Association of osteoporotic fractures of femoral neck and femoral neck geometric parameters in native Chinese women.

BACKGROUND: Although it is generally believed that the femoral neck fracture is related to the femoral neck geometric parameters (FNGPs), the association between the risk of osteoporotic fracture of the femoral neck and FNGPs in native Chinese women is still unclear. METHODS: A total of 374 female patients (mean age 70.2 ± 9.32 years) with osteoporotic fracture of the femoral neck, and 374 non-fracture control groups were completely matched with the case group according to the age ratio of 1:1. Using DXA bone densitometer to measured eight FNGPs: 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 compressive strength index (CSI) at the narrowest point of the femoral neck. RESULTS: Compared with the control group, the average values of OD (2.9%), ED (4.5%), and BR (26.1%) in the patient group significantly increased (p = 0.015 to < 0.001), while CSA (‒15.3%), CT (‒18.2%), SM (‒10.3%), CSMI (‒6.4%), and CSI (‒10.8%) significantly decreased (all p < 0.001). The prevalence of osteoporosis in the lumbar spine, femoral neck, and total hip was, respectively, 82%, 81%, and 65% in fracture patients. Cox proportional hazard model analysis showed that in the age adjusted model, the fracture hazard ratio (HR) of CSA, CT, BR, SM, and CSI significantly increased (HRs = 1.60‒8.33; 95% CI = 1.08‒16.6; all p < 0.001). In the model adjusted for age and femoral neck BMD, HRs of CT (HRs = 3.90‒8.03; 95% CI = 2.45‒15.1; all p < 0.001) and BR (HRs = 1.62‒2.60; 95% CI = 1.20‒5.44; all p < 0.001) were still significantly increased. CONCLUSION: These results suggest that the majority of osteoporotic fractures of the femoral neck of native Chinese women occur in patients with osteoporosis. CT thinning or BR increase of FNGPs may be independent predictors of fragility fracture of femoral neck in native Chinese women unrelated to BMD.

Association of follicle-stimulating hormone with bone turnover markers and bone mineral density in Chinese women across the menopausal transition.

BACKGROUND: Elevated follicle-stimulating hormone (FSH) is associated with an increased risk of postmenopausal osteoporosis. This study investigated the association of serum FSH with bone turnover markers (BTMs) and bone mineral density (BMD) in healthy women undergoing menopausal transition. METHODS: A total of 487 healthy women (age 35-65 years, 50 ± 8.5 years) were enrolled in this study. Serum FSH, BTMs, and BMD at lumbar spine and total hip were measured in these subjects. RESULTS: Follicle-stimulating hormone was positively correlated with various BTMs (r = 0.339-0.583, all p < 0.001) and negatively correlated with lumbar spine and total hip BMD (r = -0.629 and -0.514, all p < 0.001). After adjusting for age and body mass index, the partial correlation coefficients of FSH with BTMs and BMD remained significant. Estimating from the regression equation, for every 10 IU/L increase in serum FSH, BTMs increased by 0.38-3.6 units, and BMD decreased by 0.03-0.05 g/cm2 , respectively. Multiple linear regression analysis showed that FSH was a positive factor for serum bone-specific alkaline phosphatase, osteocalcin, and N-telopeptide of collagen type 1 (ß = 0.188-0.403, all p < 0.001), and a negative factor for lumbar spine BMD and serum C-telopeptide of collagen type 1 (ß = -0.629 and -0.183, all p < 0.001). CONCLUSIONS: This study suggests that serum FSH levels are an independent risk factor for BTMs and BMD in menopause-transitioning women, particularly for serum BAP and lumbar spine BMD.

A phase III randomized, double-blind, placebo-controlled trial of the denosumab biosimilar QL1206 in postmenopausal Chinese women with osteoporosis and high fracture risk.

The current study evaluated the efficacy and safety of a denosumab biosimilar, QL1206 (60 mg), compared to placebo in postmenopausal Chinese women with osteoporosis and high fracture risk. At 31 study centers in China, a total of 455 postmenopausal women with osteoporosis and high fracture risk were randomly assigned to receive QL1206 (60 mg subcutaneously every 6 months) or placebo. From baseline to the 12-month follow-up, the participants who received QL1206 showed significantly increased bone mineral density (BMD) values (mean difference and 95% CI) in the lumbar spine: 4.780% (3.880%, 5.681%), total hip :3.930% (3.136%, 4.725%), femoral neck 2.733% (1.877%, 3.589%) and trochanter: 4.058% (2.791%, 5.325%) compared with the participants who received the placebo. In addition, QL1206 injection significantly decreased the serum levels of C-terminal crosslinked telopeptides of type 1 collagen (CTX): -77.352% (-87.080%, -66.844%), and N-terminal procollagen of type l collagen (P1NP): -50.867% (-57.184%, -45.217%) compared with the placebo over the period from baseline to 12 months. No new or unexpected adverse events were observed. We concluded that compared with placebo, QL1206 effectively increased the BMD of the lumbar spine, total hip, femoral neck and trochanter in postmenopausal Chinese women with osteoporosis and rapidly decreased bone turnover markers. This study demonstrated that QL1206 has beneficial effects on postmenopausal Chinese women with osteoporosis and high fracture risk.

Effect of Body Surface Area on Severe Osteoporotic Fractures: A Study of Osteoporosis in Changsha China.

Clinical vertebral fractures and femoral neck fractures are severe osteoporotic fractures that increase morbidity and mortality. Anthropometric variables are associated with an increased risk of osteoporotic fractures, but it is not clear whether body surface area (BSA) has an effect on clinically severe osteoporotic fractures. The study included total of 3,694 cases of clinical vertebral fractures and femoral neck fractures (2,670 females and 1,024 males) and 3,694 controls without fractures who were matched with the cases by sex and age. There was a significant positive correlation between BSA and bone mineral density (BMD) in female and male fracture patients (females: r = 0.430-0.471, P < 0.001; males: r = 0.338-0.414, P < 0.001). There was a significant systematic increase in BMD in both genders at various skeletal sites, grouped by BSA quartile. The osteoporosis rates of the lumbar spine (97.9%), femoral neck (92.4%) and total hip (87.1%) in the female Q1 group were significantly higher than those in the Q4 group (P < 0.001), which were 80.0%, 57.9% and 36.9%, respectively, in the Q4 group; the osteoporosis rates of the lumbar spine, femoral neck, and total hip were 53.9%, 59.4%, and 36.3% in the male Q1 group, and 15.2%, 21.9%, and 7.03% in the Q4 group, which were significantly lower than those in the Q1 group (P < 0.001). In age-adjusted Cox regression models, the risk of fracture in the remaining three groups (Q2, Q3, and Q4) for weight, BMI, and BSA for both genders, compared with the highest quartile (Q1 by descending quartile stratification) were significantly higher. In models adjusted for age and BMD, only men in the BSA Q3 (HR = 1.55, 95% CI = 1.09-2.19) and BSA Q4 groups (HR = 1.41, 95% CI = 1.05-1.87) had significantly higher fracture risks. In models adjusted for age, height, weight, BMI, and BSA, low BMD was the greatest fracture risks for both sexes. Our results showed that BSA was closely related to BMD, prevalence of osteoporosis, and fracture risk, and that a decline in BSA may be a new potential risk factor for osteoporotic fractures in Chinese men.

Aromatase deficiency caused by mutation of CYP19A1 gene: A case report. / CYP19A1åŸºå› çªå˜è‡´èŠ³é¦™åŒ–é ¶ç¼ºä¹ç—‡1例.

Aromatase deficiency (AD) is a rare autosomal recessive genetic disease caused by loss-of-function mutations in aromatase gene (CYP19A1), leading to congenital estrogen deficiency syndrome. Both mothers of AD patients during pregnancy and female AD fetus show virilization, while male patients are usually diagnosed in adulthood due to continued height increase and metabolic abnormalities. In 2019, a patient with AD was admitted in the Second Xiangya Hospital. The patient was a 37-year-old adult male who continued to grow linearly after adulthood. His estradiol was below the measurable line, the follicle-stimulating hormone (FSH) increased, bone age delayed, epiphysis unfused, and the bone mass reduced. CYP19A1 gene detection showed that c.1093C>T, p.R365W was homozygous mutation. This disease is rare in clinic. Clinicians need to raise awareness of the disease for early diagnosis and treatment to improve the long-term prognosis of patients.

Comparison of femoral neck geometric parameters between Chinese and Japanese females. / ä¸­å›½å¥³æ€§ä¸Žæ—¥æœ¬å¥³æ€§è‚¡éª¨é¢ˆå‡ ä½•å‚æ•°çš„æ¯”è¾ƒ.

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.

Relationship between bone mineral density and fragility fracture risk: a case-control study in Changsha, China.

BACKGROUND: Fragility fracture is associated with bone mineral density (BMD), and most databases used in related researches are instrument-matched. Little is known about the relationship between BMD and fragility fracture risk of native Chinese, especially using local databases as reference databases. OBJECTIVE: To investigate relationship between BMD and risk of fragility fracture in native China. METHODS: 3,324 cases, including 2,423 women (67.7 ± 8.9 years) and 901 men (68.4 ± 11.6 years) having radiological fragility fractures and 3,324 age- and gender-matched controls participated in the study. We measured BMD at posteroanterior spine and hip using dual-energy X-ray absorptiometry (DXA), calculated BMD measurement parameters based on our own BMD reference database. RESULTS: BMDs and mean T-scores were lower in case group (with clinical fragility) than in control group (without clinical fragility). In patients with fragility fractures, prevalence of lumbar osteoporosis, low bone mass, and normal BMD were 78.9 %, 19.3 %, and 1.8 %, respectively, in women, and 49.5, 44.8 %, and 5.7 %, respectively, in men. In hip, these prevalence rates were 67.2 %, 28.4 %, and 4.4 % in females, and 43.2 %, 45.9 %, and 10.9 % in males, respectively, showing differences between females and males. Multivariate Cox regression analysis showed that after adjusting age, height, weight, and body mass index, fracture hazard ratio (HR) increased by 2.7-2.8 times (95 % CI 2.5-3.1) and 3.6-4.1 times (95 %CI 3.0-5.1) for women and men respectively with decreasing BMD parameters. In both sexes, risk of fragility fracture increased approximately 1.6-1.7 times (95 % CI 1.5-1.8) for every 1 T-score reduction in BMD. CONCLUSIONS: Risk of clinical fragility fracture increases with decreasing BMD measurement parameters and anthropometric indicators in native China, and fracture HR varies from gender and site.

Novel homozygous protein-truncating mutation of BBS9 identified in a Chinese consanguineous family with Bardet-Biedl syndrome.

BACKGROUND: Bardet-Biedl syndrome (BBS) is a rare and genetically heterogeneous disease with a broad spectrum of clinical features, including but not limited to rod-cone dystrophy, postaxial polydactyly, central obesity, intellectual disability, hypogonadism, and renal dysfunction. Twenty-one BBS (Bardet-Biedl syndrome) genes have been identified to date. There is minimal mutation information on BBS in Chinese populations and the exact pathogenic mechanism of the null mutation of BBS9 remains unknown. METHODS: A patient from a Chinese consanguineous family presented with polydactyly, truncal obesity, intellectual disability, genital anomaly, and retinitis pigmentosa was analyzed in this study. Blood DNA and RNA were extracted from the blood of the proband and the parents. The proband was screened for mutations by whole-exome sequencing. The likely pathogenic mutation detected in the proband was further confirmed by the Sanger sequence in the family. Real-time RT-PCR was used to measure the expression of BBS9 in the proband and the control. RESULTS: Targeted exome sequencing identified a novel homozygous null mutation (NM_198428.3: c.445C>T) in the 6th exon of the BBS9 gene in the proband and Sanger sequencing was used to validate the heterozygosity in the parents. The mutation was validated to induce the nonsense-mediated decay of BBS9 messenger RNAs by real-time RT-PCR. CONCLUSIONS: The molecular findings helped to explain the clinical manifestations. The novel homozygous pathogenic variation expanded the mutational spectrum of the BBS9 gene in the Chinese population and will help to understand the pathogenic mechanism of BBS9 null mutation.

Serum exosomes from young rats improve the reduced osteogenic differentiation of BMSCs in aged rats with osteoporosis after fatigue loading in vivo.

BACKGROUND: Osteoporosis is a major public health concern for the elderly population and is characterized by fatigue load resulting in bone microdamage. The ability of bone mesenchymal stem cells (BMSCs) to repair bone microdamage diminishes with age, and the accumulation of bone microdamage increases the risk of osteoporotic fracture. There is a lack of effective means to promote the repair of bone microdamage in aged patients with osteoporosis. Exosomes have been shown to be related to the osteogenic differentiation of BMSCs. Here, we aimed to evaluate the changes in the osteogenic differentiation capacity of BMSCs in aged osteoporotic rats after fatigue loading and the treatment potential of serum exosomes from young rats. METHODS: The tibias of six aged osteoporotic rats were subjected to fatigue loading in vivo for 2 weeks, and the bone microdamage, microstructures, and mechanical properties were assessed. Subsequently, BMSCs were extracted to evaluate their proliferation and osteogenic differentiation abilities. In addition, the BMSCs of aged osteoporotic rats after fatigue loading were treated with serum exosomes from young rats under osteogenic induction conditions, and the expression of osteogenic-related miRNAs was quantified. The osteogenetic effects of miRNA-19b-3p in exosomes and the possible target protein PTEN was detected. RESULTS: Obvious bone microdamage at the fatigue load stress point, the bone microstructure and biomechanical properties were not obviously changed. A decreased osteogenic differentiation ability of BMSCs was observed after fatigue loading, while serum exosomes from young rats highly expressing miRNA-19b-3p improved the decreased osteogenic differentiation ability of BMSCs. Transfection with miRNA-19b-3p mimic could promote osteoblastic differentiation of BMSCs and decreased the expression of PTEN. After transfection of miRNA-19b-3p inhibitor, the promotional effect of exosomes on bone differentiation was weakened. Treatment with transfected exosomes increased the expression of PTEN. CONCLUSION: Serum exosomes derived from young rats can improve the decreased osteogenic differentiation ability of BMSCs in aged rats with osteoporosis after fatigue loading and can provide a new treatment strategy for the repair of bone microdamage and prevention of fractures.

Bone mineral density spectrum in individuals with type 1 diabetes, latent autoimmune diabetes in adults, and type 2 diabetes.

OBJECTIVE: To assess bone mineral density (BMD) and associated clinical factors in patients with type 1 diabetes (T1D), latent autoimmune diabetes in adults (LADA), and type 2 diabetes (T2D) and in non-diabetic subjects. METHODS: Total 108 age-, sex-, disease duration-, and postmenopausal ratio-matched patients with T1D, LADA, and T2D each and 216 age-, sex-, and postmenopausal ratio-matched non-diabetic controls. Anthropometric, biochemical, and BMD data were collected and analysed. RESULTS: BMD of total hip and lumbar spine of individuals in the LADA group was lower than those in the T2D and control groups but higher than those in the T1D group. After adjusting for body mass index (BMI), a significant difference in BMD in the lumbar spine was seen between groups. After adjustment for smoking, BMI, 25-(OH) vitamin D, calcium, haemoglobin A1c, and diabetic complication scores, BMD values of patients in LADA group were not significantly different from those of patients in T1D and T2D groups. Multiple stepwise regression analysis showed that BMD was (a) positively associated with weight and C-peptide, and negatively associated with age in patients with diabetes, (b) positively associated with C-peptide in the T1D and LADA groups. The proportion of patients with osteoporosis in the T1D, LADA, T2D, and control groups was 55.6%, 45.4%, 34.3%, and 26.9%, respectively. CONCLUSIONS: BMD values in T1D, LADA, and T2D were in an increasing order of mention. Patients with autoimmune diabetes were more susceptible to osteoporosis. A lower C-peptide level may be responsible for decreased BMD in individuals with autoimmune diabetes.

Immunodominant regions prediction of nucleocapsid protein for SARS-CoV-2 early diagnosis: a bioinformatics and immunoinformatics study.

COVID-19 caused by SARS-CoV-2 is sweeping the world and posing serious health problems. Rapid and accurate detection along with timely isolation is the key to control the epidemic. Nucleic acid test and antibody-detection have been applied in the diagnosis of COVID-19, while both have their limitations. Comparatively, direct detection of viral antigens in clinical specimens is highly valuable for the early diagnosis of SARS-CoV-2. The nucleocapsid (N) protein is one of the predominantly expressed proteins with high immunogenicity during the early stages of infection. Here, we applied multiple bioinformatics servers to forecast the potential immunodominant regions derived from the N protein of SARS-CoV-2. Since the high homology of N protein between SARS-CoV-2 and SARS-CoV, we attempted to leverage existing SARS-CoV immunological studies to develop SARS-CoV-2 diagnostic antibodies. Finally, N229-269, N349-399, and N405-419 were predicted to be the potential immunodominant regions, which contain both predicted linear B-cell epitopes and murine MHC class II binding epitopes. These three regions exhibited good surface accessibility and hydrophilicity. All were forecasted to be non-allergen and non-toxic. The final construct was built based on the bioinformatics analysis, which could help to develop an antigen-capture system for the early diagnosis of SARS-CoV-2.

Fetal bovine serum-derived exosomes regulate the adipogenic differentiation of human bone marrow mesenchymal stromal cells in a cross-species manner.

Fetal bovine serum (FBS) contains a large number of exosomes which may disturb the analysis of exosomes derived from cultured cells. We investigated the effect of FBS-derived exosomes (FBS-Exos) on the adipogenic differentiation of human bone marrow mesenchymal stromal cells (hBM-MSCs) and the underlying molecular mechanism. The uptake of FBS-Exos by hBM-MSCs could be detected by the laser confocal microscopy, and the treatment of exosomes resulted in the decreased lipid droplet formation and reduced expression of genes associated with adipogenic differentiation of hBM-MSCs. miR-1246 was identified as an abundant microRNA in FBS-Exos by public sequencing data identification and RT-qPCR validation. Moreover, miR-1246 overexpression in hBM-MSCs led to decreased adipogenic differentiation level, while miR-1246 knockdown in FBS-Exos attenuated the inhibitory effect on the adipogenic differentiation. Our results indicate that FBS-Exos inhibit the adipogenic differentiation of hBM-MSCs in a cross-species manner and miR-1246 transferred by FBS-Exos partly contributes to this effect.

Microstructural properties of trabecular bone autografts: comparison of men and women with and without osteoporosis.

The microstructure of autologous bone grafts from men over 50 years old and postmenopausal women undergoing spinal fusion were evaluated using micro-CT. We demonstrated postmenopausal women, especially those with osteoporosis (OP) presented more serious microarchitectural deterioration of bone grafts. PURPOSE: This study was undertaken to determine microstructural properties of cancellous bone used as autologous bone grafts from osteoporosis patients undergoing lumbar fusion by comparing microstructural indices to controls. METHODS: Cancellous bone specimens from spinous processes were obtained from 41 postmenopausal women (osteoporosis women, n = 19; controls, n = 22) and 26 men over 50 years old (osteoporosis men, n = 8; controls, n = 18) during lumbar fusion surgery. The microstructural parameters were measured using micro-CT. RESULTS: Significant difference in bone volume fraction (BV/TV), specific bone surface (BS/BV), trabecular thickness (Tb.Th), and structure model index (SMI) value existed between postmenopausal women with OP and controls. Significant difference in trabecular number (Tb.N) existed between men over 50 years old with OP and controls. Postmenopausal women exhibited lower BV/TV, Tb.Th, and higher SMI value than men over 50 years old. Postmenopausal women with OP exhibited lower BV/TV, Tb.Th, and higher BS/BV than men over 50 years old with OP. CONCLUSIONS: Post-menopausal women and older men with OP have worse bone quality in autografts than non-osteoporotic men and women. Postmenopausal women with OP presented serious microarchitectural deterioration in older population.

Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist Liraglutide Alters Bone Marrow Exosome-Mediated miRNA Signal Pathways in Ovariectomized Rats with Type 2 Diabetes.

BACKGROUND Compared with normal postmenopausal women, estrogen deficiency and hyperglycemia in postmenopausal women with type 2 diabetes (T2DM) lead to more severe bone property degradation. Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has been reported to improve bone condition among people with T2DM but the precise mechanisms remain unclear. Exosomes work as mediators in cell-to-cell communication, delivering functional miRNAs between cells. We aimed to explore the role of exosomes in T2DM-related bone metabolic disorders and the bone protective mechanisms of liraglutide. MATERIAL AND METHODS We made comparative analyses of bone marrow-derived exosomal miRNAs from ovariectomized (OVX) control rats, OVX + T2DM rats, and OVX + T2DM + liraglutide-treated rats. miRNA profiles were generated using high-throughput sequencing. Target gene prediction and pathway analysis were performed to investigate the signal pathway alterations. Three miRNAs were randomly chosen to validate their absolute expression levels by real-time quantitative PCR. RESULTS Bone marrow-derived exosomal miRNAs were different with respect to miRNA numbers, species, and expression levels. miRNA spectra varied under T2DM condition and after liraglutide treatment. By bioinformatics analysis, we found T2DM and liraglutide administration lead to significant changes in exosomal miRNAs which targeted to insulin secretion and insulin-signaling pathway. Wnt signaling pathway alteration was the critical point regarding bone metabolism. CONCLUSIONS Our findings show the selective packaging of functional miRNA cargoes into exosomes due to T2DM and liraglutide treatment. Bone marrow exosome-mediated Wnt signaling pathway alteration may play a part in the bone protective effect of liraglutide.

Gender differences in a reference database of age-related femoral neck geometric parameters for Chinese population and their association with femoral neck fractures.

Femoral neck geometric parameters (FNGPs) are closely related to the strength of the femoral neck and the risk of fragility fractures. No reference database is available for FNGPs for Chinese population, and gender-related differences in FNGPs as well as their association with the risk of femoral neck fractures are unknown. This investigation aimed to set up reference databases for FNGPs, understand gender-related differences in FNGPs, and examine the association between FNGPs and the risk of osteoporotic fractures of the femoral neck. This study included 5268 females and 2156 males (aged 15-91years) from Chinese population. A total of 384 patients (282 females and 102 males) had sustained femoral neck fractures; 384 age- and sex-matched individuals without any fractures served as controls. Femoral neck DXA images were used to measure bone mineral density (BMD) and eight FNGPs. Our results showed that the age-related trends of FNGPs were fitted with the best goodness-of-fit by applying the cubic regression model. The trends shown by FNGPs were significantly different between male and female subjects, and the fitting curves were significantly higher in male subjects. After adjustments were made for age, height, weight, and body mass index, Cox regression analysis showed that changes in all FNGPs were related to increased hazard ratios (HRs) of femoral neck fractures. After further adjustment was made for BMD of the femoral neck, the HRs related to a cortical thickness (CT) decrease and buckling ratio (BR) increase in females went up by 3.35-folds (95% CI: 2.75-4.07) and 1.86-folds (95% CI: 1.33-2.60), respectively. In males, the HRs related to the decrease in CT and cross-sectional area (CSA) increased by 3.21-folds (95% CI: 2.32-4.45) and 1.88-folds (95% CI: 1.03-3.44), respectively. In conclusions, the reference databases of FNGPs established in this study will assist in the evaluation and prediction of femoral neck fracture risk in the clinic. The decrease in CT and increase in BR of the femoral neck were independent risk factors for osteoporotic fractures of the femoral neck in females from mainland China, while a decrease in CT and CSA were risk factors in male.

Micro/Nanostructures and Mechanical Properties of Trabecular Bone in Ovariectomized Rats.

Bone mechanical properties encompass both geometric and material factors, while the effects of estrogen deficiency on the material and structural characteristics of bone at micro- to nanoscales are still obscure. We performed a series of combined methodological experiments, including nanoindentation assessment of intrinsic material properties, atomic force microscopy (AFM) characterization of trabecular (Tb) nanostructure, and Tb microarchitecture and 2D BMD. At 15 weeks after surgery, we found significantly less Tb bone mineral density (BMD) at organ (-27%) and at tissue level (-12%), Tb bone volume fraction (-29%), Tb thickness (-14%), and Tb number (-17%) in ovariectomy (OVX) rats than in sham operated (SHAM) rats, while the structure model index (+91%) and Tb separation (+19%) became significantly greater. AFM images showed lower roughness Tb surfaces with loosely packed large nodular structures and less compacted interfibrillar space in OVX than in SHAM. However, no statistically significant changes were in the Tb intrinsic material properties-nanoindentation hardness, elastic modulus, and plastic deformation-nanoindentation depths, and residual areas. Therefore, estrogen deprivation results in a dramatic deterioration in Tb micro/nanoarchitectures, 3D volumetric BMD at both organ and tissue levels, and 2D BMD, but not in the nanomechanical properties of the trabeculae per se.

Association of microstructural and mechanical properties of cancellous bone and their fracture risk assessment tool scores.

This study is to investigate the association between fracture probabilities determined by using the fracture risk assessment tool (FRAX) and the microstructure and mechanical properties of femoral bone trabecula in osteoporosis (OP) and osteoarthritis (OA) patients with hip replacements. By using FRAX, we evaluated fracture risks of the 102 patients with bone replacements. Using micro CT scanning, we obtained the analysis parameters of microstructural properties of cancellous bone. Through morphometric observations, fatigue tests and compression tests, we obtained parameters of mechanical properties of cancellous bones. Relevant Pearson analysis was performed to investigate the association between the fracture probability and the microstructure and mechanical properties of femoral bone trabecula in patients. Fifteen risk factors in FRAX were compared between OP and OA patients. FRAX hip fracture risk score and major osteoporotic in OP and OA patients were significantly different. FRAX was associated with tissue bone mineral density and volumetric bone mineral density. Our study suggests that the probabilities of major osteoporotic and hip fracture using FRAX is associated with bone mass but not with micro bone quality.

[Effect of methylprednisolone on bone mass, microarchitecture and microdamage in cortical bone of ulna in rats].

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.

Age-related bone turnover markers and osteoporotic risk in native Chinese women.

BACKGROUND: The rate of bone turnover is closely related to osteoporosis risk. We investigated the correlation between bone turnover markers and BMD at various skeletal sites in healthy native Chinese women, and to study the effect of changes in the levels of bone turnover markers on the risk of osteoporosis. METHODS: A cross-section study of 891 healthy Chinese women aged 20-80 years was conducted. The levels of serum osteocalcin (OC), bone-specific alkaline phosphatase (BAP), serum cross-linked N-terminal telopeptides of type I collagen (sNTX), cross-linked C-terminal telopeptides of type I collagen (sCTX), urinary NTX (uNTX), urinary CTX (uCTX) and total urinary deoxypyridinoline (uDPD) were determined. BMD at the posteroanterior spine and the hip was measured using DXA. RESULTS: Pearson's correlation coefficient found significant negative correlation between bone turnover marker and BMD T-score at different skeletal sites (r = -0.08 to -0.52, all P = 0.038-0.000). After adjustments for age and body mass index, the partial correlation coefficients between the OC, BAP, sNTX, sCTX and uCTX, and the T-scores at various skeletal sites were still significant. After adjustment of height and weight, the correlation coefficients between most BTMs and PA lumbar spine BMD were also significant. Multiple linear regression analysis showed that bone turnover markers were negative determinants of T-scores. BAP and OC accounted for 33.1% and 7.8% of the variations in the T-scores of the PA spine, respectively. Serum OC, BAP, uDPD, and sNTX accounted for 0.4-21.9% of the variations in the femoral neck and total hip T-scores. The bone turnover marker levels were grouped as per quartile intervals, and the T-scores, osteoporosis prevalence and risk were found to markedly and increase with increase in bone turnover marker levels. CONCLUSIONS: This study clarified the relationship between bone turnover markers and osteoporosis risk in native Chinese women. Bone turnover marker levels were found to be important determinants of BMD T-scores. Furthermore, osteoporotic risk significantly increased with increase in the levels of bone turnover markers.