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Abstract: Osteocytes actively regulate bone modeling and remodeling, direct skeletal mineralization, and regulate calcium/phosphate homeostasis and extracellular matrix metabolism; yet the specific role of osteocytes in maintaining bone structural integrity and strength is unknown. Studies have shown that the density of osteocytes decreases with age and estrogen deficiency, as seen in postmenopausal women. Here, we examined the relationships between osteocyte density and the related variables, including biomechanics, bone mineral density, microcrack and microstructure of vertebral trabeculae, in ovariectomized rats. We found that osteocyte density correlated with some of the parameters that determine the biomechanical quality of bone. Our findings suggest that osteocytes could play a crucial role in maintaining the mechanical quality of bone, and osteocyte density could be considered as an alternative index in assessing bone quality. [Copyright &y& Elsevier]

The BMD reference curve is the reference value used for diagnosing osteoporosis and assessing bone mass changes. Its accuracy would affect the correctness of T -score and Z -score values and thus the reliability of diagnostic results. In this paper, we report the use of a new method, a Cartesian coordinate numeration system, to establish BMD reference curves at different skeletal sites in women. In a reference population of 3,919 women ranging in age from 5–85 years, we used the dual X-ray absorptiometry (DXA) bone densitometer to measure BMD at the posteroanterior spine (PA; vertebrae L1–L4), followed by a paired PA/lateral spine scan of the vertebral bodies of L2–L4, expressed in g/cm2 and g/cm3, and of the hip and forearm. We chose the cubic regression model to best fit BMD curves that varied with age at different skeletal sites. We then referred the BMD of the fitting curves established by the method of the coordinate numeration system as reference curves, compared them to BMD reference curves derived from the fitting curve equation or age cross-section, and calculated the deflection degrees of the BMD reference curves acquired from the fitting curve equation. At the PA spine, lateral spine (expressed in g/cm3), femoral neck, Ward’s triangle and radius + ulna ultradistal, the reference curves calculated from the equation were significantly lower than those confirmed by the method of the coordinate numeration system; whereas, at the lateral spine (expressed in g/cm2), total hip, and radius + ulna 1/3 sites, the reference curves derived from the equation were markedly higher than those acquired from the coordinate numeration system. The differences in the two kinds of reference curves calculated by these two different methods gradually increased along with the increment in ages of the women. At the peak value of the reference curves, the BMD calculated from the equation deflected from 2.02% to −10.0% from the BMD acquired from the coordinate numeration system at different skeletal sites, and from 21.5% to −121.8% until the age of 85 years. The highest positive deflection of 65.2% existed at the lateral spine (expressed in g/cm2) and the lowest positive deflection of 21.5% at the total hip. The maximum negative deflection of −121.8% was at the radius + ulna ultradistal, and the minimum negative deflection of −32.6% at the PA spine. The BMD curve acquired from age cross-section was highly positive compared with the one derived from the coordinate numeration system ( r =0.955–0.985 p =0.000) with no significant difference between them. Various analysts used such a method to obtain the coefficient of variance (CV) in BMD precision on each curve that was from 0.05–0.19%. Our study shows that the Cartesian coordinate numeration system is an accurate, precise and reliable method and can serve to reveal the serious drawbacks of using the fitting curve equation to calculate BMD. The BMD reference curves established by this coordinate numeration system maintained the authenticity of the fitting curve, whereas, using the fitting curve equation to obtain BMD reference curves at different skeletal sites led to distortion, and resulted in false increases or decreases in T -score and Z -score values. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 15–91 years) 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. [ABSTRACT FROM AUTHOR]

Abstract: Background: It remains unclear whether gonadotropins or estrogen is responsible for early bone mineral density (BMD) decrease in Chinese women. Methods: A cross-sectional study was conducted on 368 healthy adult women, aged 35–60years. We measured BMD, calculated BMD decrease rates (BDRs) and assessed serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) levels. Results: BDR was significantly negatively correlated with serum FSH (r =−0.429 to −0.622, all p =0.000) and LH (r =−0.359 to −0.526, all p =0.000). After adjustment for age and body mass index, the negative correlations of serum FSH and LH with BDR persisted, but there was no overall correlation between serum E2 and BDR. Multiple linear stepwise regression analysis suggested that serum FSH is a negative determinant of BDR. Serum E2 seems to be a positive determinant of BDR in a few parts of the skeleton. Conclusions: The decrease of BMD during the menopause is associated with FSH and LH levels, rather than E2 in Chinese women. [Copyright &y& Elsevier]

Abstract: 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 20–81y 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±1.91pmol/l and 10.5±1.99μg/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. [Copyright &y& Elsevier]

Objective. To determine an optimal dosage combination for a nylestriol/levonorgestrel (NYL/LNG) regimen in the treatment of female Sprague-Dawley (SD) rats with retinoic acid (RA)-induced osteoporosis in order to examine the rationale of NYL/LNG use for postmenopausal women. Methods: This study included two sets of experiments; one was designed to confirm the success of the RA-induced osteoporosis model involving 48 SD rats, and the other to determine the optimal dosage combination of NYL/LNG. In the second set of experiments, a total of 160 female SD rats at 7 months of age were randomly divided according to their basal body weights into 16 groups (10 in each). Treatment dosages of NYL and LNG were arrayed in a 2 factor-4 level (2[sup 4]) factorial design, i.e., NYL level I (N1 0.015 mg/kg), level II (N2 0.05 mg/kg), level III (N3 0.15 mg/kg) and level IV (N4 0.5 mg/kg) and LNG level I (L1 0.005 mg/kg), level II (L2 0.015 mg/kg), level III (L3 0.05 mg/kg) and level IV (L4 0.15 mg/kg). For 14 d, 70 mg/kg/d RA was given intragastrically to establish the osteoporofic model and NYL and LNG were then administered in different dosages on alternate days over a 3 wk period. Subsequently, body weight, uterine weight, endometrial status, Bone mineral density (BMD), bone turnover, and morphometry as well as parameters of biomechanics, serum sex hormones and lipids and estrogen receptor-α expression were determined for these rats. Results. Uterine weights at L2, L3, and L4 dosage levels were significantly lower than those at L1 (P < 0.05). Serum estradiol at N4 and progesterone at N2, N3, and N4 had decreased. Bone mineral density at distal tibiae (R5) in L3 and L4, and at proximal femora (R3) in L4 had increased. The peak loading of lumbar vertebrae at N3 was higher than that at N1, N2, and N4 dosage levels and that of femora higher at N3 than that at N1 and N4. Serum alkaline phosphatase (ALP) levels at N3, N4, L2, L3, and L4 dosage levels were lower than those at... [ABSTRACT FROM AUTHOR]