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Summary: We developed a new tool to assess the severity of osteoporotic vertebral fracture using radiographs of the spine. Our technique can be used in patient care by helping to stratify patients with osteoporotic vertebral fractures into appropriate treatment pathways. It can also be used for research purposes. Purpose: The aim of our study was to propose a semi-quantitative (SQ) grading scheme for osteoporotic vertebral fracture (OVF) on anteroposterior (AP) radiographs. Methods: On AP radiographs, the vertebrae are divided into right and left halves, which are graded (A) vertical rectangle, (B) square, (C) traverse rectangle, and (D) trapezoid; whole vertebrae are graded (E) transverse band or (F) bow-tie. Type A and B were compared with normal and Genant SQ grade 1 OVF, Type C and D with grade 2 OVF, and Type E and F with grade 3 OVF. Spine AP radiographs and lateral radiographs of 50 females were assessed by AP radiographs SQ grading. After training, an experienced board-certified radiologist and a radiology trainee assessed the 50 AP radiographs. Results: The height-to-width ratio of the half vertebrae varied 1.32–1.48. On lateral radiographs, 84 vertebrae of the 50 patients had OVFs (38 grade 1, 24 grade 2, and 22 grade 3). On AP radiographs, the radiologist correctly assigned 84.2%, 91.7%, and 77.2% and the trainee correctly assigned 68.4%, 79.2%, and 81.8% of grade 1, 2, and 3 OVFs, respectively. Compared with lateral radiographs, the radiologist had a weighted Kappa of 0.944 including normal vertebrae and 0.883 not including normal vertebrae, while the corresponding Kappa values for the trainee were 0.891 and 0.830, respectively. Conclusion: We propose a new semi-quantitative grading system for vertebral fracture severity assessment on AP spine radiographs. [ABSTRACT FROM AUTHOR]

Summary: This study revealed that there was no significant linear relationship between fasting C-peptide (FCP) level and bone mineral density (BMD) or fracture risk in type 2 diabetes mellitus (T2DM) patients. However, in the FCP ≤ 1.14 ng/ml group, FCP is positively correlated with whole body (WB), lumbar spine (LS), and femoral neck (FN) BMD and negatively correlated with fracture risk. Purpose: To explore the relationship between C-peptide and BMD and fracture risk in T2DM patients. Methods: 530 T2DM patients were enrolled and divided into three groups by FCP tertiles, and the clinical data were collected. BMD was measured by dual-energy X-ray absorptiometry (DXA). The 10-year probability of major osteoporotic fractures (MOFs) and hip fractures (HFs) was evaluated by adjusted fracture risk assessment tool (FRAX). Results: In the FCP ≤ 1.14 ng/ml group, FCP level was positively correlated with WB, LS, and FN BMD, while FCP was negatively correlated with fracture risk and osteoporotic fracture history. However, FCP was not correlated with BMD and fracture risk and osteoporotic fracture history in the 1.14 < FCP ≤ 1.73 ng/ml and FCP > 1.73 ng/ml groups. The study has shown that FCP was an independent factor influencing BMD and fracture risk in the FCP ≤ 1.14 ng/ml group. Conclusions: There is no significant linear relationship between FCP level and BMD or fracture risk in T2DM patients. In the FCP ≤ 1.14 ng/ml group, FCP is positively correlated with WB, LS, and FN BMD and negatively correlated with fracture risk, and FCP is an independent influencing factor of BMD and fracture risk. The findings suggest that FCP may predict the risk of osteoporosis or fracture in some T2DM patients, which has a certain clinical value. [ABSTRACT FROM AUTHOR]

Summary: Arrhythmia, pneumonia, cardiac insufficiency, a high leukocyte count, and low albumin concentrations were associated with increased 30-day mortality in elderly hip fracture patients after surgery. It is important to improve short-term survival rates by optimizing the respiratory and cardiac function of geriatric patients before they undergo surgery. Introduction: This study aims to investigate the 30-day mortality and related risk factors for elderly patients following surgery for hip fractures. Methods: This retrospective study examined chart reviews for evaluating associations of gender, age, fracture site, biochemical indicators, pre-surgery comorbidities, number of pre-surgery comorbidities, time to surgery and anesthesia and surgery methods with postoperative 30-day mortality in elderly hip fracture surgery patients. Results: A total of 1,004 patients were included in the study and 43 (4.3%) patients died within 30 days after surgery. Univariate analysis showed that patients in the non-survival group had a higher mean age, higher leukocyte counts, lower hemoglobin and albumin levels, a higher proportion of arrhythmias, pneumoniae and cardiac insufficiency and number of presurgical comorbidities than the survival group (all P-values < 0.05). Multivariate logistic analysis further confirmed that arrhythmia (OR = 2.033, P = 0.038), pneumonia (OR = 2.246, P = 0.041), cardiac insufficiency (OR = 2.833, P = 0.029), high leukocyte count (OR = 1.139, P = 0.009), and low albumin (OR = 0.925, P = 0.041) were all significant risk factors for mortality 30 days after surgery. Conclusions: This study demonstrates that arrhythmia, pneumonia, cardiac insufficiency, a high leukocyte count, and low albumin concentrations were associated with increased 30-day mortality in elderly hip fracture patients after surgery. [ABSTRACT FROM AUTHOR]

Summary: Postmenopausal osteoporosis is a major health problem with important genetic factors in postmenopausal women. We thoroughly evaluated the relationship of CNR2 polymorphisms with osteoporosis in a cohort of 1032 osteoporosis patients and 2089 healthy controls from Han Chinese postmenopausal women. Statistically significant differences, depending on different genotypes, were presented. Introduction: Osteoporosis is a major health problem in postmenopausal women, which is a multifactorial disease in which genetic determinants are modulated by hormonal, environmental, and nutritional factors. An important clinical risk factor in the pathogenesis of osteoporosis is the presence of genetic polymorphism in susceptibility genes. The aim of our study was to investigate whether CNR2 gene, which attributes to osteoporosis susceptibility in some populations, is associated with bone mineral density (BMD) or osteoporosis in Han Chinese postmenopausal women. Methods: We examine 39 SNPs covering the region of CNR2 gene in 3121 Han Chinese postmenopausal women, consisting of 1032 osteoporosis patients and 2089 healthy controls, to evaluate the association with BMD and osteoporosis. Results: We found that rs4237 and rs2501431 were significantly associated with BMD and osteoporosis (corrected p = 0.020085 and 0.017199) in our sample, and the TT genotype of rs2501431 and the AA genotype of rs4237 had lower lumbar spine BMD and femoral neck BMD compared with the other genotypes. Additionally, analyses by haplotypes indicated that two haplotype blocks, containing rs4237 and rs2501431 respectively, in the CNR2 gene significantly associated with BMD and osteoporosis (both global permutation p < 0.001), and a risk haplotype (ATTT) in the block of rs3003336-rs2501431-rs2502992-rs2501432 had almost 4-fold increase in the cases. Conclusions: Our results provide further supportive evidence for an important role of CNR2 gene in the etiology of osteoporosis and suggest that it may be a genetic risk factor for BMD and osteoporosis in Han Chinese postmenopausal women. [ABSTRACT FROM AUTHOR]

Summary: Treatment with curcumin attenuated modeled microgravity-induced bone loss, possibly through abating oxidative stress and activating vitamin D receptor. Curcumin might be an effective countermeasure for microgravity-induced bone loss but remains to be tested in humans. Introduction: Bone loss is one of the most important complications for human crewmembers who are exposed to long-term microgravity in space and also for bedridden people. The aim of the current study was to elucidate whether treatment with curcumin attenuated bone loss induced by microgravity. Methods: We used hind-limb suspension (HLS) and rotary wall vessel bioreactor (RWVB) to model microgravity in vivo and in vitro, respectively. We investigated the effects of curcumin consumption (40 mg kg body weight day, via daily oral gavages) on Sprague-Dawley (SD) rats exposed to HLS for 6 weeks. Then, we investigated the effects of incubation with curcumin (4 μM) on MC3T3-E1 and RAW264.7 cells cultured in RWVB. Results: Curcumin alleviated HLS-induced reduction of bone mineral density in tibiae and preserved bone structure in tibiae and mechanical strength in femurs. Curcumin alleviated HLS-induced oxidative stress marked by reduced malondialdehyde content and increased total sulfhydryl content in femurs. In cultured MC3T3-E1 cells, curcumin inhibited modeled microgravity-induced reactive oxygen species (ROS) formation and enhanced osteoblastic differentiation. In cultured RAW264.7 cells, curcumin reduced modeled microgravity-induced ROS formation and attenuated osteoclastogenesis. In addition, curcumin upregulated vitamin D receptor (VDR) expression in femurs of rats exposed to HLS and MC3T3-E1 cells exposed to modeled microgravity. Conclusion: Curcumin alleviated HLS-induced bone loss in rats, possibly via suppressing oxidative stress and upregulating VDR expression. [ABSTRACT FROM AUTHOR]

Summary: In a cohort of 393 Chinese women, by using high-resolution peripheral quantitative computed tomography (HR-pQCT), we found that significant cortical bone loss occurred after midlife. Prominent increase in cortical porosity began at the fifth decade but reached a plateau before the sixth decade. Trabecular bone loss was already evident in young adulthood and continued throughout life. Introduction: This study aimed to investigate age-related differences in volumetric bone mineral density (vBMD), microarchitecture, and estimated bone strength at peripheral skeleton in Chinese female population. Methods: In a cross-sectional cohort of 393 Chinese women aged 20-90 years, we obtained vBMD, microarchtecture, and micro-finite element-derived bone strength at distal radius and tibia using HR-pQCT. Results: The largest predictive age-related difference was found for cortical porosity (Ct.Po) which showed over four-fold and two-fold differences at distal radius and tibia, respectively, over the adulthood. At both sites, cortical bone area, vBMD, and thickness showed significant quadratic association with age with significant decrease beginning after midlife. Change of Ct.Po became more prominent between age of 50 and 57 (0.26 %/year at distal radius, 0.54 %/year at distal tibia, both p ≤ 0.001) but thereafter, reached a plateau (0.015 and 0.028 %/year, both p > 0.05). In contrast, trabecular vBMD and microarchitecture showed linear association with age with significant deterioration observed throughout adulthood. Estimated age of peak was around age of 20 for trabecular vBMD and microarchitecture and Ct.Po and age of 40 for cortical vBMD and microarchitecture. Estimated stiffness and failure load peaked at mid-30s at the distal radius and at age 20 at distal tibia. Conclusions: Age-related differences in vBMD and microarchitecture in Chinese women differed by bone compartments. Significant cortical bone loss occurred after midlife. Prominent increase in Ct.Po began at the fifth decade but appeared to be arrested before the sixth decade. Loss of trabecular bone was already evident in young adulthood and continued throughout life. [ABSTRACT FROM AUTHOR]

Summary: In this study, we characterized longitudinal changes of volumetric bone mineral density and cortical and trabecular microstructure at the distal radius using HR-pQCT in female systemic lupus erythematosus (SLE) patients on long-term glucocorticoids. Cortical thinning and increased cortical porosity are the major features of longitudinal microstructural deterioration in SLE patients. Introduction: The study aims to characterize longitudinal changes of volumetric bone mineral density (vBMD) and bone microstructure at distal radius in female systemic lupus erythematosus (SLE) patients on long-term glucocorticoids. Methods: This 2-year case-control study consisted of 166 premenopausal subjects (75 SLE patients and 91 controls) and 79 postmenopausal subjects (44 SLE patients and 35 controls). We obtained areal BMD (aBMD) by dual-energy X-ray absorptiometry at multiple skeletal sites and indices of vBMD and microstructure at distal radius by high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline, 12 and 24 months. Results: In either premenopausal or postmenopausal subjects, changes in aBMD did not differ between patients and controls except that decrease in aBMD at total hip at 24 months in premenopausal patients was significantly higher. In premenopausal subjects, decrease in cortical area (−0.51 vs. −0.06 %, p = 0.039) and thickness (−0.63 vs. 0.02 %, p = 0.031) and increase in cortical porosity (21.7 vs. 7.16 %, p = 0.030) over study period were significantly larger in patients after adjustment of age and body mass index. Decreased in trabecular vBMD was significantly less (−0.63 vs. −2.32 %, p = 0.001) with trabecular microstructure better maintained in patients. In postmenopausal subjects, decrease in cortical vBMD (−2.66 vs. −1.56 %, p = 0.039) and increase in cortical porosity (41.6 vs. 16.3 %, p = 0.021) were significantly higher in patients, and there was no group-wise difference in change of trabecular microstructure. Conclusion: Longitudinal microstructural deterioration in SLE is characterized by cortical thinning and increased cortical porosity. Cortical bone is an important source of bone loss in SLE patients on glucocorticoids. [ABSTRACT FROM AUTHOR]

Summary: This study aims to longitudinally assess the effect of oxytocin on bone and bone fat masses using micro-CT, in vivo magnetic resonance spectroscopy (MRS), and histopathological adipocyte quantification. Early in vivo oxytocin (OT) treatment to the osteoporosis (OP) rabbit model may reliably inhibit bone degeneration and reduce bone marrow fat accumulation by decreasing marrow adipocyte size and density. Introduction: This study aims to longitudinally assess the effect of early OT treatment on bone and bone fat masses in a rabbit OP model by comparing the results of MRS and micro-CT with histopathological findings. Methods: Sixty 20-week-old female rabbits were randomly assigned into three groups. The control and OP groups were subjected to either sham surgery or bilateral ovariectomy (OVX). The OT group was subcutaneously injected with OT daily from the second week after OVX for 8 weeks. The left proximal femurs of the rabbits were evaluated through MRS, micro-CT, and histopathological examination at 0, 4, 8, 10, and 12 weeks after operation. Differences in fat fraction (FF) values, micro-CT parameters, and calculated pathological marrow adipocytes among three groups were analyzed. Results: The FF values of the OP group significantly increased ( p = 0.019), but the tissue mineral density (TMD) decreased ( p = 0.037) from eighth week compared with those of the control group. The FF values of the OT group significantly decreased ( p = 0.044), but the TMD values increased ( p = 0.042) from eighth week compared with those of the OP group. The adypocyte diameter of the OT group significantly decreased ( p = 0.041) from eighth week and then adypocyte density did so too from tenth week, compared with those of the OP group at the same time point. No difference in adypocyte calculation was found between the OT and control groups until the 12th week after operation. Conclusion: Early in vivo OT treatment slowed down bone deterioration and reduced bone marrow adiposity accumulation in a rabbit OP model, which is consistent with pathologic findings. OT treatment is a promising preventive OP therapy. [ABSTRACT FROM AUTHOR]

Summary: We established a chronic kidney disease (CKD) mouse model with estrogen deficiency and inserted titanium implants into the femur of such mice to investigate the fixation of the implants. Both the histomorphometry and implant resistance indicated that estrogen deficiency impaired the fixation of titanium implants inserted into such mice. Introduction: CKD has been regarded as a worldwide public health problem. Estrogen is a critical factor for both renal protection and bone remodeling. A previous study demonstrated that CKD impairs the early healing of titanium implants. However, the combined effect of estrogen deficiency and CKD on the fixation of titanium implants is largely unknown. Methods: Forty 9-week-old female C57BL mice were randomly divided into sham, ovariectomy (OVX), CKD, and CKD + OVX groups. Uremia and estrogen deficiency were induced by 5/6 nephrectomy and OVX, respectively. Experimental titanium implants were inserted into the distal end of the femur. Bone-implant contact (BIC) ratio and bone volume (BV/TV) around the implants were histomorphometrically analyzed. The fixation strength of the implant was measured by a biomechanical push-in resistance test. Results: Serum measurement confirmed a significant increase in serum blood urea nitrogen (BUN) in the CKD group, which was further increased by OVX. Estrogen deficiency led to significant decreases in the BIC ratio, BV/TV, and the push-in resistance in CKD animals. There was a significant interaction between the effects of OVX and CKD, with OVX exacerbating the effects of CKD on BIC ratio and push-in resistance. Conclusions: The results indicated that estrogen deficiency exerts a synergistic effect with CKD and further impairs the fixation of titanium implants in CKD mice. [ABSTRACT FROM AUTHOR]

Summary: The local renin-angiotensin system (RAS) is closely related to bone metabolism. However, it is unknown whether the local RAS is related to bone mineral density (BMD) in glucocorticoid-induced osteoporosis (GIOP). Here, we revealed that the two main characteristics of GIOP might inhibit bone formation and enhance bone resorption. Introduction: The aim of this study is to assess the expression of the main RAS components in the trabecular bone of lumbar vertebrae in GIOP and analyze the relationship between the major RAS components and BMD. Methods: We collected 96 inpatient cases of lumbar disc herniation from patients who underwent dual-energy X-ray absorptiometry examinations followed by surgical treatment in our hospital. Patients were divided into the GIOP group ( n = 48) and control group ( n = 48). The circulating and local expression levels of the main RAS components were examined. The correlation between the main RAS components and BMD was then analyzed. Results: The mRNA expression of local bone angiotensin type 1 and 2 receptors (AT1R and AT2R, respectively) and RANKL was higher in the GIOP group compared with the control group ( p < 0.001), but there was no difference in the circulating protein levels between groups ( p > 0.05). Multiple logistic regression analysis revealed that AT1R and AT2R expression and the RANKL/OPG ratio in local bone were negatively associated with BMD ( p < 0.001, odds ratio (OR) 1.236, 95 % confidence interval (CI) 1.207-1.333; p < 0.001, OR 1.971, 95 % CI 1.809-2.233; and p < 0.001, OR 1.676, 95 % CI 1.546-1.845, respectively). Conclusion: This study provides evidence that the role of local RAS is related to BMD in GIOP patients, and suggests that local RAS might influence RANKL/OPG signaling to modulate bone metabolism. [ABSTRACT FROM AUTHOR]

Summary: We sought to evaluate the effects of antiretroviral therapy on skeletal metabolism in Chinese individuals with human immunodeficiency virus. Patients switched to tenofovir/lamivudine + lopinavir/ritonavir after treatment failure had an increase in bone resorption marker levels by nearly 60 %, which is greater than the magnitude previously described in non-Chinese populations. Introduction: Few studies have evaluated the effects of antiretroviral therapy on skeletal metabolism in Asian populations infected with human immunodeficiency virus (HIV). Methods: We performed a secondary analysis of bone turnover markers (BTM) at baseline and 2 years in stored plasma samples collected from 2/2009 to 1/2013 as part of a multi-center trial. Two groups were compared: (1) treatment-naïve patients initiated on zidovudine (AZT)/lamivudine (3TC) plus nevirapine (NVP) and (2) patients who failed first-line therapy and were switched to tenofovir (TDF)/3TC plus lopinavir/ritonavir (LPVr). Tests included the bone resorption marker, C-terminal cross-linking telopeptide of type-1 collagen (CTX), and the bone formation marker procollagen type 1 N-terminal propeptide (P1NP). Results: In the TDF/3TC + LPVr group, samples were available from 59 patients at baseline and 56 patients at 2 years. Of these, 36 patients had samples available from both time points. In the AZT/3TC + NVP group, plasma samples were analyzed from 82 participants at baseline and of those, 61 had samples at 2 years. Median change over 2 years was greater in the TDF/3TC + LPVr group for both CTX (+0.24 ng/mL, interquartile ranges (IQR) 0.10-0.43 vs. +0.09 ng/mL, IQR −0.03 to 0.18, p = 0.001) and P1NP (+25.5 ng/mL, IQR 2.4-51.3 vs. +7.11 ng/mL, IQR −4.3 to 21.6, p = 0.012). Differences remained after adjusting for potential confounders in the multivariable analysis. Conclusions: Switching to TDF/3TC + LPVr after treatment failure resulted in greater increases in BTMs than initiation with AZT/3TC + NVP in Chinese patients with HIV. Following this change, bone resorption marker levels increased by nearly 60 %, which is greater than the 25-35 % increase from baseline described previously in non-Chinese populations. Further studies are warranted to elucidate these findings. [ABSTRACT FROM AUTHOR]

Summary: The influence of various stroke impairments on bone health is poorly understood. This study showed that muscle function and small artery compliance were more strongly associated with the bone strength index at the tibial diaphyseal and epiphyseal regions, respectively. These impairments should be targeted in promoting bone health post-stroke. Introduction: This study examined the bone structural properties of the tibial distal epiphysis and diaphysis after chronic stroke and identified the clinical correlates of the bone strength index measured at these sites. Methods: The tibial distal epiphysis (4 % site) and diaphysis (66 % site) were scanned on both sides in 66 chronic stroke patients and 23 control participants using peripheral quantitative computed tomography. Dynamic knee muscle strength, balance function, spasticity, arterial compliance, and endurance were also measured in the stroke group. Results: At the 4 % site, multivariate analysis showed a significant side × group interaction effect (Wilk's lambda = 3.977, p < 0.001), with significant side-to-side differences in total volumetric bone mineral density (vBMD), trabecular vBMD, and bone strength index in the stroke group, but not in the control group. A significant side × group interaction was also found at the 66 % site (Wilk's lambda = 4.464, p < 0.001), with significant side-to-side differences in cortical vBMD, cortical area, cortical thickness, and bone strength index in the stroke group only. Balance and endurance were independently associated with bone strength index at both tibial sites in the paretic leg ( p < 0.05) after adjusting for relevant factors in multivariate regression analysis. Small artery compliance and muscle strength were significantly associated with the bone strength index at the 4 % site and 66 % site, respectively. Conclusions: The influence of various stroke impairments on bone was region-specific. While muscle function was more strongly associated with the bone strength index in the diaphyseal region, the effect of vascular health was more apparent in the tibial epiphysis in the paretic leg. [ABSTRACT FROM AUTHOR]

Summary: This study seeks to investigate the effect of electrical stimulation (ES) at dorsal root ganglion (DRG) on disuse bone loss in a rat model. Hindlimb unloading for 14 days resulted in significant bone loss in rat tibia while rats with ES at DRG showed a significant reduced bone loss Introduction: Mechanical unloading induces osteoporosis in both human and animals. Previous studies demonstrated that electrical stimulation (ES) to dorsal root ganglion (DRG) could trigger secretion of calcitonin gene-related peptide (CGRP) which plays an important role in bone modeling and remodeling. This study seeks to investigate the effect of ES to DRG on disuse bone loss in a rat model. Methods: Twenty-four rats were randomly assigned in three experimental groups: cage control (CC), hindlimb unloading (HU), and hindlimb unloading with ES (HUES). ES was applied via implantable micro-electrical stimulators (IMES) to right DRGs at vertebral levels L4-L6 in HUES group. Results: Hindlimb unloading for 14 days resulted in 25.9 % decrease in total bone mineral content (BMC), 29.2 % decrease in trabecular BMD and trabecular microarchitecture and connectivity were significantly deteriorated in the proximal tibia metaphysis in HU group, while rats with ES at DRG showed significant reduced bone loss that there was 3.8 % increase in total BMC, 2.3 % decrease in trabecular BMD, and significant improvement in trabecular microarchitecture. There was a concurrent enhancement of expression of CGRP in stimulated DRGs. Conclusions: The results confirm the effect of ES at DRG on enhancing CGRP expression and suggest potential applications of IMES for the prevention and treatment of disuse bone loss. [ABSTRACT FROM AUTHOR]

Summary: We investigated the densitometric and microstructural features of the distal radius in psoriatic arthritis (PsA) patients using high-resolution peripheral quantitative computed tomography. PsA patients have unique bone microstructural deficits, manifested as lower cortical bone density and higher cortical porosity, which are associated with a propensity to bone fragility. Introduction: The aim of this study was to investigate the densitometric, geometric, microstructural, and biomechanical features of the distal radius in psoriatic arthritis (PsA) patients. Methods: This study cohort consisted of 53 PsA patients (24 males and 29 females), with an average age of 53.1 years and 53 gender- and age-matched controls. Areal bone mineral density (aBMD) of the hip, lumbar spine, and ultradistal radius was measured by dual-energy X-ray absorptiometry. High-resolution peripheral quantitative computed tomography (HR-pQCT) was performed at the distal radius to obtain measures of volumetric BMD (vBMD), microstructure, and derived biomechanical indices. Results: There were no significant between-group differences in aBMD at the femoral neck, total hip, and ultradistal radius, while aBMD at the lumbar spine was significantly higher in patients. The only indices indicating compromised bone quality in PsA patients were related to cortical bone quality. Cortical vBMD were −3.8 % significantly lower, while cortical pore volume, porosity index, and pore diameter were 108, 79.5, and 8.6 %, respectively, significantly higher in patients. Cortical stress was marginally lower (−1.3 %, p = 0.077) in patients with stress significantly more unevenly distributed (4.9 %, p = 0.035). Endocortical perimeter and cortical pore volume were significantly higher in patients with vertebral fracture. Deficits in cortical bone quality were associated with indices of disease activity/severity and were more prominent in patients with type 2 diabetes mellitus or hypertension. Conclusions: There is an intertwined relationship between chronic inflammation, cardiovascular risk factors, and bone loss in PsA. PsA patients seem to have unique bone microstructural deficits which are associated with a propensity to bone fragility. [ABSTRACT FROM AUTHOR]

Summary: Association between 22 single nucleotide polymorphisms (SNPs) in the TNFSF11, TNFRSF11A, and TNFRSF11B genes in the RANKL/RANK/OPG pathway with bone mineral density (BMD) in 881 post-menopausal women. Our results suggest that TNFSF11 and TNFRSF11A, but not TNFRSF11B, genetic polymorphisms influence BMD mainly in the femoral neck in post-menopausal Chinese women. Introduction: The aim of this study was to assess the relationship of polymorphisms in the TNFSF11, TNFRSF11A, and TNFRSF11B genes in the RANKL/RANK/OPG pathway with bone mineral density (BMD) in a cohort of Chinese post-menopausal women. Methods: A cross-sectional study was conducted in 881 post-menopausal women aged 50-89 years. All participants underwent lumbar spinal (LS) and femoral neck (FN) BMD evaluation by dual-energy X-ray absorptiometry. Twenty-two TNFSF11, TNFRSF11A, and TNFRSF11B SNPs were genotyped. We tested whether a single SNP or a haplotype was associated with BMD variations. Results: Two SNPs in the TNFSF11 gene (rs2277439 and rs2324851) and one in the TNFRSF11A gene (rs7239261) were found to be significantly associated with FN BMD ( p = 0.014, 0.013, and 0.047, respectively). Haplotype TGACGT of TNFSF11 rs9525641-rs2277439-rs2324851-rs2875459-rs2200287-rs9533166 was a genetic risk factor toward a lower FN BMD (beta = −0.1473; p = 0.01126). In contrary, haplotype TAGCGT of TNFSF11 rs9525641-rs2277439-rs2324851-rs2875459-rs2200287-rs9533166 was genetic protective factor for LS BMD (beta = 0.3923; p = 0.04917). Conclusions: Our findings suggest that TNFSF11 and TNFRSF11A, but not TNFRSF11B, genetic polymorphisms influence BMD mainly in the femoral neck in post-menopausal Chinese women. This contributes to the understanding of the role of genetic variation in this pathway in determining bone health. [ABSTRACT FROM AUTHOR]

Summary: The study is about the regulatory effects of estrogen and parathyroid hormone (PTH) on sclerostin, a protein that inhibits the Wnt/β-catenin pathway. The results indicate that estrogen may down-regulate sclerostin expression and that estrogen displays synergistic action with PTH. These results provide a new perspective on the relationship between estrogen and bone. Purpose: To investigate whether estrogen can down-regulate SOST and MEF2 (myocyte enhancer factor 2) expression and whether co-treatment with estrogen and PTH has a stronger effect on suppressing SOST than PTH applied alone in ovariectomized rats. Methods: Forty-three-month-old virgin female Sprague-Dawley (SD) rats were ovariectomized and divided into four groups ( n = 10). Another ten age-matched rats received sham operations as controls. After allowing 8 weeks for the development of vertebral osteopenia, the rats were administered the drug intervention. For this intervention, the estrogen group was subcutaneously injected with 17β-estradiol at 25 μg/kg body weight, the PTH group was injected with 80 μg/kg synthetic human PTH (1-34), and the co-treatment group was concurrently treated with PTH and estrogen at the above dosage. The OVX group and sham group were treated with vehicle. The drug treatment was conducted for 12 weeks. After the lumbar spine bone mineral density (BMD) was measured, the rats were sacrificed, and the lumbar spine and blood were collected for qPCR, Western blot, immunohistochemistry and other tests. Results: Estrogen can down-regulate MEF2 and sclerostin expression, and co-treatment with estrogen and PTH has a stronger effect on suppressing MEF2 and SOST mRNA than PTH alone. The co-treatment group displayed slightly higher bone mass and biomechanical properties than the PTH group, but the differences were not significant. Conclusions: Estrogen appears to be a regulator of sclerostin, and the effect may involve suppressing MEF2s. Combined treatment with PTH and estrogen is not more beneficial for vertebral bone mass and strength than treatment with PTH alone in ovariectomized rats. [ABSTRACT FROM AUTHOR]

Summary: The bone mineral density (BMD) of a total of 1,379 healthy postmenopausal Chinese women was measured. Ten tagging SNPs of the sclerostin ( SOST) gene were genotyped. Our results suggest that the polymorphisms of the rs2023794 and rs74252774 in the SOST gene were associated with BMD of the lumbar spine in postmenopausal Chinese women. Introduction: The purpose of the study was to determine the associations between polymorphisms of SOST gene and BMD in postmenopausal Chinese women. Methods: A total of 1,379 independent healthy postmenopausal Chinese women including 703 in our previous study were recruited. The BMD of the lumbar spine 1-4 (L1-4) and left proximal femur including total hip and femoral neck were measured by dual-energy X-ray absorptiometry. Ten tagging SNPs (rs1234612, rs1513670, rs1634330, rs1708635, rs2023794, rs7220711, rs74252774, rs851057, rs851058, and rs865429) of the SOST gene were genotyped. Results: The rs2023794 and rs74252774 and the haplotype ACCATTCT of SOST gene were associated with age and body mass index (BMI) adjusted L1-4 BMD ( P values were 0.010, 0.007, and 0.007, respectively) even after performing the Bonferroni multiple-significance-test correction. There was a clear trend in these regions that the CC genotype of the rs2023794 and the TT genotype of the rs74252774 have higher BMD values than other genotypes. The contributions of the rs2023794 and rs74252774 to the phenotypic variation of L1-4 BMD were 0.6 and 0.7 %, respectively. We failed to find any association between the 10 SNPs and 6 haplotypes of the SOST gene and BMD at the hip site in this study. Conclusions: Our results suggest that the polymorphisms of the rs2023794 and rs74252774 in the SOST gene were associated with BMD of the lumbar spine in a large sample of postmenopausal Chinese women. [ABSTRACT FROM AUTHOR]

Summary: This large cross-sectional study examined the associations of dietary intakes of total flavonoids and their subtypes with bone density in women and men. We found that greater flavonoid intake was associated with higher bone density in women but not in men. Introduction: Studies in vitro and in animal models suggest a potential effect of flavonoids on bone health. Few studies have examined the association between the habitual intake of flavonoids and bone mineral density (BMD) in humans. Methods: The cross-sectional study recruited 2,239 women and 1,078 men. A semiquantitative food frequency questionnaire was administered in face-to-face interviews to assess habitual dietary flavonoid intake using food composition databases. BMD was measured over the whole body (WB) and in the femoral neck (FN) and lumbar spine (LS) by dual-energy X-ray absorptiometry (DXA). Results: After adjusting for covariates, women who consumed higher total flavonoids, and the subtypes of flavonols, flavan-3-ols, flavones, and proanthocyanidins tended to have greater BMD at the WB, LS, and FN (all P-trend < 0.05). Women in the highest (vs. the lowest) quartile of total flavonoids intake had 0.020 (1.91 %), 0.021 (2.51 %), and 0.013 (1.99 %) g/cm greater BMD at the whole body, LS, and FN, respectively. For the subtypes of flavonoids, the corresponding differences in BMD (in g/cm) were 0.012-0.021 (flavan-3-ols), 0.013-0.020 (flavonols), 0.016-0.019 (flavones), and 0.014-0.016 (proanthocyanidins), respectively. A higher intake of flavonones was associated with a greater BMD at the whole body (P-trend 0.041) and the FN (P-trend 0.022). In men, there were no significant positive associations between the consumption of total flavonoids and the subclasses and BMD at any sites. Conclusion: Dietary flavonoids intake was positively associated with BMD in women. Further large studies are needed to clarify this issue in men. [ABSTRACT FROM AUTHOR]

Summary: Recently, the use of the pharmacological agent strontium ranelate has come to prominence for the treatment of osteoporosis. While much investigation is focused on preventing disease progression, here we fabricate strontium-containing scaffolds and show that they enhance bone defect healing in the femurs of rats induced by ovariectomy. Introduction: Recently, the use of the pharmacological agent strontium ranelate has come to prominence for the treatment of osteoporosis due to its ability to prevent bone loss in osteoporotic patients. Although much emphasis has been placed on using pharmacological agents for the prevention of disease, much less attention has been placed on the construction of biomaterials following osteoporotic-related fracture. The aim of the present study was to incorporate bioactive strontium (Sr) trace element into mesoporous bioactive glass (MBG) scaffolds and to investigate their in vivo efficacy for bone defect healing in the femurs of rats induced by ovariectomy. Methods: In total, 30 animals were divided into five groups as follows: (1) empty defect (control), (2) empty defects with estrogen replacement therapy, (3) defects filled with MBG scaffolds alone, (4) defects filled with MBG + estrogen replacement therapy, and (5) defects filled with strontium-incorporated mesopore-bioglass (Sr-MBG) scaffolds. Results: The two groups demonstrating the highest levels of new bone formation were the defects treated with MBG + estrogen replacement therapy and the defects receiving Sr-MBG scaffolds as assessed by μ-CT and histological analysis. Furthermore, Sr scaffolds had a reduced number of tartrate-resistant acid phosphatase-positive cells when compared to other modalities. Conclusion: The results from the present study demonstrate that the local release of Sr from bone scaffolds may improve fracture repair. Future large animal models are necessary to investigate the future relationship of Sr incorporation into biomaterials. [ABSTRACT FROM AUTHOR]

Summary: This case-control study compared the associations of four widely used diet-quality scoring systems with the risk of hip fractures and assessed their utility in elderly Chinese. We found that individuals avoiding a low-quality diet have a lower risk of hip fractures in elderly Chinese. Introduction: Few studies examined the associations of diet-quality scores on bone health, and no studies were available in Asians and compared their validity and utility in a study. We assessed the associations and utility of four widely used diet-quality scoring systems with the risk of hip fractures. Methods: A case-control study of 726 patients with hip fractures (diagnosed within 2 weeks) aged 55-80 years and 726 age- (within 3 years) and gender-matched controls was conducted in Guangdong, China (2009-2013). Dietary intake was assessed using a 79-item food frequency questionnaire with face-to-face interviews, and the Healthy Eating Index-2005 (HEI-2005, 12 items), the alternate Healthy Eating Index (aHEI, 8 items), the Diet Quality Index-International (DQI-I, 17 items), and the alternate Mediterranean Diet Score (aMed, 9 items) (the simplest one) were calculated. Results: All greater values of the diet-quality scores were significantly associated with a similar decreased risk of hip fractures (all p trends <0.001). The multivariate-adjusted odds ratios (ORs) and 95 % confidential intervals (95 % CIs) comparing the extreme groups of diet-quality scores were 0.29 (0.18, 0.46) (HEI-2005), 0.20 (0.12, 0.33) (aHEI), 0.25 (0.16, 0.39) (DQI-I), and 0.28 (0.18, 0.43) (aMed) in total subjects; and the corresponding ORs ranged from 0.04 to 0.27 for men and from 0.26 to 0.44 for women (all p trends <0.05), respectively. Conclusions: Avoiding a low-quality diet is associated with a lower risk of hip fractures, and the aMed score is the best scoring system due to its equivalent performance and simplicity for the user. [ABSTRACT FROM AUTHOR]

Summary: This study is a prospective cluster-randomized controlled clinical trial involving 710 elderly subjects to investigate the long-term effects of low-magnitude high-frequency vibration (LMHFV) on fall and fracture rates, muscle performance, and bone quality. The results confirmed that LMHFV is effective in reducing fall incidence and enhancing muscle performance in the elderly. Introduction: Falls are direct causes of fragility fracture in the elderly. LMHFV has been shown to improve muscle function and bone quality. This study is to investigate the efficacy of LMHFV in preventing fall and fractures among the elderly in the community. Methods: A cluster-randomized controlled trial was conducted with 710 postmenopausal females over 60 years. A total of 364 participants received daily 20 min LMHFV (35 Hz, 0.3 g), 5 days/week for 18 months; 346 participants served as control. Fall or fracture rate was taken as the primary outcome. Also, quadriceps muscle strength, balancing abilities, bone mineral density (BMD), and quality of life (QoL) assessments were done at 0, 9, and 18 months. Results: With an average of 66.0 % compliance in the vibration group, 18.6 % of 334 vibration group subjects reported fall or fracture incidences compared with 28.7 % of 327 in the control (adjusted HR = 0.56, p = 0.001). The fracture rate of vibration and control groups were 1.1 and 2.3 % respectively ( p = 0.171). Significant improvements were found in reaction time, movement velocity, and maximum excursion of balancing ability assessment, and also the quadriceps muscle strength ( p < 0.001). No significant differences were found in the overall change of BMD. Minimal adverse effects were documented. Conclusion: LMHFV is effective in fall prevention with improved muscle strength and balancing ability in the elderly. We recommend its use in the community as an effective fall prevention program and to decrease related injuries. [ABSTRACT FROM AUTHOR]

Summary: Intermittent treatment with high-dose parathyroid hormone (PTH) enhances the quantity and quality of the fusion callus and reduces healing time of posterolateral spinal fusion with autologous iliac bone grafts in ovariectomized osteoporotic female Sprague-Dawley rats. Intermittent PTH (1-34) could be an appropriate adjunctive therapy for osteoporotic patients undergoing posterolateral intertransverse process fusion. Introduction: The study was designed to test the hypothesis that intermittent administration of PTH improves spinal fusion rates in a randomized controlled, ovariectomized osteoporotic rat spinal fusion model. Methods: Thirty-six 10-week-old Sprague-Dawley rats were ovariectomized and underwent bilateral posterolateral L4-L5 spinal fusion with autologous iliac bone graft 6 weeks later. The experimental (PTH) group (18 rats) received daily subcutaneously administered injections of PTH (1-34) at 30 μg/kg/day starting on the day of operation. The control group (18 rats) received a subcutaneously administered injection of normal saline of the same volume. Nine rats from each group were sacrificed at 4 and 6 weeks. After sacrifice, the L4-L5 vertebral segments were removed and analyzed by plain radiographs, μ-CT, histomorphometry, and serum bone metabolism marker. Results: The PTH group had a significantly higher fusion rate and X-ray fusion score than the control group at 4 and 6 weeks ( p < 0.05). μ-CT and histological analysis showed that the fusion bone volume and cortical thickness for the PTH group were significantly higher than those for the control group at 4 and 6 weeks ( p < 0.05). Metabolic marker analysis also showed significant difference between the two groups. The serum osteocalcin was significantly higher in the PTH group at 4 and 6 weeks, and levels of N-terminal peptide of type I collagen were significantly higher at 4 weeks ( p < 0.05). Conclusion: Intermittent treatment with high-dose PTH enhances the quantity of the fusion callus and reduces the healing time of posterolateral spinal fusion with autologous iliac bone grafts in ovariectomized osteoporotic female Sprague-Dawley rats. [ABSTRACT FROM AUTHOR]

Summary: The secreted protein acidic and rich in cysteine (SPARC), also known as osteonectin, plays an important role in osteoblast formation, maturation, and survival. Here, we report the effects of recombinant human parathyroid hormone (1-34) [rhPTH (1-34)], a bone formation-stimulating agent, and elcatonin on plasma SPARC levels in patients with osteoporosis. The rhPTH (1-34) treatment significantly increased plasma SPARC levels, and the change of plasma SPARC correlated positively with changes of lumbar bone mineral density (BMD) at L2-L4. These results unveil that SPARC may be a novel marker related to the regulation of bone formation. Introduction: rhPTH (1-34) is known to influence osteoclast maturation and activity through modulation of osteoblast-derived cytokines. SPARC is the most abundant noncollagenous extracellular matrix protein in the bone. So far, however, no study has reported the effects of rhPTH (1-34) administration on plasma SPARC levels in patients with osteoporosis. The purpose of this study was to compare the response of SPARC and BMD to rhPTH (1-34) and elcatonin in postmenopausal women with osteoporosis. Methods: Women were randomized to either once-daily subcutaneous injection of rhPTH (1-34) (20 μg, N = 89) or once-weekly intramuscular injection of elcatonin (200 U, N = 35) for 12 months. Plasma biochemical markers of bone turnover and BMD were measured at baseline, 6 and 12 months after treatment. Results: At baseline, plasma SPARC levels correlated positively with lumbar spine BMD in all patients ( r = 0.45, p = 0.001). Compared with baseline, at 12 months, rhPTH (1-34) significantly increased lumbar spine BMD and plasma SPARC levels ( p = 0.008 and p = 0.001, respectively), whereas elcatonin was ineffective. More importantly, the changes of plasma SPARC correlated positively with changes of lumbar BMD at L2-L4 ( r = 0.47, p = 0.001) in the rhPTH (1-34)-treated group, but not in the elcatonin group. Conclusion: The increase in plasma SPARC levels during the rhPTH (1-34) treatment may have contributed to the anabolic effect on bone formation, and SPARC may be a novel marker related to the regulation of bone formation. [ABSTRACT FROM AUTHOR]

Summary: Treatment with molecular hydrogen alleviates microgravity-induced bone loss through abating oxidative stress, restoring osteoblastic differentiation, and suppressing osteoclast differentiation and osteoclastogenesis. Introduction: Recently, it has been suggested that hydrogen gas exerts a therapeutic antioxidant activity by selectively reducing cytotoxic reactive oxygen species (ROS). The aim of the present study was to elucidate whether treatment with molecular hydrogen alleviated bone loss induced by modeled microgravity in rats. Methods: Hindlimb suspension (HLS) and rotary wall vessel bioreactor were used to model microgravity in vivo and in vitro, respectively. Sprague-Dawley rats were exposed to HLS for 6 weeks to induced bone loss and simultaneously administrated with hydrogen water (HW). Then, we investigated the effects of incubation with hydrogen-rich medium (HRM) on MC3T3-E1 and RAW264.7 cells exposed to modeled microgravity. Results: Treatment with HW alleviated HLS-induced reduction of bone mineral density, ultimate load, stiffness, and energy in femur and lumbar vertebra. Treatment with HW alleviated HLS-induced augmentation of malondialdehyde content and peroxynitrite content and reduction of total sulfhydryl content in femur and lumbar vertebra. In cultured MC3T3-E1 cells, incubation with HRM inhibited modeled microgravity-induced ROS formation, reduction of osteoblastic differentiation, increase of ratio of receptor activator of nuclear factor kappa B ligand to osteoprotegerin, inducible nitric oxide synthetase upregulation, and Erk1/2 phosphorylation. In cultured RAW264.7, incubation with HRM aggravated modeled microgravity-induced ROS formation, osteoclastic differentiation, and osteoclastogenesis. Conclusion: Treatment with molecular hydrogen alleviates microgravity-induced bone loss in rats. Molecular hydrogen could thus be envisaged as a nutritional countermeasure for spaceflight but remains to be tested in humans. [ABSTRACT FROM AUTHOR]

Summary: Cordyceps sinensis has been known as a traditional medicine in China, and C. sinensis plus strontium could prevent osteoporosis in ovariectomized rats. The present study shows that daily oral administration of C. sinensis at higher doses in adult hind limb suspension rats can prevent disuse-induced bone loss and deterioration of trabecular microarchitecture. Introduction: Cordyceps sinensis induces estradiol production and prevents osteoporosis in ovariectomized rats. This study was to examine whether C. sinensis can prevent disuse-induced osteoporosis. Methods: Rats were randomly divided into six groups, and five groups were treated with hind limb suspension (HLS). One HLS group received alendronate (2.0 mg/kg/day) orally, and to the three other HLS groups to each group, a different amount of C. sinensis (100, 300, and 500 mg/kg/day) was orally administered for 8 weeks before and after HLS. The remaining HLS group was set as a control without treatment. Each group consisted of 10 males and females. The body weights, biochemical parameters in serum and urine, bone mineral density (BMD), bone mineral content (BMC), mechanical testing, and bone microarchitecture were examined. Results: Treatments with higher C. sinensis dosage (300 and 500 mg/kg/day) or alendronate had a positive effect on body weights, mechanical strength, BMD, and BMC compared to the other HLS groups. C. sinensis decreased markers of bone turnover dose dependently and increased the osteocalcin levels in HLS rats. The result of micro-CT analysis from the L4 vertebra showed that C. sinensis (500 mg/kg) significantly prevented the reduction of the bone volume fraction, connectivity density, trabeculae number, and thickness as well as improved the trabeculae separation and structure model index in HLS rats. Conclusions: The present study demonstrates that administration of C. sinensis at higher doses over an 8-week period can prevent the disuse osteoporosis in rats. It implies that C. sinensis might be an alternative therapy for prevention of disuse-induced osteoporosis also in humans. [ABSTRACT FROM AUTHOR]

Summary: The objective of this study was to examine the associations of neuromuscular and cardiovascular impairments with the bone strength index of the hemiparetic distal radius epiphysis in chronic stroke survivors. The results showed that grip strength is the most predominant predictor of the bone strength index. Introduction: The pupose of the study was to examine the associations of neuromuscular and cardiovascular impairments with the bone strength index of the hemiparetic distal radius epiphysis in chronic stroke survivors. Methods: Sixty-five chronic stroke survivors and 34 healthy control subjects underwent scanning of the distal radius epiphyseal site on both sides using peripheral quantitative computed tomography to measure trabecular volumetric bone mineral density (vBMD) (mg/cm), total vBMD (mg/cm), total area (mm), and compressive bone strength index (cBSI) (g/cm). Various indicators of neuromuscular (grip strength, spasticity) and cardiovascular function (vascular elasticity, oxygen consumption during 6-min walk test) were evaluated. Results: Analysis of variance revealed a significant main effect of side ( p < 0.001) and group × side interaction ( p < 0.05) for total BMC, total vBMD, trabecular vBMD, and cBSI ( p < 0.05), with the stroke group showing greater side-to-side difference in these variables. However, no significant side-to-side difference in total area was detected in either group ( p > 0.05). Sex-specific analysis yielded similar results. Multiple regression analyses revealed that the cBSI of the hemiparetic distal radius epiphysis had a stronger association with neuromuscular factors than cardiovascular factors. Overall, grip strength was the strongest determinant of the cBSI of the hemiparetic distal radius epiphysis ( p < 0.01). Conclusions: Muscle weakness is the most predominant determinant of cBSI in the hemiparetic distal radius epiphysis among chronic stroke patients. Future studies should investigate the efficacy of different muscle-strengthening strategies in enhancing bone strength of this skeletal site in the chronic stroke population. [ABSTRACT FROM AUTHOR]

Summary: Countermeasures are desirable to retard bone loss during long-term space flight. We evaluated the effect of an intervention protocol on bed rest-induced bone loss. Introduction: We developed a resistive vibration exercise (RVE) platform to test if an intervention RVE protocol would be effective to protect bed rest-induced bone loss. Methods: Fourteen male subjects were assigned randomly to either the RVE group ( n = 7) that performed daily supervised resistive vibration exercise or to the no any exercise control (CON) group ( n = 7). Both dual-energy X-ray absorptiometry and peripheral quantitative computed tomography were used to monitor changes in bone mineral density. Results: RVE significantly prevented bone loss at multiple skeletal sites, including calcaneus, distal tibia, hip, and lumbar spine (L2-L4). The ratio of urinary calcium and creatinine was found higher after starting bed rest in CON group while no significant changes were observed in RVE group. No significant temporal change was found for osteocalcin-N during and after bed rest in CON group. However, a significant increase was shown after bed rest in RVE group. In both groups, the urinary concentration of bone resorption markers, such as C-telopeptide of type I collagen (CTX-I) and deoxypyridinoline (DPD), were significantly elevated after bed rest. In the CON group, no significant temporal effect was found for hydroxyproline (HOP), CTX-I, and DPD during bed rest and the serum concentration of HOP and TGF-β significantly increased about 52.04% and 24.03%, respectively only after bed rest. However, all these markers tended to decrease in the RVE group. Conclusions: Our results might imply that the intervention of RVE retarded bone loss induced by simulated microgravity in humans that was mainly attributed to its anabolic effects. [ABSTRACT FROM AUTHOR]

Summary: We tested whether two genetic variants were associated with BMD at multiple clinically relevant skeletal sites in Caucasians. We found that variant rs7776725 is consistently associated with hip, spine, wrist and whole-body BMD, which highlights the potential importance of this variant or linked variants for osteoporosis. Introduction: A recent genome-wide association study identified two single nucleotide polymorphisms (SNPs), rs7776725 and rs1721400, that were associated with bone mineral density (BMD) variation at the radius, tibia and calcaneus in a Korean population. In this study, we aimed to test whether the association of these two genetic variants can be replicated in Caucasians and whether their association with BMD can be extended to other clinically relevant skeletal sites. Methods: We performed this study in two large cohorts of unrelated US Caucasians. Area BMD at the hip, spine, wrist (ultra-distal radius) and whole body were measured with Hologic dual-energy X-ray absorptiometer. SNPs were genotyped with Affymetrix human genome-wide genotyping arrays. Association analyses were performed using PLINK. Results: We detected highly significant association (combined p = 1.42 × 10) of rs7776725 with wrist BMD but only borderline association signal (combined p = 0.017) for rs1721400 with wrist BMD. In addition, we found that rs7776725 was associated with BMD at the hip, spine and whole body. At the FAM3C gene locus where rs7776725 was located, we identified several other SNPs (rs4727922, rs1803389, rs718766 and rs7793554) that were also associated with BMD. Conclusions: This is the first follow-up association study of rs7776725 and rs1721400 with BMD. The rs7776725 showed consistent association with BMD at multiple clinically important skeletal sites, which highlighted the potential importance of rs7776725 or linked SNPs for risk of osteoporosis. Further in-depth re-sequencing studies and functional assays are necessary to elucidate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Summary: Eighteen months of daily consumption of milk containing 250 mg calcium prevented bone mineral density (BMD) loss at the hip and the femoral neck in postmenopausal Chinese women aged 45 to 65. Introduction: Estrogen-related bone loss in postmenopausal women can be prevented by the consumption of milk with high doses of calcium and soymilk with high doses of isoflavones. However, high doses of calcium and isoflavones may not be necessary to attain a beneficial effect of milk and soymilk on BMD. We hypothesized that BMD will increase in postmenopausal Chinese women who consume daily 250 mg calcium in milk or soymilk. Milk prevented bone loss at the hip and the femoral neck in postmenopausal Chinese women. Methods: A total of 141 eligible Chinese women without osteoporosis, aged 45-65, and postmenopausal for more than 2 years were randomized into groups receiving for 18 months (A) milk with 250 mg calcium daily, (B) soymilk with 250 mg calcium daily, or (C) neither milk nor soymilk. Dual-energy X-ray absorptiometry measured the BMD of the spine and hip at 0, 6, 12, and 18 months. Results: The BMD in the hip (2.52%) and the femoral neck (2.82%) of the women consuming milk was significantly higher (hip, P = 0.01; femoral neck, P < 0.0000001). The women in the control group experienced a reduction in BMD at all sites; the reduction in BMD was only significant at the hip during 12 months ( P = 0.008) and at the femoral neck during 18 months ( P = 0.005). Conclusions: Daily consumption of milk containing 250 mg calcium over 18 months prevents BMD loss at the hip and the femoral neck in postmenopausal Chinese women. [ABSTRACT FROM AUTHOR]

Summary: This study examines the association between sex steroids, bone mineral density (BMD), and incident fractures in 1,489 community-living Chinese men aged 65 and over. Chinese men with low serum estradiol levels display elevated bone loss and increased risk of fractures similar to findings in Caucasians. Introduction: This study examines the association between serum total testosterone (TT), free testosterone (free T), estradiol (E), bioavailable estradiol (bioE), sex hormone binding globulin (SHBG), BMD, and incident fractures. Methods: This is a cohort study with 4-year follow-up in the community in Hong Kong SAR, China. One thousand four hundred eighty-nine community-living Chinese men aged 65 and over participated. Sex steroid levels and BMD were measured at baseline; BMD was repeated after 4 years of follow-up, and fracture incidence from ascertainment from hospital databases was determined over 4 years of follow-up. Results: The strongest age-adjusted positive association with total hip and femoral neck BMD was with bioE, followed by E. Greater bone loss occurred in the lowest quartile of E and bioE. The lowest quartile of free T and bioE and the two highest quartile of SHBG were associated with the highest percentage of participants with incident fractures. Those in the lowest quartile of E and bioE had approximately a 50% increased risk of incident fractures compared with the other three quartiles. This relationship remains significant for nonvertebral incident fractures (hip, radius, pelvis, and humerus) for E only, but not bioE. Compared with the group with the three highest quartiles of TT and E, the group with the lowest quartile of both had approximately twice the risk of nonvertebral osteoporosis-related incident fractures. Conclusion: Chinese men with low serum estradiol levels display elevated bone loss and increased risk of fractures similar to findings in Caucasians. [ABSTRACT FROM AUTHOR]

Summary: Calcaneal QUS is comparable to DXA in predicting non-vertebral fractures in older Chinese men. Introduction: The predictive values of calcaneal quantitative ultrasound (QUS) and dual-energy X-ray absorptiometry (DXA) for non-vertebral fractures in older Chinese men were examined. Methods: One thousand nine hundred twenty-one Chinese men aged 65-92 years had calcaneal QUS and axial DXA bone mineral density (BMD) measurements. The incidence of non-vertebral fractures was documented. Cox regression and receiver operating curve (ROC) analysis were used to examine the associations of QUS parameters and BMD with the incidence of non-vertebral fractures. Results: The duration of follow-up was (mean±SD) 6.5 ± 1.7 years. One hundred thirty-one non-vertebral fractures were recorded, 71 of which were major fragility fractures. Broadband ultrasound attenuation (BUA) and quantitative ultrasound index (QUI) were significantly associated with non-vertebral fractures and major fragility fractures, with age and fracture history-adjusted hazard ratio (95% CI) of 1.23 (1.03, 1.47) and 1.32 (1.10, 1.59) per standard deviation reduction, respectively, for non-vertebral fractures; 1.32 (1.04, 1.68) and 1.43 (1.11, 1.84), respectively, for major fragility fractures. Age and fracture history-adjusted areas under ROC curves of hip or spine BMDs were significantly greater than that of BUA or QUI in predicting major fragility fractures, but not in predicting all non-vertebral fractures. The addition of BUA or QUI had no effect on AUCs of total hip BMD alone. Conclusions: The ability of calcaneal QUS to predict non-vertebral fractures was comparable to that of axial BMD by DXA, but was inferior to BMD in predicting major fragility fractures in older Chinese men. [ABSTRACT FROM AUTHOR]

Summary: The impairment of osteoblast differentiation is one cause of the glucocorticoid-induced osteoporosis (GCOP). The quantitative proteomic analysis of the dexamethasone (DEX)-induced effects of osteoblast differentiation, proliferation, and apoptosis using stable-isotope labeling by amino acids in cell culture (SILAC) demonstrated drastic changes of some key proteins in MC3T3-E1 cells. Introduction: The impairment of osteoblast differentiation is one of the main explanations of GCOP. SILAC enables accurate quantitative proteomic analysis of protein changes in cells to explore the underlying mechanism of GCOP. Methods: Osteoprogenitor MC3T3-E1 cells were treated with or without 10 M DEX for 7 days, and the differentiation ability, proliferation, and apoptosis of the cells were measured. The protein level changes were analyzed using SILAC and liquid chromatography-coupled tandem mass spectrometry. Results: In this study, 10 M DEX inhibited both osteoblast differentiation and proliferation but induced apoptosis in osteoprogenitor MC3T3-E1 cells on day 7. We found that 10 M DEX increased the levels of tubulins (TUBA1A, TUBB2B, and TUBB5), IQGAP1, S100 proteins (S100A11, S100A6, S100A4, and S100A10), myosin proteins (MYH9 and MYH11), and apoptosis and stress proteins, while inhibited the protein levels of ATP synthases (ATP5O, ATP5H, ATP5A1, and ATP5F1), G3BP-1, and Ras-related proteins (Rab-1A, Rab-2A, and Rab-7) in MC3T3-E1 cells. Conclusions: Several members of the ATP synthases, myosin proteins, small GTPase superfamily, and S100 proteins may participate in functional inhibition of osteoblast progenitor cells by GCs. Such protein expression changes may be of pathological significance in coping with GCOP. [ABSTRACT FROM AUTHOR]

Summary: The purpose of this study is to investigate the dose-dependent effects of SWH on bone properties and the mechanism involved in mediating the osteoprotective actions of SWH. The results indicated that SWH could improve bone properties by inhibiting the process of bone resorption and stimulating the process of bone formation. Introduction: Our previous study showed that Sambucus williamsii HANCE (SWH) improved trabecular bone mass and cortical bone strength in ovariectomized (OVX) rats. The purpose of this study is to investigate the dose-dependent effects of SWH on bone properties and the mechanism involved in mediating the osteoprotective actions of SWH. Methods: Three-month-old C57BL/6J mice were fed a phytoestrogen-free diet and subjected to either ovariectomy or sham operation. OVX mice were treated with genistein (50 mg/kg), or a low (200 mg/kg), medium (500 mg/kg), or high (1,000 mg/kg) dose of SWH extract. Results: SWH could dose-dependently decrease urinary Ca excretion and increase serum Ca level in OVX mice. It could increase tibial bone mineral density and exert beneficial effects on the microarchitecture of trabecular bone in the OVX mice. SWH suppressed the ovariectomy-induced expression of Cbfa1 mRNA and cathepsin K mRNA and enhanced the ratio of OPG/RANKL mRNA expression in the tibia. In vitro study showed that SWH dramatically reduced the number of TRAP-positive cells in RANKL-induced RAW 264.7 cells. Conclusions: The present study indicated that SWH could improve bone properties by inhibiting the process of bone resorption and stimulating the process of bone formation. [ABSTRACT FROM AUTHOR]