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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., (© 2021. The Author(s).)

Objective: To explore the relationship between the changes of estrogen, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and bone mineral density (BMD) decreasing rate (BDR) at different skeletal regions and examine the effects of hormones levels on BDR., Methods: An age cross-sectional study was conducted in 694 healthy adult women excluded from diseases and drugs affecting bone metabolism. Their age range was 20-80 years. The serum concentrations of FSH, LH and estradiol (E2) were measured with radioimmunoassay. And BDR was measured with a DXA fan-beam bone densitometer at various skeletal regions including lumbar spine, left hip and left forearm., Results: The serum levels of FSH (r = -0.597 to -0.479, all P < 0.01) and LH r = -0.452 to -0.283, all P < 0.01) were significantly negatively correlated with BDR at various skeletal regions. Meanwhile, the serum level of E2 only had slightly positive correlation with hip and distal forearm (r = 0.077 to 0.122, all P < 0.05). After adjusting age and body mass index (BMI), serum FSH still had markedly negative correlation with BDR at various skeletal regions. However, the correlation coefficients became weak. Multiple line regression stepwise analysis revealed that serum FSH was a negative determinant factor of BDR at various skeletal regions: 20%-32% changes in BDR of various skeletal regions were determined by FSH, while LH only produced very small negative effects (0.6%-0.8%) on BDR of lumbar spine. Serum E2 seemed to be a positive determinant factor of skeletal regions and 2.5%-5.4% changes in BDR were determined by E2. The effects of serum FSH on BDR were approximately 3.8-12.8 folds than those of serum E2., Conclusions: BDR is correlated with increased FSH in women. The most critical factor for aging-related BDR is FSH in women while a decreased level of estrogen may be secondary.

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 © 2011. Published by Elsevier B.V.)

Background: Adiponectin and leptin, as the main circulating peptides secreted by adipose tissue, are potential contributors to bone metabolism. However, their association with bone mineral density (BMD) is unknown. We investigated whether these serum adipocytokines concentrations are associated with BMD and bone turnover markers., Methods: Serum adiponectin, leptin concentrations, bone turnover biochemical markers, and BMD were determined in 265 premenopausal and 336 postmenopausal Chinese women., Results: In postmenopausal Chinese women, the multiple linear stepwise regression analysis showed that year since menopause, lean mass, estradiol, and adiponectin, but not fat mass, leptin, were independent predictors of BMD in postmenopausal Chinese women. However, in premenopausal Chinese women, adiponectin was not the predictor of BMD. The significant positive correlations between adiponectin and bone-specific alkaline phosphatase (BAP), bone cross-linked N-telopeptides of type I collagen (NTX) were found only in postmenopausal women. Serum BAP, and NTX, but not adiponectin, decreased in response to alendronate therapy., Conclusions: Adiponectin was an independent predictor of BMD, and positively correlated with bone turnover biochemical markers in postmenopausal Chinese women, but not premenopausal women. It suggested that adiponectin may exert a negative effect on bone mass by promoting excessive bone resorption associated with bone loss. However, these effects may be mediated by menopausal status., (Copyright 2010 Elsevier B.V. All rights reserved.)

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.

Bone mineral density (BMD) and its association with body mass index (BMI) are uncertain in postmenopausal women with type 2 diabetes mellitus (T2DM) in mainland China. This study was performed to assess this association including 1,042 postmenopausal women with T2DM and 919 non-diabetic control subjects. Bone mineral density of the posteroanterior spine and of the left hip was measured by use of dual-energy X-ray absorptiometry. Diabetic participants were divided into three groups according to BMI, i.e. low BMI (DML < 18.5 kg/m(2)), intermediate BMI (DMM 18.5-24.9 kg/m(2)), and high BMI (DMH >or= 25 kg/m(2)). The BMD values of diabetic subjects between groups exhibited a significant gradient difference, with DML < DMM < DMH. On the fitting curves, where BMD in various skeletal regions varied with age, BMDs of DML were approximately 15% lower than those of DMM, and those of DMM were approximately 10% lower than those of DMH. For prevalence and risks of osteoporosis a gradient difference was observed among diabetic groups, DML > DMM approximately control > DMH. The osteoporosis risk was higher for the hip than for the lumbar spine, especially in DML. This study indicated that postmenopausal women with T2DM had higher BMD and lower osteoporosis risk in the lumbar spine, and that lower BMI was an indicator of osteoporosis in mainland China.

The center of rotation is a physical location in the microCT scanner, defined by the axis of rotation of the sample stage. This physical location is always well defined during calibration of the instrument and fitted by an appropriate algorithm. However, in real images of limited contrast and with X-ray photon noise, this algorithm exhibits poorer precision and the optimum center of rotation cannot be always acquired. Thus, adjustment by operator is necessary to determine whether the center of rotation was correct, in order that the structural information of the sample can be correctly interpreted. In this paper, the effect of center of rotation on the assessment of densitometric and structural properties of trabecular bone was firstly evaluated. Twenty female Sprague-Dawley rats of 7-month-old were randomly assigned to ovariectomized (OVX) and SHAM-operated (SHAM) groups. The left tibiae were harvested at 3 weeks postoperatively. High resolution microCT was used to identify the densitometric and microstructural properties of trabeculae in the proximal ends of tibia. After CT scanning, the best artificial center of rotation for each scan was obtained. Bone parameters analyses were performed on the centers at different places away from the best artificial center of +/-0.2, +/-0.5, +/-1.0, +/-1.5, and +/-2.0 pixels, respectively. The general linear model (GLM) repeated measures procedure was used to investigate the difference in the parameters between the two groups (OVX vs. SHAM) and the possible effects of center displacements. A significant difference between OVX and SHAM groups was found in all parameters (p < 0.05) except Tb.Th, DA, and BS/BV. TBMD, DA, BS/BV, and Conn.D were decreased while BV/TV and Tb.Th were increased with the center deflection. Variations of these parameters were acceptable when the displacements were limited within +/-1.5 pixels for tBMD, BV/TV, DA, and Conn.D, and +/-1.0 pixels for Tb.Th and BS/BV. These changes were similar in both OVX and SHAM groups. The changing curves of bone parameters vs. centers could be well fitted by quadric regression models, by which the real center could be acquired, and thus the precision of microCT analysis would be improved. There were some inevitable differences between the best artificial and real centers.

Objective: To investigate the Dynamic effects of glucocorticoid (GC) on bone mineral density and microarchitecture time-related changes of trabecular bone in bone mineral density (BMD) and microarchitecture in glucocorticoid-treated rats., Methods: Fifty-two 3.5-month-old female SD rats were randomly divided into 3 groups. Ten rats were killed at the beginning of experiment with their right tibiae taken out as the baseline group; 22 rats underwent subcutaneous injection of methylprednisolone once daily (GC-treated group), and the other 20 rats underwent subcutaneous injection of normal saline once daily as control group. One and 9 weeks after the beginning of experiment 11 and 10 rats from GCT Group and control group each were killed with their right tibiae taken out. High resolution micro-CT was used to identify the densitometric and microarchitectural properties of the trabecula in the proximal metaphysic of tibia., Results: Compared with the control group the values of volumetric BMD (vBMD), tissue BMD (tBMD), bone volume fraction (BVF), trabecular number (Tb.N), degree of anisotropy (DA), and trabecular connectivity (Conn.D) in the trabecular bone at different time-points, of the GCT group all decreased; and the values in the ninth week were the lowest (all P < 0.05). The values of trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), and structure model index (SMI) at different time-points of the GCT group were higher than those of the control group. A time-related analysis within the GCT group showed there was a declination in BVF, Conn.D, Tb.N, and DA with administration time, but Tb.Th and Tb.Sp were increased significantly (all P < 0.05). The mean values of Tb.Th in the first week and the ninth week of GCT Group were (0.076 +/- 0.020) mm and (0.086 +/- 0.026) mm respectively, both higher than the baseline value [(0.067 +/- 0.014) mm] and the values of the control group in the first and ninth weeks [(0.075 +/- 0.022) mm and (0.072 +/- 0.009) mm respectively]., Conclusion: Administration of GC time dependently decreases the BMD and causes deterioration in microarchitecture of trabecular bone; and the remaining trabeculae seem thicken to increase their strength as compensation.

Background: Recently, membrane type matrix metalloproteinase-1 (MT1-MMP) was found to participate in bone metabolism. We investigated the relationship between serum MT1-MMP and bone mineral density (BMD) as well as bone metabolic markers in 206 Chinese postmenopausal women aged 43-80 years., Methods: Western analysis and ELISA were performed to detect serum soluble MT1-MMP levels. BMD was measured by dual energy X-ray absorptiometry (DXA). Serum alkaline phosphatase (BAP) and N-telopeptides of type I collagen (NTX) were assayed using ELISA., Results: We found that soluble MT1-MMP abundantly existed in human serum as protein lack of transmembrane domain. Serum MT1-MMP levels were detectable in all participants and the range of value was 221.2-863.0 ng/ml (435.6+/-98.2 ng/ml). We found a significant negative weaker correlation between MT1-MMP and BMD at lumbar spine, total hip (Thip), and femoral neck (FN) (all P<0.05). After adjustment for age and BMI, the correlation with BMD at FN and Thip disappeared (all P>0.05). Multiple linear stepwise regression analysis showed that MT1-MMP was not a determinant factor for BMD. The significant positive correlations between MT1-MMP and BAP, NTX were found, and remained significant after adjustment for age and BMI (all P<0.05). Moreover, serum MT1-MMP, BAP, and NTX decreased in response to alendronate therapy., Conclusion: Circulating MT1-MMP and bone turnover markers are correlated, and serum MT1-MMP levels may rise with increase in bone turnover.

Background: Adiponectin, leptin, resistin, and visfatin, as the main circulating peptides secreted by adipose tissue, are potential contributors to bone metabolism. We investigated whether these serum adipocytokines levels are associated with BMD and bone turnover biochemical markers in 232 Chinese men (20-80 y)., Methods: Serum adiponectin, leptin, resistin, and visfatin levels were determined by ELISA., Results: Leptin had a positively correlation with fat mass, and remained significant after adjustment for age and BMI. There was a significant negative weak correlation between adiponectin and fat mass, and disappear after adjustment for age and BMI. Resistin and visfatin were not significantly correlated with fat mass. In the multiple linear stepwise regression analysis, lean mass and adiponectin, but not leptin, resistin and visfatin, were independent predictors of BMD. The significant positive correlations between adiponectin and bone-specific alkaline phosphatase (BAP), bone cross-linked N-telopeptides of type collagen (NTX) were found, and remained significant after adjustment for age and fat mass., Conclusions: Adiponectin was an independent predictor of BMD in Chinese men, and positively correlated with bone turnover biochemical markers. It suggested that adiponectin exert a negative effect on bone mass in men.

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 determine the relationship between bone alkaline phosphatase (BAP) and cross-linked N-telopeptides of type I collegen(NTX) and bone mineral density in healthy men aged 20-80., Methods: BAP and NTX of 389 healthy men were measured by ELISA. BMD at the lumbar spine and the hip as measured by dual energy X-ray absorptiometry. The correlation of bone biochemical markers with age and BMD fit 10 regression models., Results: BAP and NTX negatively correlated with age. The cubic regression model was better with age-related changes of bone biochemical markers as compared with the other regression models and the coefficients of determination of fitting curve were 0.013-0.029 (P< 0.05). The value of bone biochemical markers as the highest during 20-29 age groups, then they decreased to a nadir level in the 50-59 years age. After 60 years, bone formation markers remained stable; however resorption marker increased slightly. After adjustment for age, weight, height, BMI, and smoking, bone biochemical markers were negatively correlated with most sites of BMD., Conclusion: BAP and NTX may be relatively sensitive and specific markers to evaluate age-related changes of bone turnover. It may benefit the prevention of osteoporosis by monitoring the level of BAP and NTX.

Objective: To determine the relationship of serum leptin concentration and bone mineral density(BMD), body fat mass in males., Methods: Plasma concentrations of leptin in 350 Chinese males, aged 20 to 80 years were measured with ELISA; BMD values at lumbar spine, hip and total body BMD, and body composition, including lean tissue mass (LTM) and fat tissue mass (FTM), were measured using dual-energy-X-ray absorptiometry (DXA). The relationship between changes in serum leptin concentration with age, body weight, body mass index, body fat mass, and BMD values at 5 skeletal sites was fit by 10 regression models, and the models giving the best fit were selected., Results: The S regression model best described the changes in serum leptin level with age (R(2)=0.104, P<0.009), while the compound regression model best described the changes in serum leptin concentration with BMI and weight (R(2)=0.296, P<0.001; R(2) =0.304, P<0.001). Leptin concentration was correlated with FTM (R(2)=0.448, P<0.001) and rate of body fat(R(2)=0.461, P<0.001). The serum leptin level was significantly correlated with BMD of multiple skeletal sites (R(2) was 0.115 for anterior spine BMD, 0.102 for lateral spine BMD,0.098 for femoral neck BMD, 0.112 for total hip BMD, respectively). In a multivariate analysis, leptin concentration was not a significant predictor of BMD at any site., Conclusion: Serum leptin concentration correlates with body fat mass and percentage of body fat, but is not a significant predictor of BMD at any site in Chinese males.

Substantial racial differences in bone mass and bone loss rate have been reported, but the extent of the difference between native Chinese women and women of different races in the United States is not clear. We used a DXA bone densitometer to measure bone mineral density (BMD), bone mineral content (BMC), bone area (BA), and volumetric BMD (vBMD) in different regions of the proximal femur in 3614 Chinese women aged 20 years and older. Regression models were chosen to best fit the changes of these parameters with increasing age. The values in their fitted curves were determined by the Cartesian coordinate numeration system. Subsequently, we compared these fitted curves to full-matched data of non-Hispanic black, non-Hispanic white, and Mexican American women reported by the third National Health and Nutrition Examination Survey (NHANES III). We found that all fitted curves of bone mass of non-Hispanic black women were significantly higher than those of Chinese, non-Hispanic white, and Mexican American women (P = 0.000). The BMD and BMC fitted curves in various regions of the hip for non-Hispanic blacks were 22%-28% and 26%-43% higher than those for Chinese women, 8.3%-13% and 7.9%-9.5% higher than those for non-Hispanic whites, and 8.8%-10% and 13%-19% higher than those for Mexican Americans, respectively. However, when the expression of difference was transformed from BMD to vBMD at the femoral neck, the difference between Chinese and non-Hispanic black women was reduced from 22% to 18% and that between Chinese and non-Hispanic white women from 7.4% to 0.8%, but the difference increased from 3.2% to 9.6% between non-Hispanic white and Mexican American women and from 13% to 17% between non-Hispanic white and non-Hispanic black women. By the age of 80 years, the accumulated bone loss rate in various regions of the proximal femur for Chinese, Mexican Americans, non-Hispanic whites, and non-Hispanic blacks were -38.9% +/- 1.8%, -34.4% +/- 3.1%, -27.8% +/- 5.9%, and -28.4% +/- 4.8%, respectively. In conclusion, bone mass in the proximal femur of native Chinese women is significantly lower, and the bone loss rate greater, than those of non-Asian women in the United States. At the femoral neck, the vBMD of Chinese women is similar to that of non-Hispanic white women.

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.

Background: Osteoblast-derived matrix metalloproteinse-1 (MMP-1), MMP-2 and tissue inhibitor of metalloproteinase-1 (TIMP-1) play a role in bone metabolism by degrading bone matrix., Methods: We measured MMP-1, MMMP-2, TIMP-1 and associated results with age and bone metabolism in 591 Chinese women aged 20-80 y., Results: Serum MMP-1, MMP-2, and TIMP-1 concentrations exhibited positive correlation with age. Serum concentrations of MMP-1 were higher in 40-69 y old women. The concentrations of MMP-2 were significantly increased in the 50-69 y olds. Serum TIMP-1 concentrations were significantly lower in women aged 30-59 y, and then these were followed by an increase at >60 y olds. We found a significant negative weaker correlation between MMP-2 and BMD. But multiple linear stepwise regression analysis showed that MMP-2 was not a determinant factor for BMD. There were significant positive correlations between MMP-2 and bone alkaline phosphatase (BAP), osteocalcin (OC), and cross-linked N-telopeptides of type I collagen (NTX)., Conclusions: The serum concentrations of MMP-1, MMP-2, and TIMP-1 exhibit age-related changes, and circulating MMP-2 and bone turnover are related.

Objective: To study the age-related changes of bone formation markers, i.e., serum bone alkaline phosphatase (sBAP) and serum osteocalcin (sOC), bone resorption marker, i.e., cross-linked N-telopeptides of type 1 collagen (sNTX), and bone mineral density (BMD) in healthy men., Methods: Serum sBAP, sOC, and sNTX of 389 randomly selected males, aged 20 - 80, all of Han nationality, were measured by using enzyme-linked immunosorbent (ELISA). Dual energy X-ray densitometer was used to measure the BMD of the lumbar vertebrae, left femoral neck, Ward's triangle, and hip. The relationships of these markers to age were analyzed., Results: (1) The sBAP, sOC, and sNTX were negatively correlated with age, the cubic regression model being better with age-related changes of bone biochemical markers as compared with the other regression models (R(2) = 0.013 - 0.029, P < 0.05); (2) When all subjects were stratified by 10-years, the bone biochemical marker values were the highest in the age group 20 - 29, with the sBAP of 30.9 U/L +/- 12.6 U/L, sOC of 12.6 microg/L +/- 6.2 microg/L, and sNTX of 18.2 micromol/L +/- 6.6 micromol/L; then decreased with aging and to a nadir level in the age group 50 - 59, with the sBAP of 26.9 U/L +/- 8.6 U/L, sOC of 9.2 microg/L +/- 5.3 microg/L, and sNTX of 15.6 micromol/L +/- 6.1 micromol/L. After the age of 60, sNTX increased slightly 16.0 micromol/L +/- 6.1 micromol/L, however, BAP and sOC remained stable; (3) After adjustment for age, height, weight, BMI and smoking, serum BAP was negatively correlated with BMD of multiple skeletal sites. sOC was inversely associated with BMD of multiple skeletal sites except lateral spine; and sNTX was negatively correlated with BMD of the lumbar spine and total hip., Conclusion: Negatively correlated with BMD, sBAP, sOC, and sNTX may be sensitive and relatively specific markers to evaluate age-related changes of bone turnover.

Objective: To study the relationship between serum matrix metalloproteinase (MMP)-1, MMP-2 and bone turnover markers, bone mineral density (BMD) in Chinese women aged 20-80 years., Methods: Serum MMP-1, MMP-2, bone alkaline phosphatase (BAP), osteocalcin (OC) and cross-linked N-telopeptide of collagen type I (NTX) were measured using ELISA. BMD were measured using DEXA in 591 women., Results: (1) MMP-1 and MMP-2 were positively correlated with age (both P < 0.001). (2) Level of MMP-2 in postmenopausal women was significantly higher than that in premenopausal women (P < 0.001). (3) Significant negative relationship was found between MMP-2 and BMD, but multiple linear stepwise regression analysis showed MMP-2 was not the determinant factor of BMD. (4) Positive correlation was found between MMP-2 and BAP, OC, NTX (all P < 0.001). (5) Serum MMP-2 concentrations were significantly higher in postmenopausal osteoporotic women than in age-matched normal controls and osteopenic subjects., Conclusion: Circulating MMP-2 and markers of bone turnover are related and they may increase with the increase in bone-turnover. The increase of serum MMP-2 appears possibly as a concomitant event in high bone turnover state such as postmenopausal osteoporosis.

Background: Previous studies have shown that bone turnover rate changes with age. At the same time, there is no definitive research regarding age-related changes of bone turnover level and its association with bone mineral density (BMD) in Chinese mainland women., Methods: In a cohort of 663 Chinese mainland women aged 20-70 years, serum bone alkaline phosphatase (BAP) and serum cross-linked C-telopeptides of type I collagen (sCTX) were measured to evaluate the state of bone formation and resorption, respectively. BMD was measured in the posteroanterior spine, supine lateral spine, hip and forearm using a dual-energy X-ray absorptiometry., Results: The cubic polynomial regression model best fit age-related changes in serum BAP (R2=0.398, p<0.001) and sCTX concentrations (R2=0.148, p<0.001) with largest R2 from comparison 8 different regression models. Their values reached a minimal level in the 30-39 years age group, and increased dramatically in the 40-59 years groups. There was a decreasing trend of BAP in women >60 years. The levels of BAP and sCTX were inversely correlated to BMD in various skeletal regions over the entire population (r=-0.096 to -0.357, p<0.05). sCTX was a significant predictor of a T-score< or =-2.5 of BMD in postmenopausal women with sCTX levels above mean+2 SD of women aged 30-39 years compared with other postmenopausal women, which indicated by odds ratios 1.9-3.7 (p<0.05) for various skeletal regions, especially for the lateral lumbar spine (2.2, p<0.01), Ward's triangle (3.7, p<0.01), and ultradistal end of radius + ulna (2.8, p<0.001)., Conclusions: Age-dependent serum BAP and sCTX were inversely correlated to BMD, and sCTX was a useful parameter for the prediction of a low T-score of BMD at skeletal sites with abundant cancellous bone in postmenopausal women.

Objective: To investigate the distribution of parathyroid hormone (PTH) gene polymorphisms and the relationships of PTH gene polymorphisms with bone mass and serum bone relative biochemical markers., Methods: Blood samples of 314 normal female volunteers, aged 20 - 80, were collected. Serum PTH, bone alkaline phosphatase (sBAP), cross-linked N-telopeptide of collagen type I (sNTX), cross-linked C-telopeptide of collagen type I (sCTX), osteoprotegerin (OPG) and leptin were determined by ELISA. Polymorphisms of PTH gene were detected by polymerase chain reaction fragment length polymorphisms (PCR-RFLP) of restriction enzyme BstBI. BMD (QDR4500A) of the anteroposterior spine (AP), supine lateral spine (Lat), and femoral neck (FN) were measured., Results: (1) The genotype frequency of BB, Bb, and bb were 75.8%, 23.3% and 0.9% respectively in normal females volunteers. The frequencies of RFLP alleles B and b were 87.5% and 12.5% respectively. There was no difference in the polymorphism frequency of PTH gene between the post- and pre menopausal women. (2) There were no significant differences in the BMD of the AP, Lat, and FN and the serum biochemical markers between the BB and Bb genotypes. (3) Multiple stepwise regression analysis showed that PTH did not influence the BMD values., Conclusion: PTH gene polymorphism has no relationship with bone mass and serum bone biochemical markers in normal females.

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.

Measurements of bone biochemical markers are increasingly being used to evaluate the state of bone turnover in the management of bone metabolic diseases, especially osteoporosis. However, changes in the bone turnover rate vary with age. The aim of this study was to establish the laboratory reference range of serum bone-specific alkaline phosphatase (sBAP), serum type I collagen cross-linked C-terminal telopeptide (sCTx), and urine CTx (uCTx), based on values from 665 healthy Chinese women aged 20-80 years. We measured the levels of sBAP, sCTx, serum alkaline phosphatase (sALP), and uCTx and evaluated the age-related changes and their relationship with bone mineral density (BMD) in the anteroposterior (AP) lumbar spine, hip, and left forearm. We found significant correlations between biochemical markers and age, with coefficients of determination (R (2)) of 0.358 for sBAP, 0.126 for sCTx, 0.125 for uCTx, and 0.336 for sALP. The net changes in different biochemical markers were inversely correlated with the rates of BMD loss in the AP lumbar spine. After correction for age, body weight, and height, the levels of the markers had significant negative correlations with the BMD of the AP lumbar spine, femoral neck, and ultradistal forearm. All four biochemical markers had the highest negative correlation with BMD of the AP lumbar spine (partial correlation coefficients of -0.366, -0.296, -0.290, and -0.258 for sBAP, sCTx, uCTx, and sALP, respectively). The mean and SD values of these markers in premenopausal and postmenopausal women with normal BMD values were used as the normal reference ranges. The reference ranges of sBAP, sCTx, and uCTx for pre- vs postmenopausal women were 17.3 +/- 6.23 vs 18.9 +/- 7.52 U/l, 3.18 +/- 1.49 vs 3.23 +/- 1.57 nmol/l, and 15.5 +/- 11.4 vs 16.2 +/- 12.4 nM bone collagen equivalents/mM urinary creatinine, respectively. Levels of the bone formation marker (sBAP) and bone resorption markers (sCTx, uCTx) increased rapidly in women with osteopenia or osteoporosis, indicating that they may be sensitive markers to determine the bone turnover rate in healthy Chinese women.

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.

The aim of this study is to explore the differences of BMD reference curves at various skeletal sites among Chinese women from different regions of China and to investigate the feasibility of establishing a unified national BMD reference database for Chinese women. We measured BMD at the posteroanterior (PA) lumbar spine, femoral neck, trochanter and Ward's triangle by dual-energy X-ray absorptiometry bone densitometer in 3,422 Changsha women of South Central China, aged 20-84 years. The documented BMDs of reference populations of women in all other areas included Shanghai ( n =2,111) and Nanjing ( n =3,174) in the East, Shenyang ( n =1,213) in the Northeast, Kunming ( n =523) in the Southwest, Chongqing ( n =811) in the Midwest and Xian ( n =1,320) in the Northwest. We adopted the cubic regression as the fitting model for reference curves of BMD that varied with age, conducted conversions of BMD measured by various bone densitometers from different manufacturers and compared the differences between standardized BMD (sBMD) reference curves and combined ones for women from different areas. Our results revealed that by comparing variances in women from different areas, the average variances of non-standard BMD were 0.8-30.8% at the PA spine, 0.7-24.5% at the femoral neck, 0.6-29.9% at the trochanter and 1.1-54.7% at Ward's triangle, while average variances of sBMD either significantly decreased or disappeared (0.8-3.9% at the PA spine, 0.7-8.6% at the femoral neck, 0.6-8.3% at the trochanter and 1.1-29.9% at Ward's triangle). The sBMD reference curves were highly positive-dependent with combined ones ( r =0.913-0.999, P =0.000). At the PA spine and trochanter, the effect of combined sBMD curves presented well in women from different areas, except for those from Shanghai at the PA spine and Shenyang at the trochanter, indicating that sBMD curves were significantly different from pooled ones; at the femoral neck and Ward's triangle, the effect of combined sBMD reference curves was poor, indicating that sBMD curves demonstrated significant differences from pooled ones in women from a majority of these areas. We conclude that, in high density population areas, sBMD reference curves showed no significant geographic differences in women from various regions. In women from different areas, sBMD reference curves present good pooled results at the PA spine and trochanter. The less ideal combining effect of the sBMD curves at both femoral neck and Ward's triangle might be caused by the intrinsic differences from the different measuring instruments.

Objective: To study the serum matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels, and the correlations of MMP-1, MMP-2, and TIMP-1 with bone turn-over markers and bone mineral density (BMD) in aged postmenopausal Chinese women., Methods: The serum MMP-1, MMP-2, TIMP-1, serum bone alkaline phosphatase (BAP), serum osteocalcin (OC), serum cross-linked N-telopeptides of type I collagen (NTX) of 297 Chinese female volunteers aged 48 - 89 were measured using ELISA. BMD were measured using dual energy X-ray absorptiometry in aged postmenopausal Chinese women., Results: (1) There were no significant negative relationships between MMP-1, TIMP-1 and BMD and bone biochemical markers. (2) A weak negative relationships were found between MMP-2 and BMD. Adjusted by age and body weight, the correlation of MMP-2 with BMD of neck of femur and hip disappeared. (3) Positive correlations between MMP-2 and BAP, OC, NTX was found (all r = 0.193, 0.231, 0.249, P < 0.01) (4) Serum MMP-2 concentrations were significantly higher in postmenopausal women with osteoporosis (1466 microg/L +/- 313 microg/L) than in age-matched normal controls (1222 microg/L +/- 243 microg/L) and osteopenia subjects (1282 microg/L +/- 220 microg/L)., Conclusion: There are significant correlations between serum MMP-2 and bone metabolism, and MMP-2 may increase with increases in bone-turnover. The increases of serum MMP-2 appear possibly as a concomitant event in high bone turnover state, such as postmenopausal osteoporosis.

As the mechanical competence of trabecular bone is a function of its apparent density and 3-D distribution, assessment of 3-D trabecular structural characteristics may improve our ability to understand the pathophysiology of osteoporosis, to test the efficacy of pharmaceutical intervention, and to estimate bone biomechanical properties. We have studied ovariectomy-induced osteopenia in rats and its treatment with agents such as estrogen and sodium fluoride. We have demonstrated that 3-D micro-computed tomography (microCT) can directly quantify mouse trabecular and cortical bone structure with an isotropic resolution of 6 microm(3). MicroCT is also useful for studying osteoporosis in mice and phenotypes of mice with gene manipulation, such as SHIP-knockout mice, which are severely osteoporotic due to increased numbers of hyperresorptive osteoclasts, PTHrP heterozygous-null mice, and mice with Zmpste24 deficiency. MicroCT can quantify osteogenesis in mouse Ilizarov leg-lengthening procedures, osteoconduction in a rat cranial defect model, and structural changes in arthritic rabbits, rats, and mice. In clinical studies, we evaluated longitudinal changes in the iliac crests. Paired bone biopsies from the same premenopausal and postmenopausal women showed the changes in 3-D trabecular structure, such as decreased trabecular thickness, shifting of trabecular model from platelike structure to rodlike structure, and decreased degree of anisotropy were remarkable. Treatment with PTH in postmenopausal women with osteoporosis significantly improved trabecular morphology with a shift toward a more platelike structure, increased trabecular connectivity density, and increased cortical thickness. Paired bone biopsy specimens from the iliac crest in postmenopausal women with osteoporosis before and an average of 2 years after beginning of estrogen replacement therapy demonstrated that posttreatment biopsies showed a significant change in the ratio of plates to rods and statistically insignificant changes in other 3-D trabecular parameters. Thus, microCT can characterize 3-D structure of various animal models, and the longitudinal changes in 3-D bone microarchitectural integrity that deteriorates in the transmenopausal period, is preserved with HRT, and is improved with PTH treatment in postmenopausal women.

Bone mass acquisition from different genders and races of children and adolescents may vary. To explore gender- and age-related differences in bone mineral density (BMD) measurements in Chinese children and adolescents, we used the dual-energy X-ray absorptiometry (DXA) bone densitometer to take BMD measurements at the posteroanterior (PA) and lateral spine, hip, and forearm in 1286 healthy children and adolescents, ranging from 6 to 24 years of age. Our results show a correlation between BMD measurements taken from different skeletal sites and from different ages of subjects. Male data were best fit to a power regression model, yielding the largest determinant coefficients (R (2)), whereas S regression was the best fitting model for females. In individuals younger than 17 years of age, the rate of BMD accumulation in the PA spine is more rapid in females than in males, whereas in individuals older than 19 years of age, the converse was found to be true. In children younger than 14 years of age, BMD measurements, taken from the lateral spine, the neck and trochanter of the femur, and the total hip, correlated with age similarly in both genders. Additionally, in measurements taken from the forearm ultradistal and 1/3 region, BMD measurements from similar ages of both genders are similar. With increasing age, BMD measurements in males become significantly higher than those of females. However, volumetric BMD (vBMD) measurements from both genders show good uniformity at the lateral spine with a near overlap of the two models. Our findings suggest that vBMD acquisition measurements in Chinese children and adolescents show no gender differences, with gender differences only demonstrated in areal BMD (aBMD) measurements taken from different skeletal sites.

Background: Serum leptin concentration is associated with age, fat and bone mineral density (BMD), and there are ethnic differences in physique and BMD values. The relationship between serum leptin concentration and BMD in Chinese women is presently unknown. We examined the relationship of serum leptin concentration with age, body weight, BMI and BMD in mainland Chinese women., Methods: Serum leptin concentration in a population of 676 Chinese females, aged 20-80 years (45.4+/-14.8 years, mean+/-S.D.), was measured using an enzyme-linked immunosorbent assay (ELISA). BMD values were measured by dual-energy X-ray absorptiometry (DXA) at a number of sites: the posteroanterior lumbar spine (PA, L1-L4), lateral lumbar spine (Lat, L2-L4), hip (including the femoral neck (FN) and total hip (T-hip)), and forearm (one-third region (RU1/3) and total region (RUT)). The relationship between changes in serum leptin concentration with age, body weight, height, body mass index (BMI) and BMD values at six sites were analyzed using 10 different regression models, and the models giving the best fit were selected., Results: The cubic regression model best described the changes in serum leptin concentration with age (R(2)=0.048, p<0.001) and body weight (R(2)=0.352, p<0.001), while the quadratic regression model was best for serum leptin concentration changes with BMI (R(2)=0.410, p<0.001); serum leptin concentration was not correlated with height. Serum leptin concentration was significantly higher in postmenopausal than premenopausal women (p<0.001). Serum leptin concentration was correlated with Lat BMD (R(2)=0.012, p<0.018), FN BMD (R(2)=0.006, p<0.041) and T-hip BMD (R(2)=0.013, p<0.004) in the whole population. In premenopausal women, leptin was positively associated with BMD except for Lat (R(2)=0.029-0.055, p<0.008); in postmenopausal women, leptin was also positively associated with AP, FN, T-hip BMD (R(2)=0.026-0.042, p<0.007). However, after adjusting for BMI not for body weight, there was no association between serum leptin concentration and age. Meanwhile, after adjustment for age, body weight and BMI, there was no association between serum leptin concentration and BMD values in premenopausal and postmenopausal women., Conclusions: Age-related changes in serum leptin concentration is dependent on BMI, but not a direct determinant of BMD in Chinese females.

Objective: To study the relationships of serum bone alkaline phosphatase (sBAP), serum osteocalcin (sOC) and the ratio of urine cross-linked N-telopeptide of collagen type I (uNTX)/creatine (Cr) with age and bone mineral density (BMD) in healthy women aged 20 - 80 years., Methods: sBAP, sOC and uNTX were measured using ELISA. BMD at lumbar spine 1 - 4 anteroposterior (AP) and at femoral neck (FN) was studied using DXA (QDR 4500A) in 668 healthy women. Correlations of bone biomarkers with age and BMD were fitted in entire female population by ten kinds of regression models., Results: (1) sBAP, sOC and uNTX were positively correlated with age (all P < 0.001). The cubic regression model was better fitted with age-related changes of bone biomarkers as compared with the other regression models and the coefficients of determination (R(2)) of fitting curve were 0.181 - 0.381 (P < 0.001). (2) When all subjects were stratified by 10-year age groups, the bone biomarker values during 30 - 39 years of age were the lowest, then they increased gradually to a highest level in the 50 - 59 years of age. (3) When subjects were stratified by menopause, levels of sBAP, sOC and uNTX in postmenopausal women with a low value of BMD at AP and FN were significantly higher than those in premenopausal women (all P < 0.001). (4) Positive correlation among sBAP, sOC and uNTX was found (all P < 0.001) and BMD values at AP and FN were negatively correlated with all the bone biomarkers (all P < 0.001)., Conclusions: sBAP, sOC and uNTX may be the sensitive and relatively specific markers to evaluate age- and menses-dependent changes of bone turnover, but they are negatively correlated with BMD, suggesting that individuals with increased bone biomarker levels are associated with a decreased BMD value.

Objective: To study the relationships of serum osteoprotegrin (sOPG), serum bone gamma-carboxyglutamine acid-containing protein (sBGP), and urine deoxypyridinoline (uDPD)/creatinine (Cr) with age and bone mineral density (BMD) in women., Methods: ELISA was used to examine the sOPG, sBGP, and uDPD/Cr of 672 female volunteers aged 20-80. The BMD (QDR4500A) value of the anteroposterior lumbar spine and femoral neck were measured by DXA., Results: (1) The levels of sOPG, sBGP, and uDPD/Cr in the age group of 30-39 were 2.8 pmol/L +/- 1.4 pmol/L, 5 microg/L +/- 3 microg/L, and 4.9 nmol/mmol +/- 2.5 nmol/mmol respectively, all significantly lower than those in the age groups 40-49, 50-59, and 60-69 (all P < 0.05). (2) In the age group 40-49, the values of sOPG, sBGP, and uDPD in menopausal subjects were significantly higher than those of the non-menopausal subjects (5.7 pmol/L +/- 3.1 pmol/L vs 3.4 pmol/L +/- 2.0 pmol/L, 11 microg/L +/- 5 microg/L vs 6 microg/L +/- 3 microg/L, and 6.9 nmol/mmol +/- 3.3 nmol/mmol vs 5.2 nmol/mmol +/- 3.9 nmol/mmol, all P < 0.001). (3) Age was positively correlated with sOPG, sBGP, uDPD/Cr, and BMD of anteroposterior lumbar spine and femoral neck (r = 0.130, 0.355, 0.106, -0.600, -0.545; P < 0.01). sOPG and sBGP were negatively correlated to anteroposterior lumbar spine BMD (r = -0.183, -0.108, P < 0.01; and r = -0.541, -0.441, P < 0.001). sOPG was positively correlated with sBGP and uDPD/Cr (r = 0.216 and 0.083; both P < 0.05)., Conclusion: sOPG, sBGP, and uDPD/Cr can be used as sensitive markers to determine the bone turnover status, which is changeable with age, and menopausal status in women, and predict the bone lose prior to BMD determination by DXA.

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.

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.

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.

Results of previous studies have indicated that bone mineral density (BMD) is decreased in aged animals and elderly humans, and that treatment with nitric oxide (NO) donors prevents bone loss. Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase (NOS) inhibitor, can inhibit NO synthesis. In the study reported here, we examined age-related changes in the serum content of ADMA and in BMD in various skeletal regions. The BMD in the lumbar part of the spine, the femur, and the tibia in 12-month-old rats was markedly increased, compared with that in 6-month-old rats, and the BMD in 20-month-old rats was decreased, compared with that in 12-month-old rats. Serum concentration of ADMA in 20-month-old rats was significantly increased, compared with that in 6- or 12-month-old rats. A similar age-related change in the concentration of lipid peroxide also was seen in the three age groups. These results suggest that the increased amount of endogenous ADMA may be associated with an age-related decrease in BMD in rats.

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]

Abstract: Background: The relationship between the levels of gonadotropic hormones and bone metabolism-related cytokines in Chinese women is unclear. We investigated the relationship between FSH and LH and OPG, leptin, TGF-β1, and TGF-β2 in Chinese women. Methods: A cross-sectional study of 694 Chinese women, aged 20 to 82y was conducted. Levels of serum FSH, LH, OPG, leptin, TGF-β1, and TGF-β2 were determined. Results: In premenopausal females, serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels seemly showed no correlation with the cytokine levels. In perimenopausal females, serum FSH and LH levels showed significant positive correlation with osteoprotegerin (OPG) and transforming growth factor-β2 (TGF-β2) levels (r =0.286 to 0.405, all P =0.000), whereas they showed negative correlation with TGF-β1 levels (r =−0.413 and −0.354, all P =0.000). In postmenopausal females, FSH and LH levels showed positive correlation with OPG levels (r =0.247 and 0.241, all P =0.000), negative correlation with leptin and TGF-β1 levels (r =−0.234 to −0.319, all P =0.000), and no correlation with TGF-β2 levels. Multiple linear regression stepwise analysis revealed the following results. In premenopausal females, 2.0% and 1.5% of the changes in LH could be explained by OPG and leptin, respectively, while 1.9% of the changes in OPG could be explained by LH. In perimenopausal females, the determinants of OPG and TGF-β1 on FSH were 10.9% and 17.0%, respectively, and the determinants of OPG, TGF-β1 and TGF-β2 on LH were 4.5%, 4.9% and 16.4%, respectively. The determinants of FSH and LH on OPG were 14.5% and 2.5%, respectively. The determinant of FSH on TGF-β1 was 4.5%, while the determinant of LH on TGF-β2 was 16.4%. In postmenopausal females, the determinants of leptin and OPG on FSH were 10.2% and 2.8%, respectively, and the determinants of OPG and TGF-β1 on LH were 5.8% and 2.3%, respectively. The determinant of FSH on OPG, leptin and TGF-β1 were 6.1%, 3.4% and 9.2%. Conclusions: These results indicate that age-related gonadotropic hormone levels are associated with changes in OPG, TGF-β1, TGF-β2 and leptin, and change with menopausal status. [Copyright &y& Elsevier]

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: 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 20–80years. 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 &y& Elsevier]

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]