Serum Sclerostin Levels Research Articles

Bone Sclerostin and Dickkopf-related protein-1 are positively correlated with bone mineral density, bone microarchitecture, and bone strength in postmenopausal osteoporosis

BackgroundWnt-catenin signaling antagonists sclerostin and dickkopf-related protein-1 (Dkk-1) inhibit bone formation and are involved in the pathogenesis of postmenopausal osteoporosis (PO). However, the association between sclerostin and Dkk-1 and bone mineral density (BMD) in women with PO remains unclear.ObjectiveThis study aimed to determine the association between sclerostin and Dkk-1 and BMD, bone microarchitecture, and bone strength in PO.MethodsTrabecular bone specimens were obtained from the femoral heads of 76 Chinese women with PO who underwent hip arthroplasty for femoral neck fractures. Micro-computed tomography (Micro-CT) was used to assess the BMD and bone microarchitecture of the trabecular bone. Subsequently, a mechanical test was performed. Finally, sclerostin and Dkk-1 in the bone were measured by enzyme-linked immunosorbent (Elisa) assay. Serum ionized serum ionised calcium, propeptide of type 1 collagen, C-terminal β-telopeptide of type-1 collagen, sclerostin, and Dkk-1 were also detected.ResultsBone sclerostin was positively correlated with serum ionised calcium, serum sclerostin, BMD, bone volume/tissue volume (BV/TV), trabecular number (Tb.N), maximum compressive force, and yield strength (r = 0.32, 0.906, 0.355, 0.401, 0.329, 0.355, and 0.293, respectively, P < 0.05) and negatively correlated with age and trabecular separation (Tb.Sp) (r = − 0.755 and − 0.503, respectively, P < 0.05). Bone Dkk-1 was positively correlated with serum ionised calcium, serum Dkk-1, BMD, BV/TV, trabecular thickness, Tb.N, maximum compressive force, yield strength, and Young’s modulus (r = 0.38, 0.809, 0.293, 0.293, 0.228, 0.318, 0.352, 0.315, and 0.266, respectively, P < 0.05) and negatively correlated with age and Tb.Sp (r = − 0.56 and − 0.38, respectively, P < 0.05). Serum levels of sclerostin and Dkk-1 reflected the levels of sclerostin and Dkk-1 in the bone.ConclusionBone sclerostin and Dkk-1 were positively correlated with BMD in women with PO, and higher levels of bone sclerostin and Dkk-1 might predict better BMD, bone microarchitecture, and bone strength. The potential molecular mechanisms still require further study.

Prevalence of vertebral fractures and serum sclerostin levels in acromegaly.

An increased prevalence of vertebral fractures (VFs) has been reported in previous studies. The aim of this study was to evaluate the association between bone mineral density (BMD), bone turnover markers, serum sclerostin levels, and vertebral fractures (VFs) in acromegaly patients. We also evaluated the effects of gonadal status, disease activity, treatment modality, age, sex, and body mass index (BMI) on skeletal endpoints. Case-control study. Seventy acromegaly patients (M/F:36/34, mean age 45.5 ± 11.9 years) and 70 controls (M/F:31/39; mean age 45.66 ± 11.9 years) were included. VFs, BMD, calcium metabolism, markers of bone turnover, and sclerostin levels were evaluated. BMD was measured by dual-energy X-ray absorptiometry (Hologic QDR 4500). Conventional lateral radiography of the spine was performed and the Genant method was used for the assessment of fractures of T4-L5 vertebrae. The prevalence of vertebral fractures was higher in acromegalic patients as compared with the control group (72.9 vs. 20%; p < 0.001). Serum phosphate (P) levels (3.46 ± 0.59 mg/dl vs. 3.11 ± 0.44 mg/dl; p < 0.001) and b-cross laps (CTx) levels (0.47 µg/l, range 0.04-2.38 vs. 0.28 µg/l, range 0.11-0.80; p < 0.001) were significantly higher in acromegaly patients than control subjects. Serum sclerostin levels were similar between either acromegaly patients and control subjects or acromegaly patients with VF and without VF. In the means of treatment modality, VFs were more frequent in patients treated with adjuvant gamma knife radiosurgery (GKS) (p = 0.07). In the binary logistic regression analysis, the age of the acromegaly patients, the presence of hypogonadism, and GKS treatment were the factors significantly correlated with the occurrence of spinal fractures. The prevalence of VFs in patients with acromegaly is higher than in control subjects. Since advanced age, the presence of hypogonadism and GKS treatment were the factors predicting VFs in acromegaly; radiological evaluations should be considered as an emerging tool especially in those patients. Although markers of bone turnover elevated in acromegaly, they were not useful for the prediction of fractures. Serum sclerostin levels showed no discrepancy between the two groups and further studies are required for assessment of sclerostin role in this form of secondary osteoporosis.

Bone densitometry versus bone histomorphometry in renal transplanted patients: a cross-sectional study.

Bone loss leads to increase risk of fractures in renal transplantation. The aim of this study was to analyse the relationship between bone densitometry (DXA) findings, bone histomorphometry and bone-related molecules 1-year after renal transplantation. We performed a cross-sectional study of de novo renal transplanted patients that agreed to perform a bone biopsy and a DXA examination 1year after transplantation. All patients underwent a laboratory evaluation, bone biopsy, DXA examination and cardiac CT 1year after transplantation. 67 patients were included, 16 had a normal examination, and 18 patients were classified as having osteoporosis by DXA. Correlations between bone mineral density and T-scores of total femur and femoral neck were the ones that best correlated with bone volume assessed by a bone biopsy. The sensitivity of DXA for osteoporosis diagnosis was 47.0%, and the specificity was 81.2%. The positive predictive value was 50.0%, and the negative predictive value (NPV) was 80.0%. DXA parameters also correlated with klotho and sclerostin serum levels. In this population, a normal examination excluded the presence of osteoporosis, helping in identifying patients that would not benefit from therapy. Overall, densitometry in total femur and femoral neck correlated well with bone volume measured by bone biopsy.

Serum Sclerostin Is Associated With Central Fat Distribution in Patients With Type 2 Diabetes and Peripheral Neuropathy

Background: Peripheral neuropathy (PN) is the most common chronic diabetic complication occurring in both type 1 and type 2 (T2DM) patients as well as in prediabetes states. Metabolic syndrome seems to be as important as glycemic control in determining the onset and course of DPN, but the mechanisms underlying this association is far from conclusive. Sclerostin (SCL) is a glycoprotein secreted by osteocytes that has an antagonistic effect on the Wnt/beta-catenin pathway which is related to bone formation as well as to increased ectopic fat including marrow fat. Besides to its well-documented role in bone metabolism, the relationship between SCL and adiposity and metabolic syndrome is poorly understood. Objective: To determine SCL levels in patients with T2DM and DPN and evaluate their relationship with metabolic and body composition parameters. Design: Cross-sectional study including 56 patients with T2DM and DPN. Serum SCL levels, glycemic and lipid profile, anthropometric measurements, and percent body fat (PBF) were determined. Results: Mean age was 61.80 ± 10.67 years, duration of T2DM 13.30 ± 8.13 years, 57.1% men, 78.6% hypertensive, body mass index 28.74 ± 5.04 kg/m2, abdominal circumference 99.86 ± 13.37 cm, waist-to-hip ratio (WHR) 0.97 ± 0.08, fasting plasma glucose 169.73 ± 83.13 mg/dL, HbA1c 8.88 ± 2.09%, Triglycerides (TG) 163.54 ± 75.93 mg/dL, SCL 207.41 ± 215.13 pg/mL, and PBF 34.45 ± 8.42%. There were significant correlations between SCL and TG (r=0.407, p=0.003) and significant differences in TG according to quartiles (< p25 vs >p75) of SCL: 125.15 ± 47.45 mg/dL vs 223.50 ± 88.77 mg/dL, p = 0.002; and in WHR: 0.97 ± 0.07 vs 1.01 ± 0.07, p = 0.027. Conclusion: We found that increased levels of SCL were associated with WHR and TG in T2DM patients with DPN.

Evaluation of Serum Level of Sclerostin in Patients with Psoriatic Arthritis

Background: Psoriatic arthritis is a chronic, immune-mediated, inflammatory arthropathy that presents with inflammation of the joints and entheses, including those of the axial skeleton, and is associated with increased mortality from cardiovascular disease. The aim of the work is to evaluate serum level of sclerostin in patients with psoriatic arthritis and to correlats its level with the severity and activity of psoriatic arthritis. Methods: This case control study included (50) subjects classified into two groups: Group I: 30 patients with psoriatic arthritis. Group II: 20 healthy age and sex matched individuals as a control group. Results: there were no statistically significant differences between case group and control group, with a mean value of 42.45±12.90 vs 41.05±9.84 respectively. Regarding sclerostin , it found that there were no statistically significant differences between case group and control group with a mean value of 2787.92±1838.06 vs 2235.53±1830.67 respectively, And it found that there were highly statistically significant differences between groups with high mean value in patients with psoriasis group of 4276.72±1239.7 when it compared with other groups. Conclusion: The significantly higher serum sclerostin levels in PsA patients, compared with controls; there was positive significant correlation between sclerostin and each of age and PASI score. Sclerostin plays an important role in the pathogenesis of PsA and its associated bone damage, either systemic or localized.

Circulating Levels of Sclerostin Predict Glycemic Improvement after Sleeve Gastrectomy.

Among the different effects of bariatric surgery, here we focus on bone-derived inflammatory molecules, and in particular, sclerostin; an osteocyte product potentially associated with cardio-metabolic diseases. In 94 morbidly obese patients undergoing laparoscopic sleeve gastrectomy (SG), over-time changes in anthropometric and biochemical measures—including insulin resistance (IR) indexes—were correlated with serum sclerostin levels. Sclerostin was positively associated with anthropometric indexes of obesity, and inversely with IR, namely homeostatic model assessment for peripheral insulin sensitivity (HOMA2%S) (r = −0.218; p = 0.045). Sclerostin emerged as the only significant predictor of HOMA2-%S normalization, independently of demographic and anthropometric variables (OR 1.01 (95% CI 1.00–1.02); p = 0.024). We also identified two distinct patterns of serum sclerostin change: the higher/lower sclerostin levels at baseline, the greater their post-surgical reduction/increase (p < 0.001 for all subgroups). Among those two patterns, especially the post-surgery increase in serum sclerostin was associated with lean mass reduction, without any association with IR indexes. Although counterintuitive, this change was likely dependent on the post-surgical increase in bone turnover. In conclusion, baseline serum levels of sclerostin correlate with anthropometric measures of obesity and IR, and the ability to predict glycemic improvements after SG. Specifically, serum sclerostin was closely associated with peripheral insulin sensitivity (HOMA2-%S), thus supporting the role of skeletal muscle/bone interactions in metabolic diseases.

Effects of one-year tofacitinib therapy on bone metabolism in rheumatoid arthritis

SummaryJanus kinase (JAK) inhibitors are used to treat rheumatoid arthritis (RA). We assessed the effects of tofacitinib on bone density and bone markers in association with clinical and laboratory parameters in RA. Tofacitinib stabilized bone density and resulted in a positive balance of bone turnover.IntroductionJanus kinase (JAK) inhibitors emerged as new therapeutic options in rheumatoid arthritis (RA). We have little information on how it affects areal and volumetric bone mineral density (BMD) and bone turnover markers. The aim of this study was to assess the effects of 1-year tofacitinib therapy on bone metabolism in RA.MethodsThirty RA patients with active disease were treated with either 5 mg bid or 10 mg bid tofacitinib for 12 months. We determined DAS28, CRP, IgM rheumatoid factor (RF), and anti-cyclic citrullinated peptide (CCP) levels, as well as serum levels of sclerostin, osteocalcin (OC), P1NP, DKK-1, OPG, RANKL, and 25-hydroxy-vitamin D3. Areal and volumetric BMD were assessed by DXA and peripheral quantitative CT (QCT), respectively.ResultsTwenty-six patients (13 on each arm) completed the study. Tofacitinib was clinically effective by suppressing DAS28, CRP, and HAQ. This was accompanied by the attenuation of further bone loss. Tofacitinib therapy significantly increased OC, OPG, and vitamin D3, while decreased CTX levels (p < 0.05). Age and multiple bone markers (OC, CTX, P1NP, RANKL) inversely correlated with L2–4 and femoral neck BMD by DXA. CRP, DAS28, and RANKL inversely determined volumetric BMD by QCT. Age, CRP, anti-CCP, and DKK-1 influenced the effects of tofacitinib therapy on BMD changes.ConclusionsOne-year tofacitinib treatment stabilized BMD in RA patients and resulted in a positive balance of bone turnover as indicated by bone biomarkers. Further studies are needed to evaluate the potential beneficial effects of JAK inhibitors on inflammatory bone loss.

Circulating bioactive sclerostin levels in an Austrian population-based cohort

BackgroundCirculating serum sclerostin levels are supposed to give a good estimation of the levels of this negative regulator of bone mass within bone. Most studies evaluating total serum sclerostin found different levels in males compared to females and in older compared to younger subjects. Besides an ELISA detecting total sclerostin an ELISA determining bioactive sclerostin has been developed. The aim of this study was to investigate serum levels of bioactive sclerostin in an Austrian population-based cohort.MethodsWe conducted a cross-sectional observational study in 235 healthy subjects. Using the bioactive ELISA assay (Biomedica) bioactive sclerostin levels were evaluated.ResultsSerum levels of bioactive sclerostin were higher in men than in women (24%). The levels correlated positively with age (r = 0.47). A positive correlation could also be detected with body mass index and bone mineral density.ConclusionUsing the ELISA detecting bioactive sclerostin our results are consistent with data in the literature obtained by different sclerostin assays. The determination of sclerostin concentrations in peripheral blood thus appears to be a robust parameter of bone metabolism.

Role of osteogenic Dickkopf-1 in bone remodeling and bone healing in mice with type I diabetes mellitus

Type 1 diabetes mellitus (T1DM) is associated with low bone mass and a higher risk for fractures. Dickkopf-1 (Dkk1), which inhibits Wnt signaling, osteoblast function, and bone formation, has been found to be increased in the serum of patients with T1DM. Here, we investigated the functional role of Dkk1 in T1DM-induced bone loss in mice. T1DM was induced in 10-week-old male mice with Dkk1-deficiency in late osteoblasts/osteocytes (Dkk1f/f;Dmp1-Cre, cKO) and littermate control mice by 5 subsequent injections of streptozotocin (40 mg/kg). Age-matched, non-diabetic control groups received citrate buffer instead. At week 12, calvarial defects were created in subgroups of each cohort. After a total of 16 weeks, weight, fat, the femoral bone phenotype and the area of the bone defect were analyzed using µCT and dynamic histomorphometry. During the experiment, diabetic WT and cKO mice did not gain body weight compared to control mice. Further they lost their perigonadal and subcutaneous fat pads. Diabetic mice had highly elevated serum glucose levels and impaired glucose tolerance, regardless of their Dkk1 levels. T1DM led to a 36% decrease in trabecular bone volume in Cre− negative control animals, whereas Dkk1 cKO mice only lost 16%. Of note, Dkk1 cKO mice were completely protected from T1DM-induced cortical bone loss. T1DM suppressed the bone formation rate, the number of osteoblasts at trabecular bone, serum levels of P1NP and bone defect healing in both, Dkk1-deficient and sufficient, mice. This may be explained by increased serum sclerostin levels in both genotypes and the strict dependence on bone formation for bone defect healing. In contrast, the number of osteoclasts and TRACP 5b serum levels only increased in diabetic control mice, but not in Dkk1 cKO mice. In summary, Dkk1 derived from osteogenic cells does not influence the development of T1DM but plays a crucial role in T1DM-induced bone loss in male mice by regulating osteoclast numbers.

Association of rs865429 C/T polymorphism in SOST gene with Coronary Heart Disease in Iraqi Type 2 Diabetes Mellitus Patients

Sclerostin, encoded by the SOST gene, It has also been shown that sclerostin is expressed in aortic VSMC(vascular smooth muscle) and upregulation of SOST gene has inhibitory effects on the aortic aneurysmand atherosclerosis development. Aims: The current study aims to explore potential the associationbetween SOST gene single nucleotide polymorphisms (rs865429 C/T) and coronary artery diseases (CHD)in type 2 diabetes mellitus (T2DM) patients, in addition to the effect of this SNP on the level of serumsclerostin and other glycemic parameters. Material and methods: From the Iraqi population, we enrolled300 T2DM patients (150 T2DM with CHD and 150 T2DM without CHD). Serum blood glucose, seruminsulin, HbA1C, and sclerostin were estimated. Genotyping for rs865429 C/T in SOST gene was achievedby RFLP (polymerase chain reaction-restriction fragment length polymorphism). Results: T2DM patientshaving CT + TT genotype included in the studied were at increased risk for CHD in T2DM (odd ratio:0.4444 CI: 0.2800 to 0.7054) and related to a high serum sclerostin level in comparison with type 2 diabeticpatients with CC genotype. Conclusions: Type 2 diabetic patients with T allele who have elevated plasmaconcentrations of sclerostin are at high risk for coronary artery diseases.

Association of serum sclerostin levels with atherosclerosis severity in patients referred for invasive coronary angiography.

Association of serum sclerostin levels with atherosclerosis severity in patients referred for invasive coronary angiography.

Mango ginger (curcuma amada) inhibits collagen-induced arthritis by modulating inflammatory cytokine levels in rats

Background/aimMango ginger (MG: curcuma amada) has antioxidant and antiinflammatory activities. The aim was to evaluate the antiarthritic potential efficacy of MG on collagen-induced arthritis.Materials and methodsTwenty-one female Wistar-albino rats were divided into three groups. Arthritis was induced by intradermal injections of type II collagen and Freund’s adjuvant. MG extract was orally administered starting from the first collagen injection. TNF-α, IL-6, IL-17, obestatin, sclerostin, and DKK-1 serum levels were determined, and perisynovial inflammation and cartilage-bone destruction in the paws were histologically evaluated. Moreover, joint tissue TNF-α, IL-17, NF-κB, and COX-2 levels were analyzed.ResultsTNF-α, IL-17, IL-6, and DKK-1 serum levels were increased, and obestatin and sclerostin serum levels were decreased in the arthritis group compared to the control group. However, MG supplements decreased TNF-α, IL-17, IL-6, and DKK-1 serum levels and increased obestatin and sclerostin serum levels. Similarly, while collagen injection increased tissue TNF-α, IL-17, NF-κB, and COX-2 levels, MG decreased TNF-α, IL-17, and NF-κB levels. Moreover, MG ameliorated perisynovial inflammation and cartilage-bone destruction in the paws.ConclusionMG ameliorates arthritis via actions on inflammatory ways and wingless (Wnt) signaling pathway. These results suggest that MG may have a considerable potential efficacy for the treatment of rheumatoid arthritis.

A Novel in-Vivo Model to Examine Homing of Multiple Myeloma Cells in Postnatal, Inducible, and Reversible Loss of Mature Osteoblasts

The initiation of Multiple myeloma (MM) coincides with a decrease in osteoblasts and an increase in osteoclasts and adipocytes. However, the contribution of osteoblasts to the initiation and progression of MM remains mostly unknown. In-vitro studies have shown that co-cultures with MC3T3 murine osteoblast cell-line induced quiescence in 5TGM1 murine myeloma cells. In SCID or C57BL/KaLwRijHsd mice, the fluorescently labeled MM cell lines, injected through tail-vein, co-localized with endosteal osteoblasts and were found to be quiescent. We previously demonstrated that increased osteoblast numbers using Activin A inhibition in SCID mice with human-origin MM.1S cells resulted in inhibition of MM growth (Vallet et al., PNAS 2010). Here we aimed to develop a genetic in-vivo model for a better understanding of the interactions between osteoblasts and MM cells. Osteolineage cells develop through the stages of pre-osteoblasts, committed osteoblasts, mature osteoblasts, and osteocytes; each stage governed by a distinct molecular signature and function. To delineate these differences, individual osteoblast populations were FACS-sorted from long bones of Osterix-GFP+ (Osx+) mice (pre-osteoblasts), Collagen 2.3-GFP+ (Col2.3+) mice (committed osteoblasts), and Osteocalcin-YFP+ (OCN+) mice (mature osteoblasts). Co-cultured of these osteoblast populations with 5TGM1 MM cells showed that the OCN+ mature osteoblasts suppressed MM proliferation the most. Therefore, we focused our studies on the role of mature osteoblasts in MM homing and engraftment. We next generated mice in which mature osteoblasts were postnatally deleted in an inducible and reversible manner to better understand the molecular mechanisms of engraftment, proliferation, and migration of 5TGM1 injected intra-tibialy. To achieve this, mice carrying floxed diphtheria toxin receptor (DTR) alleles were mated with mice expressing Cre-recombinase driven by the osteocalcin promoter (OC-Cre). This led to the expression of DTR in mature osteoblasts (OC-Cre/iDTR) only. The control mice were littermates lacking the OC-Cre allele (iDTR). The OC-Cre/iDTR mice were indistinguishable from the controls until treated with diphtheria toxin (DT). We chose to induce mature osteoblast-deficiency at 8-weeks to allow skeletal maturation which is assumed to be completed by 6-7weeks of age. To induce postnatal deletion of mature osteoblasts, the OC-Cre/iDTR and control mice both were treated with 50 µg/Kg DT once a week, beginning at 8-weeks of age. Micro-CT analysis showed a significant increase in cortical porosity within 1-week after DT injection. 8-weeks of DT treatment significantly reduced trabecular bone fraction (BV/TV), trabecular numbers (Tb.N), and bone mineral density (BMD) with a significant increase in trabecular spacing (Tb.Sp). Immunohistochemistry for osteocalcin showed rapid loss of mature and endosteal osteoblasts (N.Ob/T.Ar). This was accompanied with a marked decreased in serum sclerostin and serum osteocalcin levels suggesting reduced osteocytes and mature osteoblasts, respectively. Importantly, serum CTX levels or numbers of osteoclasts (N.Oc/T.Ar) were unchanged. To study MM engraftment and progression, 3x106 5TGM1 luciferase eGFP positive (5TGM1-Luc-GFP) MM cells were injected into the tibia of OC-Cre/iDTR and control iDTR mice followed by weekly injection of DT for 8-weeks. Flow cytometry analysis showed a 4-fold increase in the 5TGM1-GFP cells in the BM from OC-Cre/iDTR mice compared to controls. Bioluminescence imaging (BLI) for 5TGM1-Luc-GFP cells at 4-weeks showed 600-fold increase in the OC-Cre/iDTR mice compared to controls. Interestingly, by 8-weeks, the BLI imaging showed 5TGM1-Luc-GFP cells in other long-bones of OC-Cre/iDTR mice but not the controls. These data show that MM cells engraft and proliferate rapidly in the absence of mature osteoblasts in-vivo. Moreover, in the absence of mature osteoblasts, MM cells have a propensity to migrate to other long bones. These data further suggest that expanding the mature osteoblast niche may provide novel therapeutic avenues and reduce disease burden and create an environment for long term tumor control. Importantly, this model will allow us to follow and analyze the sequential engraftment, dormancy, reactivation, proliferation, and migration of myeloma cells, and evaluate the effects of osteoanabolic and anti-myeloma therapies. Disclosures Fulzele: FORMA Therapeutics, Inc: Current Employment, Other: Shareholder of Forma Therapeutics. Raje:BMS: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy; Astrazeneca: Consultancy; Bluebird, Bio: Consultancy, Research Funding; Takeda: Consultancy; Immuneel: Membership on an entity's Board of Directors or advisory committees; Caribou: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy.

Sclerostin and osteoprotegerin: new markers of chronic kidney disease mediated mineral and bone disease in children.

Background Sclerostin and osteoprotegerin (OPG) are new markers of chronic kidney disease (CKD) mediated mineral bone disease (CKD-MBD) which were extensively evaluated in adult population. We aimed to evaluate the associations between serum levels of sclerostin/OPG and parameters of bone turnover and compare the serum levels of sclerostin/OPG in different stages of CKD in children. Methods 70 children with CKD stage 1-5, aged 2-21 years were examined. Serum levels of alkaline phosphatase (ALP), creatinine, total calcium, phosphorus , intact parathyroid hormone (iPTH) and vitamin D were measured. Serum sclerostin and OPG levels were measured in children with different levels of CKD stage and their association with bone turnover parameters were noted. Results We did not observe any significant correlation between serum levels of sclerostin and OPG and stages of CKD. A negative relationship was present between serum sclerostin and 25-OH vitamin D levels. Osteoprotegerin was positively and significantly correlated with ALP but serum sclerostin was negatively correlated with ALP. Conclusion Our study, which includes only children and adolescents with a growing skeleton under uremic conditions and excluding diabetes and atherosclerosis interference, is very valuable. We couldn't find any significant relationship between either sclerostin or OPG levels among different stages of CKD. Also our study demonstared a strong negative relationship between ALP and sclerostin levels and a strong positive relationship between ALP and OPG levels, reminding the importance of ALP levels to predict the bone-mineral status of the children with CKD.

Diffuse Idiopathic Skeletal Hyperostosis (DISH) in Type 2 Diabetes: A New Imaging Possibility and a New Biomarker.

We performed a cross-sectional study to investigate the prevalence of Diffuse Idiopathic Skeletal Hyperostosis (DISH) through Dual-Energy X-ray absorptiometry (DXA) Vertebral Fracture Assessment (VFA) in a group of post-menopausal women with Type 2 Diabetes Mellitus (T2DM). We also explored several biomarkers of bone turnover metabolism, including Wnt pathway modulators. DXA-VFA was performed to detect the presence of DISH. Serum samples were collected from all patients at the time of study recruitment. 16 different serum biomarkers were tested between the two subgroups. Given the exploratory nature of the study, we did not adjust for multiplicity. At VFA analysis, among 96 individuals enrolled in the study 20 (20.8%) showed features of DISH. No statistically significant difference was found for BMD values, between the DISH and NO-DISH subgroups. Concerning blood biomarkers, DISH patients showed a significant difference only in the sclerostin serum levels (32 vs 35.5pmol/L, for the DISH and NO-DISH subgroup, respectively; p = 0.010). After adjustment for confounding factors, sclerostin serum levels remained significantly lower in DISH group (p = 0.002). We demonstrated a non-negligible prevalence of DISH in a population of post-menopausal women affected by T2DM and suggested low serum sclerostin as a possible key feature associated with DISH presence. In addition, we propose DXA-VFA analysis, whose radiation dose is considerably lower than conventional radiography, as a viable diagnostic and prognostic mean to obtain data not only on bone health, but also for the screening for DISH in subjects at risk.

Serum sclerostin and glucose homeostasis: No association in healthy men. Cross-sectional and prospective data from the EGIR-RISC study.

Sclerostin, an inhibitor of bone formation, has emerged as a potential negative regulator of glucose homeostasis. We aimed to investigate if serum sclerostin associates with insulin sensitivity, beta cell function, prediabetes or metabolic syndrome in healthy men. Serum sclerostin was measured in basal and insulin-stimulated samples from 526 men without diabetes from the RISC cohort study. An OGTT was performed at baseline and after 3years. An IVGTT and a hyperinsulinaemic-euglycaemic clamp were performed at baseline. Insulin sensitivity was estimated by the oral glucose sensitivity index (OGIS) and the M-value relative to insulin levels. Beta cell function was assessed by the acute and total insulin secretion (ISRtot) and by beta cell glucose sensitivity. Serum sclerostin levels correlated positively with age but were similar in individuals with (n=69) and without (n=457) prediabetes or the metabolic syndrome. Serum sclerostin was associated with measures of neither insulin sensitivity nor beta cell function at baseline in age-adjusted analyses including all participants. However, baseline serum sclerostin correlated inversely with OGIS at follow-up in men without prediabetes (B: -0.29 (-0.57, -0.01) p=0.045), and inversely with beta cell glucose sensitivity in men with prediabetes (B: -13.3 (-26.3, -0.2) p=0.046). Associations between serum sclerostin and 3-year changes in measures of glucose homeostasis were not observed. Acute hyperinsulinemia suppressed serum sclerostin (p=0.02), and this reduction correlated with OGIS and ISRtot. Overall, serum sclerostin was not associated with prediabetes, insulin sensitivity or insulin secretion in healthy men. The inverse relationship between serum sclerostin and insulin sensitivity at follow-up was weak and likely not of clinical relevance. The ability of insulin to reduce sclerostin, possibly promoting bone formation, needs to be clarified.

Bone turnover biomarkers, disease activity, and MRI changes of sacroiliac joints in patients with spondyloarthritis.

The lack of valid biomarkers in patients with spondyloarthritis (SpA) requires searching for additional options to increase sacroiliac joint (SIJ) evaluation effectiveness. We assessed the serum levels of bone turnover markers and their relationships with active and chronic changes in SIJs using magnetic resonance imaging (MRI), indices, and laboratory parameters of disease activity in SpA patients. 102 patients with SpA and 15 healthy subjects were included. Testing of serum levels of transforming growth factor-beta (TGF-β1), Wnt3, sclerostin, and Dickkopf-1 (Dkk-1) was conducted. Active inflammatory lesions in SIJs were evaluated using Spondyloarthritis Research Consortium of Canada (SPARCC) MRI SIJ score, and chronic changes using the Danish scoring method. Bath Ankylosing Spondylitis Disease Activity Index, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), Ankylosing Spondylitis Disease Activity Scores with CRP, and ESR were used to assess disease activity. Serum levels of Dkk-1, TGF-β1, and sclerostin were significantly lower in SpA patients compared to healthy controls. The serum levels of Dkk-1 positively correlated with CRP. Dkk-1 had a significant negative correlation with Danish score. The sclerostin serum level had a weak negative correlation with the active inflammatory MRI SIJ lesions. There were positive correlations between TGF-β1 and sclerostin with Dkk-1, and negative correlation between Wnt3 and sclerostin. Dkk-1 positively correlated with CRP and negatively with chronic SIJ changes by Danish score. Sclerostin negatively correlated with the active SIJ lesions by SPARCC. This suggests that Dkk-1 and sclerostin are the most promising candidates to reveal inflammation and bone turnover in patients with SpA.

Relationship between sclerostin and coronary tortuosity in postmenopausal females with non-obstructive coronary artery disease

BackgroundCoronary tortuosity (CT) is commonly encountered in postmenopausal females and is usually present without obstructive lesions. Circulating sclerostin levels are elevated in postmenopausal females. In view of sclerostin's vasculoprotective effect, we aimed to find possible association between circulating sclerostin and CT. MethodWe prospectively enrolled 273 consecutive postmenopausal females with non-obstructive coronary artery disease diagnosed by coronary angiography. Presence and severity (by tortuosity score) of CT as well as serum sclerostin levels were assessed for each patient. ResultsPatients with CT (128, 47% of study group) were significantly older (P < 0.001), with higher prevalence of hypertension (P = 0.001) and had significantly higher levels of both sclerostin (P < 0.001) and hs-CRP (P = 0.001). Multivariate binary logistic regression revealed that the presence of CT (dependent variable) was associated with high sclerostin level (OR 8.9, 95% CI: 4.9–16.2, P < 0.001). Using ROC curve analysis, Sclerostin at a cut-off value of >650 pg/ml was found to be associated with presence of CT (AUC 0.69, 95% CI: 0.61–0.75, P < 0.001) with sensitivity and specificity of 75% and 72.4%, respectively. Using Pearson's correlation analysis, significant positive correlation between sclerostin and severity of CT was found (r = 0.29, P = 0.001). ConclusionHigh circulating sclerostin is associated with the presence and severity of CT in postmenopausal females. This may add to the literature on the incompletely understood pathogenesis of CT.

Changes in bone formation regulator biomarkers in early axial spondyloarthritis.

The hallmark of advanced axial SpA (axSpA) is spine ankylosis due to excessive ectopic bone formation. This prospective study aimed to describe the changes in serum levels of different regulators [sclerostin, dickkopf-1 (DKK-1)] and markers of bone formation [bone morphogenetic protein 7 (BMP-7)] over 5 years in early axSpA patients and to assess determinants of such changes. The DEvenir des Spondyloarthropathies Indifférenciées Récentes cohort is a prospective, multicentre French study of 708 patients with early (>3 months-<3 years) inflammatory back pain suggestive of axSpA. Serum levels of BMP-7, sclerostin and DKK-1 were assessed at baseline and after 2 and 5 years. Changes in bone formation regulators over time were analysed using mixed linear models. Serum BMP-7 significantly increased over time, with a median relative change of 223.7% [interquartile range (IQR) 0-10700 (0.17 pg/ml/month), P < 0.001]. Serum sclerostin significantly increased over time, with a median relative change of 14.8% [IQR -7.9-41.4% (0.001 ng/ml/month), P < 0.001]. Serum DKK-1 did not significantly change over time. Serum BMP-7 increased over time in active disease (Ankylosing Spondylitis Disease Activity Score with CRP ≥1.3, P = 0.01), but the increase was less pronounced with TNF inhibitor (TNFi) use (P < 0.001). No determinant was associated with serum sclerostin change. Serum BMP-7 change over 5 years was related with inflammation; it was increased in active disease, but the increase was low with TNFi use. Serum sclerostin levels significantly increased over time, but to a lesser degree than for serum BMP-7. https://clinicaltrials.gov/, NCT01648907.

Serum Sclerostin Level in Relation to Bone Status in Children with Chronic Kidney Disease

Abstract Background: To assess the serum level of sclerostin as a bone marker in children with different stages of Chronic Kidney Disease and its relation to bone status in children with CKD. Aime of Study: Is to assess the serum level of sclerostin in children with different stages of CKD and its relation to bone status in those children. Patients and Methods: The study was conducted on total of 90 children, 60 children of them were followed-up for diagnosis of CKD stages from II to V at Mansoura University Children Hospital (MUCH) Nephrology Unit. This study was done from March 2015 to March 2016. They were 34 (56.7%) males and 26 (43.3%) females with mean age SD of 11.06±3.4. Control group of 30 healthy children and were 18 male (60%) and 12 (40%) female with mean age SD of 9.6±2.3. Age ranges from three to seventeen years, complete blood picture, serum creatinine, parathyroid hormone, alkaline phosphatase, calcium, phosphorous and sclerostin serum level and also DEXA scan were measured in both groups. All patients were free from acute illness or symptoms suggestive of a urinary infection in the previous 3 months and none of them were receiving corticosteroids. Children with CKD who have diabetes, vascular calcifications or had undergone renal transplantation were excluded. Results: Elevated serum sclerostin in CKD & ESRD groups compared to control. Non-significant correlation between serum sclerostin level, biochemical bone markers and different anthropometeric measures. Conclusions: Serum sclerostin was elevated in CKD & ESRD suggesting as an indicator of bone mineral density in CKD patients but it is level didn't correlate as expected with observed BMD or bone turnover markers, suggesting presence of confounding variables that must be taken into account before routine clinical implementation. Non-significant cor-relation between serum sclerostin level and other biochemical bone markers as regard Calcium, phosphate, alkaline phos-phatase and patathemone hormone. Non-significant correlation was also detected between sclerostin, bone mineral density and body composition.