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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.

MicroRNAs (miRNAs) interfere with translation of specific target mRNAs and are thought to thereby regulate many cellular processes. Recent studies have suggested that miRNAs might play a role in osteoblast differentiation and bone formation. Here, we identify a new miRNA (miR-2861) in primary mouse osteoblasts that promotes osteoblast differentiation by repressing histone deacetylase 5 (HDAC5) expression at the posttranscriptional level. miR-2861 was found to be transcribed in ST2 stromal cells during bone morphogenetic protein 2-induced (BMP2-induced) osteogenesis, and overexpression of miR-2861 enhanced BMP2-induced osteoblastogenesis, whereas inhibition of miR-2861 expression attenuated it. HDAC5, an enhancer of runtrelated transcription factor 2 (Runx2) degradation, was confirmed to be a target of miR-2861. In vivo silencing of miR-2861 in mice reduced Runx2 protein expression, inhibited bone formation, and decreased bone mass. Importantly, miR-2861 was found to be conserved in humans, and a homozygous mutation in pre-miR-2861 that blocked expression of miR-2861 was shown to cause primary osteoporosis in 2 related adolescents. Consistent with the mouse data, HDAC5 levels were increased and Runx2 levels decreased in bone samples from the 2 affected individuals. Thus, our studies show that miR-2861 plays an important physiological role in osteoblast differentiation and contributes to osteoporosis via its effect on osteoblasts., Introduction MicroRNAs (miRNAs) are a growing class of small (~22 nucleotides), single-stranded noncoding RNAs found in diverse organisms (1). They negatively regulate translation of specific mRNAs by base pairing with [...]

This cross-sectional study aimed to examine the association between selenium levels and diabetes in an older population with life-long natural exposure to selenium in rural China. A total of 1856 subjects aged 65 years or older from four Chinese rural counties with different environmental selenium levels were evaluated. Analysis of covariance models and logistic regression models were used to examine the relationship between nail selenium levels and serum glucose, serum insulin, insulin resistance [using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)], and the risk of diabetes. The mean nail selenium level was 0.461 μg/g and the prevalence rate of diabetes was 8.3% in this population. The mean nail selenium level was significantly higher in the group with diabetes than in the group without diabetes ( P <0.0001). The adjusted odds ratios for diabetes were 2.65 (95% CI : 1.48 to 4.73), 2.47 (95% CI : 1.37 to 4.45), and 3.30 (95% CI : 1.85 to 5.88) from the second selenium quartile to the fourth quartile, respectively, compared with the first quartile group. The mean serum glucose and HOMA-IR in the higher selenium quartile groups were significantly higher than those of the lowest quartile group. However, no significant differences in insulin were observed among the four quartile groups. A long-term, higher level of exposure to selenium may be associated with a higher risk of diabetes. Future studies are needed to elucidate the association between selenium and insulin resistance. [ABSTRACT FROM AUTHOR]

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

Objectives: Moderate to vigorous physical activity is recommended to prevent hypertension according to the current guidelines. However, the degree to which the total physical activity (TPA) and its changes benefit normotensives and hypertensives is uncertain. We aimed to examine the effects of TPA and its changes on the incidence, progression, and remission of hypertension in the large-scale prospective cohorts., Methods: A total of 73,077 participants (55,101 normotensives and 17,976 hypertensives) were eligible for TPA analyses. During a mean follow-up of 7.16 years (394,038 person-years), 12,211 hypertension cases were identified. TPA was estimated as metabolic equivalents and categorized into quartiles. Cox proportional hazards regression and multivariable logistic regression were used to estimate associations of TPA and changes in TPA with incident hypertension and progression/remission of hypertension., Results: Compared with the lowest quartile of TPA, normotensives at the third and the highest quartile had a decreased risk of incident hypertension, with hazard ratios (HRs) of 0.86 [95% confidence interval (CI): 0.81-0.91] and 0.81 (95% CI: 0.77-0.86), respectively. Hypertensives at the highest quartile of TPA demonstrated a decreased risk of progression of hypertension [odds ratio (OR) = 0.87, 95% CI: 0.79-0.95], and an increased probability of hypertension remission (OR = 1.17, 95% CI: 1.05-1.29). Moreover, getting active from a sedentary lifestyle during the follow-up period could reduce 25% (HR = 0.75, 95% CI: 0.58-0.96) risk of incident hypertension, whereas those becoming sedentary did not achieve benefit from initially being active., Conclusions: Our findings indicated that increasing and maintaining TPA levels could benefit normotensives, whereas higher TPA levels were needed to effectively control progression and improve remission of hypertension. Physical activity played undoubtedly an essential role in both primary and secondary prevention of hypertension., (Copyright and License information: Journal of Geriatric Cardiology 2021.)

Background: In China, lack of evidence remains a significant challenge for the national initiative to promote physical activity (PA). We aimed to quantify the beneficial effects of meeting or maintaining the recommended PA level [150 minutes per week (min/wk) of moderate PA or 75 min/wk of vigorous PA or an equivalent combination] on incident cardiovascular disease (CVD) among Chinese population., Methods: We included 100,560 participants without history of CVD from three cohorts in the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD events and its subtypes, including stroke, coronary heart disease, heart failure, and CVD death., Results: During a median follow-up of 7.3 years (range: 6-15 years), 777,163 person-years and 4693 incident CVD events were observed. Compared with participants who were inactive at baseline, the multivariable adjusted HR (95% CI) of developing CVD was 0.74 (0.69-0.79) for those who met recommended moderate to vigorous physical activity (MVPA) level at baseline. Furthermore, the risk of CVD incidence was reduced with increment of MVPA ( P trend < 0.001), and the HR (95% CI) of highly-active versus inactive category was 0.62 (0.56-0.68). Compared with individuals who were inactive both at the baseline and follow-up, those keeping active over the period of follow-up had a substantial lower risk of incident CVD with the HR (95% CI) of 0.57 (0.43-0.77)., Conclusions: The findings demonstrated that meeting and maintaining the recommended MVPA level could reduce the cardiovascular risk. Wider adoption of the PA recommendations would have considerable health impacts to the Chinese population., (Institute of Geriatric Cardiology.)

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

Objective: To explore the relationship between body fat distribution, insulin resistance, islet β cell function and metabolic disorders in adult population., Methods: From February to November 2012, a total of 174 subjects aged 20-68 years were recruited. Their anthropometric parameters, blood biochemical indices and the results of oral glucose tolerance test (OGTT) and insulin releasing test (IRT) were collected. Body fat distribution was measured with dual energy X-ray absorptiometry (DEXA)., Results: The values of trunk/total fat mass (T/B) and android/gynoid fat mass ratio (A/G) were positively correlated with blood pressure, blood lipid, plasma glucose, insulin resistance index (HOMA-IR) and high-sensitivity C-reactive protein. Compared with the group of normal metabolism, the group of metabolic disorders had higher T/B and A/G (P < 0.05). After multiple stepwise regression analysis, the main influencing factors of lnHOMA-IR and lnHOMA-β were T/B and Grespectively.Logistic regression showed that A (OR = 3.01, 95%CI 1.86-8.17) was a risk factor for diabetes and A/G (OR = 2.71, 95%CI 1.75-6.56) a risk factor for dyslipidemia., Conclusions: Trunk and android fat deposition aggravates insulin resistance, metabolic disorders. And the main influencing factors of insulin resistance and islet β cell function are trunk and gynoid fat respectively. Android fat mass is a major risk factor for glycolipid metabolism.

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.

The objective of this study was to investigate the relationship between serum levels of OPG, TGF- β 1, and TGF- β 2 and BMD decrease rate (BDR) in native Chinese women. This cross-sectional study was performed on 465 healthy native Chinese women aged 35-80 years. Serum levels of OPG, TGF- β 1, and TGF- β 2 were determined. BDR was measured by DXA at the posteroanterior spine, hip, and distal forearm. At all skeletal sites tested, there was a negative correlation between BDR and serum levels of both OPG (r = -0.122 to -0.230, all P = 0.007-0.000) and TGF- β 2 (r = -0.100 to -0.173, all P = 0.029-0.000) and a positive correlation between BDR and serum TGF- β 1 (r = 0.245 - 0.365, all P = 0.000). After adjustment for age and BMI, there were no statistically significant correlations between serum levels of OPG or TGF- β 2 and BDR. However, statistically significant correlations between serum TGF- β 1 and BDR at the lumbar spine and ultradistal forearm remained. Multiple linear regression stepwise analysis showed that serum OPG could explain 1.4-3.7% of BDR variation. Serum TGF- β 1 was a positive determinant of BDR and could explain 5.3-13.3% of BDR variation.

Recently, a membrane-based estrogen receptor (ER), ER-α36, was identified and cloned that transduces membrane-initiated estrogen signaling such as activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway. Here we show that the postmenopausal level of estradiol (E2) induces mitogenic, antiapoptotic, and antiosteogenic effects and proapoptotic effects in postmenopausal osteoblasts and osteoclasts with high levels of ER-α36 expression, respectively. We also found that ER-α36 mediated the effects of postmenopausal-level E(2) on proliferation, apoptosis, and differentiation of osteoblasts through transient activation of the MAPK/ERK pathway, whereas ER-α36-mediated postmenopausal-level E(2) induces apoptosis of osteoclasts through prolonged activation of the MAPK/ERK pathway with the involvement of reactive oxygen species. We also show that the levels of ER-α36 expression in bone are positively associated with bone mineral density but negatively associated with bone biochemical markers in postmenopausal women. Thus the higher levels of ER-α36 expression are required for preserving bone mass in postmenopausal and menopausal women who become osteoporotic if ER-α36-mediated activities are dysregulated., (© 2011 American Society for Bone and Mineral Research.)

Objective: To evaluate the effect of ultra-early hyperbaric oxygenation on spinal edema and hind limb motor function in rats with complete spinal cord transection., Methods: Fifty-five healthy 3-month-old female SD rats were randomly divided into sham-operated group (n=15), complete spinal cord transection group (CSCT group, n=20) and hyperbaric oxygen group (HBO group, n=20). The rats in the sham-operated group underwent only laminectomy, while those in the other 2 groups underwent CSCT at the T10 level. The rats in HBO group were placed in an oxygen chamber 3 h after the operation for 10 days as a treatment course, and 3 treatment courses were administered at the interval of 6 days. In the first treatment course, 2 hyperbaric oxygenation sessions were given daily, and in the following 2 course, only 1 session was given daily. The recovery of hindlimb motor function was evaluated using the open-field Basso-Beattie-Bresnahan (BBB) scoring system once a week for 6 weeks. All the rats were sacrificed 6 weeks after the operation to measure the water content in the injured tissues., Results: The BBB scores of CSCT group and HBO group gradually increased with the passage of time after the operation, and from week 2 to week 6, HBO group had significantly higher scores than CSCT group (P<0.05). The water content was markedly increased in CSCT group at 6 weeks after the operation as compared with that in the sham-operated group (P<0.01), and significantly reduced in HBO group in comparison with that in the CSCT group (P<0.05)., Conclusion: Ultra-early HBO can suppress spinal cord edema and promote hindlimb locomotor recovery in rats with complete spinal cord transection.

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.

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

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

Objective: To 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.

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.

Objective: To characterize the clinical manifestations, features of roentgenography and MR imaging, and the pathology of articular cartilage and matrix of spondyloepiphyseal dysplasia tarda with progressive arthropathy (SEDT-PA), to screen the mutations of the disease-causing CCN6 gene, and try to elucidate the molecular pathogenesis of SEDT-PA., Methods: A questionnaire survey on the clinical manifestations and history was conducted among a pedigree of SEDT-PA with 57 persons (53 living members) in tolal, including 2 probands, a 19-year old female and a 9-year old male. Physical examination and roentgenography and MR imaging were used on the 2 probands to characterize the features of their joints and articular cartilage. The femoral head extracted during replacement of hip of the proband 1 underwent hematoxylin-eosin staining and toludine blue (TB) staining to observe the pathological changes and ultra-microstructure of the articular chondrocytes and cartilage matrix using electron microscopy. Peripheral blood samples were collected from these 53 living members and 100 healthy controls. PCR was used to examine and sequence the exons of CCN6. 3D-conformational illustration of mutant CCN6 proteins were predicted using the Prospect Software., Results: The clinical manifestations, radiology, and MR imaging established the diagnosis of SEDT-PA. Pathologic examination demonstrated that the articular cartilage chondrocytes became hyper-proliferative and immature, while the density and diameter of matrix collagens were dramatically decreased. Mutation studies showed the two probands carried a deletion (840delT) mutation in maternal allele, that caused the truncated CCN6 protein to miss 43 residues in C-terminus; and a substitution mutation (1000T-->C, Ser334Pro) in paternal allele, which was also inherited down to other 4 members in the SEDT-PA kindred. The predicted 3D-conformational changes of the truncated mutant and the Ser334Pro mutant CCN6 proteins demonstrated that in comparison with the wild CCN6 protein, the single long peptide loop in the region from signal peptide to the beginning 24 amino acid residues in the first domain (IGFBP) was subjected to folding into two smaller cross-loops accompanied with a much shorter C-terminus in 840 delT truncated mutant CCN6 protein, and no substantial 3D-conformational change of Ser334Pro mutant CCN6 protein was detected except for the C-terminal peptide towards the opposite direction., Conclusion: Novel 840delT mutation of CCN6 gene is the leading cause of SEDT-PA though coexistence of T1000C substitution is necessary for the clinical onset of SEDT-PA, in which marked abnormalities of cartilage chondrocytes and matrix are morphologically and functionally presented.

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.

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.