BackgroundWith the advancement of world population aging, age-related osteoporosis (OP) and sarcopenia (SP) impose enormous clinical and economic burden on society. Evidence from accumulating studies indicates that they mutually influence one another. However, an observational study may be affected by potential confounders. Meanwhile, a Mendelian randomization (MR) study can overcome these confounders to assess causality.ObjectivesThe aim of this study was to evaluate the causality between OP and SP, informing new strategies for prevention, diagnosis, and treatment of osteosarcopenia.MethodsInstrumental variables (IVs) at the genome‐wide significance level were obtained from published summary statistics, and the inverse variance weighted method and several other MR methods were conducted to evaluate the bi-directional causality between SP and OP. Myopia was analyzed as a negative control outcome to test the validity of IVs.ResultsFemoral neck bone mineral density (FN BMD), lumbar spine BMD (LS BMD), and forearm BMD (FA BMD) had a direct causal effect on appendicular lean mass (ALM) [FA BMD-related analysis: odds ratio (OR) = 1.028, 95% confidence interval (CI) = (1.008,1.049), p = 0.006; FN BMD-related analysis: OR (95% CI) = 1.131 (1.092,1.170), p = 3.18E-12; LS BMD-related analysis: OR (95% CI) = 1.080 (1.062,1.098), p = 2.86E-19]. ALM had a significant causal effect on LS BMD [OR (95% CI) = (1.033,1.147), p = 0.001]. There was no evidence for causal association between BMD and low grip strength.ConclusionsOP and SP might mutually have a significant causal effect on each other. Our results supported the idea that the patient with severe OP was more susceptible to lose ALM and severe ALM loss might reduce LS BMD.

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Aim To investigate the potential causal relationship between non‐alcoholic fatty liver disease (NAFLD) and complications in type 1 diabetes (T1D) and type 2 diabetes (T2D). Materials and Methods Two‐sample Mendelian randomization (MR) analysis was conducted to appraise after controlling for the confounding factors. Genetic instrument variables for NAFLD surrogated by chronically elevated serum alanine transferase were derived from a recent genome‐wide association study. Diabetes‐related complications, including diabetic ketoacidosis, nephropathy and retinopathy, were included as outcomes. Four complementary MR methods were used to test reliability. Results Genetically instrumented NAFLD showed a suggestive causal association with ketoacidosis in T1D (odds ratio [OR]: 1.574; 95% confidence interval [CI]: 1.076, 2.302; P = .019; false discovery rate [FDR] = 0.096) and a significant causal association with early‐stage kidney disease in T1D (OR: 1.249; 95% CI: 1.089, 1.432; P = 1.457 × 10−3, FDR = 0.015). Sensitivity analysis indicated low heterogeneity, low pleiotropy and high reliability of the causal estimates. However, the MR analyses failed to show a causal association between NAFLD and T1D retinopathy, T2D ketoacidosis, nephropathy and retinopathy. Conclusions This study supports a causal effect of genetically driven chronic serum alanine aminotransferase‐associated NAFLD on early‐stage kidney disease in T1D and a suggestive causal effect on ketoacidosis in T1D. However, MR studies did not provide enough evidence to suggest that NAFLD independently increases the risk of retinopathy in T1D and of ketoacidosis, nephropathy and retinopathy in T2D.

Central nervous system (CNS) diseases are common diseases that threaten human health. The CNS is highly enriched in lipids, which play important roles in maintaining normal physiological functions of the nervous system. Moreover, many CNS diseases are closely associated with abnormal lipid metabolism. Exosomes are a subtype of extracellular vesicles (EVs) secreted from multivesicular bodies (MVBs) . Through novel forms of intercellular communication, exosomes secreted by brain cells can mediate inter-neuronal signaling and play important roles in the pathogenesis of CNS diseases. Lipids are essential components of exosomes, with cholesterol and sphingolipid as representative constituents of its bilayer membrane. In the CNS, lipids are closely related to the formation and function of exosomes. Their dysregulation causes abnormalities in exosomes, which may, in turn, lead to dysfunctions in inter-neuronal communication and promote diseases. Therefore, the role of lipids in the treatment of neurological diseases through exosomes has received increasing attention. The aim of this review is to discuss the relationship between lipids and exosomes and their roles in CNS diseases.