Dissecting Causal Relationships Between Plasma Metabolites and Osteoporosis: A Bidirectional Mendelian Randomization Study.

Objective To investigate the causal relationships between plasma metabolites and osteoporosis via Mendelian randomization (MR) analysis. Methods Bidirectional MR was used to analyze pooled data from different genome-wide association studies (GWAS) to investigate the causal relationships between plasma metabolites and osteoporosis. The causal effect of plasma metabolites on osteoporosis was estimated using the inverse variance weighted method, intersections of statistically significant metabolites obtained from different sources of osteoporosis-related GWAS aggregated data was determined, and then sensitivity analysis was performed on these metabolites. Heterogeneity between single nucleotide polymorphisms was evaluated by Cochran's Q test. Horizontal pleiotropy was assessed through the application of the MR-Egger intercept method and the MR-PRESSO method. The causal effect of osteoporosis on plasma metabolites was also evaluated using the inverse variance weighted method. Additionally, pathway analysis was conducted to identify potential metabolic pathways involved in the regulation of osteoporosis. Results After primary analysis and a series of sensitivity analyses, 77 and 61 plasma metabolites were identified as having a causal relationship with osteoporosis from the GWAS data in the GCST90038656 and GCST90044600 datasets , respectively. Five common metabolites were identified via intersection. X-13684 levels (GCST90038656: OR = 0.999, 95% CI, 0.998-1.000, P = 0.004; GCST90044600 (OR = 0.834, 95% CI, 0.700-0.993, P = 0.042), and the glucose-to-maltose ratio (GCST90038656: OR = 0.998, 95% CI, 0.997-1.000, P = 0.025; GCST90044600: OR = 0.752, 95% CI, 0.576-0.981, P = 0.036) were negatively associated with osteoporosis, whereas glycoursodeoxycholate levels (GCST90038656: OR = 1.002, 95% CI, 1.000-1.003, P = 0.032; GCST90044600: OR = 1.331, 95% CI, 1.036-1.709, P = 0.025) and arachidoylcarnitine (C20) levels (GCST90038656: OR = 1.001, 95% CI, 1.000-1.003, P = 0.039; GCST90044600: OR = 1.237; 95% CI, 1.008-1.518, P = 0.042) were positively associated with osteoporosis. The relationship between X-11299 levels and osteoporosis showed contradictory results (GCST90038656: OR= 0.998, 95% CI, 0.997-1.000, P = 0.026; GCST90044600: OR = 1.402, 95% CI, 1.071-1.834, P = 0.014). Pathway analysis indicated that glycine, serine, and threonine metabolism, valine, leucine, and isoleucine biosynthesis, galactose metabolism, arginine biosynthesis, and starch and sucrose metabolism pathways were participated in the development of osteoporosis. Conclusion We found a causal relationship between plasma metabolites and osteoporosis. These results offer novel perspectives that have implications for targeted interventions focused on metabolites in the management of osteoporosis.

Novel Hydrogel Adjuvant of Chinese Medicine External Preparations for Accelerated Healing of Deep Soft Tissue Injuries.

Traditional Chinese medicine external prescriptions have displayed excellent clinical effects for treating deep soft tissue injuries. However, the effects cannot be fully utilized due to the limitations of their dosage forms and usage methods. It is still a challenge to develop a satisfactory adjuvant of traditional Chinese medicine external prescriptions. Herein, a hydrogel adjuvant was prepared based on gallic acid coupled ε-poly-l-lysine and partially oxidized hyaluronic acid. The resulting adjuvant shows great physicochemical properties, low hemolysis rate (still much less than 5% at 5 mg/mL), excellent antibacterial ability (about 95% at 2 mg/mL), strong antioxidant ability (1.687 ± 0.085 mmol FeSO4/(g hydrogel) at 1 mg/mL), as well as outstanding biocompatibility. A clinically used Chinese medicine external preparation was selected as an example to investigate the effectiveness of the adjuvant in treating deep soft tissue injuries. The results show that the prescription can be evenly dispersed in the adjuvant. Moreover, the introduction of the prescription has not significantly changed these advanced properties of the adjuvant. Importantly, the hydrogel adjuvant significantly improves the effectiveness of the prescription in treating deep soft tissue injuries. This work offers an alternative approach to the development of a new-type adjuvant of Chinese medicine external preparations and also provides a new strategy for the combination of traditional Chinese medicine and hydrogel to treat clinical diseases.

Association between osteoporosis or osteopenia and taking antiplatelet agents in general US population of NHANES.

Background: Osteoporosis (OP) and osteopenia are common bone disorders in old age, and lots of patients suffering from OP or osteopenia need to take antiplatelet agents to treat basic diseases. However, clinical data on the link between osteopenia or OP and antiplatelet agents are limited. Methods: Data in this study were collected and screened from the NHANES from 2013 to 2014 and 2017 to 2018. The variables were extracted from interviews and compared between OP or osteopenia participants and normal. The relationship between OP or osteopenia and taking antiplatelet drugs was analyzed by weighted multivariate logistic regression. Results: After excluding individuals who were not eligible and had invalid data, we finally identified 894 participants for inclusion in the study. We found a negative association between OP or osteopenia and taking antiplatelet agents (OR = 0.53; 95% CI, 0.33-0.84; p < 0.05). These results did not change on multiple imputations (OR = 0.32, 95% CI, 0.19-0.56; p <0.01). In the subgroup analyses, the associations were more significant in women (OR = 0.18, 95% CI, 0.05-0.62; p <0.05). Conclusion: This study demonstrated that the association between OP or osteopenia and taking antiplatelet agents was significant. Therefore, it is necessary to confirm the result by extending further research.