OBJECTIVES: Femoral neck fracture is the most serious osteoporotic fractures that is responsible for high medical costs and high mortality. Femoral neck geometric parameters (FNGPs) are important parameters that reflect the geometrical characteristics of femoral neck, and are closely related to the strength of femoral neck and the risk of fragility fracture.There are differences in the incidence of femoral neck fractures among races. However, whether there is difference in FNGPs among races is unknown.Therefore, this study aims to compare the differences in FNGPs between Chinese and Japanese females. METHODS: This study was a cross-sectional study, in which 3 859 healthy females aged 10-86 (45.7±17.1) years old were recruited from Changsha City of Hunan Province and surrounding areas. The weight and height were measured and recorded, and the body mass index (BMI) was calculated. A dual energy X-ray absorptiometry (DXA) bone densitometer was used to measure femoral neck projective bone area (BA) and bone mineral density (BMD). FNGPs were calculated using the BMD and BA, which included the outer diameter (OD), cross-sectional area (CSA), cortical thickness (CT), endocortical diameter (ED), buckling ratio (BR), section modulus (SM), cross-sectional moment of inertia (CSMI), and compression strength index (CSI). The data of FNGPs in Japanese females was collected from literature. These subjects were grouped by 10-year age. The mean and standard deviation of height, weight, BMI, femoral neck BMD, and FNGPs of each group were calculated. The model with the best goodness-of-fit was selected from various mathematical regression models to analyze the distribution trend and the best fitting curve of FNGPs with age. The differences in FNGPs between Chinese and Japanese females were analyzed by using age-corresponding mean fitting curve for paired t-test, and the relative change rates of FNGPs were compared. RESULTS: The mean values of FNGPs were significantly different among different years old healthy females (all P<0.01). The mean values of OD, CSA, CT, SM, and CSMI in femoral neck were high at 30 to 39 years old, and then they were gradually decreased with age. The CSI reached its peak at 20-29 years old, and it was decreased gradually after 30 years old. ED and BR were at a low level before 40 years old, they were gradually increased after 40 years old, and reached the maximum average value at 80-86 years old. The variations in FNGPs with age were fitted with the best goodness-of-fit by applying the cubic regression model and the determination coefficients of regression equations (R²: 0.062-0.404) were significant (all P<0.01). The distribution trend of FNGPs with age varied with the indices, among which CSA, CT, SM, CSMI and CSI were increased with age before 35 years old, and then they were decreased with age; BR was at a low level in the early stage, and then it was increased with age after about 40 years. There were significant differences in the fitting curves of FNGPs related to age between Chinese and Japanese females (all P<0.01). The fitting curves of OD, ED, BR and SM in Chinese females were significantly higher than those in Japanese females (all P<0.01), while those of CSA and CT in Chinese females were significantly lower than those in Japanese females (all P<0.01). Before the age of 50, the curves of CSMI and CSI of Chinese females were significantly higher than those of Japanese females (all P<0.01), while after the age of 60 the situation was reversed (all P<0.01). Except for SM and CSI, there were significant differences in the rate of OD, CSA, CT, ED, BR and CSMI with age (all P<0.01). By the age of 80 years old, the rates of change in OD, ED, and BR with the age in Chinese females were increased by 0.91%,3.94%, and 47.5%, respectively, while those in Japanese females were increased by 8.57%, 15.8% and 85.3%, respectively；the rates of change of CSA, CT, and CSMI with the age in Chinese females were declined 28.0%, 29.6%, and 25.2%, respectively, while those in Japanese females were declined 29.9%, 36.2%, and 10.9%, respectively. There were significant difference in the rates of change in FNGPs with the age between Chinese and Japanese females (all P<0.01). CONCLUSIONS The study reveals the variation of FNGPs with age in Chinese, and confirms that there are racial differences in FNGPs between Chinese and Japanese females, which may be one of the important reasons for the difference in the incidence of femoral neck fracture between Chinese and Japanese females.
Absorptiometry, Photon ; Adult ; Aged, 80 and over ; Bone Density ; China/epidemiology* ; Cross-Sectional Studies ; Female ; Femoral Neck Fractures/epidemiology* ; Femur Neck ; Humans ; Japan ; Middle Aged ; Young Adult

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. Conclusion The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. Conclusion The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.

Adult onset Still's disease (AOSD) is a clinical syndrome with multiple organ failure.The patients normally show intermittent high fever for a long time,a transient rash,arthritis or joint pain as the main performance,accompanied by an increase in granulocytes and enlargement in liver,spleen and lymph node.A 71-years-old female patient with type 2 diabetes admitted hospital because of high fever,skin rash,joint pain and increased granulocyte.After review of the iron protein,she was diagnosed as AOSD.We found that clinicians need to improve the understanding for this disease in order to make the early diagnosis,especially in elderly patients with diabetes mellitus.In such patients,ferritin may not be high at early time.However,when the symptoms and signs are consistent with clinical manifestations,and anti-infection treatment effect is poor,we should pay attention to the disease,and repeated review of ferritin is necessary to assist the early diagnosis.

OBJECTIVE: To explore the effect of methylprednisolone on bone mass, microarchitecture and microdamage in cortical bone of ulna in rats. METHODS: Twenty female Sprague-Dawley rats (3.5 months old) were randomly assigned to two groups: a treatment group and a control group (n=10 per group). The treatment group was subcutaneously injected with methylprednisolone 3.5 mg/(kg.d) while the control group was subcutaneously injected with same volume of vehicle (saline). Rats were sacrificed at 9 weeks after the treatments. Before the sacrifice, the body weight and total bone mineral density (BMD) were measured. The right forelimb was separated through humeral shoulder and then single axial fatigue loading was performed on the right ulna. After fatigue load, the middle ulna section was bulkstained in basic fuchsin. Bone histomorphometry and microdamage analysis were performed on the middle ulna section. RESULTS: Compared with the control group, the body weight, total bone BMD and ulnas BMD in the treatment group were decreased by 15%, 6.4% and 4.3% respectively (all P<0.05); the ulna inner perimeter and marrow area in the treatment group were increased by 23.3% and 32%, respectively (both P<0.05), while the outer perimeter were decreased by 3.1% (P>0.05). There was no significant difference in the cortical and total area between the 2 groups (both P>0.05). The number of microcrack, microcrack density and microcrack surface density in the treatment group were increased by 43%, 48% and 50%, respectively, compared with those in the control group (all P<0.05), but there was no significant difference in the mean length of microcrack between the 2 groups (P>0.05). CONCLUSION Methylprednisolone can significantly induce the bone loss and the deterioration of microarchitecture and microdamage in ulna of rats.
Animals ; Bone Density ; drug effects ; Female ; Methylprednisolone ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Ulna ; drug effects ; pathology

BACKGROUNDGenetic factors are important in the pathogenesis of osteoporosis, but less is known about the genetic determinants of osteoporosis treatment. We aimed to explore the association between the gene polymorphisms of key enzyme farnesyl diphosphate synthase (FDPS) in mevalonate signaling pathway of osteoclast and response to alendronate therapy in osteoporotic postmenopausal women in China.

METHODSThe study group comprised 639 postmenopausal women aged (62.2 ± 7.0) years with osteoporosis or osteopenia who had been randomly assigned to low dose group (70 mg/2 w) or standard dose group (70 mg/w) of alendronate in this 1-year study. We identified allelic variant of the FDPS gene using the polymerase chain reaction and restriction enzyme Faul. Before and after treatment, serum levels of calcium, phosphate, alkaline phosphatase (ALP), cross linked C-telopeptide of type I collagen (β-CTX) were detected. Bone mineral density (BMD) at lumbar spine and proximal femur was measured. The association was analyzed between the polymorphisms of FDPS gene and the changes of BMD, bone turnover biomarkers after the treatment.

RESULTSThe FDPS rs2297480 polymorphisms were associated with baseline BMD at femoral neck, and patients with CC genotype had significantly higher baseline femoral neck BMD ((733.6 ± 84.1) mg/cm(2)) than those with AC genotypes ((703.0 ± 86.9) mg/cm(2)) and AA genotypes ((649.8 ± 62.4) mg/cm(2)) (P < 0.01). No significant difference in BMD at lumbar spine was observed among different genotypes of FDPS. The percentage change of serum ALP level was significantly lower in patients with CC genotype (-22.9%) than that in those with AC genotype (-24.1%) and AA genotype (-29.8%) of FDPS after 12 months of alendronate treatment (P < 0.05). Neither percentage change of BMD nor β-CTX level after alendronate treatment had association with FDPS genotype.

CONCLUSIONSFDPS gene was probably a candidate gene to predict femoral neck BMD at baseline. FDPS gene alleles could predict change percentage of ALP after treatment of alendronate, but possibly had no significant relationship with the responsiveness of BMD to alendronate therapy.

Alendronate ; therapeutic use ; Asian Continental Ancestry Group ; Bone Density Conservation Agents ; therapeutic use ; Female ; Geranyltranstransferase ; genetics ; Humans ; Middle Aged ; Osteoporosis, Postmenopausal ; drug therapy ; genetics ; Polymorphism, Genetic

Genotypes of estrogen receptor gene (ER) α and β in 110 patients with non-alcoholic fatty liver disease (NAFLD) and 100 control subjects were examined by polymerase chain reaction-based restriction fragment length polymorphism.The haplotype analysis was conducted by SHEsis on-line computing platform.The results showed that there were no differences in the genotype frequencies and allele frequencies of ERα at Xba Ⅰ and Pvu Ⅱ enzyme cutting sites between two groups (P ＞ 0.05).There existed significant differences in the genotype frequencies and allele frequencies of ERβ at Rsa Ⅰ and Alu Ⅰ enzyme cutting sites between these two groups (P ＜ 0.05 or P ＜0.01).The risk of NAFLD in postmenopausal women with R or a allele was 1.833 (95％ CI1.209-2.779,P＜0.05)or 1.782 (95％ CI 1.037-3.061,P＜0.05) fold of that with allele r or A.The frequency of r-A haplotype in ERβ was significantly lower in NAFLD group than that in control group (OR =0.529,95％ CI 0.348-0.805).Logistic regression analysis showed the relationship of fasting blood glucose,triglyceride,body mass index,diastolic pressure,Alu Ⅰ genotype with NAFLD (all P＜0.01).The risk of NAFLD in postmenopausal women with Aa/aa genotype was 1.345 (95％ CI 1.028-2.505,P＜0.05) folds of that with AA genotype.

The osteocyte has been found to be an orchestrator of bone remodeling.The damage of bone leads to osteocyte apoptosis.Sclerostin secreted by osteocyte causes feedback inhibition of bone formation,so inhibition of sclerostin expression has become a new target of treatment for osteoporosis.It seems resonable to direct clinical practise and treatment of metabolic bone diseases through understanding the function of osteocyte in the process of bone remodeling.

It has been demonstrated that connective tissue growth factor(CTGF) may enhance proliferation and differentiation of osteoblasts,inhibit the functions of osteoblasts,increase osteoclastogenesis in patients with Rheumatoid Arthritis,stimulate proliferation and differentiation of chondrocytes,and induce angiogenesis in vivo and vitro.Above all,CTGF plays an important role in sustaining growth of skeleton and cartilage,and thus maintaining bone quantity.

This paper is aimed to explore the effects of mechanical stimulation on proliferation and differentiation of osteoblasts. Cultured MG-63 osteoblast-like cells were strained by the four-point bending cell mechanics loader. In the study, we observed the effects of different magnitudes and duration of mechanical strain on the markers of proliferation and differentiation in osteoblasts. The protein levels and Alkaline phosphatase (ALP) activity were determined by western blot and alpha-nitrophenyl phosphate assay respectively. The mineralization nodules were stained using Alizarin Red-S method. We found: (1) the expression of proliferating cell nuclear antigen (PCNA), ALP activity in strained group were significantly increased compared to those in the control group, but the role did not increase with the increase of the magnitude of the stimulation; and (2) under appropriate stimulation (2000 microstrain), the expression of PCNA, COL I protein and ALP activity increased gradually with the increase of loading time, and appropriate stimulation promoted the formation of mineralization nodules. It indicated that appropriate mechanical stimulation could promote proliferation and differentiation of osteoblasts.
Alkaline Phosphatase ; metabolism ; Cell Differentiation ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Osteoblastoma ; pathology ; Osteoblasts ; cytology ; Proliferating Cell Nuclear Antigen ; metabolism ; Stress, Mechanical