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.

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.

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.

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.

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.

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.

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.

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.

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.

[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.

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.

Relationship of body composition with prevalence of osteoporosis in central south Chinese postmenopausal women.

OBJECTIVES: To elucidate the relationship between body composition and bone mineral density (BMD) and the prevalence of osteoporosis in central south Chinese postmenopausal women. METHODS: A cross-sectional study was conducted on 954 healthy central southern Chinese postmenopausal women, aged 50-82. Total body, lumbar spine and left femur BMD and total body soft tissue composition were measured by dual X-ray absorptiometry. RESULTS: Among the study population, 578 (60.5%) subjects were without osteoporosis and 376 (39.4%) subjects were osteoporotic. The osteoporotic women were older, shorter and thinner, had an earlier age at menopause, a lower BMD and bone mineral content (BMC) of the total body and at different sites, and had lower body mass and body mass components than the women without osteoporosis. Both fat mass and lean mass were positively correlated with age at menopause, height, weight, body mass index (BMI) and BMD at all sites. Fat mass and lean mass were also inversely correlated with age and years since menopause (P<0.05). After controlling for age, age at menopause and height, both fat mass and lean mass were positively correlated with BMD at the lumbar(1-4) spine, the femoral neck and the total hip. Fat mass was the most significant determinant of BMD at the lumbar(1-4) spine with a higher R(2) change and a partial R(2) compared with that of lean mass, while lean mass had more impact on the total hip values. Either a fat mass below 18.4 kg or a lean mass below 33.9 kg was correlated with a higher prevalence of osteoporosis at the lumbar spine or total hip. CONCLUSIONS: In central south Chinese postmenopausal women, both fat mass and lean mass are correlated with BMD at the lumbar spine and hip. Fat mass was the most significant determinant of BMD at the lumbar spine, while lean mass had more impact on the total hip value. Both lower values of fat mass and lean mass are related to a higher prevalence of osteoporosis at either the lumbar spine or the total hip. Thus, it is important to maintain a reasonable body weight to balance bone health and other metabolic disorders.

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.

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.

[The effects of glucocorticoid on expression of cannabinoid-1 receptors in osteoclasts from tibial proximal metaphysis of rats].

OBJECTIVE: To explore the molecular mechanism of glucocorticoid (GC)-induced osteoporosis (GIOP). METHODS: Thirty-two female SD rats after matching body weight were divided randomly into three groups: baseline group (n = 10), control group (n = 11) and GC-treated group (n = 11). The administration time was 9 weeks. Bone mineral density (BMD) was measured with dual energy X-ray absorptiometry. A high resolution micro-CT was used to quantify the densitometric and microarchitectural properties of trabeculae in the proximal metaphysis of right tibia. In situ hybridization histochemistry and immunohistochemistry were used to detect the expression of cannabinoid type 1 receptor (CB1R) in the proximal metaphysis of left tibia. RESULTS: At the end of the experiment, whole-body BMD in vivo in the control group [(0.156 +/- 0.008) g/cm(2)] was higher than that in the baseline group [(0.147 +/- 0.006) g/cm(2)], while the whole-body BMD in vivo [(0.147 +/- 0.006) g/cm(2)] and total BMD in vitro at femurs in the GC-treated group [(0.220 +/- 0.011) g/cm(2)] was lower than those in the control group [(0.240 +/- 0.024) g/cm(2)]. Compared with the baseline group and control group, there was a remarkable decrease in the volumetric BMD, tissue BMD, trabecular number and trabecular connectivity (P < 0.05) in the GC-treated group, while there was a significant increase in trabecular separation (P < 0.05) and trabecular thickness also increased in the proximal metaphysis of tibiae in the GC-treated group. The expression level of CB1R mRNA and protein in osteoclasts in the GC-treated group was markedly higher than that in the baseline group and control group (P < 0.05). There was a close correlation between the expression level of CB1R mRNA, protein in osteoclasts and some microarchitectural parameters in the proximal metaphysis in the GC-treated group (P < 0.05). CONCLUSIONS: The administration of GC is associated with a decrease in BMD and deterioration in microarchitecture of trabecular bone in rats tibiae. Glucocorticoid may up-regulate the CB1R expression level in osteoclasts and this may be a kind of molecular mechanism of GIOP.

Comparison of the effects of genistein and zoledronic acid on the bone loss in OPG-deficient mice.

UNLABELLED: Using osteoprotegerin (OPG)-knockout mice, we demonstrated that in vivo the effects of both genistein and 17beta-estradiol (E2) on bone metabolism were completely abolished. In contrast, zoledronic acid could effectively suppress bone resorption and prevent bone loss. INTRODUCTION: The anti-resorptive effects of E2 on bone metabolism are considered to be mediated via modulation of the osteoblast-derived paracrine factor OPG. Recently, the phytoestrogen genistein was found to suppress bone resorption by enhancing osteoblastic production of OPG. However, the mechanism underlying the in vivo effects of E2 and genistein on bone is not entirely understood, and a central question in this regard is whether E2 regulates bone metabolism via an OPG-dependent pathway. METHODS: After mating heterozygous (OPG+/-) mice, homozygous (OPG-/-) and wild-type (WT) with a mixed C57BL/6J x 129/SV background were obtained. The study involved 6-week-old female OPG-/- (n=40) and WT mice (n=8). The OPG-/- mice were randomly divided into 5 groups (n=8 per group) as follows: (1) genistein-treated mice (Gen) that were subcutaneously injected with genistein at a maximal dose (0.8 mg/day); (2) E2-treated mice (E2) that were subcutaneously injected with E2 at a dose (0.03 microg/day); (3) DMSO control mice (DMSO) that were subcutaneously injected with a mixture of dimethylsulfoxide (DMSO) and polyethyleneglycol-300; (4) zoledronic acid-treated mice (Zol) that were subcutaneously injected with zoledronic acid at a dose of (150 microg/kg) twice per week; and (5) H2O control mice that were subcutaneously injected with sterilized water twice per week. The doses of genistein, estrogen and zoledronic acid were selected based on the results of dose-response effect of agents on bone versus uterus in OPG-/- mice. The mice were sacrificed 6 weeks after this intervention. The microarchitecture of the trabecular and cortical bone was assessed by performing microcomputed tomography (micro-CT) for the right proximal tibia. The bone mineral density (BMD) of the left femur was measured by dual-energy X-ray absorptiometry (DXA). The biomechanical parameters of the right femur were determined by a three-point bend testing. Serum levels of bone alkaline phosphatase (B-ALP), tartarate-resistant acid phosphatase-5b (TRACP-5b), and receptor activator of nuclear factor kappaB ligand (RANKL) were determined by performing ELISA. RESULTS: DXA analysis revealed that the total BMD of the femur was not significantly altered in the Gen, E2, H2O, and DMSO groups. The three-point bending test revealed no significant differences in the biomechanical parameters, including ultimate loading, ultimate stress, stiff index, and elastic modulus, and micro-CT analysis revealed that the microarchitectural parameters of the trabecular bone (vBMD, tBMD, BVF, BSF, SMI, Tb.N, Conn.D, Tb.Sp, and Tb.Th) and cortical bone (Ct.Th, Mm, In.Pm, Ot.Pm, Ma.Ar, Ct.Ar, Tt.Ar, Ct.BMD, and Ct.BMC) did not differ among the groups. Genistein and E2 treatment did not alter the serum TRACP-5b, B-ALP, or RANKL levels. However, in addition to increasing the bone mass, zoledronic acid could effectively improve biomechanical parameters and could completely prevent deterioration of the bone architecture in the OPG-/- mice. CONCLUSIONS: The effects of genistein and E2 on bone metabolism in vivo were lost completely in OPG-deficient mice, suggesting that the effect of these agents on bone metabolism seems to be entirely dependent on OPG. In contrast, zoledronic acid could effectively suppress bone resorption and completely prevent the bone loss in the OPG-/- mice--an effect that is likely to be independent of the OPG pathway.

Experimental study of damage and fracture of cancellous bone using a digital speckle correlation method.

Cancellous bone is a widespread structure in a creatural body, for instance, in the femoral head and spondyle. The damage evolution and crack growth of cattle cancellous bone were studied under three-point-bending load conditions. A series of speckle images with deformation information surrounding the crack tip were recorded, and the full-field displacement distributions were obtained at different loading levels by means of digital speckle correlation method (DSCM). Characterizations of the damage deformation and fracture of cancellous bone were analyzed. These results provide some useful information for studying the fracture behavior of cancellous bone.

Relationship between age-related reference values of serum osteoprotegerin and leptin in native Chinese women and compared with those in women of other races.

BACKGROUND: Osteoprotegerin (OPG) and leptin are important cellular factors in the regulation of bone remodeling. We investigated the serum OPG and leptin in Chinese women. METHODS: The serum OPG and leptin in 690 Chinese women aged 20-81 y were measured by an ELISA. The values of OPG and leptin in women of other races were acquired from previous reports on the same. RESULTS: The geometric mean values (+/- SD) of the serum OPG and leptin in Chinese women were 3.42+/-1.91 pmol/l and 10.5+/-1.99 microg/l, respectively. Further, the serum OPG (4.39+/-1.85 vs 2.74+/-1.81) and leptin (11.4+/-2.21 vs 9.68+/-1.81) in postmenopausal women were significantly higher than in premenopausal women. The serum OPG in middle-aged Chinese women was significantly higher than that in middle-aged Austrian and Icelandic women; however, this is quite contrary to the results obtained in the case of old-aged women. The values of serum leptin in Chinese women were significantly lower than those in white, black, and Mexican American women. CONCLUSIONS: These results provide reliable reference values for OPG and leptin in Chinese adult women. The serum of OPG and leptin differ with ethnicity.