Bone Turnover and Metabolism in Patients with Early Multiple Sclerosis and Prevalent Bone Mass Deficit: A Population-Based Case-Control Study

Background

Low bone mass is prevalent in ambulatory multiple sclerosis (MS) patients even shortly after clinical onset. The mechanism is not known, but could involve shared etiological risk factors between MS and low bone mass such as hypovitaminosis D operating before disease onset, or increased bone loss after disease onset. The aim of this study was to explore the mechanism of the low bone mass in early-stage MS patients.

Methodology/Principal Findings

We performed a population-based case-control study comparing bone turnover (cross-linked N-terminal telopeptide of type 1 collagen; NTX, bone alkaline phosphatase; bALP), metabolism (25-hydroxy- and 1, 25-dihydroxyvitamin D, calcium, phosphate, and parathyroid hormone), and relevant lifestyle factors in 99 patients newly diagnosed with clinically isolated syndrome (CIS) or MS, and in 159 age, sex, and ethnicity matched controls. After adjustment for possible confounders, there were no significant differences in NTX (mean 3.3; 95% CI −6.9, 13.5; p = 0.519), bALP (mean 1.6; 95% CI −0.2, 3.5; p = 0.081), or in any of the parameters related to bone metabolism in patients compared to controls. The markers of bone turnover and metabolism were not significantly correlated with bone mass density, or associated with the presence of osteoporosis or osteopenia within or between the patient and control groups. Intake of vitamin D and calcium, reported UV exposure, and physical activity did not differ significantly.

Conclusions/Significance

Bone turnover and metabolism did not differ significantly in CIS and MS patients with prevalent low bone mass compared to controls. These findings indicate that the bone deficit in patients newly diagnosed with MS and CIS is not caused by recent acceleration of bone loss, and are compatible with shared etiological factors between MS and low bone mass.     

Correlation Between Bone Markers and Bone Mineral Density in Postmenopausal Women with Osteoporosis

ObjectiveTo study the relationship between bone markers and bone mineral density (BMD) in an effort to identify their utility in postmenopausal women with osteoporosis.MethodsEighty-two consecutive postmenopausal women with untreated osteoporosis were included in the study. Forearm, spinal, and femoral BMD by dual-energy x-ray absorptiometry and markers of bone formation (serum osteocalcin and bone-specific alkaline phosphatase) and bone resorption (urinary free deoxypyridinoline) were measured in all patients. Patients with low serum vitamin D levels, secondary osteoporosis, or clinically significant systemic disease were excluded from the study. The patients were classified on the basis of BMD of the lumbar spine into the following 3 groups: mild (n = 23) (T score -2.5 through -3), moderate (n = 42) (T score -3.1 through -4), or severe (n = 17) (T score ≤-4.1) osteoporosis. One-way analysis of variance and Pearson correlation were used for statistical analysis, with a P value < .05 being considered significant.ResultsSerum osteocalcin was significantly different among the 3 study groups (4.1 ± 2.7, 4.5 ± 3.1, and 6.7 ± 5.6 ng/mL, respectively; P = .0349) and had a significant negative correlation with BMD (r² = -0.0779; P = .0168). Other bone markers such as bone-specific alkaline phosphatase and urinary free deoxypyridinoline did not correlate with the underlying BMD.ConclusionIn our study, osteocalcin was significantly correlated with BMD in postmenopausal women with osteoporosis. Other bone markers did not correlate with BMD. Further large-scale population data and analyses are needed to confirm these findings. (Endocr Pract. 2008;14:1102-1107)     

Characteristics of Bone Turnover in the Long Bone Metaphysis Fractured Patients with Normal or Low Bone Mineral Density (BMD)

The incidence of osteoporotic fractures increases as our population ages. Until now, the exact biochemical processes that occur during the healing of metaphyseal fractures remain unclear. Diagnostic instruments that allow a dynamic insight into the fracture healing process are as yet unavailable. In the present matched pair analysis, we study the time course of the osteoanabolic markers bone specific alkaline phosphatase (BAP) and transforming growth factor β1 (TGFβ1), as well as the osteocatabolic markers crosslinked C-telopeptide of type-I-collagen (β-CTX) and serum band 5 tartrate-resistant acid phosphatase (TRAP5b), during the healing of fractures that have a low level of bone mineral density (BMD) compared with fractures that have a normal BMD. Between March 2007 and February 2009, 30 patients aged older than 50 years who suffered a metaphyseal fracture were included in our study. BMDs were verified by dual energy Xray absorptiometry (DXEA) scans. The levels of BTMs were examined over an 8-week period. Osteoanabolic BAP levels in those with low levels of BMD were significantly different from the BAP levels in those with normal BMD. BAP levels in the former group increased constantly, whereas the latter group showed an initial strong decrease in BAP followed by slowly rising values. Osteocatabolic β-CTX increased in the bone of the normal BMD group constantly, whereas these levels decreased significantly in the bone of the group with low BMD from the first week. TRAP5b was significantly reduced in the low level BMD group. With this work, we conduct first insights into the molecular biology of the fracture healing process in patients with low levels of BMD that explains the mechanism of its fracture healing. The results may be one reason for the reduced healing qualities in bones with low BMD.     

股骨近端三维有限元模型评价髋部骨折患者骨密度

目的：探究骨密度与老年髋部骨折股骨近端三维有限元模型密度的关系。方法：选取8 例老年髋部骨折,其中4 例股骨颈骨 折,4 例股骨转子间骨折;左侧肢体3 例,右侧肢体5 例。分别测定腰椎骨密度和双侧髋关节CT 资料,运用Mimics软件和abaqus 软件对健侧股骨近端进行重建和计算出该模型的密度。结果：股骨转子间骨折组腰椎骨密度为(-4.05± 0.24) g/cm2,三维有限元模 型密度为[(1.15± 0.02)× 106],均低于股骨颈骨折组的(-3.15± 0.54) g/cm2,[(1.34± 0.06)× 106],两组比较差异均有统计学意义（均 P<0.05）。腰椎的骨密度与三维有限元模型密度成线性正相关（r=0.881,P=0.004）。结论：骨密度与老年髋部骨折股骨近端三维有限 元模型密度成线性正相关的关系,可为进一步用有限元分析法探讨老年髋部骨折部位与骨密度的关系提供理论依据。     

Relationship between Body Mass Composition,Bone Mineral Density,Skin Fibrosis and 25(OH) Vitamin D Serum Levels in Systemic Sclerosis

A reduced bone mineral density (BMD) is observed in several rheumatic autoimmune diseases, including Systemic Sclerosis (SSc); nevertheless, data concerning the possible determinants of bone loss in this disease are not fully investigated. The aim of this study is to evaluate the relationship between BMD, body mass composition, skin sclerosis and serum Vitamin D levels in two subsets of SSc patients. 64 post-menopausal SSc patients, classified as limited cutaneous (lcSSc) or diffuse cutaneous (dcSSc) SSc, were studied. As control, 35 healthy post-menopausal women were recruited. Clinical parameters were evaluated, including the extent of skin involvement. BMD at lumbar spine, hip, femoral neck and body mass composition were determined by dual-energy X-ray absorptiometry. Serum calcium, phosphorus, alkaline phosphatase, urine pyridinium cross-links, intact parathyroid hormone and 25-hydroxyvitamin D (25OHD) were measured. BMD at spine, femoral neck and total hip was significantly lower in SSc patients compared to controls. In dcSSc subset, BMD at spine, femoral neck and total hip was significantly lower compared to lcSSc. No differences in both fat and lean mass were found in the three study groups even if patients with dcSSc showed a slightly lower total body mass compared to healthy controls. Total mineral content was significantly reduced in dSSc compared to both healthy subjects and lcSSc group. Hypovitaminosis D was observed both in healthy post-menopausal women and in SSc patients, but 25OHD levels were significantly lower in dcSSc compared to lcSSc and inversely correlated with the extent of skin thickness. These results support the hypothesis that the extent of skin involvement in SSc patients could be an important factor in determining low circulating levels of 25OHD, which in turn could play a significant role in the reduction of BMD and total mineral content.     

Bone Mineral Density Measurements,Bone Markers and Serum Vitamin D Concentrations in Men with Chronic Non-Cirrhotic Untreated Hepatitis C

Introduction

The high prevalence of chronic hepatitis C (CHC) and its consequent cirrhosis has been associated with bone fragility. Whether CHC may cause bone and mineral abnormalities in the absence of hepatocellular dysfunction is still unknown. In this study we aimed to determine the prevalence of osteoporotic vertebral fractures and low BMD measurements in men with non-cirrhotic CHC. Risk factors for low BMD and fractures were also investigated.

Methods

Morphometric vertebral fractures and BMD measurements were performed in 60 non-cirrhotic untreated men with CHC and 59 healthy controls, matched for age and gender, weight and current smoking. Serum CTx, calcium, phosphate, intact PTH, alkaline phosphatase and vitamin D (25OHD) concentrations were measured in all participants. Clinical risk factors for low BMD and fractures were evaluated by a structured questionnaire as well as details regarding HCV infection.

Results

Trochanter and total femur BMD were significantly lower in CHC patients as compared to healthy men (p = 0.04). In men 50 years and older, the prevalence of osteoporosis was significantly higher among CHC patients (p = 0.01). Lower levels of physical activities and more often report of prolonged immobilization were observed among CHC patients (p<0.05). Liver inflammation and fibrosis, viral load and genotype did not correlate with BMD measurements. Bone markers and 25OHD concentrations were similar in both groups. Only a few vertebral fractures were observed.

Conclusions

Our results demonstrate that non-cirrhotic untreated CHC patients have lower BMD at the femur as compared to healthy men in spite of the absence of significant bone and mineral abnormalities.     

Association of JAG1 with Bone Mineral Density and Osteoporotic Fractures: A Genome-wide Association Study and Follow-up Replication Studies

Bone mineral density (BMD), a diagnostic parameter for osteoporosis and a clinical predictor of fracture, is a polygenic trait with high heritability. To identify genetic variants that influence BMD in different ethnic groups, we performed a genome-wide association study (GWAS) on 800 unrelated Southern Chinese women with extreme BMD and carried out follow-up replication studies in six independent study populations of European descent and Asian populations including 18,098 subjects. In the meta-analysis, rs2273061 of the Jagged1 (JAG1) gene was associated with high BMD (p = 5.27 × 10⁻⁸ for lumbar spine [LS] and p = 4.15 × 10⁻⁵ for femoral neck [FN], n = 18,898). This SNP was further found to be associated with the low risk of osteoporotic fracture (p = 0.009, OR = 0.7, 95% CI 0.57–0.93, n = 1881). Region-wide and haplotype analysis showed that the strongest association evidence was from the linkage disequilibrium block 5, which included rs2273061 of the JAG1 gene (p = 8.52 × 10⁻⁹ for LS and 3.47 × 10⁻⁵ at FN). To assess the function of identified variants, an electrophoretic mobility shift assay demonstrated the binding of c-Myc to the “G” but not “A” allele of rs2273061. A mRNA expression study in both human bone-derived cells and peripheral blood mononuclear cells confirmed association of the high BMD-related allele G of rs2273061 with higher JAG1 expression. Our results identify the JAG1 gene as a candidate for BMD regulation in different ethnic groups, and it is a potential key factor for fracture pathogenesis.     

Multiple Sclerosis and CCSVI: A Population-Based Case Control Study

Background

Chronic cerebrospinal venous insufficiency (CCSVI) has been associated to multiple sclerosis (MS).

Objective

To evaluate the possible association between CCSVI and MS, using a population-based control design.

Methods

A random cohort of 148 incident MS patients were enrolled in the study. We have also studied 20 patients with clinically isolated syndrome (CIS), 40 patients with other neurological diseases (OND), and 172 healthy controls. Transcranial (TCC) and Echo Color Doppler (ECD) were carried out in 380 subjects. A subject was considered CCSVI positive if ≥2 venous hemodynamic criteria were fulfilled.

Results

CCSVI was present in 28 (18.9%) of the MS patients, in 2 (10%) of CIS patients, in 11 (6.4%) of the controls, and in 2 (5%) of the OND patients. A significant association between MS and CCSVI was found with an odds ratio of 3.41 (95% confidence interval 1.63–7.13; p = 0.001). CCSVI was significantly more frequent among MS subjects with a disease duration longer than 144 months (26.1% versus 12.6% of patients with duration shorter than 144 months; p = 0.03) and among patients with secondary progressive (SP) and primary progressive (PP) forms (30.2% and 29.4, respectively) than in patients with relapsing remitting (RR) MS (14.3%). A stronger association was found considering SP and PP forms (age adjusted OR = 4.7; 95% CI 1.83–12.0, p = 0.001); the association was weaker with the RR patients (age adjusted OR = 2.58; 95%CI 1.12–5.92; p = 0.02) or not significant in CIS group (age adjusted OR = 2.04; 95%CI 0.40–10.3; p = 0.4).

Conclusions

A higher frequency of CCSVI has been found in MS patients; it was more evident in patients with advanced MS, suggesting that CCSVI could be related to MS disability.     

Plasma Copper and Bone Mineral Density in Osteopenia: An Indicator of Bone Mineral Density in Osteopenic Females

Copper concentrations in blood plasma have been determined in 25 osteopenic females using inductively coupled plasma–mass spectrometry. A high degree of correlations has been demonstrated between the copper concentrations in plasma and the bone mineral density of the lumbar spine as measured using dual energy X-ray absorptiometry and quantitative computerized tomography. Results clearly indicate the involvement of copper in bone health and osteopenia. It is further suggested that plasma copper might be useful as a cheap and simple method indicative of bone mineral density in osteopenic postmenopausal females.     

Relationship between Bone Mineral Density and Serum Osteoprotegerin in Patients with Chronic Heart Failure

Purpose

Heart failure (HF) had been reported with increased risk of hip fractures. However, the relationship between circulating biomarkers and bone mineral density (BMD) in chronic HF remained unclear.

Methods

This is a cross-sectional study which recruited stable chronic HF from registry of the Heart Failure Center of National Taiwan University Hospital. Patients underwent dual-energy x-ray absorptiometry (DEXA) measurements at hip and lumbar spines and biochemical assessments including B-type natriuretic peptide (BNP-32), myostatin, follistatin and osteoprotegerin (OPG).

Results

A total of 115 stable chronic HF individuals with left ventricular ejection fraction (EF) <45% (74% of male, mean age at 59) were recruited with 24 patients in NYHA class I, 73 patients in NYHA class II and 18 patients in NYHA class III. Results of BMD showed that Z scores of hip in NYHA III group (−0.12±1.15) was significantly lower than who were NYHA II (0.58±1.04). Serum OPG was significantly higher in subjects of NYHA III (9.3±4.6 pmol/l) than NYHA II (7.4±2.8 pmol/l) or NYHA I (6.8±3.6 pmol/l) groups. There’s a significant negative association between log transformed serum OPG and trochanteric BMD (R = −0.299, P = 0.001), which remained significant after multivariate analysis.

Conclusions

Our study demonstrated an inverse association between serum OPG and trochanteric BMD in patients with HF. OPG may be a predictor of BMD and an alternative to DEXA for identifying at risk HF patients for osteoporosis.     

Decreased Bone Mineral Density in Adults Born with Very Low Birth Weight: A Cohort Study

Background

Very-low-birth-weight (VLBW, <1,500 g) infants have compromised bone mass accrual during childhood, but it is unclear whether this results in subnormal peak bone mass and increased risk of impaired skeletal health in adulthood. We hypothesized that VLBW is associated with reduced bone mineral density (BMD) in adulthood.

Methods and Findings

The Helsinki Study of Very Low Birth Weight Adults is a multidisciplinary cohort study representative of all VLBW births within the larger Helsinki area from 1978 to 1985. This study evaluated skeletal health in 144 such participants (all born preterm, mean gestational age 29.3 wk, birth weight 1,127 g, birth weight Z score 1.3), and in 139 comparison participants born at term, matched for sex, age, and birth hospital. BMD was measured by dual energy X-ray absorptiometry at age 18.5 to 27.1 y. Adults born with VLBW had, in comparison to participants born at term, a 0.51-unit (95% confidence interval [CI] 0.28–0.75) lower lumbar spine Z score and a 0.56-unit (95% CI 0.34–0.78) lower femoral neck Z score for areal BMD. These differences remained statistically significant after adjustment for the VLBW adults'' shorter height and lower self-reported exercise intensity.

Conclusions

Young adults born with VLBW, when studied close to the age of peak bone mass, have significantly lower BMD than do their term-born peers. This suggests that compromised childhood bone mass accrual in preterm VLBW children translates into increased risk for osteoporosis in adulthood, warranting vigilance in osteoporosis prevention. Please see later in the article for the Editors'' Summary     

藏红花提取液对去卵巢大鼠骨密度及骨代谢生化指标的影响

目的：研究中药藏红花提取液对去卵巢大鼠股骨骨密度及血清骨代谢生化指标的影响。方法：选用48只4月龄SD雌性大鼠,随机分为6组：假手术组、模型组、戊酸雌二醇组、藏红花低、中、高剂量组。术后4周各组分别给予相应制剂灌胃,术后12周处死,分别测定股骨骨密度、子宫指数、雌二醇、血钙、血磷、碱性磷酸酶。结果：与模型组相比,藏红花各剂量组股骨骨密度明显升高（p〈0.01）,雌二醇测定值升高（p〈0.01）,碱性磷酸酶显著降低（p〈0.01）,血钙及血磷无统计学差异（p〉0.05）;与戊酸雌二醇组比较,藏红花各剂量组子宫指数显著降低（p〈0.01）。结论：藏红花提取液有助于抑制去卵巢大鼠骨量的丢失,改善骨代谢,对骨质疏松症具有防治作用。     

藏红花提取液对去卵巢大鼠骨密度及骨代谢生化指标的影响

目的:研究中药藏红花提取液对去卵巢大鼠股骨骨密度及血清骨代谢生化指标的影响。方法:选用48只4月龄SD雌性大鼠,随机分为6组:假手术组、模型组、戊酸雌二醇组、藏红花低、中、高剂量组。术后4周各组分别给予相应制剂灌胃,术后12周处死,分别测定股骨骨密度、子宫指数、雌二醇、血钙、血磷、碱性磷酸酶。结果:与模型组相比,藏红花各剂量组股骨骨密度明显升高(p<0.01),雌二醇测定值升高(p<0.01),碱性磷酸酶显著降低(p<0.01),血钙及血磷无统计学差异(p>0.05);与戊酸雌二醇组比较,藏红花各剂量组子宫指数显著降低(p<0.01)。结论:藏红花提取液有助于抑制去卵巢大鼠骨量的丢失,改善骨代谢,对骨质疏松症具有防治作用。     

Status of Bone Mineral Density in Patients Selected for Cardiac Transplantation

ObjectiveTo determine the prevalence and correlates of low bone mineral density (BMD) in ambulatory outpatients with end-stage heart failure who were awaiting cardiac transplantation.MethodsFifty-five cardiac transplant candidates with end-stage heart failure were enrolled in this study. Bone mineral density at the lumbar spine and proximal femur was determined by dual-energy x-ray absorptiometry. Laboratory studies included serum alkaline phosphatase, calcium, intact parathyroid hormone, and 25-hydroxyvitamin D.ResultsThe mean proximal femur and lumbar spine Z scores were 0.3 ± 1.1 and 0.3 ± 1.5, respectively. The mean BMD was not lower than that of the age- and sex- matched reference population. Z scores were less than -1 in 23% at the lumbar spine and 15% at the proximal femoral neck. On the basis of T scores, osteopenia (T scores between -1 and -2.5) was present in 24% (confidence interval, 13% to 35%) of patients at the lumbar spine and in 20% (confidence interval, 10% to 30%) at the proximal femur; osteoporosis (T scores of less than -2.5) was present in 4% of the study population. Half of the patients in this study sample had elevated intact parathyroid hormone levels, and a third of the patients had low 25-hydroxyvitamin D levels.ConclusionLumbar spine and hip BMD measurements were not significantly low relative to age and sex in ambulatory patients with heart failure awaiting cardiac transplantation. (Endocr Pract. 2008;14:704-712)     

The Local Complement Activation on Vascular Bed of Patients with Systemic Sclerosis: A Hypothesis-Generating Study

ObjectiveThe role of complement system in the pathogenesis of systemic sclerosis (SSc) has been debated during the last decade but an evident implication in this disease has never been found. We carried out an explorative study on SSc patients to evaluate the expression of soluble and local C5b-9 complement complex and its relation with a complement regulator, the Membrane Cofactor Protein (MCP, CD46) on skin vascular bed as target distinctive of SSc disease. We also analyzed two polymorphic variants in the complement activation gene cluster involving the MCP region.MethodsC5b-9 plasma levels of SSc patients and healthy subjects were analyzed by ELISA assay. Archival skin biopsies of SSc patients and controls were subjected to immunofluorescence analysis to detect C5b-9 and MCP on vascular endothelial cells. The expression of MCP was validated by immunoblot analysis with specific antibody. Polymorphic variants in the MCP gene promoter were tested by a quantitative PCR technique-based allelic discrimination method.ResultsEven though circulating levels of C5b-9 did not differ between SSc and controls, C5b-9 deposition was detected in skin biopsies of SSc patients but not in healthy subjects. MCP was significantly lower in skin vessels of SSc patients than in healthy controls and was associated with the over-expression of two polymorphic variants in the MCP gene promoter, which has been related to more aggressive phenotypes in other immune-mediated diseases.ConclusionsOur results firsty document the local complement activation with an abnormal expression of MCP in skin vessels of SSc patients, suggesting that a subset of SSc patients might be exposed to more severe organ complications and clinical evolution due to abnormal local complement activation.     

Diabetic Polyneuropathy Relates to Bone Metabolism and Markers of Bone Turnover in Elderly Patients With Type 2 Diabetes: Greater Effects in Male Patients

BackgroundThere is evidence that diabetic polyneuropathy (PNP) is associated with reduced bone mineral density (BMD) in type 1 diabetes but little is known about the impact of diabetic PNP on bone metabolism in type 2 diabetes.ObjectivesThe aim of this study was to evaluate differences in bone metabolism by measuring markers of bone turnover and BMD in men and postmenopausal women with type 2 diabetes and diabetic PNP compared with those without PNP. Gender differences were analyzed for both groups of patients.MethodsOne hundred twenty patients with type 2 diabetes, 68 without PNP (43 men, 25 women, mean age 62 [8] years) and 52 with PNP (28 men, 24 women, mean age 64 [8] years) were studied. Clinical parameters with bone turnover biomarkers such as osteocalcin, bone alkaline phosphatase, procollagen type 1 amino-terminal propeptide, and carboxy-terminal telopeptide of type 1 collagen were measured in all patients. Dual energy x-ray absorptiometry to evaluate BMD was performed in a subgroup of patients.ResultsAfter controlling for age, body mass index, duration of diabetes, smoking, glycosylated hemoglobin, homeostasis model assessment index for insulin resistance, serum C-reactive protein, creatinine, calcium, gamma-glutamyltransferase, parathyroid and sex hormones levels, presence of micro/macrovascular complications, statin- as well as diabetes-related therapies, levels of carboxy-terminal telopeptide of type 1 collagen and procollagen type 1 amino-terminal propeptide were significantly higher among patients with PNP when compared with patients without PNP (P = 0.01 and P = 0.03, respectively). Differences in bone biomarkers were more pronounced among men with diabetes. BMD did not differ significantly between patients with and without PNP, independent of gender.ConclusionsMale patients with PNP exhibit a higher rate of bone turnover than men without PNP. High rate of bone turnover increases the susceptibility for developing osteoporosis. Prevention of diabetic PNP might also reduce the incidence of osteoporosis and fractures in patients with type 2 diabetes.     

Bone Mineral Density in Patients with Nonalcoholic Steatohepatitis among End-Stage Liver Disease Patients Awaiting Liver Transplantation

ObjectiveSeveral studies have shown that patients with end-stage liver disease (ESLD) have lower bone mineral density (BMD) and a higher prevalence of osteoporosis compared to an age-matched population. Hyperinsulinemia and insulin resistance are typically associated with increased BMD. We hypothesized that patients with nonalcoholic steatohepatitis (NASH) and underlying insulin resistance may have higher BMD than patients with cirrhosis from other causes.MethodsWe performed a retrospective chart review of patients with ESLD who underwent liver transplant evaluation at Ochsner Clinic Foundation and had a BMD study as part of initial work up and compared BMD values of patients diagnosed with NASH to patients with cirrhosis due to other causes. Patients were categorized into 3 groups based on the etiology of their liver disease as NASH, alcoholic cirrhosis, or viral hepatitis C or B (HCV/ HBV).ResultsA total of 63 patients met the study inclusion criteria, including 15 with NASH, 17 with alcoholic cirrhosis, and 31 with HCV/HBV. The overall prevalence rates of osteopenia and osteoporosis were 44% and 12%, respectively. BMD values were higher in the NASH group than the HCV/HBV group at lumbar spine, total hip, and femoral neck (P = .01, .03, and .02, respectively). There were no statistical differences in BMD values between NASH and alcoholic cirrhosis groups at any site.ConclusionsWe found a high prevalence of low BMD among patients with ESLD awaiting liver transplantation. NASH patients had higher BMDs than HCV/ HBV patients. The effects of NASH and insulin resistance on bone are complex and should be examined further. (Endocr Pract. 2013;19:414-419)     

Increased Nitric Oxide Production in Patients with Systemic Sclerosis

Nitric oxide (NO, nitrogen monoxide) is a messenger molecule whose synthesis can be induced by proinflammatory cytokines. Increased production of NO has been reported in various inflammatory and autoimmune diseases. We studied serum nitrite and citrulline as surrogate markers for NO production in patients with systemic sclerosis (SSc) and looked for correlation with extent of disease, disease duration, age, and systemic involvement. Thirty-four patients were studied against 20 controls. The nitrite levels were significantly higher in the disease group (1588.4 +/- 998.2 nmol/ml compared to 327.8 +/- 137.7 nmol/ml; P < 0.001). The citrulline levels of the disease group were also significantly higher (5490.1 +/- 2518.3 nmol/ml compared to 3264.5 +/- 2509.7 nmol/ml in the controls; P = 0.005). There was no significant difference among limited and diffuse subgroups. There was no significant difference in patients with or without arthritis or interstitial lung disease or with other systemic involvement. On multivariate analysis there was a trend toward a rising level of nitrite with worsening lung functions (P = 0.07). Hence, there is evidence of increased NO production in patients with SSc. There is no difference between NO levels in disease subgroups or those with systemic involvement.     

1型糖尿病患者骨密度的变化及相关因素分析(英文)

目的:观察1型糖尿病患者骨密度(bone mineral density,BMD)的变化及其影响因素。方法:采用双能X线骨密度仪测定108例1型糖尿病患者及106例非糖尿病人群腰椎1至4(L1、L2、L3、L4、、L1-4总体)及左侧髋部(股骨颈、大转子、ward's三角、股骨干及左髋总体)骨密度,同时测定受试者年龄、身高、体重、腰围、臀围,1型糖尿病患者病程、糖化血红蛋白(HbA1c)等指标,利用多元回归分析1型糖尿病患者骨密度的相关因素。结果:L1-4总体BMD和左髋总体BMD与年龄、HbA1c呈负相关,与BMI呈正相关(P0.05);左髋总体BMD与性别有关(P0.05)。结论:1型糖尿病患者BMD低于对照人群,1型糖尿病患者的性别、年龄、BMI、HbA1c水平与BMD关系密切。