Fragility fractures represent the final clinical manifestation of osteoporosis and are influenced by a range of risk factors. This article discusses the findings from two large-scale studies utilizing biobank and genomic data to investigate the relationships among obesity, type 2 diabetes and fracture risk, and to explore their implications for health management. The studies suggest that general obesity(defined by body mass index, BMI), central obesity(defined by waist circumference), and peripheral obesity exert different effects on fracture risk in older adults. Specifically, individuals who are overweight based on BMI have a lower fracture risk compared to those with normal weight, whereas an increased waist circumference is associated with a higher fracture risk. Moreover, genetic research indicates that genetically determined type 2 diabetes is not causally associated with increased fracture risk. In contrast, observational studies have reported a higher fracture risk in patients with type 2 diabetes; however, this association becomes non-significant after adjusting for diabetes-related risk factors. These findings highlight that maintaining a moderately elevated BMI may benefit bone formation in the elderly by providing mechanical loading to stimulate bone formation. Additionally, effective management of type 2 diabetes complications is essential for reducing fracture risk, and a certain degree of obesity may confer a protective effect against fractures in individuals with type 2 diabetes.

Fragility fractures represent the final clinical manifestation of osteoporosis and are influenced by a range of risk factors. This article discusses the findings from two large-scale studies utilizing biobank and genomic data to investigate the relationships among obesity, type 2 diabetes and fracture risk, and to explore their implications for health management. The studies suggest that general obesity(defined by body mass index, BMI), central obesity(defined by waist circumference), and peripheral obesity exert different effects on fracture risk in older adults. Specifically, individuals who are overweight based on BMI have a lower fracture risk compared to those with normal weight, whereas an increased waist circumference is associated with a higher fracture risk. Moreover, genetic research indicates that genetically determined type 2 diabetes is not causally associated with increased fracture risk. In contrast, observational studies have reported a higher fracture risk in patients with type 2 diabetes; however, this association becomes non-significant after adjusting for diabetes-related risk factors. These findings highlight that maintaining a moderately elevated BMI may benefit bone formation in the elderly by providing mechanical loading to stimulate bone formation. Additionally, effective management of type 2 diabetes complications is essential for reducing fracture risk, and a certain degree of obesity may confer a protective effect against fractures in individuals with type 2 diabetes.

OBJECTIVE：To initially evaluate the safety of ceritinib after it is marketed ，and to provide reference for the rational use of drug. METHODS The report odd ratio method and proportional reporting ratio method were used to mine the signals of ceritinib-related adverse events from FDA adverse event reporting system （FAERS）during the second quarter of 2014 to the third quarter of 2019. The patients ’gender，age，body weight ，daily dose and course of treatment were collected. SPSS 26.0 software was used to test the number of ADR cases of this system group and other system groups by chi square test. RESULTS ：A total of 10 318 ADR reports with ceritinib as the first suspicious drug were collected ， and 236 ADR signals of seretinib were excavated. After excluding the ineffective treatment ，187 ADR signals were obtained ，involving 16 systems. Inaddition to those mentioned in the drug instructions ，the signals also included various nervous disease ，blood and lymph system disease ，infections and infectious disease ，etc.，such as hand-foot-genital syndrome ，mutation of anaplatic lymphoma kinase gene. Among them ，the ADR reports of gastrointestinal diseases were the most （576 cases）. Compared with ADR of other systems ，gender，age，body weight，daily dose and treatment course had significant effects on ADR of gastrointestinal diseases （P＜0.05）. Most of the patient with gastrointestinal ADR after using ceritinih were female （59.9％），45 years old and above （70.3％），body weight ≤65 kg （68.1％），daily dose 451-750 mg/d（50.2％），and medication duration less than 3 months（75.7％）. CONCLUSIONS ：The risk of gastrointestinal ADR in female patients over 45 years old and with body weight less than 65 kg after using seretinib is relatively high. This kind of ADRs are also related to daily dose ，and most of which occur within 3 months. Therefore ，great importance should be attached to drug monitoring during clinical use.

Bone mass is a key determinant of osteoporosis and fragility fractures. Epidemiologic studies have shown that a 10% increase in peak bone mass (PBM) at the population level reduces the risk of fracture later in life by 50%. Low PBM is possibly due to the bone loss caused by various conditions or processes that occur during adolescence and young adulthood. Race, gender, and family history (genetics) are responsible for the majority of PBM, but other factors, such as physical activity, calcium and vitamin D intake, weight, smoking and alcohol consumption, socioeconomic status, age at menarche, and other secondary causes (diseases and medications), play important roles in PBM gain during childhood and adolescence. Hence, the optimization of lifestyle factors that affect PBM and bone strength is an important strategy to maximize PBM among adolescents and young people, and thus to reduce the low bone mass or osteoporosis risk in later life. This review aims to summarize the available evidence for the common but important factors that influence bone mass gain during growth and development and discuss the advances of developing high PBM.
Adolescent ; Adult ; Bone Density ; Bone and Bones ; Child ; Exercise ; Female ; Humans ; Life Style ; Osteoporosis/epidemiology* ; Risk Factors ; Young Adult

This commentary on the paper " Assessment of the genetic and clinical determinants of fracture risk: genome wide association and mendelian randomisation study" published recently on the British Medrcal Journal (BMJ), has been focused on the analysis of the study design and the advantages/disadvantages of large-scale design. Besides discussing the main findings of the study, it is pointed out that the negative relationship between the traits should be interpreted carefully. Finally, we introduce the study design of Mendelian randomization ( MR) and randomized controlled trial (RCT), the similarities and differences between them are compared. We believe that more and more MR studies based on large-scale genome wide association study (GWAS) data will be carried out in the next few years.

Osteoporosis, which is characterized by reduced bone mineral density (BMD) and an increased risk of fragility fractures, is the result of a complex interaction between environmental factors and genetic variants that confer susceptibility. Fracture and other complications caused by osteoporosis have serious impact on the life quality and life span of patients. Although previous linkage and candidate gene studies have provided few replicated loci for osteoporosis, genome-wide approaches and next generation sequencing have produced clear and reproducible findings. To date, 25 genome-wide studies for osteoporosis and related traits have been conducted, identifying 76 genes and loci. In this review, we will update the genetic study of osteoporosis and provide some perspective views.