Context:
Diabetes mellitus is a risk factor for osteoporotic fractures. Sclerostin is an inhibitor of bone formation. However, there are no data about sclerostin levels in type 2 diabetes mellitus ...(T2DM).
Objectives:
The aims were to evaluate serum sclerostin in T2DM patients and to analyze its relationship with bone metabolism.
Design, Setting, and Patients:
This was a cross-sectional study. We compared serum sclerostin in the T2DM group (n = 74) and control group (n = 50), and we analyzed its relationship with calciotropic hormones, bone turnover markers, bone mineral density (BMD), and morphometric vertebral fractures.
Results:
Sclerostin levels were significantly higher in T2DM patients than control subjects (P < 0.001) and in T2DM males than in T2DM females (P < 0.001). Serum sclerostin was positively correlated with age in males T2DM (P = 0.031). In linear regression analysis, gender, study group, and age were predictive of sclerostin levels (P < 0.05). Sclerostin concentrations were positively associated with duration of T2DM (P = 0.064) and glycated hemoglobin (P = 0.074) independently of age in T2DM patients. Sclerostin was inversely related to bone turnover markers (P < 0.05) and positively related to lumbar spine, femoral neck, and total hip BMD (P < 0.05) in the T2DM group. Sclerostin was significantly lower in osteoporotic than nonosteoporotic patients with T2DM (P = 0.048).
Conclusions:
Circulating sclerostin is increased in T2DM independently of gender and age. Serum sclerostin is also correlated with duration of T2DM, glycated hemoglobin, bone turnover markers, and BMD in T2DM patients. Additional studies are needed to evaluate the role of sclerostin on bone metabolism in this population.
Wnt/β-catenin signaling is related to the pathogenesis of several diseases. Sclerostin is an inhibitor of Wnt/β-catenin signaling. However, there are few data regarding the sclerostin levels and ...vascular disease. Our aim was to examine the relationship between serum sclerostin and atherosclerotic disease (AD) in type 2 diabetes mellitus (T2DM).
We performed a cross-sectional study including 78 T2DM patients (45.3% females, mean age 59 ± 5.7 years; 54.7% males, 57.4 ± 6.7 years).
Serum sclerostin concentrations of T2DM patients in the AD group were significantly higher than in the non-AD group (P = 0.006). For each increase of 1 pmol/L in sclerostin level, there was a 4% increase of the risk of AD in T2DM patients. A concentration of ≥ 42.3 pmol/L showed a sensitivity of 69% and a specificity of 54.8% to detect an increased risk of AD. In males, sclerostin levels were higher in those with AD (P = 0.04), abnormal intima-media thickness (IMT) (P = 0.004), carotid plaques (P < 0.001), and aortic calcification (P < 0.001). In females, higher levels of sclerostin were related to abnormal IMT (P = 0.03) and aortic calcifications (P = 0.004). Homocysteine (β = 0.319 95% CI 0.561-2.586, P = 0.003) and IMT (β = 0.330 14.237-67.693, P = 0.003) were positively correlated with sclerostin.
Circulating sclerostin is increased in T2DM patients with atherosclerotic lesions. Although the sample size of our study was small, these data suggest that sclerostin levels could be a major modulator of Wnt signaling in AD with implications in T2DM patients.
Abstract
Context
Primary hyperparathyroidism (PHPT) has been related to bone loss. Dual-energy x-ray absorptiometry (DXA) cannot distinguish between trabecular and cortical bone compartments but the ...recently developed three-dimensional (3D)-DXA software might overcome this issue.
Objective
To examine the differences in DXA-derived areal bone mineral density (aBMD) and 3D-DXA parameters at the hip site between patients with PHPT and a healthy control group.
Design
Cross-sectional pilot study
Setting
Hospital
Patients
80 adults (59.5 ± 9.1 yrs), 40 with PHPT and 40 age- and sex-matched healthy controls.
Measures
aBMD (g/cm2) of the femoral neck, trochanter, shaft, and total hip was assessed using DXA. Cortical surface (sBMD, mg/cm2), cortical volumetric BMD (vBMD, mg/cm3), trabecular vBMD (mg/cm3), integral vBMD (mg/cm3) and cortical thickness (mm) was assessed using 3D-DXA software.
Results
Mean-adjusted values showed lower aBMD (7.5%-12.2%, effect size: 0.51-1.01) in the PHPT group compared with the control group (all P < 0.05). 3D-DXA revealed bone impairment (3.7%-8.5%, effect size: 0.47-0.65) in patients with PHPT, mainly in cortical parameters (all P < 0.05). However, differences in trabecular vBMD were not statistically significant (P = 0.055). The 3D mapping showed lower cortical sBMD, cortical vBMD, and cortical thickness at the trochanter and diaphysis in the PHPT group (P < 0.05) compared with the control group. In both groups, the presence of osteopenia or osteoporosis is related to lower cortical bone.
Conclusions
aBMD and cortical 3D parameters are impaired in patients with PHPT versus healthy controls. The vBMD of the trabecular compartment seems to be affected, although to a lesser extent.
Background/Objectives
The aetiology of frontal fibrosing alopecia is unknown, and its genetic aspect remains uncharacterised. The aim of this report is to elucidate if major histocompatibility ...complex is associated with familial frontal fibrosing alopecia.
Methods
A case–control study was performed of 13 patients with frontal fibrosing alopecia belonging to six families. Their human leukocyte antigen profiles were compared to the data of 636 healthy controls without frontal fibrosing alopecia. Patients underwent high‐resolution genomic typing for human leukocyte antigen class I and II loci by PCR‐SSO for Luminex. In addition, CYP21A2 gene (major histocompatibility complex class III) mutations were detected by PCR‐SSO on strips.
Results
61.5% of patients shared CYP21A2 gene p.V281L linked to the F16A human leukocyte antigen class I haplotype (HLA‐A*33:01; B*14:02; C*08:02; Pc < 0.000001). The patients F16A‐negative shared other human leukocyte antigen class I haplotypes: Y16A (3/13) and S26 (2/13).
Conclusion
CYP21A2 gene p.V281L mutation can be used as a genetic marker for susceptibility to familial frontal fibrosing alopecia. Both the linkage of the mutation to F16A and the fact that F16A‐negative patients share other human leukocyte antigen class I haplotype, point to an antigen‐driven mechanism in susceptible patients with these haplotypes.
Dickkopf-1 (DKK1) is a potent inhibitor of Wnt signalling, which exerts anabolic effects on bone and also takes part in the regulation of vascular cells. Our aims were to evaluate serum DKK1 in type ...2 diabetes (T2DM) patients and to analyze its relationships with cardiovascular disease (CVD). We also evaluated the relationship between DKK1 and bone metabolism.
We conducted a cross-sectional study in which we measured serum DKK1 (ELISA, Biomedica) in 126 subjects: 72 patients with T2DM and 54 non-diabetic subjects. We analysed its relationship with clinical CVD, preclinical CVD expressed as carotid intima media thickness (IMT), and bone metabolism.
T2DM patients with CVD (P = 0,026) and abnormal carotid IMT (P = 0,038) had higher DKK1 concentrations. DKK1 was related to the presence of CVD in T2DM, independently of the presence of risk factors for atherosclerosis. Therefore, for each increase of 28 pg/ml of serum DKK1 there was a 6,2% increase in the risk of CVD in T2DM patients. The ROC curve analysis to evaluate the usefulness of DKK1 as a marker for high risk of CVD showed an area under the curve of 0,667 (95% CI: 0,538-0,795; P = 0,016). In addition, there was a positive correlation between serum DKK1 and spine bone mineral density in the total sample (r = 0,183; P = 0,048).
In summary, circulating DKK1 levels are higher in T2DM with CVD and are associated with an abnormal carotid IMT in this cross-sectional study. DKK1 may be involved in vascular disease of T2DM patients.
Primary hyperparathyroidism (PHPT) is a common endocrinological process, characterized by chronic elevation of serum concentrations of calcium and parathyroid hormone (PTH). Many years ago, the most ...frequent forms of clinical presentation were symptomatic renal or skeletal disease with moderate or severe hypercalcemia; however, currently, most patients have few symptoms and mild hypercalcemia. A new form of presentation called normocalcemic PHPT has also been described but clinical consequences are not well established. The biochemical profile of PHPT is characterized by hypercalcemia and high or inappropriately normal PTH concentrations. Parathyroidectomy is the only definitive cure. Medical treatment with the calcimimetic cinacalcet has been shown to normalize calcemia in a high percentage of cases.
Previous studies of bone turnover markers in diabetes are limited, and the results are conflicting. Our aim was to evaluate differences in bone turnover markers and i-PTH between T2DM and ...non-diabetes subjects. Cross-sectional study including 133 subjects (78 T2DM, 55 without diabetes). BMD were measured by dual X-ray absorptiometry. Bone turnover markers were determined in serum. Serum levels of bone resorption markers (CTX and TRAP5b) were lower in T2DM compared with non-diabetes subjects. There were no differences in bone formation markers. i-PTH serum levels were lower in T2DM: 38.35 ± 18.20 pg/ml versus 50.22 ± 18.99 pg/ml,
P
< 0.05. TRAP5b and CTX were positively correlated with i-PTH (CTX:
r
= 0.443,
P
< 0.001; TRAP5b:
r
= 0.180,
P
= 0.047). There was an inverse relationship between TRAP5b levels and diabetes duration (
r
= −0.269,
P
= 0.021). T2DM patients have lower levels of bone resorption markers, and i-PTH compared with subjects without diabetes. Lower levels of PTH may induce a low turnover state as reflected by lower levels of bone resorption markers, and this situation may influence the higher risk of fracture of T2DM.
Several studies have reported the role of osteocalcin on glucose and fat metabolism. In this study, we analyzed the relationship between the concentration of osteocalcin and metabolic risk factors in ...healthy postmenopausal women.
Cross-sectional analyses of 54 postmenopausal women aged 56 ± 3.5 years were conducted. We recorded clinical and biochemical data of metabolic risk including fasting plasma glucose (FPG) level and evaluated the relationship between serum osteocalcin and bone formation markers.
Serum osteocalcin concentration was negatively correlated with FPG (β = -0.328, P = 0.035). When osteocalcin levels were divided into tertiles, we found significant differences in FPG between the highest and the lowest tertiles (84 ± 11 vs 98 ± 30 mg/dL, respectively; P = 0.029). We found significantly lower osteocalcin levels in women with impaired fasting glucose levels than in those with normoglycemia (10.7 ± 6.1 vs 17.1 ± 7.4 ng/mL, respectively; P = 0.006). We also found lower concentrations of osteocalcin in obese women versus nonobese women (14.4 ± 8.8 vs 17.3 ± 6.2 ng/mL; P = 0.034) and women with increased low-density lipoprotein cholesterol levels versus those with low LDL-c levels (14.1 ± 5.4 vs 18.9 ± 9.1 ng/mL; P = 0.045). A concentration of 13.5 ng/ mL or lower showed a sensitivity of 85.7% and a specificity of 63.8% to detect increased risk for diabetes (FPG ≥100 mg/dL). In contrast, serum levels of bone alkaline phosphatase did not correlate with any variable.
In this population, there is a consistent association between osteocalcin and markers of metabolic syndrome. We suggest potential usefulness of serum osteocalcin as a predictor for increased risk of diabetes in postmenopausal women.
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