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With the progressive aging of the population, osteoporosis has gradually grown into a global health problem for men and women aged 50 years and older because of its consequences in terms of disabilities and fragility fractures. This is especially true in the People's Republic of China, which has the largest population and an increasing proportion of elderly people, as osteoporosis has become a serious challenge to the Chinese government, society, and family. Apart from the fact that all osteoporotic fractures can increase the patient's morbidity, they can also result in fractures of the hip and vertebrae, which are associated with a significantly higher mortality. The cost of osteoporotic fractures, moreover, is a heavy burden on families, society, and even the country, which is likely to increase in the future due, in part, to the improvement in average life expectancy. Therefore, understanding the epidemiology of osteoporosis is essential and is significant for developing strategies to help reduce this problem. In this review, we will summarize the epidemiology of osteoporosis in the People's Republic of China, including the epidemiology of osteoporotic fractures, focusing on preventive methods and the management of osteoporosis, which consist of basic measures and pharmacological treatments.

Background: Cytokines including transforming growth factor beta 1 (TGF-β1) and osteoprotegerin (OPG) are closely related to bone metabolism. However, the relationships between TGF-β1, OPG and risk of osteoporosis in native Chinese women are unknown. Our research indicated that there is a positive correlation between TGF-β1 and bone mineral density (BMD) T-score, and a negative correlation between OPG and T-score. The risk of osteoporosis is reduced as TGF-β1 increases and increases as OPG was raised. We investigated correlations of BMD T-scores with circulating TGF-β1 and BMD T-scores with circulating OPG in healthy native Chinese women, and to study the effects of changes in TGF-β1 and OPG on osteoporosis., Methods: This was a cross-sectional study of 691 healthy native Chinese women aged 20-80 years. Concentrations of serum TGF-β1 and OPG were determined. BMD T-scores at the posteroanterior spine, left hip, and forearm were measured by dual-energy X-ray absorptiometry., Results: There were positive correlations between serum TGF-β1 and T-scores at the various skeletal sites (r=0.167-0.285, all P=0.000) and negative correlations between serum OPG and T-scores (r=-0.179 to -0.270, all P=0.007-0.000). After adjusting for age and BMI, correlations between TGF-β1 and T-score at the lumbar vertebrae and ultradistal forearm, and between OPG and T-score at the ultradistal forearm in premenopausal subjects, remained statistically significant. Multivariate linear stepwise analysis showed that TGF-β1 could explain 1.9-8.3% of T-score variation at each skeletal site. OPG could explain 2.4-4.4% of T-score variation. When TGF-β1 and OPG concentrations were grouped according to quartile intervals, T-score and the prevalence and risk of osteoporosis varied with changes in the cytokines., Conclusions: The risk of osteoporosis in native Chinese women increased as circulating TGF-β1 was reduced and OPG was raised., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Aims: Omentin-1 (also known as intelectin-1) is a recently identified visceral adipose tissue-derived cytokine that is inversely related to obesity. Our previous study showed that omentin-1 inhibits osteoblastic differentiation of calcifying vascular smooth muscle cells (CVSMCs) in vitro. This study was undertaken to investigate the effects of omentin-1 on arterial calcification and bone metabolism in vivo., Methods and Results: In vitro, omentin-1 stimulated production of osteoprotegerin (OPG) and inhibited production of receptor activator for nuclear factor κB ligand (RANKL) in both CVSMCs and osteoblasts. In vivo, adenovirus-mediated over-expression of omentin-1 attenuated arterial calcification and bone loss in OPG(-/-) mice. All these in vitro and in vivo actions were abrogated by blockade of the PI3K-Akt signalling pathway. Furthermore, omentin-1 reduced serum levels of RANKL, tartarate-resistant acid phosphatase-5b and osteocalcin, all of which are increased dramatically in OPG(-/-) mice., Conclusion: These data suggest that omentin-1 ameliorates arterial calcification and bone loss in vivo through the regulation of the RANK signalling pathway.

MicroRNAs (miRNAs) interfere with translation of specific target mRNAs and are thought to thereby regulate many cellular processes. Recent studies have suggested that miRNAs might play a role in osteoblast differentiation and bone formation. Here, we identify a new miRNA (miR-2861) in primary mouse osteoblasts that promotes osteoblast differentiation by repressing histone deacetylase 5 (HDAC5) expression at the post-transcriptional level. miR-2861 was found to be transcribed in ST2 stromal cells during bone morphogenetic protein 2-induced (BMP2-induced) osteogenesis, and overexpression of miR-2861 enhanced BMP2-induced osteoblastogenesis, whereas inhibition of miR-2861 expression attenuated it. HDAC5, an enhancer of runt-related transcription factor 2 (Runx2) degradation, was confirmed to be a target of miR-2861. In vivo silencing of miR-2861 in mice reduced Runx2 protein expression, inhibited bone formation, and decreased bone mass. Importantly, miR-2861 was found to be conserved in humans, and a homozygous mutation in pre-miR-2861 that blocked expression of miR-2861 was shown to cause primary osteoporosis in 2 related adolescents. Consistent with the mouse data, HDAC5 levels were increased and Runx2 levels decreased in bone samples from the 2 affected individuals. Thus, our studies show that miR-2861 plays an important physiological role in osteoblast differentiation and contributes to osteoporosis via its effect on osteoblasts.

Background: Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) may play an important role in bone mass regulation in postmenopausal women., Methods: A cross-sectional study of 699 healthy Chinese women, aged 20 to 82 y, was conducted. Serum FSH and LH and BMD were measured at the posteroanterior (PA) spine, lateral spine, total hip, and distal forearm., Results: The geometric mean values (+/-SD) of serum FSH and LH in premenopausal women were 3.94 +/- 2.08 and 7.51 +/- 2.58 IU/l, respectively, and in postmenopausal women were 28.8 +/- 1.88 and 25.6 +/- 1.95 IU/l, respectively. The correlation of FSH to BMD at different skeletal regions (r = -0.597 - -0.492, P = 0.000) was higher than that of LH to BMD (r = -0.452 - -0.332, P = 0.000). The prevalences of osteoporosis for the quartiles of FSH at various skeletal sites were 0.57%, 0.43%, 27.1%, and 30.9%, respectively; and of LH were 2.14%, 4.43%, 19.5%, and 26.0%, respectively. The prevalence of osteoporosis in 3rd and 4th quartile was more significantly increased than the 1st and 2nd quartile., Conclusions: These data suggest that FSH and LH levels in circulation are associated with BMD changes and osteoporosis occurrence in Chinese women.

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.

Osteoporosis in men is an increasingly important public health problem. This study was designed to establish bone mineral density (BMD) reference databases for central southern Chinese men at multiple skeletal sites. We recruited 2433 native Chinese males for BMD assessment. Of these, 1537 were healthy volunteers (age range, 15-85 years), and 896 were suspected to have osteoporosis. BMD values were measured at the posteroanterior (PA) and lateral spine, hip, and distal forearm using a Delphi A absorptiometer. The quadratic regression model provided the best fit for age-related changes in BMD in the spine and hip. The cubic regression model was the best for describing age-related BMD changes in the distal forearm. Peak BMD in the lumbar spine, femoral neck, and total hip occurred at 15-19 years. Peak BMD at the distal forearm occurred at 40-44 years. The prevalence of primary osteoporosis in subjects ranging from 50-85 years was 4.3%-27.7% at various skeletal sites. Compared to the databases established here, the Hologic databases led to significantly higher osteoporosis detection rates. The BMD reference databases established for central southern Chinese men provide the most reliable diagnostic standards for osteoporosis detection in men of central south China.

Objective: To investigate prospectively the annual bone loss rate at spine, proximal femur and distal radius in females and its relationship to relevant factors., Methods: The bone mineral density (BMD) at anteroposterior lumber, proximal femur and distal radius in 220 women of Mawangdui Township, aged 36 - 60, was measured twice, March to April 2000 and March to April 2004, using a Hologic QDR 4500A fan beam X-ray bone densitometer., Results: The annual bone loss rate was the highest during the period of 1 to 5 years since menopause, showing an annual bone loss of 1.70% at the anteroposterior spine, and 2.21%, 1.92%, and 1.56% at the femoral neck, greater trochanter, and distal radius respectively. Even before menopause bone loss was found at the femoral neck and distal radius. BMD loss at the anteroposterior spine and greater trochanter was found in the peri-menopause group. The bone loss rate was the highest in the early menopause group (1.56%/year, P < 0.01), and became lower, however, not significantly in the late menopause group (0.38%/year, P > 0.05). Age was positively correlated with the annual bone loss rates at the anteroposterior spine, greater trochanter, and distal radius (gamma = 0.223 - 0.547, P < 0.05 - 0.01), and the number of year since menopause was also positively correlated with the annual bone loss rate at anteroposterior spine and greater trochanter (gamma = 0.432 - 0.569 P < 0.05 - 0.01). However, body weight and body mass index were negatively correlated with the annual bone loss rates at the anteroposterior spine, femoral neck, and greater trochanter (gamma = 0.239 - 0.466, P < 0.05 - 0.01)., Conclusion: Annual bone loss varies at different skeletal region. Age, years since menopause, and body weight influence the bone loss at different skeletal regions in females.

Objective: To study the nanomechanical properties of the vertebral trabeculae of ovariectomized rat using nanoindentation., Methods: Twenty 10-month-old SD rats were randomly divided into 2 equal groups: ovariectomized (OVX) group and Sham operation (SHAM) group. Fifteen weeks post-operationally dual energy X-ray absorptiometry was used to measure the bone mineral density (BMD) of the total body and of the sixth lumbar vertebra. Then the rats were killed. The BMD values of the sixth lumbar vertebrae were measured by DXA. Bone histomorphometry was performed on the proximal metaphysis of the right tibia. Three of the sixth lumbar vertebrae were randomly selected from each group and embedded in methyl methacrylate. Each vertebra was cut into two parts along the transverse direction in the middle point of longitudinal axis so as to expose the trabeculae on the cross section. The lower part was polished, trabeculae were randomly selected from 4 places, and 5 points from each place were randomly selected to undergo nanoindentation so as to measure the nanomechanical properties., Results: Compared with the SHAM rats, the BMD of the sixth lumbar vertebra of the OVX rats was reduced significantly (P < 0.05). The histomorphometry of the tibia showed an increase in trabecular separation and a decrease in trabecular bone area fraction (both P < 0.05); the trabecular number and thickness decreased in these 2 groups, however, without significant difference between them. Nanoindentation tests showed that the values of hardness and elastic modulus of the trabeculae of the OVX rats were 0.91 GPa +/- 0.13 GPa and 21.01 GPa +/- 2.48 GPa respectively, not significantly different from those of the SHAM rats, 0.90 GPa +/- 0.09 GPa and 22.03 GPa +/- 2.44 GPa respectively., Conclusion: A novel technique, nanoindentation is able to directly measure the nanomechanical properties of trabeculae. Estrogen deficiency after ovariectomy induces significant osteoporotic change, but has no significant influence on the trabecular nanomechanical properties.

Objective: To study the age-related and menopause-related changes of urinary excretion of C- and N-terminal cross-linked telopeptides of type I collagen (uCTX/Cr and uNTX/Cr) and the relationships thereof with menopause state, years after menopause, bone mineral density (BMD), and menopause-related bone loss in healthy women., Methods: ELISA was used to examine the uCTX/Cr and uNTX/Cr of 659 female volunteers aged 20 - 80 in Changsha. Dual energy X-ray absorptiometry (DXA) was used to measure the BMD of various skeletal sites, including the lumbar vertebrae (L1 - L4) at anteroposterior (AP) position, L(2) - L(4) at lateral (LAT) position, hip, and forearm. 339 postmenopausal women among the 659 subjects were divided into 3 groups, osteoporotic, osteopenic, and normal groups according to the WHO criteria of osteoporosis diagnosis., Results: (1) Both the curves of uCTX/Cr and uNTX/Cr with age were fit the best by regression analysis of cubic equation. The coefficients of determination (R(2)) were 0.139 for uCTX/Cr and 0.149 for uNTX/Cr. The levels of uCTX/Cr and uNTX/Cr of the women aged > 35 increased with age. (2) The values of uCTX/Cr and uNTX/Cr were 253 mg/mol +/- 101 mg/mol Cr and 63 nmol +/- 34 nmol BCE/mmol Cr respectively in the postmenopausal women, remarkably higher than those of the premenopausal women (149 mg/mol +/- 80 mg/mol Cr and 33 nmol +/- 17 nmol BCE/mmol Cr respectively), increased by 69.5% and 93.4% respectively. The annual change rates of uCTX/Cr and uNTX/Cr were the highest within the first 5 years after menopause, and these increases were in agreement with the significant decrease of BMD at most skeletal sites by 10.8% approximately 27.6%. (3) After controlled for age and body weight, both uCTX/Cr and uNTX/Cr showed significant negative correlation with BMD (r = -0.078 to -0.283, P < 0.05 or 0.01), and there was a significant positive correlation between uCTX/Cr and uNTX/Cr. (4) The elevation of the levels of uCTX/Cr and uNTX/Cr in the osteoporotic and osteopenic postmenopausal subgroups were significantly higher than those in the postmenopausal women with normal BMD (P < 0.05 or 0.01). For example, the uCTX/Cr levels of the osteoporotic, osteopenic, and normal BMD subgroups according to the DXA results at the anteroposterior lumbar spine were 189 +/- 87, 272 +/- 108, and 366 +/- 135 mg/mol Cr respectively, while the uNTX/Cr levels were 52 +/- 22, 68 +/- 34 and 108 +/- 41 nmol BCE/mmol Cr respectively., Conclusion: uCTX/Cr and uNTX/Cr can be used as sensitive markers to determine the bone turnover status, which is changeable with age and menopausal status in women. They present a significantly negative correlation with BMD, and increase significantly in the postmenopausal women with osteopenia or osteoporosis, which indicates that measuring uCTX/Cr and uNTX/Cr can predict age-related and menopause-related bone loss in women.

The aim of this study was to investigate the relationship between body surface area (BS) and bone mineral density (BMD) and the associated osteoporosis risk at various skeletal regions in women from mainland China. BMD was measured at the posteroanterior (PA) spine (L1-L4), supine lateral spine (L2-L4) including volumetric BMD (vBMD), hip including femoral neck, trochanter and total hip, and forearm, including radius + ulna ultradistal (R + UUD), 1/3 site (R + U1/3) and total region (R + UT) using a dual-energy X-ray absorptiometry (DXA) fan-beam bone densitometer (Hologic QDR 4500A) in 3418 females aged from 18 to 75 years. Data analysis revealed a positive correlation between BS and BMD at the various skeletal regions (r = 0.114-0.373, all P = 0.000), but no correlation with vBMD (r = 0.000, P = 0.934). Using the stepwise regression model, BMDs at various skeletal regions were dependent variables while height, weight, body mass index (BMI), BS and projective bone area (BA) were independent variables; BS was determined to be the most important variable that affected the PA spine, hip and forearm BMDs. Subjects were divided into three groups according to size: large BS group (LBSG), intermediate BS group (IBSG) and small BS group (SBSG). The BMD at different skeletal regions of subjects between groups exhibited a significant gradient difference, with LBSG > IBSG > SBSG, but this was not seen for vBMD. On the fitting curves where BMD varied with age at the PA spine, femoral neck, total hip and R + UUD, BMDs of LBSG were 6.93-9.29% higher than those of IBSG and 12.1-16.9 % higher than those of SBSG, whereas those of SBSG were 6.12-9.59% lower than those of IBSG at various skeletal regions, respectively. The prevalence rates and risks of osteoporosis of LBSG were significantly lower than those of SBSG and IBSG, whereas those of IBSG were obviously lower than those of SBSG at various skeletal regions, respectively, presenting a gradient difference among the three study groups, LBSG < IBSG < SBSG. Our study shows that the relationship between BS and BMD exceeds that between BMD and height or weight in women in mainland China. When areal BMD is employed, those with a larger BS have higher areal BMD and lower risks of osteoporosis while, conversely, those with a smaller BS have lower areal BMD, and therefore higher risk for osteoporosis. However, when vBMD is used, these differences diminish or even disappear.

Objective: To investigate the effects of compound nylestriol tablet (CNT), containing nylestriol and levonorgestrel with a ratio of 1:0.3) and its components on the osteoporotic rat model induced by retinoic acid (RA) and ovariectomy (OVX)., Methods: We randomly divided 144 female SD rats (aged 7-month-old) into 12 groups (12 in each). In addition, 120 female SD rats aged 4-month were randomly divided into 10 groups (10 in each). Three dosage levels of CNT (0.039, 0.117 and 0.39 mg/kg body weight, daily), nylestriol (NYL, 0.30, 0.09 and 0.03 mg/kg body weight, daily) and levonorgestrel (LEV, 0.09, 0.027 and 0.009 mg/kg body weight, daily) were designed to prevent the bone loss of the osteoporotic rat model induced by RA and OVX respectively. Serum total calcium (Ca), phosphate (Pi), ALP, triglyceride (TG), total cholesterol (TC), HDL-C, total body BMD, isolated left femoral BMD and femoral Ca, and Pi after ashing were determined., Results: Osteoporotic models could be induced by RA (70 mg/kg body weightdaily given intragastrically for 14 days) or by ovariectomy; CNT and its components had the preventive effects on bone loss in both models; The preventive effect of CNT was dose-dependent and stronger than its components; Many observed markers showed us the levels of high and moderate CNT given to be the strongest, corresponding to an optimal choice of the moderate dose CNT about one tablet per week in adult women., Conclusions: CNT therapy can prevent the bone loss of RA-induced and OVX-induced osteoporotic rats, and its therapeutic and preventive effect is better than its components used alone.

The aim of this study was to determine age-specific bone mineral density (BMD) at various skeletal regions in a native Chinese reference population, and to explore the differences in the diagnosis of primary osteoporosis and estimated prevalence of osteoporosis based on both Chinese criteria (BMD of subjects, 25% lower than the peak BMD) and WHO criteria (BMD of subjects, 2.5 SD [T-score < or = -2.5] lower than the young adult mean [YAM]). There were 3,406 subjects in our female reference population, ranging in age from 10 to 90 years. A dual-energy X-ray absorptiometry (DXA) fan-beam bone densitometer (Hologic QDR 4500A) was used to measure the BMD in subjects at the posteroanterior (PA) spine (L1-L4), supine lateral spine (L2-L4 including areal BMD [aBMD] and volumetric BMD [vBMD]), hip (including femoral neck and total hip), and radius + ulna ultradistal (R + UUD) of the forearm. Cross-sectional data analysis in stratified 5-year age intervals revealed that the peak BMD (PBMD) at various skeletal regions occurred within the age range of 30-44 years, with PBMD at the lateral spine and femoral neck occurring at 30-34 years, posteroanterior spine and total hip at 35-39 years, and ultradistal forearm at 35-44 years. The reference values of BMD (PBMD) calculated using Chinese criteria for the diagnosis of primary osteoporosis were significantly higher than the young adult mean (YAM) using WHO criteria for all skeletal regions except for the total hip, at a range of 0.9%-3.8% higher. The BMD cutoff values using Chinese criteria for the diagnosis of osteoporosis were 3.7%-10.9% higher than those using WHO criteria for various skeletal regions. The prevalence rate of primary osteoporosis according to Chinese criteria in subjects ranging from 50 to 90 years was 41.5% at the PA spine, 53.9% at the lateral spine, 34.2% at the femoral neck, 30.7% for total hip, and 51.4% at R + UUD; while according to WHO criteria, this rate was 32.1% at the PA spine, 34.9% at the lateral spine, 16.3% at the femoral neck, 18.9% for total hip, and 45.2% at R + UUD. The prevalence of primary osteoporosis according to both criteria varied with the age and skeletal region of the subjects. The prevalence of primary osteoporosis using Chinese criteria, compared with WHO criteria was 31% higher at the lumbar spine, 109% higher at the femoral neck, and 14% higher at the ultradistal forearm. In conclusion, PBMD occurs in the age range of 30-44 years in native Chinese females. The BMD reference values, BMD cutoff values, and prevalence of primary osteoporosis determined by Chinese criteria are all higher than those determined by the WHO criteria; thus, the application of Chinese criteria may overestimate the number of patients with primary osteoporosis.

Osteoporosis is a major public health problem, particularly in women. Bone mineral density (BMD) reference plot is a basic, and the peak BMD (PBMD) an important, parameter in the diagnosis of osteoporosis. In order to establish reference plots of BMD at multiple skeletal sites in Chinese women and improve the diagnostic accuracy for osteoporosis, we measured BMDs at several skeletal regions in 3,378 Chinese women, aged 5-96 years, using a dual-energy X-ray absorptiometry fan-beam bone densitometer. After determining that the cubic regression model best fit all skeletal regions, we utilized the curve-fitting to establish BMD reference plots and utilized the curve-fitting equation to calculate the highest BMDs at all skeletal regions using three different methods of calculation--actual PBMD (method A), PBMD of each 5-year age group (method B), and a cross-section of age (method C). When the three methods were compared, we found significant differences among them at the majority of skeletal regions studied. When we utilized these three methods to determine the prevalence of osteoporosis in 2,120 women aged 40 years and older, except for the Ward's triangle, we observed significant differences among them at all skeletal regions. In the present study, we established new BMD reference plots at multiple skeletal regions for women of mainland China. Our findings also indicate that curve-fitting equations can be employed to calculate actual PBMDs specific to individual regions, and that the use of different methods to calculate PBMD may have a significant impact on both PBMD and the diagnosis of osteoporosis. Therefore, we suggest that a standardized method be established to calculate site-specific PBMDs based on the peak values of best-fit reference curves in appropriate age groups.

To understand the effects of skeletal size of the lumbar spine on areal bone mineral density (aBMD), volumetric bone mineral density (vBMD), and the diagnosis of osteoporosis in postmenopausal women, we measured the projected bone area, bone mineral content (BMC), aBMD, and vBMD at the anteroposterior and lateral lumbar spines in a population of 1081 postmenopausal Chinese women, 42 to 86 years of age. The results indicated that, at the anteroposterior and lateral lumbar spine, there were significant positive correlations between bone area and both BMC ( r = 0.606; P = 0.000 and r = 0.610; P = 0.000) and aBMD ( r = 0.270; P = 0.000 and r = 0.182; P = 0.000), but not vBMD ( r = -0.055; P = 0.000 and r = 0.000; P = 0.929). When bone area at the anteroposterior spine changed by +/-1 SD, the BMC, aBMD, and vBMD correspondingly changed by 28.2%, 10.1%, and 1.69% on the basis of their respective means. When a variation of +/-1 SD was observed in bone area at the lateral spine, BMC and aBMD, correspondingly changed by 25.9% and 6.18% on the basis of their respective means, while vBMD indicated no change. Through comparisons among large-, intermediate-, and small-bone area groups, significant differences were found in the means of subjects' heights, weights, BMC, and vBMD at the anteroposterior and lateral lumbar spines, as well as in the detection rates of osteoporosis by aBMD ( P = 0.000). Detection rates of osteoporosis by aBMD at the anteroposterior spine and by aBMD at the lateral spine, and by vBMD were 44.1%, 55.5%, and 49.7%, respectively, in the total population; 31.4%, 41.7%, and 53.7%, respectively, in the large-bone area group; 43.3%, 55.9%, and 50.5%, respectively, in the intermediate-bone area group; and 61.7%, 70.0%, and 42.5%, respectively, in the small-bone area group. No significant differences were found in the detection rates of osteoporosis by vBMD among the groups. The results of multiple linear regression revealed that the major factors influencing skeletal size and aBMD of the lumbar spine were height and weight. Therefore, in menopausal women of the same ethnic group and age, the skeletal size of the lumbar spine would have significant influence upon aBMD and the diagnosis of osteoporosis, i.e., the larger the spinal size, the greater the aBMD and the lower the osteoporosis detection rate, while, conversely, the smaller the skeletal size, the smaller the aBMD and the higher the osteoporosis detection rate. When we use aBMD of the lumbar spine to diagnose osteoporosis in a population with different body sizes, we need to take this body size difference into account. When we use vBMD to diagnose osteoporosis, the effect of body size on BMD will diminish.

Objective: Recently our studies have shown that nylestriol in combination with levonorgestrel prevented bone loss, decreased bone turnover rate and increased the maximal loading of bone without obvious side effects in retinoic acid (RA) induced osteoporotic rats. In addition to the animal experiments, we evaluate the effect of Compound Nylestriol Tablet (CNT) on bone mineral density (BMD) in women with postmenopausal osteoporosis. Compound Nylestriol Tablet, which contains 0.5 mg of nylestriol (cyclopentylethinyl estriol) and 0.15 mg of levonorgestrel per tablet, was authorized as a new anti-osteoporotic agent for clinical trial in postmenopausal osteoporosis., Methods: One year's clinical observation was performed in 191 eligible patients who were randomly divided into two groups (A and B). In group A, 119 patients were treated for one year with CNT (one tablet per week) and in group B, 72 patients with placebo. Bone mineral density of lumbar antero-posterior spine (L1-L4), lateral spine, total hip and total forearm positions including radius+ulna at the ultra distal areas, mid areas, and one-third areas, were measured before and after treatment. Biochemical parameters and effects of CNT on uterus, and breast were observed., Results: We found that patients treated with CNT had a significant decrease of bone loss in total forearm, including radius+ulna at the ultra distal, mid, and 1/3 areas compared with control subjects (all P < 0.05). An improved BMD tendency could be seen at the lumbar spine. There were no differences in the observed biochemical variables. No side-effects on uterus, or mammary glands observed. None of the patients had uterine bleeding or vertebral fractures during one year's CNT treatment., Conclusion: These data suggested that CNT is effective, safe and convenient in treating postmenopausal osteoporosis.

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(4)) factorial design, i.e., NYL level I (N1 0.015 mg/kg), level II (N(2) 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 osteoporotic 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-alpha 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 L and LA, 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 N1, N2, and L1 (P < 0.05). Moreover, there were lower levels of trabecular separation (Tb.Sp) at N3 and N4. The mineral apposition rates (MAR) at N2, N3, N4, L2, L3, and L4 were lower than those at N1 or L1. Bone formation rates (BFR) at L3 and L4 had significantly decreased as compared with that at L1. Levels of serum total cholesterol (TC) at N2, N3, and N4 were lower than that at N1 (P < 0.05). Marked squamatization of uterine endometrium with an increased expression of estrogen receptor (ER)-alpha was observed at N4., Conclusion: The dosage of 0.15 mg/kg NYL prevented bone loss, decreased bone turnover rate and increased the maximal loading of bone without obvious side effects in RA-induced osteoporotic rats. The addition of 0.015-0.15 mg/kg of LNG (L2-L4) reduced uterine weights and serum ALP levels. Overall results showed that 0.15 mg/kg of NYL in combination with 0.015 mg/kg of LNG produced beneficial effects on bone metabolism in RA-induced osteoporotic rats.

This study was designed to establish Bone Mineral Density (BMD) Reference Databases for multiple skeletal sites appropriate for the diagnosis and evaluation of osteoporosis (OP) in Chinese women. We recruited 2702 healthy Chinese women, 5-96 years of age, for BMD assessment. BMD values at multiple skeletal sites including anteroposterior (AP) and lateral (Lat) lumbar spine, hip, and forearm were measured by dual-energy X-ray absorptiometry (DXA) using a QDR 4500A device; results were analyzed according to age group using eight regression models. BMD Reference Databases (CWD) were established according to the best regression equation and compared with Hologic reference databases for "Oriental Women" (OWD). Results indicated that the cubic regression model was superior to the quadratic, linear, logarithmic, and exponential regression models, etc. for our purpose, with a determinate coefficient ( R(2)) of 0.363-0.650 ( P = 0.000). We included 1636 female patients, aged 35-86 years, in our tests. In comparison with Hologic Reference Databases, the mean detection rate of OP in the newly established BMD Reference Databases for Chinese Women (CWD) was 16.0% +/- 2.68% lower (range, 13.7%-20.5%) at the AP spine, 16.8% +/- 11.0% lower (range, 3.5%-32.8%) at the Lat spine (except for L4), 18.7% +/- 4.6% lower (range, 12.6%-24.2%) at the hip, and 14.3% +/- 6.9% higher (range, 4.7%-24.3%) at the forearm. The difference in detection rates for OP was significant between the two reference databases ( P = 0.000), which was consistent with the differences in peak BMD values and the biological variability between them. Based upon our data, we confirmed that the Hologic BMD Reference Databases for Oriental Women (OWD) were not suitable for the diagnosis of OP in Chinese women; the BMD Reference Databases for Chinese Women (CWD) established in this study would provide reliable diagnostic standards for detection of OP in the women of South China.

We investigated the age-related bone mineral density (BMD), accumulated bone loss rate (ABLR) and the prevalence of osteoporosis at different skeletal sites in Chinese women. BMD was measured at the anteroposterior (AP) spine, supine lateral spine (areal BMD at the midarea [mLat] and the whole region [Lat], volumetric BMD at the middle region [MVD] and total region [TVD]), hip (femoral neck [FN], trochanter [Troc] and Ward's triangle [Ward's]) and forearm (radius + ulna ultradistal [RUUD], 1/3 region [RU1/3] and total region [RUT]) using a dual-energy X-ray absorptiometry (DXA) fan-beam bone densitometer (Hologic QDR 4500A) in 2702 females aged from 5 to 96 years old. Data were analyzed by eight different regression models. We found that the cubic regression model was the best for describing age-related changes in BMD. The coefficients of determination ( R(2)) of the fitting curve were 0.398 to 0.612 ( p = 0.000). The data were then analyzed by 5-year age groups. This showed that the earliest peak BMD was at the age of 20-24 years at Troc and Ward's, and the latest at the age of 40-44 years at RU1/3 and RUT of the distal forearm. Compared with BMD, the ABLRs were highest at Ward's (-66.2%) and the lowest at RU1/3 of the distal forearm (-31.3%) in subjects over 80 years old. The prevalence of osteoporosis at at least one site in these women was 0.5 +/- 0.4% in those 30-39, 4.6 +/- 4.4% in those 40-49, 23.9 +/- 13.3% in those 50-59, 56.3 +/- 20.3% in those 60-69, 71.8 +/- 16.7% in those 70-79 and 83.2 +/- 12.1% those over 80 years of age, respectively. The prevalence of osteoporosis in these women was 8.6-11.1% at the age of 40-49 and 36.5-40.6% at the age of 50-59 at the lateral spine regions (mLat, Lat, MVD and TVD), and 0.5-3.7% at the age of 40-49 and and 3.9-21.7% at the age of 50-59 years at the other skeletal sites (AP, FN, Troc, Ward's, RUUD, RU1/3 and RUT). Significant differences were found in the prevalence of osteoporosis between the lateral spine regions and other skeletal sites ( p<0.001) at the age of 40-59 years. In summary, we demonstrated significant age-related differences in peak BMD, ABLR and osteoporosis prevalence among various skeletal sites. Our data suggest that the supine lateral spine is the most sensitive site for the diagnosis of osteoporosis, especially in the early menopausal period, although the prevalence of osteoporosis varied with age and with different sites measured.

Purpose: There are limited clinical studies aimed at solving the problem of the efficiency of conventional treatment with oral phosphate and calcitriol in adults with hypophosphatemic osteomalacia (HO). In addition, there still had no good non-hazardous markers to evaluate the severity of bone loss of osteomalacia before and after treatment. Therefore, the purpose of this study was to assess the efficacy of conventional treatment with a self-blended phosphate supplementation and calcitriol on patients with HO and whether bone mineral density (BMD) can be helpful for monitoring the efficacy. Patients and Methods: A total of 21 HO patients and 105 healthy controls were enrolled. All patients were tested for serum biomarkers and BMD of the lumbar spine (L1–L4), femoral neck, and total left hip. After three years of treatment, 11 of 21 HO patients were recalled for BMD measurement. According to the administration of drugs, HO patients with calcium and calcitriol were divided into three phosphate treatment groups: patients in group A (n = 3) received continuous phosphate supplementation, patients in group B (n = 5) received intermittent phosphate supplementation and patients in group C (n = 3) received no phosphate supplementation. Results: The diagnoses of 21 HO patients were 5 cases of hereditary hypophosphatemic rickets, 4 cases of Fanconi syndrome with the features of renal tubular acidosis and vitamin D deficiency, and 12 cases of hereditary vitamin D abnormality. The average initial serum phosphorus level of the patient group was approximately 50% lower than that of the control group. Lower BMD was significantly observed in the HO group than the control group at the lumbar spine and total hip. Continuous treatment with the phosphate supplement could increase BMD in the lumbar spine and total hip by 33.4– 52.3% and in the femoral neck increased by 43.2– 79.3% compared with baseline, and the effect appears to be continued once treatment is discontinued. Conclusion: These findings suggest that conventional therapy can improve bone mineral defects in patients with HO, especially in the femoral neck. Detection of BMD in HO patients is a good tool to assess the extent of bone defects and the therapeutic effect. Trial Registration: Chinese Clinical Trial Registry, ChiCTR-OOC-16010095. Registered 7 December 2016. Retrospectively registered. [ABSTRACT FROM AUTHOR]

Growth Differentiation Factor 8 ( GDF8), also called myostatin, is a member of the transforming growth factor ( TGF)-β super-family. As a negative regulator of skeletal muscle growth, GDF8 is also associated with bone metabolism. However, the function of GDF8 in bone metabolism is not fully understood. Our study aimed to investigate the role of GDF8 in bone metabolism, both in vitro and in vivo. Our results showed that GDF8 had a negative regulatory effect on primary mouse osteoblasts, and promoted receptor activator of nuclear factor κB ligand ( RANKL)-induced osteoclastogenesis in vitro. Intraperitoneal injection of recombinant GDF8 repressed bone formation and accelerated bone resorption in mice. Furthermore, treatment of aged mice with a GDF8 neutralizing antibody stimulated new bone formation and prevented bone resorption. Thus, our study showed that GDF8 plays a significant regulatory role in bone formation and bone resorption, thus providing a potential therapeutic pathway for osteoporosis. [ABSTRACT FROM AUTHOR]

ABSTRACT MicroRNAs (miRNAs) play important roles in osteoclastogenesis and bone resorption. However, no study has investigated the role of miRNA in postmenopausal osteoporosis. Here, we report that miR-503 was markedly reduced in circulating progenitors of osteoclasts-CD14+ peripheral blood mononuclear cells (PBMCs) from postmenopausal osteoporosis patients compared with those from postmenopausal healthy women. Overexpression of miR-503 in CD14+ PBMCs inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. Conversely, silencing of miR-503 in CD14+ PBMCs promoted osteoclastogenesis. RANK, which is activated by the binding of RANKL and inducing osteoclast differentiation, was confirmed to be a target of miR-503. In vivo, silencing of miR-503 using a specific antagomir in ovariectomy (OVX) mice increased RANK protein expression, promoted bone resorption, and decreased bone mass, whereas overexpression of miR-503 with agomir inhibited bone resorption and prevented bone loss in OVX mice. Thus, our study revealed that miR-503 plays an important role in the pathogenesis of postmenopausal osteoporosis and contributes to a new therapeutic way for osteoporosis. © 2014 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) play crucial roles in bone metabolism. In the present study, we found that miR-148a is dramatically upregulated during osteoclastic differentiation of circulating CD14+ peripheral blood mononuclear cells (PBMCs) induced by macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). Overexpression of miR-148a in CD14+ PBMCs promoted osteoclastogenesis, whereas inhibition of miR-148a attenuated osteoclastogenesis. V-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) is a transcription factor negatively regulating RANKL-induced osteoclastogenesis. miR-148a directly targeted MAFB mRNA by binding to the 3′ untranslated region (3′UTR) and repressed MAFB protein expression. In vivo, our study showed that silencing of miR-148a using a specific antagomir-inhibited bone resorption and increased bone mass in mice receiving ovariectomy (OVX) and in sham-operated control mice. Furthermore, our results showed that miR-148a levels significantly increased in CD14+ PBMCs from lupus patients and resulted in enhanced osteoclastogenesis, which contributed to the lower bone mineral density (BMD) in lupus patients compared with normal controls. Thus, our study provides a new insight into the roles of miRNAs in osteoclastogenesis, and contributes to a new therapeutic pathway for osteoporosis. © 2013 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

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]

Abstract: Background: The relationship between bone turnover markers (BTMs) and BMD decreasing rate (BDR) in Chinese women is unclear. Wu investigated the relationship between (BTMs) and BDR at various skeletal sites in Chinese middle-aged women. Methods: A cross-section study of 555 healthy Chinese women over 35–60years of age. BMD at posteroanterior spine, the left hip, and the left forearm were measured with a DXA. Levels of serum osteocalcin (OC), bone-specific alkaline phosphatase (BAP), cross-linked N-terminal telopeptides of type I collagen (sNTX) and total urinary deoxypyridinoline (uDPD) were determined. Results: BDR at various skeletal sites had significant negative correlation with serum OC(r =−0.395 to −0.530), BAP(r =−0.297 to −0.486), and sNTX(r =−0.207 to −0.272). After adjustment of age and weight, serum OC, BAP, and sNTX rather than total uDPD still exhibited significant correlations with BDR. Stepwise regression analyses showed that, serum OC and BAP were the significantly negative determinants of BDR. Between 4.7−27.7% and 1.2−16.1% of the changes in BDR were determined by serum OC and BAP, respectively. However, sNTX and total uDPD had no significant effect on BDR at various skeletal sites. Conclusions: This study indicated the correlation between BTMs and early-stage BDR in Chinese middle-aged women and suggested that serum OC and BAP, rather than sNTX and total uDPD, are the key determining factors of early BMD decreases. [Copyright &y& Elsevier]