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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: 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.)

Objective: To study bone mass changes and its mechanisms in murine knockout apolipoprotein E (ApoE-/-)., Methods: Both 28-week-old male ApoE-/- mice (n = 6) and wild-type (WT) mice (n = 10) were euthanized. The trabecular and cortical bone microarchitecture were assessed by micro-CT (microCT) in right distal femur. The total body BMD (bone mineral density) of left femur was determined by dual-energy X-ray absorptiometry (DXA). The serum concentrations of osteoprotegerin (OPG) and receptor activator of nuclear factor kappaB ligand (RANKL) were analyzed using enzyme-linked immunosorbent assay (ELISA). The left tibias were dissected and fixed in 4% paraformaldehyde after decalcified in 0.15M EDTA buffer for 30 days. And the expressions of OPG and RANKL were detected by immunohistochemical staining., Results: Compared with WT mice, the ApoE-/- mice showed an increased volumetric BMD (294 +/- 38) mg/mm(3), tissue BMD (627 +/- 23) mg/mm(3), BMC (bone mineral content) (0.57 +/- 0.08) mg, bone volume fraction (20.38 +/- 4.74)%, trabecular number (6.67 +/- 0.78) mm(-1), trabecular thickness (0.03 +/- 0.01) mm with an decreased bone surface fraction (69 +/- 18) mm(-1), trabecular separation (0.12 +/- 0.01) and structure mode index (1.73 +/- 0.24). The total body BMD was higher in ApoE-/- mice than WT mice [(0.063 +/- 0.004) g/cm(2) vs (0.056 +/- 0.004) g/cm(2)]. The serum level of OPG was significantly higher in ApoE-/- mice than WT mice [(4.98 +/- 0.97) ng/ml vs (3.54 +/- 0.65) ng/ml]. The results of immunohistochemical staining showed that the OPG expression was at a higher level in bone cell of ApoE-/- mice and RANKL showed no obvious change in either sera or bone cells., Conclusion: A decreased bone resorption causes an increased bone mass in ApoE-/- mice and leads to an imbalanced ratio of OPG/ RANKL.

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.

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.

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.

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 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.

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.

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.

Bone marrow mesenchymal stem cells (BMSCs) exhibit an age-related lineage switch between osteogenic and adipogenic fates, which contributes to bone loss and adiposity. Here we identified a long noncoding RNA, Bmncr, which regulated the fate of BMSCs during aging. Mice depleted of Bmncr (Bmncr-KO) showed decreased bone mass and increased bone marrow adiposity, whereas transgenic overexpression of Bmncr (Bmncr-Tg) alleviated bone loss and bone marrow fat accumulation. Bmncr regulated the osteogenic niche of BMSCs by maintaining extracellular matrix protein fibromodulin (FMOD) and activation of the BMP2 pathway. Bmncr affected local 3D chromatin structure and transcription of Fmod. The absence of Fmod modified the bone phenotype of Bmncr-Tg mice. Further analysis revealed that Bmncr would serve as a scaffold to facilitate the interaction of TAZ and ABL, and thus facilitate the assembly of the TAZ and RUNX2/PPARG transcriptional complex, promoting osteogenesis and inhibiting adipogenesis. Adeno-associated viral-mediated overexpression of Taz in osteoprogenitors alleviated bone loss and marrow fat accumulation in Bmncr-KO mice. Furthermore, restoring BMNCR levels in human BMSCs reversed the age-related switch between osteoblast and adipocyte differentiation. Our findings indicate that Bmncr is a key regulator of the age-related osteogenic niche alteration and cell fate switch of BMSCs., IntroductionGuided by genetic and molecular mediators, as well as the local microenvironment, bone marrow mesenchymal stem cells (BMSCs) differentiate into various mature cell types, including adipocytes and osteoblasts (1-3). Age-related [...]

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]