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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.

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.

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.)

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.

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 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.

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.)

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.

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.

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.

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.

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.

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)

Methylene diphosphonate (MDP) was formulated as a complex of 99mTc for skeletal imaging. This agent was compared with three other bone-seeking technetium agents: ethane-1-hydroxy-1, 1-diphosphonate (EHDP), pyrophosphate, and polyphosphate. In tissue radioassay experiments in rodents, the technetium complexes of MDP and EHDP were similar, but skeletal concentration with both of these agents was higher than that with pyrophosphate or polyphosphate. The total-body retention of MDP and EHDP complexed with 95mTc was studied in beagle dogs for 35 days by excretion measurements and total-body counting and compared with polyphosphate and pertechnetate. The long-term retention was greater for MDP. The 5-day cumulative fecal excretion of 95mTc was low when administered as EHDP or polyphosphate complexes and negligible when administered as MDP complex. In six human volunteers the blood clearance of 99mTc-mdp was similar to that of 18F and significantly faster than that of 99mTc-EHDP. Pyrophosphate cleared from the blood much faster than polyphosphate but slower than the diphosphonates. The urinary excretion of the MDP complex was greater than for EHDP within the first 2-3 hr after injection. The 24-hr urinary excretion of pyrophosphate and polyphosphate complexes was not as complete as for the diphosphonates. All four 99mTc complexes proved satisfactory for clinical imaging studies. The MDP complex produced images of superior quality as early as 2 hr after administration, attributable to its more rapid clearance from the blood and soft tissues. On the contrary, a longer interval of 3-4 hr after injection was usually needed for 99mTc-EHDP; pyrophosphate and polyphosphate complexes regularly required a waiting period of 4 hr. Comparitive radiation dose estimates were made based on the available biologic distribution data for these 99mTc skeletal-localizing agents.