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Severe bleeding is the major cause of death in unstable pelvic ring fractures. Therefore, a quick and efficient emergency stabilization and bleeding control is inevitable. C-clamp and pelvic binder are efficient tools for temporary bleeding control, especially from the posterior pelvic ring. Yet the C-clamp requires more user knowledge, training and equipment. However, whether this makes up for a more efficient bleeding control, is still under debate. Patients with a type-C pelvic ring fracture were identified from the German Pelvic Registry (GPR) and divided into three groups of 40 patients (1. no emergency stabilization, 2. pelvic binder, 3. C-clamp). The matching occurred according to the parameters age, gender, initial RR and initial HB. Complication-and mortality rates were compared especially regarding bleeding control. Regarding ISS and fracture dislocation there was no difference. The use of the C-clamp resulted in more complications, a higher mortality rate due to severe bleeding and more blood transfusions were admitted. Moreover the pelvic binder was established noticeably faster. However, the C-clamp was more often rated as effective. There is no evidence of advantage comparing the C-clamp to the pelvic binder, regarding bleeding control in type-C pelvic ring fractures. In fact, using the pelvic binder even showed better results, as the time until established bleeding control was significantly shorter. Therefore, the pelvic binder should be the first choice. The C-clamp should remain a measure for selected cases only, if an adequate bleeding control cannot be achieved by the pelvic binder.

Purpose: Sparing active bone marrow (ABM) can reduce acute hematologic toxicity in patients undergoing chemoradiotherapy for cervical cancer, but ABM segmentation based on positron emission tomography/computed tomography (PET/CT) is costly. We sought to develop an atlas-based ABM segmentation method for implementation in a prospective clinical trial., Methods and Materials: A multiatlas was built on a training set of 144 patients and validated in 32 patients from the NRG-GY006 clinical trial. ABM for individual patients was defined as the subvolume of pelvic bone greater than the individual mean standardized uptake value on registered 18 F-fluorodeoxyglucose PET/CT images. Atlas-based and custom ABM segmentations were compared using the Dice similarity coefficient and mean distance to agreement and used to generate ABM-sparing intensity modulated radiation therapy plans. Dose-volume metrics and normal tissue complication probabilities of the two approaches were compared using linear regression., Results: Atlas-based ABM volumes (mean [standard deviation], 548.4 [88.3] cm 3 ) were slightly larger than custom ABM volumes (535.1 [93.2] cm 3 ), with a Dice similarity coefficient of 0.73. Total pelvic bone marrow V 20 and D mean were systematically higher and custom ABM V 10 was systematically lower with custom-based plans (slope: 1.021 [95% confidence interval (CI), 1.005-1.037], 1.014 [95% CI, 1.006-1.022], and 0.98 [95% CI, 0.97-0.99], respectively). We found no significant differences between atlas-based and custom-based plans in bowel, rectum, bladder, femoral heads, or target dose-volume metrics., Conclusions: Atlas-based ABM segmentation can reduce pelvic bone marrow dose while achieving comparable target and other normal tissue dosimetry. This approach may allow ABM sparing in settings where PET/CT is unavailable., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Osteoporosis is a metabolic bone disease. Bisphosphonate (BP) and eldecalcitol (ELD) are two clinical first-line drugs for osteoporosis patients. However, the effect of ELD + BP vs. BP alone on osteoporosis treatment is still unclear. The present meta-analysis was conducted to evaluate the different therapeutic effect of BP + ELD vs. BP alone in osteoporosis treatment., Methods: Eligible documents that selected from online databases including PubMed, Embase, and Cochrane Library were included in this study (updated to March 3, 2020). The quality assessment of the included studies was based on the guidelines of Cochrane. Meta-analysis was performed according to criteria such as intervention plan and outcome. The indicators including bone mineral density (BMD) in all enrolled studies were included in the current analysis. Pooled odds ratios (ORs) and weighted mean differences (WMDs) with 95% confidence intervals (CI) were calculated using fixed- or random-effects models. Then, heterogeneity analysis was performed based on Cochran's Q test and I 2 statistics., Results: A total of 4 studies (456 cases) with high quality were enrolled in this study. The effect of ELD + BP was superior to BP alone based on indicators including femoral neck BMD (FN-BMD) and total hip BMD (TH-BMD) in patients with followed up ≤ 6 months. Moreover, the effect of ELD + BP was superior to BP alone based on lumbar spine BMD (LS-BMD) in patients with 12 months followed up., Conclusion: Therapeutic effect of ELD + BP was superior to BP alone in osteoporotic patients based on the influence of BMD.

Study Design: Randomized double blind, placebo-controlled trial., Objectives: To examine the effect of early intravenous zoledronic acid (ZA) on bone markers and areal bone mineral density (aBMD) in persons with acute ASIA Impairment Scale (AIS) A traumatic spinal cord injury (SCI)., Setting: Two inpatient rehabilitation units., Methods: Thirteen men, 2 women, aged 19-65, C4-T10 AIS A SCI, received 5 mg intravenous ZA vs. placebo 12-21 days post injury. Markers of bone formation (procollagen N-1 terminal propeptide [P1NP]), bone resorption (serum C-telopeptide [CTX]), and aBMD by dual-energy X-ray absorptiometry (DXA) for hip (femur-proximal, intertrochanteric, neck), and knee (distal femur, proximal tibia) were obtained at baseline, 2 weeks post infusion (P1NP, CTX only), 4 and 12 months post injury., Results: P1NP remained unchanged, while CTX decreased in ZA but increased in controls at 2 weeks (mean difference = -97%, p < 0.01), 4 months (mean difference = -54%, p < 0.05), but not 12 months (mean difference = 3%, p = 0.23). Changes in aBMD at the hip favored ZA at 4 months (mean difference 10.3-14.1%, p < 0.01) and 12 months (mean difference 10.8-13.1%, p < 0.02). At 4 months, changes in aBMD favored ZA at the distal femur (mean difference 6.0%, 95% CI: 0.7-11.2, p < 0.03) but not proximal tibia (mean difference 8.3%, 95% CI: -6.9 to 23.6, p < 0.23). Both groups declined in aBMD at 12 months, with no between group differences., Conclusion: ZA administered ≤21 days of complete traumatic SCI maintains aBMD at the hip and distal femur at 4 months post injury. This effect is partially maintained at 12 months.

Background: Glucocorticoid-induced osteoporosis and vertebral fracture are common complications in patients on glucocorticoid treatment for rheumatological diseases. The present study aimed to identify the risk factors of vertebral fracture in Japanese female patients with glucocorticoid-induced osteoporosis., Methods: This study included 225 Japanese women with glucocorticoid-induced osteoporosis and 72 patients with postmenopausal osteoporosis. All participants were treated with bisphosphonate or denosumab for osteoporosis with active form of vitamin D for at least 3 years. The differences of clinical parameters, including age, disease duration, body mass index (BMI), bone mineral density (BMD), and the dose and treatment duration of glucocorticoid were assessed between patients with and without vertebral fracture. Multivariate logistic regression analysis was also performed to evaluate the association of vertebral fracture with clinical parameters., Results: The significant differences related to age, BMD of the hip, disease duration, glucocorticoid treatment duration between patients with and without vertebral fractures were demonstrated. The present study indicated that disease duration, BMI, and the total hip BMD were independent risk factors for vertebral fractures in patients with glucocorticoid-induced osteoporosis., Conclusions: Prolonged disease duration, low BMI, and low total hip BMD could be risk factors of vertebral fracture in patients on glucocorticoid treatment for rheumatological diseases.

In tetrapods, the scapular and pelvic girdles perform the important function of anchoring the limbs to the trunk of the body and facilitating the movement of each appendage. This shared function, however, is one of relatively few similarities between the scapula and pelvis, which have significantly different morphologies, evolutionary histories, embryonic origins, and underlying genetic pathways. The scapula evolved in jawless fish prior to the pelvis, and its embryonic development is unique among bones in that it is derived from multiple progenitor cell populations, including the dermomyotome, somatopleure, and neural crest. Conversely, the pelvis evolved several million years later in jawed fish, and it develops from an embryonic somatopleuric cell population. The genetic networks controlling the formation of the pelvis and scapula also share similarities and differences, with a number of genes shaping only one or the other, while other gene products such as PBX transcription factors act as hierarchical developmental regulators of both girdle structures. Here, we provide a detailed review of the cellular processes and genetic networks underlying pelvis and scapula formation in tetrapods, while also highlighting unanswered questions about girdle evolution and development., (© 2019 Elsevier Inc. All rights reserved.)

Introduction: Parity has been suggested as a possible factor affecting bone health in women. However, study results on its association with bone mineral density are conflicting., Methods: PubMed, EMBASE, the Cochrane Library, and Korean online databases were searched using the terms "parity" and "bone mineral density", in May 2016. Two independent reviewers extracted the mean and standard deviation of bone mineral density measurements of the femoral neck, spine, and total hip in nulliparous and parous healthy women., Results: Among the initial 10,146 studies, 10 articles comprising 24,771 women met the inclusion criteria. The overall effect of parity on bone mineral density was positive (mean difference=5.97mg/cm 2 ; 95% CI 2.37 to 9.57; P=0.001). The effect appears site-specific as parity was not significantly associated with the bone mineral density of the femoral neck (P=0.09) and lumbar spine (P=0.17), but parous women had significantly higher bone mineral density of the total hip compared to nulliparous women (mean difference=5.98mg/cm 2 ; 95% CI 1.72 to 10.24; P=0.006). No obvious heterogeneity existed among the included studies (femoral neck I 2 =0%; spine I 2 =31%; total hip I 2 =0%)., Conclusion: Parity has a positive effect on bone in healthy, community-dwelling women and its effect appears site-specific., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The optimal dose of vitamin D to optimize bone metabolism in the elderly is unclear. We tested the hypothesis that vitamin D, at a dose higher than recommended by the Institute of Medicine (IOM), has a beneficial effect on bone remodeling and mass. In this double-blind trial we randomized 257 overweight elderly subjects to receive 1000 mg of elemental calcium citrate/day, and the daily equivalent of 3750 IU/day or 600 IU/day of vitamin D3 for 1 year. The subjects' mean age was 71 ± 4 years, body mass index 30 ± 4 kg/m 2 , 55% were women, and 222 completed the 12-month follow-up. Mean serum 25 hydroxyvitamin D (25OHD) was 20 ng/mL, and rose to 26 ng/mL in the low-dose arm, and 36 ng/mL in the high-dose arm, at 1 year (p < 0.05). Plasma parathyroid hormone, osteocalcin, and C-terminal telopeptide (Cross Laps) levels decreased significantly by 20% to 22% in both arms, but there were no differences between the two groups for any variable, at 6 or 12 months, with the exception of serum calcitriol, which was higher in the high-dose group at 12 months. Bone mineral density (BMD) increased significantly at the total hip and lumbar spine, but not the femoral neck, in both study arms, whereas subtotal body BMD increased in the high-dose group only, at 1 year. However, there were no significant differences in percent change BMD between the two study arms at any skeletal site. Subjects with serum 25OHD <20 ng/mL and PTH level >76 pg/mL showed a trend for higher BMD increments at all skeletal sites, in the high-dose group, that reached significance at the hip. Adverse events were comparable in the two study arms. This controlled trial shows little additional benefit in vitamin D supplementation at a dose exceeding the IOM recommendation of 600 IU/day on BMD and bone markers, in overweight elderly individuals. © 2017 American Society for Bone and Mineral Research., (© 2017 American Society for Bone and Mineral Research.)

Metabolic bone disease may appear as a complication of obesity surgery. Because an imbalance in the osteoprotegerin and receptor-activator of nuclear factor-κB ligand system may underlie osteoporosis, we aimed to study this system in humans in the metabolic bone disease occurring after obesity surgery. In this study we included sixty women with a mean age of 47 ± 10 years studied 7 ± 2 years after bariatric surgery. The variables studied were bone mineral density, β-isomer of C-terminal telopeptide of type I collagen cross-links (a bone resorption marker), the bone formation markers osteocalcin and N-terminal propeptide of procollagen 1, serum osteoprotegerin and receptor-activator of nuclear factor-κB ligand. Serum osteoprotegerin inversely correlated with the bone remodeling markers osteocalcin, β-isomer of C-terminal telopeptide of type I collagen cross-links and N-terminal propeptide of procollagen 1. The osteoprotegerin and receptor-activator of nuclear factor-κB ligand ratio also correlated inversely with serum parathormone and osteocalcin. Bone mineral density at the lumbar spine was associated with age (β = -0.235, P = 0.046), percentage of weight loss (β = 0.421, P = 0.001) and osteoprotegerin and receptor-activator of nuclear factor-κB ligand ratio (β = 0.259, P = 0.029) in stepwise multivariate analysis (R 2  = 0.29, F = 7.49, P < 0.001). Bone mineral density at the hip site was associated only with percentage of weight loss (β = 0.464, P < 0.001) in stepwise multivariate regression (R 2  = 0.21, F = 15.1, P < 0.001). These data show that the osteoprotegerin and receptor-activator of nuclear factor-κB ligand system is associated with bone markers and bone mineral density at the lumbar spine after obesity surgery.

The purpose of the present study is to determine if a correlation exists between bone mineral density (BMD) obtained from dual energy X-ray absorptiometry (DXA) and Hounsfield unit (HU) from pelvic diagnostic computed tomography (dCT), and to evaluate whether HU could be used to identify osteoporosis. Seventy-nine patients were included in this study. HU values were measured in three different sections: the head-neck junction of the femur, the middle portion of the femoral neck, and the intertrochanter of the femur (IT). In each sectional image, HU values were measured at two regions of interest: cortical and cancellous bone (HU&#95;t) and cancellous bone. The correlation between BMD and HU&#95;t of IT was significant (r = 0.839, p < 0.01). In IT, the area under the curve value of HU&#95;t was 0.875 (0.796-0.955). We found that a HU&#95;t of IT <170 can be regarded as indicating osteoporosis: its positive predictive value is 96.9 %. A HU&#95;t of IT >210 can be regarded as indicating an absence of osteoporosis: its negative predictive value is 84.6 %. In conclusion, we found that a significant correlation between HU of pelvic dCT and BMD of DXA, and HU potentially provided an alternative method for determining regional BMD. Therefore, pelvic dCT could possibly be a supplementary method for initial diagnosis of osteoporosis and for initiation of treatment.

Background: Data are scant on bone health in endocrinopathies from India. This study evaluated bone mineral density (BMD) loss in endocrinopathies [Graves' disease (GD), type 1 diabetes mellitus (T1DM), hypogonadotrophic hypogonadism (HypoH), hypergonadotropic hypogonadism (HyperH), hypopituitarism, primary hyperparathyroidism (PHPT)] as compared to age-related BMD loss [postmenopausal osteoporosis (PMO), andropause]., Materials and Methods: Retrospective audit of records of patients >30 years age attending a bone clinic from August 2014 to January 2016 was done., Results: Five-hundred and seven records were screened, out of which 420 (females:male = 294:126) were analyzed. A significantly higher occurrence of vitamin D deficiency and insufficiency was noted in T1DM (89.09%), HyperH (85%), and HypoH (79.59%) compared to age-related BMD loss (60.02%; P < 0.001). The occurrence of osteoporosis among females and males was 55.41% and 53.97%, respectively, and of osteopenia among females and males was 28.91% and 32.54%, respectively. In females, osteoporosis was significantly higher in T1DM (92%), HyperH (85%), and HypoH (59.26%) compared to PMO (49.34%; P < 0.001). Z score at LS, TF, NOF, and greater trochanter (GT) was consistently lowest in T1DM women. Among men, osteoporosis was significantly higher in T1DM (76.67%) and HypoH (54.55%) compared to andropause (45.45%; P = 0.001). Z score at LS, TF, NOF, GT, and TR was consistently lowest in T1DM men. In GD, the burden of osteoporosis was similar to PMO and andropause. BMD difference among the study groups was not significantly different after adjusting for body mass index (BMI) and vitamin D., Conclusion: Low bone mass is extremely common in endocrinopathies, warranting routine screening and intervention. Concomitant vitamin D deficiency compounds the problem. Calcium and vitamin D supplementations may improve bone health in this setting.

Objectives: Elevated systemic levels of pro-inflammatory cytokines involved in the pathogenesis of osteoporosis. Our objective was to investigate whether low grade systemic inflammation was associated with bone markers, bone quality, bone mass and fracture risk in a population of older persons., Methods: Serum interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR) were measured in 1287 participants of the Longitudinal Aging Study Amsterdam (LASA), a population based study in a representative sample of older men and women (age 76 ± 6.7 years). Bone quality was measured by quantitative ultrasound measurements (QUS) at baseline and after 3 years at the calcaneus, and bone mineral density was measured by dual-energy X-ray absorptiometry (DXA) at the spine and hip in a subpopulation. Furthermore, the bone markers osteocalcin (OC) and urinary excretion of deoxypyridinoline (DPD) were determined. Incident clinical fractures were recorded during 6 years of follow-up., Results: Multivariable regression analyses revealed higher IL-6 and ESR levels were associated with lower quantitative ultrasound values in older men (β=-0.98; 95% CI -57.72 to -6.42, p<0.05) and (β=-0.221; 95% CI -15.39 to -3.27, p<0.05) respectively at baseline, but not in women. No significant associations were found between inflammatory markers and bone markers, bone loss at the spine or hips, fracture rate or time to fracture., Conclusion: Elevated inflammatory markers are associated with impaired bone quality in older men, but not in women. No associations were found with the risk for fractures., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: MicroRNAs (miRNAs) are important regulators of gene expression, with documented roles in bone metabolism and osteoporosis, suggesting potential therapeutic targets. Our aim was to identify miRNAs differentially expressed in fractured vs nonfractured bones. Additionally, we performed a miRNA profiling of primary osteoblasts to assess the origin of these differentially expressed miRNAs., Methods: Total RNA was extracted from (a) fresh femoral neck trabecular bone from women undergoing hip replacement due to either osteoporotic fracture (OP group, n = 6) or osteoarthritis in the absence of osteoporosis (Control group, n = 6), matching the two groups by age and body mass index, and (b) primary osteoblasts obtained from knee replacement due to osteoarthritis (n = 4). Samples were hybridized to a microRNA array containing more than 1900 miRNAs. Principal component analysis (PCA) plots and heat map hierarchical clustering were performed. For comparison of expression levels, the threshold was set at log fold change > 1.5 and a p-value < 0.05 (corrected for multiple testing)., Results: Both PCA and heat map analyses showed that the samples clustered according to the presence or absence of fracture. Overall, 790 and 315 different miRNAs were detected in fresh bone samples and in primary osteoblasts, respectively, 293 of which were common to both groups. A subset of 82 miRNAs was differentially expressed (p < 0.05) between osteoporotic and control osteoarthritic samples. The eight miRNAs with the lowest p-values (and for which a validated miRNA qPCR assay was available) were assayed, and two were confirmed: miR-320a and miR-483-5p. Both were over-expressed in the osteoporotic samples and expressed in primary osteoblasts. miR-320a is known to target CTNNB1 and predicted to regulate RUNX2 and LEPR, while miR-483-5p down-regulates IGF2. We observed a reduction trend for this target gene in the osteoporotic bone., Conclusions: We identified two osteoblast miRNAs over-expressed in osteoporotic fractures, which opens novel prospects for research and therapy.

The fat and bone connection is complicated, and the effect of adipose tissue on hip bone strength remains unclear. The aim of this study was to clarify the relative contribution of body fat accumulation and fat distribution to the determination of proximal femur strength in healthy postmenopausal Chinese women. This cross-sectional study enrolled 528 healthy postmenopausal women without medication history or known diseases. Total lean mass (LM), appendicular LM (ALM), percentage of lean mass (PLM), total fat mass (FM), appendicular FM (AFM), percentage of body fat (PBF), android and gynoid fat amount, android-to-gynoid fat ratio (AOI), bone mineral density (BMD), and proximal femur geometry were measured by dual energy X-ray absorptiometry. Hip structure analysis was used to compute some variables as geometric strength-related parameters by analyzing the images of the hip generated from DXA scans. Correlation analyses among anthropometrics, variables of body composition and bone mass, and geometric indices of hip bone strength were performed with stepwise linear regression analyses as well as Pearson's correlation analysis. In univariate analysis, there were significantly inverse correlations between age, years since menopause (YSM), hip BMD, and hip geometric parameters. Bone data were positively related to height, body weight, LM, ALM, FM, AFM, and PBF but negatively related to AOI and amount of android fat (all P < 0.05). AFM and AOI were significantly related to most anthropometric parameters. AFM was positively associated with height, body weight, and BMI. AFM was negatively associated with age and YSM. AOI was negatively associated with height, body weight, and BMI. AOI positively associated with age and YSM. LM, ALM, and FM had a positive relationship with anthropometric parameters (P < 0.05 for all). PLM had a negative relationship with those parameters. The correlation between LM, ALM, FM, PLM, ALM, age, and YSM was not significant. In multivariate linear regression analysis, the hip bone strength was observed to have a consistent and unchanged positive association with AFM and a negative association with AOI, whereas its association with other variables of body composition was not significant after adjusting for age, years since menopause, height, body weight, and BMI. AFM may be a positively protective effect for hip bone strength while AOI, rather than android fat, shows a strong negative association with hip bone strength after making an adjustment for confounders (age, YSM, height, body weight, and BMI) in healthy postmenopausal Chinese women. Rational weight control and AOI reduction during menopause may have vital clinical significance in decreasing postmenopausal osteoporosis.

Objectives: Given the need for easily managed treatment of osteoporosis in HIV-infected patients, we evaluated the efficacy and tolerability of two doses of zoledronate, by comparing three groups of patients: those with annual administration, those with biennial administration (one dose in 2 years) and a control group with no administration of zoledronate., Methods: We randomized (2:1) 31 patients on antiretroviral therapy with low bone mineral density (BMD) to zoledronate (5 mg administered intravenously; 21 patients) plus diet counselling and to a control group (diet counselling; 10 patients). At week 48, patients treated with zoledronate were randomized again to receive a second dose (two-dose group; n = 12) or to continue with diet counselling only (single-dose group; n = 9). Changes in lumbar spine and hip BMD and bone turnover markers were compared., Results: The median percentage change from baseline to week 96 in L1-L4 BMD was -1.74% [interquartile range (IQR) -2.56, 3.60%], 7.90% (IQR 4.20, 16.57%) and 5.22% (IQR 2.02, 7.28%) in the control, two-dose and single-dose groups, respectively (P < 0.01, control vs. two doses; P = 0.02, control vs. single dose; P = 0.18, two doses vs. single dose). Hip BMD changed by a median of 2.12% (IQR -0.12, 3.08%), 5.16% (IQR 3.06, 6.74%) and 4.47% (IQR 1, 5.58%), respectively (P = 0.04, control vs. two doses; P = 0.34, two doses vs. single dose). No differences between the two-dose and single-dose groups were detected in bone markers at week 96., Conclusions: The benefits for BMD of a single dose of zoledronate in 2 years may be comparable to those obtained with two doses of the drug after 96 weeks, although this study is insufficiently powered to exclude a real difference. Future studies should explore whether biennial administration of zoledronate is a useful alternative in the treatment of osteoporosis in HIV-infected patients., (© 2015 British HIV Association.)

The association between metabolic syndrome (MS) and bone health remains unclear. We aimed to study the association between MS and hip bone geometry (HBG), femoral neck bone mineral density (FN-BMD), and the risk of osteoporosis and incident fractures. Data of 2040 women and 1510 men participants in the third visit (1997-1999) of the Rotterdam Study (RSI-3), a prospective population based cohort, were available (mean follow-up 6.7 years). MS was defined according to the recent harmonized definition. HBG parameters were measured at the third round visit whereas FN-BMD was assessed at the third round and 5 years later. Incident fractures were identified from medical registry data. After correcting for age, body mass index (BMI), lifestyle factors and medication use, individuals with MS had lower bone width (β = -0.054, P = 0.003), lower cortical buckling ratio (β = -0.81, P = 0.003) and lower odds of having osteoporosis (odds ratio =0.56, P = 0.007) in women but not in men. Similarly, MS was associated with higher FN-BMD only in women (β = 0.028, P=0.001). In the analyses of MS components, the glucose component (unrelated to diabetes status) was positively associated with FN-BMD in both genders (β = 0.016, P = 0.01 for women and β = 0.022, P = 0.004 for men). In men, waist circumference was inversely associated with FN-BMD (β = -0.03, P = 0.004). No association was observed with fracture risk in either sex. In conclusion, women with MS had higher FN-BMD independent of BMI. The glucose component of MS was associated with high FN-BMD in both genders, highlighting the need to preserve glycemic control to prevent skeletal complications.

Background & Objectives: There is a paucity of data with conflicting reports regarding the extent and pattern of bone mineral (BM) loss in Graves' disease (GD), especially in young adults. Also, interpretation of BM data in Indians is limited by use of T-score cut-offs derived from Caucasians. This study was aimed to evaluate the occurrence of osteoporosis in active treatment naive patients with GD and determine the factors predicting BM loss, using standard T-scores from Caucasians and compare with the cut-offs proposed by the Indian Council of Medical Research (ICMR) for diagnosing osteoporosis in Indians., Methods: Patients with GD, >20 yr age without any history of use of anti-thyroid drugs, and normal controls without fracture history, drugs use or co-morbidities underwent BM density (BMD) assessment at lumbar spine, hip and forearm, thyroid function and calcium profile assessment. Women with menopause or premature ovarian insufficiency and men with androgen deficiency were excluded., Results: p0 atients with GD (n=31) had significantly lower BMD at spine (1.01±0.10 vs. 1.13±0.16 g/cm 2 ), hip (0.88±0.10 vs. 1.04±0.19 g/cm 2 ) and forearm (0.46±0.04 vs. 0.59±0.09 g/cm 2 ) compared with controls (n=30) (P<0.001). Nine (29%) and six (19.3%) patients with GD had osteoporosis as per T-score and ICMR criteria, respectively. None of GD patients had osteoporosis at hip or spine as per ICMR criteria. Serum T 3 had strongest inverse correlation with BMD at spine, hip and femur. Step-wise linear regression analysis after adjusting for age, BMI and vitamin D showed T 3 to be the best predictor of reduced BMD at spine, hip and forearm, followed by phosphate at forearm and 48 h I 131 uptake for spine BMD in GD., Interpretation & Conclusions: Osteoporosis at hip or spine is not a major problem in GD and more commonly involves forearm. Diagnostic criterion developed from Caucasians tends to overdiagnose osteoporosis in Indians. T 3 elevation and phosphate are important predictors of BMD. Baseline I 131 uptake may have some role in predicting BMD.

Background: Prior studies reveal that bone mineral density (BMD) in congenital adrenal hyperplasia (CAH) is mostly in the osteopaenic range and is associated with lifetime glucocorticoid dose. The forearm, a measure of cortical bone density, has not been evaluated., Objective: We aimed to evaluate BMD at various sites, including the forearm, and the factors associated with low BMD in CAH patients., Methods: Eighty CAH adults (47 classic, 33 nonclassic) underwent dual-energy-x-ray absorptiometry and laboratory and clinical evaluation. BMD Z-scores at the AP spine, total hip, femoral neck, forearm and whole body were examined in relation to phenotype, body mass index, current glucocorticoid dose, average 5-year glucocorticoid dose, vitamin D, 17-hydroxyprogesterone, androstenedione, testosterone, dehydroepiandrosterone and dehydroepiandrosterone sulphate (DHEAS)., Results: Reduced BMD (T-score <-1 at hip, spine, or forearm) was present in 52% and was more common in classic than nonclassic patients (P = 0·005), with the greatest difference observed at the forearm (P = 0·01). Patients with classic compared to nonclassic CAH, had higher 17-hydroxyprogesterone (P = 0·005), lower DHEAS (P = 0·0002) and higher non-traumatic fracture rate (P = 0·0005). In a multivariate analysis after adjusting for age, gender, height standard deviation, phenotype and cumulative glucocorticoid exposure, higher DHEAS was independently associated with higher BMD at the spine, radius and whole body., Conclusion: Classic CAH patients have lower BMD than nonclassic patients, with the most affected area being the forearm. This first study of forearm BMD in CAH patients suggests that low DHEAS may be associated with weak cortical bone independent of glucocorticoid exposure., (Published 2014. This article is a U.S. Government work and is in the public domain in the USA.)

Denosumab has received approval in many countries and indications include treating women with postmenopausal osteoporosis (PMO) at increased or high risk for fracture and men at high risk for fracture receiving androgen deprivation therapy (ADT) for non-metastatic prostate cancer. Increases in total hip bone mineral density (BMD) with denosumab explained a large percentage of new vertebral fracture risk reduction in women with PMO; however, this effect has not been studied in men with prostate cancer receiving ADT. We compared the relationship between the time course of BMD changes and new vertebral fracture risk reduction with denosumab in women with PMO and men with prostate cancer. After adjusting for different baseline hazards, a significant and similar relationship between time course of total hip and lumbar spine BMD changes and new vertebral fracture risk was observed in both patient populations. Time course of total hip BMD changes with denosumab was the best predictor for changes in fracture risk and explained 88% of the new vertebral fracture risk reduction in women with PMO and 91% in men with prostate cancer. Therefore, total hip BMD is a useful surrogate to measure the clinical impact of denosumab on fracture risk reduction in both patient populations., (© 2013, The American College of Clinical Pharmacology.)

In total hip arthroplasty and particularly in revision surgery, computer assisted pre-operative prediction of the best possible anchorage strategy for implant fixation would be a great help to the surgeon. Computer simulation relies on validated numerical models. In the current study, three density-elasticity relationships (No. 1-3) from the literature for inhomogeneous material parameter assignment from CT data in automated finite element (FE) modeling of long bones were evaluated for their suitability for FE modeling of human pelvic bone. Numerical modal analysis was conducted on 10 FE models of hemipelvic bone specimens and compared to the gold standard provided by experimental modal analysis results from a previous in-vitro study on the same specimens. Overall, calculated resonance frequencies came out lower than measured values. Magnitude of mean relative deviation of numerical resonance frequencies with regard to measured values is lowest for the density-elasticity relationship No. 3 (-15.9%) and considerably higher for both density-elasticity relationships No. 1 (-41.1%) and No. 2 (-45.0%). Mean MAC values over all specimens amount to 77.8% (No. 1), 78.5% (No. 2), and 83.0% (No. 3). MAC results show, that mode shapes are only slightly influenced by material distribution. Calculated resonance frequencies are generally lower than measured values, which indicates, that numerical models lack stiffness. Even when using the best suited (No. 3) out of three investigated density-elasticity relationships, in FE modeling of pelvic bone a considerable underestimation of model stiffness has to be taken into account., (© 2013 Elsevier Ltd. All rights reserved.)

The functional imaging technique of ¹⁸F-fluoride positron emission tomography (¹⁸F-PET) allows the noninvasive quantitative assessment of regional bone formation at any skeletal site, including the spine and hip. The aim of this study was to determine if ¹⁸F-PET can be used as an early biomarker of treatment efficacy at the hip. Twenty-seven treatment-naive postmenopausal women with osteopenia were randomized to receive teriparatide and calcium and vitamin D (TPT group, n = 13) or calcium and vitamin D only (control group, n = 14). Subjects in the TPT group were treated with 20 µg/day teriparatide for 12 weeks. ¹⁸F-PET scans of the proximal femur, pelvis, and lumbar spine were performed at baseline and 12 weeks. The plasma clearance of ¹⁸F-fluoride to bone, K(i), a validated measurement of bone formation, was measured at four regions of the hip, lumbar spine, and pelvis. A significant increase in K(i) was observed at all regions of interest (ROIs), including the total hip (+27%, p = 0.002), femoral neck (+25%, p = 0.040), hip trabecular ROI (+21%, p = 0.017), and hip cortical ROI (+51%, p = 0.001) in the TPT group. Significant increases in K(i) in response to TPT were also observed at the lumbar spine (+18%, p = 0.001) and pelvis (+42%, p = 0.001). No significant changes in K(i) were observed for the control group. Changes in BMD and bone turnover markers were consistent with previous trials of teriparatide. In conclusion, this is the first study to our knowledge to demonstrate that ¹⁸F-PET can be used as an imaging biomarker for determining treatment efficacy at the hip as early as 12 weeks after initiation of therapy., (Copyright © 2013 American Society for Bone and Mineral Research.)

As with most fractures associated with osteoporosis, the incidence of pelvic ring injuries in this population of patients is rising rapidly. Osteoporotic pelvic ring injuries are exceedingly different in their etiology, natural history, and treatment from the more recognizable patterns in young patients with high-energy pelvic ring injuries. Recognition of a potentially unstable fracture pattern, careful evaluation of the ambulatory and functional status of each patient before injury, and the potential pitfalls and benefits of operative versus nonoperative care are critical to the effective treatment., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to determine the effects of age and fat content on quantitative dynamic contrast-enhanced MRI (DCE-MRI) parameters in the bone marrow of the lumbar spine and pelvis. The interreader reproducibility of this technique will also be assessed., Materials and Methods: Forty-three DCE-MRI studies of the female pelvis defined the study group. Quantitative pharmacokinetic perfusion parameters of lumbar and pelvic marrow were analyzed by three readers on a DCE-MRI postprocessing platform. Linear regression analysis was performed to determine the effect of age and marrow fat fraction on the parameters of transfer constant (K(trans)), efflux rate constant (K(ep)), extravascular extracellular space (V(e)), and initial area under the gadolinium curve at 60 seconds (iAUGC(60)). Interreader agreement was assessed by means of intraclass correlation coefficient calculation., Results: A weak but statistically significant correlation was established between both age and fat fraction and the parameters K(trans) (R(2) = 0.14) and K(ep) (R(2) = 0.09). There was also a weak but statistically significant correlation between fat fraction and V(e) (R(2) = 0.116) and iAUGC(60) (R(2) = 0.108), but no correlation between age and these parameters. Intraclass correlation coefficients of parameter measurements by different readers were all greater than 0.7 at the p < 0.05 level., Conclusion: Age and fat fraction have small measurable effects on quantitative DCE-MRI parameters in bone marrow. However, given the wide interindividual variation of these parameters, these effects are unlikely to confound changes related to malignancy or treatment. Also of note, there was strong interreader reproducibility of parameter measurements among a range of experience levels, suggesting that the reader-reader experience level may not represent a significant source of variability in bone marrow DCE-MRI.

The investigation showed that reamberin application in the complex treatment of patients with severe disintegrated fractures of pelvic bones is pathogenetically grounded. Despite polyetiological origin of critical conditions in the organism in this case, all these have a common pathophysiological basis of three main processes: hypoxia, intoxication, and immunosuppression. Succinic acid, which is contained in reamberin, is a substrate antihypoxant that stimulates the synthesis of restorative equivalents in the cell. A modifying effect of succinic acid on the processes of tissue metabolism, including cell respiration, LPO/AOS system, and synthesis of proteins, is the basis of pathophysiological ground of reamberin application in a complex treatment of patients with disintegrated fractures of pelvic bones.

Background/objectives: Recent research has shown an inverse relationship between bone marrow adipose tissue (BMAT) and bone mineral density (BMD). There is a lack of evidence at the macro-imaging level to establish whether increased BMAT is a cause or effect of bone loss. This cross-sectional study compared the BMAT and BMD relationship between a younger adult group at or approaching peak bone mass (PBM; age 18.0-39.9 years) and an older group with potential bone loss (PoBL; age 40.0-88.0 years)., Subjects/methods: Pelvic BMAT was evaluated in 560 healthy men and women with T1-weighted whole-body magnetic resonance imaging. BMD was measured using whole-body dual-energy X-ray absorptiometry., Results: An inverse correlation was observed between pelvic BMAT and pelvic, total and spine BMD in the younger PBM group (r=-0.419 to -0.461, P<0.001) and in the older PoBL group (r=-0.405 to -0.500, P<0.001). After adjusting for age, sex, ethnicity, menopausal status, total body fat, skeletal muscle, subcutaneous and visceral adipose tissue, neither subject group (younger PBM vs older PoBL) nor its interaction with pelvic BMAT significantly contributed to the regression models with BMD as dependent variable and pelvic BMAT as independent variable (P=0.434-0.928)., Conclusions: Our findings indicate that an inverse relationship between pelvic BMAT and BMD is present both in younger subjects who have not yet experienced bone loss and also in older subjects. These results provide support at the macro-imaging level for the hypothesis that low BMD may be a result of preferential differentiation of mesenchymal stem cells from osteoblasts to adipocytes.

Background: Different patterns of stress shielding may lead to differences in periprosthetic bone preservation around cemented and uncemented hips in the long term?, Questions/purposes: The purpose of this study is to compare the difference in periprosthetic bone density between cemented Charnley total hip and uncemented hydroxyapatite-coated Furlong THAs at a minimum followup of 12 years (mean, 16 years; range, 12-24 years)., Methods: We studied a cohort of 17 patients who had bilateral THAs with a cemented Charnley THA on one side and an uncemented Furlong hydroxyapatite-coated THA on the other side. At a minimum followup of 12 years, Harris and Oxford hip scores were used to determine the function, and dual-energy x-ray absorptiometry was used to quantify bone mineral density adjacent to the prosthesis. The results of the dual-energy x-ray absorptiometry scan for cemented and uncemented hips were analyzed using paired-sample two-tailed t-tests. To compare the Harris hip scores, a nonparametric Wilcoxon test was used., Results: Bone mineral density was higher on the uncemented Furlong side in Gruen Zones 2, 3, 5, and 6 of the proximal femur and DeLee and Charnley Zone 1 of the acetabulum. In all other zones, there was no difference. Comparison of Harris and Oxford hip scores showed no differences between the two hips., Conclusion: Bone density is better preserved around the uncemented hydroxyapatite-coated Furlong stem compared with the Charnley cemented stem., Level of Evidence: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Objective: During a period of 12 months, we evaluated the longitudinal impact of metabolic control of diabetes on selected bone turnover markers, bone mineral density and serum adiponectin concentrations in post-menopausal women with newly diagnosed Type 2 diabetes., Methods: Serum total adiponectin, bone alkaline phosphatase, HbA(1c), urinary deoxypyridinoline excretion, bone mineral density of the total body, lumbar spine and total hip were measured in 57 women aged 50-78 years with newly diagnosed Type 2 diabetes., Results: At baseline, women had normal bone-specific alkaline phosphatase, deoxypyridinoline and bone mineral density, as evaluated by t- and z-scores. After 12 months of treatment, a significant decrease in body weight, waist circumference and HbA(1c) was observed. Bone mineral density of the total body, lumbar spine and total hip decreased by 0.4, 0.2 and 1.0% (P = 0.018) per year, respectively. Adiponectin was inversely correlated with bone mineral density at three sites (R = -0.28, -0.24 and -0.19, respectively). There was a transient increase (P < 0.05) in serum adiponectin within the first 6 months, followed by a slow decrease toward the baseline value during the next 6 months. An improvement in diabetes control had no impact on bone turnover marker levels, which did not change significantly during the entire study period., Conclusions: Bone turnover markers, bone mineral density and the rate of bone loss are within normal ranges in post-menopausal women with newly diagnosed Type 2 diabetes. Bone mineral density of the total body, lumbar spine and total hip is inversely correlated with total adiponectin., (© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.)

The aim of this study was to evaluate Singh index as a simple and inexpensive means of estimation of bone quality in patients with rheumatoid arthritis. Singh index evaluation was made on digital pelvis radiographs in 50 consecutive patients by three observers. Bone mineral density T scores of the spine and left proximal femur were assessed using dual energy X-ray absorptiometry. Singh index was correlated with densitometry measurements after grouping the patients as normal, osteopenia and osteoporosis. Intra- and interobserver agreements were evaluated by kappa correlations. Sensitivity, specificity, positive and negative predictive values and likelihood ratio's of Singh index were calculated. Both intra- and interobserver agreements were 0.71 (range, 0.69 to 0.72) on average. Singh index proved highly sensitive for the diagnosis of osteopenia at the proximal femur (91%) and spine (90%), whereas the specificity of Singh index for identifying of osteoporosis at the femoral neck (93%) and spine (91%) was higher than sensitivity. Predictive values for osteoporosis at the proximal femur and spine were acceptable and positive likelihood ratios of Singh index for osteopenia and osteoporosis at the proximal femur were 2.4 and 10.1, respectively. Singh index can identify osteoporosis with a high specificity in patients with rheumatoid arthritis. However, the patients who are graded as osteopenia by the Singh index should undergo further evaluation with dual energy X-ray absorptiometry.

Obesity and osteoporosis are closely correlated genetically. FTO gene has been consistently identified to be associated with obesity phenotypes. A recent study reported that the mice lacking Fto could result in lower bone mineral density (BMD). Thus, we hypothesize that the FTO gene might be also important for osteoporosis phenotypes. To test for such a hypothesis, we performed an association analyses to investigate the relationship between SNPs in FTO and BMD at both hip and spine. A total of 141 SNPs were tested in two independent Chinese populations (818 and 809 unrelated Han subjects, respectively) and a Caucasian population (2,286 unrelated subjects). Combining the two Chinese samples, we identified 6 SNPs in FTO to be significantly associated with hip BMD after multiple testing adjustments, with the combined P values ranged from 4.99 × 10⁻⁴-1.47 × 10⁻⁴. These 6 SNPs are all located at the intron 8 of FTO and in high linkage disequilibrium. Each copy of the minor allele of each SNP was associated with increased hip BMD values with the effect size (beta) of ∼0.025 and ∼0.015 in the Chinese sample 1 and 2, respectively. However, none of these 6 SNPs showed significant association signal in the Caucasian sample, by presenting some extent of ethnic difference. Our findings, together with the prior biological evidence, suggest that the FTO gene might be a new candidate for BMD variation and osteoporosis in Chinese populations.

Hip structural analysis (HSA) has been developed over 20 yr, applied extensively in research, and has demonstrated useful outcomes associating bone structural geometry with bone fragility (research-HSA or r-HSA). In 2007, Hologic Inc. (Bedford, MA) incorporated HSA with some modifications as an option for Hologic dual-energy X-ray absorptiometry (DXA) scanners (clinical HSA or c-HSA). This brought HSA from the research environment into the clinical environment. This article reports a comparison of r-HSA and c-HSA implementations using DXA scans from a group of 191 females. Bland-Altman plots at the narrow-neck (NN) HSA region indicated higher r-HSA areal bone mineral density (mean difference: 0.27 g/cm(2); 21.7% [of mean]); cross-sectional area (0.63 cm(2); 18.7%); cross-sectional moment of inertia (0.26 cm(4); 11.1%), and section modulus (0.22 cm(3); 14.5%) compared with c-HSA. The converse was observed for NN subperiosteal width (-0.09 cm; 3.1%). High linear correlations (r(2) > 0.81) were found between r-HSA and c-HSA NN structural geometric outcomes, with the exception of neck shaft angle (r(2) > 0.47). As differences were significant (p < 0.001), slopes and intercepts are provided to enable linear transformations from r-HSA to corresponding c-HSA structural geometric data.

Body mass index (BMI) is used to assess overweight and obesity, but it does not account for the distribution or composition of excess weight. Dual-energy X-ray absorptiometry (DXA) is widely used for the assessment of osteoporosis. We hypothesized that measures of regional fat tissue composition from spine and hip DXA done for osteoporosis assessment could be used to estimate body composition more accurately than with BMI. We identified 427 adult patients who underwent DXA evaluation of the lumbar spine, hip, and whole body at the same visit. The population was randomly divided into 2 equal-sized subgroups: one used to derive prediction equations for whole-body fat tissue, whole-body lean tissue, and trunk fat tissue, and the other for independent validation. The estimates were compared with the actual measurements from the whole-body scans. In all analyses, prediction using the regional DXA scans outperformed prediction using BMI or its component variables, height and weight. When the predicted and actual measurements were compared in the validation cohort, regression slopes did not differ significantly from unity and the intercepts did not differ significantly from zero. We conclude that regional DXA scans of the spine and hip can be used to accurately measure body composition. Further research is needed to see whether these measures can in turn predict the metabolic complications associated with overweight and obesity.

Introduction: The information available on (18)F-fluorodeoxyglucose (FDG) uptake on PET in radiation-induced pelvic insufficiency fracture (PIF) is limited. In this study, we reviewed the findings of FDG-PET in 10 cases with PIF., Materials and Methods: We diagnosed 83 cases of PIF in patients who received pelvic radiotherapy between Jan 1995 and Aug 2005. Among these patients, we selected 10 patients who performed FDG-PET and reviewed the FDG uptake., Results: Mild FDG uptake was still present at 6-months after the diagnosis of PIF in two patients. Eight patients had mild and diffuse FDG uptake and two patients had intense and heterogeneous uptake. All patients had vertical uptake parallel to the sacroiliac joints and one patient had the typical 'H' sign associated with PIF. The maximum of standardized uptake values was variable and ranged from 2.4 to 7.2. In three patients, follow-up PET images were obtained. All patients had FDG uptake that decreased with time., Conclusion: The FDG-PET demonstrated a variable degree of uptake in patients with a PIF. The pattern of uptake was diffuse and vertical, parallel to the sacroiliac joints. Therefore, clinicians should be careful with the interpretation of FDG uptake around the sacroiliac joints, and keep in mind false-positive lesions such as PIFs.

Aim: High physical activity is associated with larger bone mineral content (BMC) and density (BMD) in young males though competitive road cyclists have been reported to have similar or lower BMD than controls., Methods: BMC and BMD were assessed in 73 highly trained (42 professional and 31 elite amateur) road cyclists (CYCLIST; age: 25.8+/-4.3 years; height: 179.7+/-6.3 cm; weight: 71.6+/-6.3 kg; %Fat mass: 9.5+/-3 %; VO(2max): 68.5+/-5.7 mlxkg(-1)xmin(-1)) and in 30 healthy males used as reference (REF: 28.3+/-4.5 years; 176.6+/-6.2 cm; 74.5+/-8.4 kg; 21.3+/-6.1%)., Results: Daily calcium intake estimated from a food-questionnaire was higher in CYCLIST than in REF (942+/-374 vs 753+/-315 mgxd(-1); P=0.008). Compared to REF, CYCLIST had lower L1-L4 BMD (1.004+/-0.125 vs 1.240+/-0.163 gxcm(-2); P<0.0001) and femoral neck BMD (0.986+/-0.132 vs 1.098+/-0.137; P<0.003). In CYCLIST, daily calcium intake is correlated with total BMC and BMD (r=0.27-0.26, P=0.02) and femoral BMD (r=0.35; P=0.002). Divided by tertiles (high, medium and low Ca), CYCLIST with high Ca (1320+/-382 mgxd(-1)) had lower lumbar BMD values (-6.68%; P=0.02) and tended to have lower femoral neck BMD (-4.77%; P=0.09) and radius UD BMD (-5.9%; P=0.07) than REF., Conclusions: There was no difference between medium Ca and high Ca for any BMC or BMD parameters. Differences between low Ca and high Ca could be detected only for Total BMC (-8.4%; P=0.01), Pelvis BMD (-7.4%; P=0.01) and femoral neck BMD (-9.9%; P=0.006).

The aim is to describe the characteristics of osteoporotic pelvic fractures and their outcome. We recorded clinical and biological characteristics of 60 osteoporotic pelvic fractures hospitalized in our Department of Rheumatology and assessed their outcome in 51 cases, using a questionnaire administrated by phone call. In our population, pelvic fractures mainly affected elderly women (81.6% of women, mean age 79 years), presenting, in more than 50% of the cases, a past medical history of osteoporosis, previous fracture and cardiovascular disease. The fractures were triggered by a fall in 89% of the cases and mainly located at the pubic rami (65%). There was a high rate of vitamin D deficiency (80.6%) associated with a secondary hyperparathyroidism (51.6%). Before the pelvic fracture, all patients lived at their personal home and 84.1% were autonomous. During hospitalization, 52.5% of the patients experienced an adverse event, mostly related to urinary tract infection and bedsore. At time to discharge, only 31% directly returned to their own home. At the final assessment (mean delay from the fracture: 29 months), 11 patients were dead (mean delay: 190 days). Among living patients, 74.5% lived at home, 60% required assistance for at least one daily life activity and 18.6% experienced a new fracture. Only 63.2% were still treated for osteoporosis. Osteoporotic pelvic fractures requiring initial hospitalization share most characteristics of hip fracture: elderly people, women predominance, vitamin D insufficiency, fall triggering the fracture, and also the severity assessed by a high morbidity and mortality and loss of autonomy.

Background: Genital prolapse is a debilitating manifestation of pelvic floor dysfunction. The cause of this condition has not been elucidated. The purpose of this study was to determine elastin content and RNA expression of related enzymes of elastin synthesis in uterosacral ligament biopsies from women with severe prolapse, and controls with normal pelvic support., Methods: Biopsies were taken from the uterosacral ligament tissue of 31 women with Grade III or greater prolapse and 29 women with normal pelvic support. Elastin content was assessed by measuring desmosine using radioimmunoassay, and quantitative real time PCR was performed to quantify mRNA levels of lysyl oxidase (LOX), lysyl oxidase like-1 (LOXL1), LOXL2 and fibulin-5 (FIB-5)., Results: The mean desmosine concentration found in uterosacral ligaments of women with prolapse (n =26) was 103.3+/-59.3 pmolD/mgP compared to controls (n =29) 120.5+/-47.4 pmolD/mgP (p =0.1943). In the subgroup of subjects with complete procidentia (n =8), mean desmosine concentration was 50.6+/-25.8 and 127.1+/-42.2 pmolD/mgP in age-matched controls (n =12) (p <0.05). In tissue from subjects with more than 2 vaginal deliveries (n =18), the mean desmosine concentration was 99.9+/-60.7 and 133.0+/-44.0 pmolD/mgP in controls (n =17) (p <0.05). Expression of LOX, LOXL1 and LOXL2 decreased 8.2-fold+/-3.4, 5.0-fold+/-1.7 and 15.2-fold+/-5.2, respectively (mean+/-SD) in cases versus controls (p<0.05). Expression of FIB-5 was increased 3.1-fold+/-0.7 compared to controls (p<0.05)., Conclusions: Significantly decreased desmosine content was measured in the uterosacral ligament tissue from women with prolapse versus controls in women with parity >2 and in women with complete procidentia. Suppression of mRNA for LOX and two LOX isoenzymes was correspondingly present. These results suggest that altered elastin metabolism is present in women with uterine prolapse.

Objectives: To investigate the effect of transvaginal estradiol on bone mineral density and bone metabolism., Methods: One hundred and fifteen women (mean age 73.8+/-3.2 years) were randomly assigned to a 2-year open-label parallel group clinical trial and were treated with either transvaginal estradiol (7.5 microg/24h), or no estradiol. Both groups received 400 IU vitamin D and 500 mg calcium/day. The bone mineral density (BMD) was assessed in the hip and spine using DXA technique and in the heel using DXL technique., Results: The intention to treat analysis showed that the increase in BMD in the estradiol group was significant at total hip by 0.6% (P=0.04) while the control group decreased in their BMD by 0.7%. At lumbar spine the estradiol group increased in BMD by 2.6% (P=0.011) while the control group increased by 2.2%. Bone turnover markers and PTH-levels decreased while 25-OH vitamin D levels increased in both groups, a probable effect of the calcium and vitamin D supplementation. The bone resorption marker CTx decreased more significantly in the treatment group (P=0.016)., Conclusions: The transvaginal estradiol treatment of 7.5 microg/24h had a small but significant effect on the BMD of total hip and lumbar spine after a follow-up of 2 years.

Unlabelled: The VDR is a prime candidate gene for osteoporosis. Here, we studied three common VDR haplotypes in relation to bone phenotypes in 5014 participants of the global MrOS Study. We also studied the relative expression of the haplotypes in human bone cells. One haplotype was associated with increased fracture risk and differently expressed in primary human bone cells., Introduction: Vitamin D plays an essential role in skeletal metabolism by binding to its nuclear steroid receptor, the vitamin D receptor (VDR). The heritability of BMD is well established, and the VDR gene is considered a prime candidate suggested to partially account for genetically controlled BMD variance in the population., Materials and Methods: Here, we reconstructed common haplotypes in the VDR 3' untranslated region (UTR) and studied the association to BMD and risk of vertebral fractures in elderly men from Sweden (n = 3014) and Hong Kong (n = 2000), all participants of the global MrOS Study. To assess any functional implications of the VDR polymorphisms, we studied allele-specific expressions of the different VDR 3' UTR haplotypes in the normal chromosomal context of 70 unrelated human trabecular bone samples. This was performed by quantitative genotyping of coding polymorphisms in RNA samples and in corresponding DNA samples isolated from the bone samples., Results: Three major haplotypes were reconstructed and in agreement with the previously well-defined baT, BAt, and bAT haplotypes, herein denoted Hap1, Hap2, and Hap3. The Hap1 haplotype was independently associated with increased risk of vertebral fractures in Swedish men (OR, 1.655; 95% CI, 1.146-2.391; p < 0.01) and with lower lumbar spine BMD in elderly men from Sweden (p < 0.01) and Hong Kong (p < 0.05). The VDR gene was also shown to exhibit a 3' UTR haplotype dependent allelic imbalance, indicating that the VDR Hap1 allele was overexpressed in human trabecular bone samples., Conclusions: The results indicate that the relatively overexpressed VDR Hap1 haplotype could be considered a risk allele for osteoporosis regardless of ethnicity.

Unlabelled: Dietary supplementation with vitamin K(1), with vitamin D(3) and calcium or their combination, was examined in healthy older women during a 2-year, double-blind, placebo-controlled trial. Combined vitamin K with vitamin D plus calcium was associated with a modest but significant increase in BMC at the ultradistal radius but not at other sites in the hip or radius., Introduction: The putative beneficial role of high dietary vitamin K(1) (phylloquinone) on BMD and the possibility of interactive benefits with vitamin D were studied in a 2-year double-blind, placebo-controlled trial in healthy Scottish women > or =60 years of age., Materials and Methods: Healthy, nonosteoporotic women (n = 244) were randomized to receive either (1) placebo, (2) 200 microg/day vitamin K(1), (3) 10 microg (400 IU) vitamin D(3) plus 1000 mg calcium/day, or (4) combined vitamins K(1) and D(3) plus calcium. Baseline and 6-month measurements included DXA bone mineral scans of the hip and wrist, markers of bone turnover, and vitamin status. Supplementation effects were tested using multivariate general linear modeling, with full adjustment for baseline and potential confounding variables., Results: Significant bone mineral loss was seen only at the mid-distal radius but with no significant difference between groups. However, women who took combined vitamin K and vitamin D plus calcium showed a significant and sustained increase in both BMD and BMC at the site of the ultradistal radius. Serum status indicators responded significantly to respective supplementation with vitamins K and D. Over 2 years, serum vitamin K(1) increased by 157% (p < 0.001), the percentage of undercarboxylated osteocalcin (%GluOC) decreased by 51% (p < 0.001), serum 25-hydroxyvitamin D [25(OH)D] increased by 17% (p < 0.001), and PTH decreased by 11% (p = 0.049)., Conclusions: These results provide evidence of a modest synergy in healthy older women from nutritionally relevant intakes of vitamin K(1) together with supplements of calcium plus moderate vitamin D(3) to enhance BMC at the ultradistal radius, a site consisting of principally trabecular bone. The substantial increase in gamma-carboxylation of osteocalcin by vitamin K may have long-term benefits and is potentially achievable by increased dietary intakes of vitamin K rather than by supplementation.

Background: Chromosome 11q has not only been found to contain mutations responsible for the several Mendelian disorders of the skeleton, but it has also been linked to bone mineral density (BMD) variation in several genome-wide linkage studies. Furthermore, quantitative trait loci (QTL) affecting BMD in inbred mice and baboons have been mapped to a region syntenic to human chromosome 11q. The aim of the present study is to determine whether there is a QTL for BMD variation on chromosome 11q in the Chinese population., Methods: Nineteen microsatellite markers were genotyped for a 75 cM region on 11q13-25 in 306 Chinese families with 1,459 subjects. BMD (g/cm(2)) was measured by DXA. Linkage analyses were performed using the variance component linkage analysis method implemented in Merlin software., Results: For women, a maximum LOD score of 1.62 was achieved at 90.8 cM on 11q21 near the marker D11S4175 for femoral neck BMD; LOD scores greater than 1.0 were observed on 11q13 for trochanter BMD. For men, a maximum LOD score of 1.57 was achieved at 135.8 cM on 11q24 near the marker D11S4126 for total hip BMD., Conclusion: We have not only replicated the previous linkage finding on chromosome 11q but also identified two sex-specific QTL that contribute to BMD variation in Chinese women and men., (Copyright (c) 2006 S. Karger AG, Basel)

Although limb development has been a subject of intense research over the last decades, development of the girdles has been poorly investigated. Particularly, a detailed analysis of pelvic girdle development including functional data is not available to date. Here, we describe the early steps of the formation of mesenchymal and cartilaginous anlagen of the pelvic elements using alcian blue staining in whole mount embryos and serial histological sections, and the expression pattern of several marker genes to provide an operative basis for further research in pelvis development. Moreover, we describe pelvis development after unilateral hindlimb bud amputation and somatopleural ectoderm extirpation. We show for the first time, that ectodermal signals at pre-limb bud stages are required for pelvis formation. We present evidence suggesting that the regulation of ilium development is different from the development of ischium and pubis.

Objective: To determine the effect of raloxifene hydrochloride (RLX) on the lumbar spine and total hip bone mineral density (BMD), bone metabolism and serum lipids in Chinese postmenopausal women with osteoporosis., Methods: 204 Chinese postmenopausal women with osteoporosis from 3 hospitals in Beijing and Shanghai were randomly divided into 2 groups of 102 women: RLX group (RLX of the dosage of 60 mg/day was given for 12 months) and placebo group. In addition, 500 mg of elemental calcium and 200 units of vitamin D were given daily to all women. BMD, serum bone markers and lipids were measured before and after drug administration. The BMD of lumber spine and hip was measured by dual-energy X-ray absorptiometry (DEXA). Serum bone gamma-carboxyglutamic acid-containing protein (BGP) and C-teloppeptide were analyzed by one-step ELISA. Serum lipids were measured by enzymatic method., Results: By the end of the 12-month study period, the lumbar spine BMD was increased by 3.3% +/- 4.8% in the RLX group and 1.0% +/- 4.9% in the placebo group (P < 0.001); the hip BMD was increased by 1.4% +/- 4.8%in the RLX group and decreased by 0.9% +/- 5.0% in the placebo group (P < 0.01). New vertebral fracture occurred in none of the subjects in the RLX group and in 5 subjects of the placebo group (P = 0.059). The serum BGP and CTX decreased by 41.7% and 61.5% respectively in the RLX group, both significantly more than those in the placebo group (10.6% and 35.6% respectively, both P < 0.001). Both the total cholesterol and low-density lipoprotein cholesterol were significantly lower in the RLX group than in the placebo group (both P < 0.001), however, there were no significant differences in high-density lipoprotein cholesterol and triglycerides between these two groups. One subject in the RLX group and 5 subjects in the placebo group discontinued the study due to adverse events. There were no differences in the number of subjects with hot flushes (3 in the RLX group and 1 in the placebo group) and the number of subjects with leg cramps (9 in the RLX group and 4 in the placebo group). No venous thromboembolic event was reported., Conclusion: RLX of the dosage of 60 mg/day for 12 months significantly increases the lumbar spine and total hip bone BMD, significantly decreases bone turnover and has favorable effects on serum lipids in Chinese postmenopausal women with osteoporosis.

Our previous studies show that chronic administration of L-arginine decreases cyclosporin-A-induced bone loss. The present study was designed to investigate whether a soy diet could prevent cyclosporin A-induced osteopenia and eventually improve the protective effect of L-arginine. Rats on soy diet were treated with cyclosporin-A, L-arginine, cyclosporin-A + L-arginine or saline. Control groups received a normal diet and the same pharmacological treatment. Our results show that a soy diet prevents osteopenia only in the spinal cord (+30%) and confirm the protective effect of L-arginine in cyclosporin-A-induced osteopenia in whole body, pelvis and spine of rats on a normal diet (+31%, +55%, +55%, respectively). Moreover these data show that the osteoprotective effect of L-arginine in the whole body, pelvis and spine improves in the case of soy diet (+60%, +72%, +89%, respectively). The results suggest that a soy diet exerts a positive effect in cyclosporin-A-induced osteopenia only in sites with high turn-over and improves the osteoprotective effect of L-arginine.

Background: Thiazide may have beneficial effects on bone mineral density and may reduce risk for hip fracture. However, the existence of a causal role remains uncertain because experimental evidence is limited., Objective: To determine the effect of hydrochlorothiazide on rates of bone loss in older adults., Design: Randomized, double-blind, placebo-controlled trial with 3-year follow-up., Setting: A large health maintenance organization in western Washington State., Participants: 320 healthy, normotensive adults (205 women, 115 men) 60 to 79 years of age., Intervention: Random assignment to one of three study groups: 12.5 mg of hydrochlorothiazide per day, 25 mg of hydrochlorothiazide per day, or placebo., Measurements: Bone mineral density using dual-energy x-ray absorptiometry at the total hip, posterior-anterior spine, and total body; blood and urine markers of bone metabolism; incident falls, clinical fractures, and radiographic vertebral fractures., Results: 309 of 320 participants completed the 36-month visit (97%). Adherence to study medication throughout follow-up was high in all participants (81.6% to 89.7%) except men in the high-dose hydrochlorothiazide group (60.5%). According to intention-to-treat analysis, the 36-month differences in percentage change in total hip bone mineral density were 0.79 percentage point (95% CI, -0.12 to 1.71) for the 12.5-mg hydrochlorothiazide group and 0.92 percentage point (CI, -0.001 to 1.85) for the 25-mg group compared with placebo (P = 0.03). Percentage change at the posterior-anterior spine was significantly greater for the 25-mg hydrochlorothiazide group at 6 months (intergroup difference, 1.04 percentage points [CI, 0.22 to 1.86]) compared with placebo (P = 0.005); at 36 months, this difference was 0.82 percentage point (CI, -0.36 to 2.01; P = 0.12). No significant differences were seen in total-body bone mineral density between the treatment groups. Treatment effects were stronger in women than in men., Conclusions: In healthy older adults, low-dose hydrochlorothiazide preserves bone mineral density at the hip and spine. The modest effects observed over 3 years, if accumulated over 10 to 20 years, may explain the one-third reduction in risk for hip fracture associated with thiazide in many epidemiologic studies.

Physician awareness of the risk of osteoporosis and subsequent fractures in a patient with a history of long-term steroid treatment is high. The tendency to assume that a fracture is owing to steroid-induced osteoporosis may result in an unnecessarily intense antiresorptive treatment regimen for a patient who may not have osteoporosis. I report here about a patient with rheumatoid arthritis who presented with bone fracture despite antiresorptive therapy and without evidence of osteoporosis by bone mineral density testing.

Rats and humans respond to intermittent treatment with parathyroid hormone (PTH) with increased bone density and cancellous bone volume. In the rat, osteoblast expression of insulin-like growth factor-I (IGF-I) is elevated by intermittent PTH. We examined the effect of continuous infusion of rhPTH(1-84), a bone catabolic regime, on the IGF system in rat pelvis. Female Sprague-Dawley rats (12 weeks, 250 g) were randomly assigned to receive 0, 0.1, 1, or 5 microg/100 g body weight (b.w.) rhPTH(1-84) (0, 0.106, 1.06, or 5.305 nmol/kg) in vehicle (1% normal rat serum in saline) delivered by subcutaneous Alzet minipump. After 7 days, blood was taken for serum chemistry and pelvises were processed for immunocytochemistry. Sections of pelvis from rats continuously infused with 0.1 or 1 microg/100 g b.w. rhPTH(1-84) for 7 days did not differ significantly from those of the vehicle-treated controls. However, continuous infusion of 5 microg/100 g b.w. rhPTH(1-84) resulted in a dramatic increase in cellular development, with trabeculae surrounded by many layers of large, plump osteoblasts. All pelvis osteoblasts expressed osteocalcin, but only those from rats that received 0, 0.1, or 1 microg/100 g b.w. rhPTH(1-84) showed positive staining for IGF-I. The extra-abundant osteoblasts from rats that received 5 microg/100 g b.w. rhPTH(1-84) did not stain for IGF-I. However, although all osteoblasts stained positively for IGF binding proteins (IGFBPs)-3, -4, and -5, staining for these IGFBPs increased as the dose of rhPTH(1-84) (and osteoblast number) increased. These results suggest that continuous infusion of PTH has a direct effect on osteoblast development (either recruitment or proliferation), decreases the expression of IGF-I, and enhances the expression of IGFBPs in pelvis, factors which may interact to bring about negative bone balance.

We assessed the changes in regional bone mineral density according to age and examined the relationship between various regional bone mineral densities. The study was conducted in 985 Japanese women divided into < 50-years group (n = 435) and > or = 50 years group (n = 550). The total body bone mineral density and that of the head, arm, leg, thoracic (T)-spine, lumbar (L)-spine, ribs, and pelvis were measured using dual energy x-ray absorptiometry. There was a significant generalized reduction of bone mineral density in all regions after the age of 50 years. The most marked age-related decrease was observed in the L-spine. Bone mineral densities in all regions significantly correlated to each other in both age groups, but the degree of significance varied among regions. The relationship between bone mineral density of the L-spine and that of T-spine regions was the most significant in both groups. In the < 50-years group, the correlation between bone mineral density of the pelvis and that of L-spine and T-spine was the highest, followed by that between the pelvis and the leg. On the other hand, in the > or = 50-years group, the correlation between bone mineral density of the pelvis and that of the leg was the highest, but not the L-spine or T-spine. Since spine measurements are affected by vertebral deformity and/or aortic calcification, our findings suggest the pelvis may be a useful region for screening measurements of bone mineral density, especially in older women.

This laboratory has purified a unique insulin-like growth factor binding protein (IGFBP-4) that was previously demonstrated to be inhibitory to bone cell proliferation. In this study, the hypothesis that IGFBP-4 is inhibitory to insulin-like growth factor (IGF) actions on cartilage was tested using the pelvic cartilages of 10-day-old chick embryos as an in vitro model system. Pelvic leaflets were incubated in serum-free medium for 18 h with effectors (BSA, IGF-I, IGF-II, IGFBP-4, or a combination of IGF and IGFBP-4). After the first 8 h, 1.5 microCi [3H]thymidine per well was added. Cartilage growth was assayed by TCA-insoluble [3H]thymidine incorporation into DNA. Additional experiments were conducted under similar conditions to assess the actions of the effectors on cartilage dry weight over a 72 h time period. In separate experiments, serum-free medium conditioned by chick pelvic cartilages for 72 h was assayed for IGF-II by radioreceptorassay, IGF-I by radioimmunoassay, and IGFBP by western ligand analysis. Exogenous IGF addition increased [3H]thymidine incorporation and dry weight of cartilages compared to controls. IGFBP-4 decreased both parameters in basal cartilage growth and also inhibited IGF-mediated cartilage growth. Pelvic cartilages secreted in vitro both IGF-I and IGF-II and a 32-34 kD IGFBP. In conclusion, the IGFs are stimulatory to cartilage growth in vitro and embryonic chick cartilage in vitro produces both IGF-I and II as well as an IGFBP.(ABSTRACT TRUNCATED AT 250 WORDS)

Bibliographic references seem very controversial regarding the most appropriate anatomical area for bone mass estimation. Since some overlapping in the different bone mass measurements among normal and osteoporotic females has been observed, we have studied the bone mineral content of the pelvic bone through DEXA, and have correlated it with the total body bone mineral content, a highly discriminating measure, in order to observe whether pelvic bone mineral may be a useful measure in bone mass assessment. Pelvic and total body bone mineral values did not decrease until menopause in 104 normal premenopausal females aged 20 to 49 years. On the other hand, these values decreased in normal postmenopausal women (n = 44) aged 50 to 65 years (p < 0.001), with a 16% pelvic bone mineral content and an 11% total body bone mineral content decrease. Osteoporotic females (n = 30), showed lower values for both levels than normal postmenopausal ones (p < 0.001), with a 54% pelvic and a 24% total decrease. A 15% overlap was observed when pelvic values between normal postmenopausal and osteoporotic females were compared. The greater percentage decrease in pelvic BMC compared to total body bone mineral content and the lower overlap observed suggest that the pelvis may be an ideal anatomical area for bone mass evaluations.