structure with bone mineral density (BMD). Based on the genome-wide association study (GWAS) summary statistics of 1 325 brain imaging-derived phenotypes (BIDPs) of brain structure from the UK Biobank and GWAS summary datasets of 5 BMD locations, including the total body, femoral neck, lumbar spine, forearm, and heel from the GEFOS Consortium, linkage disequilibrium score regression (LDSC) was conducted to determine the genetic correlations, and Mendelian randomization (MR) was then performed to explore the causal relationship between the BIDPs and BMD. Several sensitivity analyses were performed to verify the strength and stability of the present MR outcomes. To increase confidence in our findings, we also performed confirmatory MR between BIDPs and osteoporosis. LDSC revealed that 1.93% of BIDPs, with a false discovery rate (FDR) < 0.01, were genetically correlated with BMD. Additionally, we observed that 1.31% of BIDPs exhibited a significant causal relationship with BMD (FDR < 0.01) through MR. Both the LDSC and MR results demonstrated that the BIDPs “Volume of normalized brain,” “Volume of gray matter in Left Inferior Frontal Gyrus, pars opercularis,” “Volume of Estimated Total Intra Cranial” and “Volume-ratio of brain segmentation/estimated total intracranial” had strong associations with BMD. Interestingly, our results showed that more left BIDPs were causally associated with BMD, especially within and around the left frontal region. In conclusion, a part of the brain structure causally influences BMD, which may provide important perspectives for the prevention of osteoporosis and offer valuable insights for further research on the brain-bone axis.

Purpose: It has been reported that bone is the primary organ for manganese (Mn) accumulation, but the association between manganese and bone loss remains debatable. Therefore, this study aimed to evaluate the relationship between blood manganese and bone mineral density/bone mineral content (BMD/BMC) by using a representative sample from the National Health and Nutrition Examination Survey (NHANES).Methods: A total of 9732 subjects over the age of 18 with available data were enrolled in this study. The relationship between blood manganese and BMD/BMC of the total body, spine and femoral regions was evaluated using multivariate linear regression models. Subgroup analyses were also performed.Results: We observed a negative association between blood manganese and BMD/BMC in the femoral neck and total body in the fully adjusted model, especially femoral neck BMD in women aged 50–70 years.Conclusion: In brief, people exposed to manganese should be aware of the increased risk of osteopenia or osteoporosis. Besides, due to the lack of available data, there are no definite values for the tolerable upper intake level (UL), average requirement (AR) and population reference intake (PRI) of manganese. The results of our study may provide some references for the establishment of AR, PRI and UL of Mn.

Backgrounds: Epidemiological studies have repeatedly investigated the association between obesity related anthropometric indicators and body compositions and osteoarthritis (OA). However, the results have remained inconsistent. This work aimed to investigate the genetic correlation and causal associations of obesity related anthropometric indicators and body compositions with knee and hip OA.Methods: Single-nucleotide polymorphisms associated with the exposures were searched from the recent genome-wide association studies (GWAS) to obtain full statistics. Summary-level results of knee and hip OA were from the UK Biobank and arcOGEN. First, linkage disequilibrium score regression (LD score regression) was applied to detect the genetic correlation (rg). We further performed a series of sensitivity analyses as validation of primary mendelian randomization (MR) results and the specific evidence of potential causal effects was defined.Results: We found that genetic components in OA had significant correlation with obesity related traits, except waist-to-hip ratio. In the univariable MR analysis, with the exception of waist-to-hip ratio, obesity related anthropometric indicators were causally associated with increased risks of knee and hip OA. For obesity related body compositions, higher fat-free mass in arm, leg, and whole body increased the risk of knee OA but only fat-free mass in leg showed a significant association with hip OA. Meanwhile trunk fat mass and trunk fat percentage, were associated with knee but not with hip OA. Higher fat mass, and fat percentage in arm, leg, and whole body increased the risk of both knee and hip OA. After adjusting for BMI, the multivariable MR showed maintained results in knee OA. However, in hip OA, only fat mass and fat-free mass in arm, leg, trunk and whole body were significantly associated with the risk of hip OA.Conclusion: The present study suggests genetic evidence for certain causal associations of obesity related anthropometric indicators and body compositions with knee and hip OA, which may provide important insights for the prevention and treatment on OA.

Background: Distal humerus fractures (DHFs) constitute one-third of elbow fractures approximately. In this study, we aim to define and analyze the fracture lines and morphological features of DHFs using mapping technique. Methods: One hundred and two DHFs were retrospectively reviewed. All the computed tomography (CT) data were used to manually reconstruct and virtually reduce the DHF fragments to fit a standard 3D model. Smooth curves were depicted accurately onto the surface of the template to represent the fracture lines. All the curves were overlapped onto the model to create the 3D fracture map and heat map. Results: Our analysis was based on 102 CT images of DHFs, contributed by 59 male and 43 female patients (mean age, 46 years; range, 18-93 years), and included 15 type A, 25 type B, and 62 type C fractures. On mapping, the hot zones were located in the radial fossa, coronoid fossa, olecranon fossa, and the external part of the trochlear. Conversely, the cold zones were noted in medial condyle, the medial side of the trochlear, and the anterolateral area on the supracondylar ridge. Conclusions: Our study firstly shows the fracture lines and morphological features of distal humeral fractures by three-dimensional mapping technology. Distal humerus fracture lines are characteristic and highly related to the micro-architecture difference of distal humerus, which may provide some guidance for the treatment plan selection and surgical fixation design.

Background: Rheumatoid arthritis (RA) is a globally prevalent chronic inflammatory disease. Environmental exposures, such as air pollution and smoking, are considered potential risk factors. However, the causal relationships and underlying mechanisms between these factors and RA are not fully understood. Methods: This study utilized large-scale genome-wide association studies (GWASs) from European ethnic backgrounds and employed bidirectional two-sample Mendelian randomization (MR) to investigate the relationships between air pollution, smoking, and RA. Genetic correlations were assessed using linkage disequilibrium score regression (LDSC). Furthermore, mediation analysis was conducted to evaluate the potential mediating roles of iron metabolism and urinary biomarkers in these relationships. Results: The MR analysis revealed that genetically predicted lifetime smoking intensity was associated with an 85% increased risk of RA. Subgroup analysis differentiating between seropositive RA (SPRA) and seronegative RA (SNRA) showed a causal association with SPRA, but not with SNRA. C-reactive protein was identified as a mediator in the relationship between lifetime smoking and both RA and SPRA, mediating 18.23% and 32.45% of the effects, respectively. Genetic correlation analysis further confirmed a positive genetic association between smoking and both RA and SPRA. Conclusions: This study provides significant insights into the genetic and causal connections between air pollution, smoking, and the development of RA, highlighting the mediating role of C-reactive protein. These findings not only offer new perspectives on how smoking might enhance RA risk through inflammatory pathways but also underscore the importance of reducing smoking exposure in public health strategies.

Rationale: Wrist-hand extension function rehabilitation is a vital and difficult part of hand function recovery in spastic stroke patients. Although botulinum toxin type A (BoNTA) injection plus post injection therapy was applied to the wrist-hand rehabilitation in previous reports, conclusion was inconsistent in promoting function. For this phenomenon, proper selection of patients for BoNTA injection and correct choice of post-injection intervention could be the crucial factors for the function recovery. Patient concerns: We reported a 46-year-old male suffered a spastic hemiplegia with wrist- hand extension deficit. Diagnoses: Computed tomography showed cerebral hemorrhage in the left basal ganglia region. Interventions: Four hundred units of BoNTA were injected into the spasticity flexors, and four-week post injection surface electromyography (sEMG) biofeedback therapy was applied to the patient. Outcomes: The patient exhibited post-intervention improvement in wrist-hand extensors performance (strength, range of motion, sEMG signals), the flexors spasticity, and upper extremity function. Lessons: The present case showed that 4-week of BoNTA injection plus sEMG biofeedback exercise improved the performance and function of wrist-hand extensors in the patient for short- and long-term. Proper selection of patients for BoNTA injection and correct choice of post injection exercise could play a vital role in the hand rehabilitation for patient with spastic hemiplegia.