Serum Sclerostin Research Articles

Association of lower serum sclerostin levels with elevated risk for increased arterial stiffness: The JPOS Cohort Study.

Studies on the relationship between serum sclerostin, a Wnt/β-catenin pathway inhibitor, and atherosclerosis have yielded inconsistent results. We aim to longitudinally investigate the relationship between serum sclerostin levels and the risk of increased arterial stiffness in Japanese community-dwelling women. Of 1044 women aged ≥50 years whose brachial-ankle pulse wave velocity (baPWV) value was available in a baseline survey in 2011-2012, we excluded 374 whose baPWVs were ≥1800 cm/s, set as the cutoff for increased arterial stiffness, and eight with missing data. Of the remaining 662 women, we included in the analysis 556 followed in the 4- to 5-year follow-up study. The coefficient of variation of the sclerostin measurement was 3.45%. We obtained odds ratios (ORs) for sclerostin at baseline categorized by tertiles, with the high tertile as reference for increased arterial stiffness. Ninety-four women showed increased arterial stiffness during a mean follow-up of 4.0 years. The increased arterial stiffness rates in the low, medium, and high tertiles were 22.2%, 16.1%, and 12.4%, respectively (trend test p = 0.013). The ORs for the medium and low tertiles for increased arterial stiffness were 1.58 (p = 0.205) and 2.16 (p = 0.027), respectively, after adjusting for age and baseline baPWV. After further adjustment for baseline BMI, hypertension, hyperlipidemia, diabetes mellitus, eGFR, and BMC at whole body, the ORs for the medium and low tertiles were 1.65 (p = 0.181) and 2.50 (p = 0.014), respectively. Lower serum sclerostin levels were associated with elevated risks for increased arterial stiffness in Japanese community-dwelling women.

Elevated Circulating Sclerostin Levels in Frail Older Adults: Implications beyond Bone Health.

Sclerostin, initially recognized for its pivotal role in bone metabolism, has gained attention for its multifaceted impact on overall human health. However, its influence on frailty-a condition that best reflects biological age-has not been thoroughly investigated. We collected blood samples from 244 older adults who underwent comprehensive geriatric assessments. Sclerostin levels were quantified using an enzyme-linked immunosorbent assay. Frailty was assessed using two validated approaches: the phenotypic model by Fried and the deficit accumulation frailty index (FI) by Rockwood. After controlling for sex, age, and body mass index, we found that serum sclerostin levels were significantly elevated in frail individuals compared to their robust counterparts (P<0.001). There was a positive correlation between serum sclerostin concentrations and the FI (P<0.001). Each standard deviation increase in serum sclerostin was associated with an odds ratio of 1.87 for frailty (P=0.003). Moreover, participants in the highest quartile of sclerostin levels had a significantly higher FI and a 9.91-fold increased odds of frailty compared to those in the lowest quartile (P=0.003 and P=0.039, respectively). These findings, which for the first time explore the association between circulating sclerostin levels and frailty, have significant clinical implications, positioning sclerostin as one of potential blood-based biomarkers for frailty that captures the comprehensive physical, mental, and social aspects of the elderly, extending beyond its traditional role in bone metabolism.

Subclinical carotid atherosclerosis in gouty patients: relation to musculoskeletal ultrasonographic findings and serum sclerostin level

Objectives. To detect subclinical carotid atherosclerosis in gout patients and its relation to musculoskeletal ultrasound (MSK US) manifestations and serum sclerostin (SCL) levels. Patients and methods. Thirty Egyptian gouty patients were classified into two groups: Group A included 15 patients with diagnostic MSK US manifestations of gout (double contour sign), and Group B included 15 patients without MSK US findings. MSK US was done for both knees and the first MTP joints. Carotid duplex ultrasonography was done to evaluate carotid intima-media-thickness (CIMT) and serum SCL level was measured in all patients by ELISA technique. Results. Gouty patients with MSK US findings had a significantly higher increase in serum SCL levels than those without MSK US findings (p &lt;0.01). Group A patients had a significantly greater CIMT than patients of group B (p &lt;0.01). Serum uric acid and SCL levels were found to be significantly positively correlated. The ROC curve revealed that the optimal SCL cutoff value for detecting positive MSK US findings in gout patients was &gt;25.05 ng/ml. At this level, there was a significant difference between the patients with a CIMT &gt;0.9 mm and the patients with a CIMT ≤0.9 mm (p &lt;0.05). Conclusions. Patients with MSK US manifestations of gout are more liable to have subclinical carotid atherosclerosis than patients without these manifestations. SCL at a certain level &gt;25.05 ng/ml in gout patients might predispose patients to radiographic findings of MSK US of gout and subclinical atherosclerosis.

SOST/Sclerostin impairs the osteogenesis and angiogesis in glucocorticoid-associated osteonecrosis of femoral head.

Glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH) is a progressive bone disorder which frequently results in femoral head collapse and hip joint dysfunction. Sclerostin (SOST) is principally secreted by osteocytes in bone and plays an important role in bone homeostasis and homeostasis of skeletal integrity. Our previous study reported that short-term use of glucocorticoid increased serum sclerostin levels. Here this study is aimed to identify whether sclerostin played an essential role in the occurrence and development of GA-ONFH. Glucocorticoid-induced osteonecrosis of femoral head (ARCO stage II) samples were collected and sclerostin staining was conducted. Osteocyte cell line Ocy454, MC3T3-E1 and endothelial cells was used. MC3T3-E1 or endothelial cells were co-cultured with Ocy454 or SOST-silencing Ocy454 in presence of dexamethasone to mimic the crosstalk of various cells in the bone niche. GA-ONFH rat model and SOST knockout model was built to better understand the phenomenon in vivo. Sclerostin was highly concentrated in osteonecrosis patient sample in the necrotic area. Co-culture with osteocytes aggravated the inhibition of dexamethasone on MC3T3-E1 and endothelial cells. Sclerostin derived from osteocytes impaired osteogenesis and angiogenesis via inhibiting the Wnt pathway. In GA-ONFH rat model, SOST knockout ameliorated the incidence of osteonecrosis and improved bone metabolism compared with the wild type group through histological, immunohistochemical and bone metabolic analyses. Sclerostin contribute to pathologic process of GA-ONFH by impairing osteogenesis and angiogenesis.

Preventing OsteoPorosis in Spinal Cord Injury (POPSCI) Study—Early Zoledronic Acid Infusion in Patients with Acute Spinal Cord Injury

Accelerated sub-lesional bone loss is common in the first 2–3 years after traumatic spinal cord injury (TSCI), particularly in the distal femur and proximal tibia. Few studies have explored efficacy of antiresorptives for acute bone loss prevention post-TSCI, with limited data for knee bone mineral density (BMD) or beyond two years follow-up. An open-label non-randomized study was performed at Royal North Shore Hospital and Royal Rehab Centre, Sydney between 2018 and 2023. An ‘acute interventional cohort’ (n = 11) with TSCI (duration ≤ 12-weeks) received a single infusion of 4 mg zoledronic acid (ZOL) at baseline. A ‘chronic non-interventional cohort’ (n = 9) with TSCI (duration 1–5-years) did not receive ZOL. All participants underwent baseline and 6-monthly blood tests (including CTx and P1NP) and 12-monthly DXA BMD scans (including distal femur and proximal tibia). Participants were predominantly Caucasian and male (mean age 38.4 years). At baseline, the ‘acute’ cohort had higher serum CTx, P1NP and sclerostin concentrations, while the ‘chronic’ cohort had lower left hip and knee BMD. Majority with acute TSCI experienced an acute phase reaction after ZOL (9/11; 82%). In the acute cohort, left hip BMD fell by mean ~ 15% by 48 months. Left distal femoral and proximal tibial BMD declined by mean ~ 6–13% at 12 months and ~ 20–23% at 48 months, with a tendency towards greater BMD loss in motor-complete TSCI. A single early ZOL infusion in acute TSCI could not attenuate rapidly declining hip and knee BMD. Prospective controlled studies are required to establish the optimal strategy for preventing early bone loss after acute TSCI.

Relation between serum sclerostin and CTRP3 levels and bone mineral density in diabetic postmenopausal women

BackgroundOsteoporosis (OP) is a common finding in diabetic patients especially high-risk populations such as postmenopausal women. Sclerostin is a glycoprotein chiefly secreted by mature osteocytes and is considered a main regulator of bone formation. The C1q/TNF-Related Protein 3 (CTRP3) was found to be significantly associated with OP in postmenopausal women. The effect of type 2 diabetes mellitus (T2DM) on sclerostin and CTRP3 levels in postmenopausal women is rarely investigated. The present study aimed to assess the impact of T2DM on sclerostin and CTRP3 levels and their relation to OP in postmenopausal women.MethodsThe study included 60 postmenopausal women with T2DM and 60 age-matched postmenopausal non-diabetic women. Bone mineral density (BMD) was assessed using dual energy X-ray absorptiometry (DEXA). Serum levels of sclerostin and CTRP3 were assessed using enzyme-linked immunosorbent assay (ELISA) technique.ResultsDiabetic group expressed significantly higher serum levels of sclerostin when compared with non-diabetic group (110.0 ± 29.0 versus 51.5 ± 23.2 ng; p < 0.001). Oppositely, CTRP3 were significantly lower in the diabetic group (3.5 ± 3.5 versus 9.9 ± 3.7 ng/ml, p < 0.001). Multivariate logistic regression analysis identified HbA1c levels [OR (95% CI): 0.49 (0.26–0.93), p = 0.028], sclerotin levels [OR (95% CI): 1.06 (1.0-1.012), p = 0.041] and CTRP3 levels [OR (95%) CI: 1.64 (1.0-2.68), p = 0.047] as significant predictors of OP in diabetic patients.ConclusionsSclerostin and CTRP3 levels are involved in OP in postmenopausal diabetic patients.

α-Klotho is associated with cardiovascular and all-cause mortality in patients with stage3band 4 chronic kidney disease(CKD): a long-term prospective cohort study.

α-Klotho deficiency may increase cardiovascular risks and worsen survival. We evaluated the association of α-Klotho with cardiovascular and all-cause mortality in pre-dialysis chronic kidney disease (CKD) patients. In this prospective study, 75 non-diabetic CKD stage 3b-4 patients werefollowed-up for a median of 8years. Primary and secondary outcomes were all-cause and cardiovascular mortality, respectively. Human soluble α-Klotho ELISA Assay (IBL-Takara 27,998-96Well), Human Fibroblast Growth Factor-23 ELISA Assay (intact FGF23, Merck Millipore MILLENZ FGF23-32K), and Human Sclerostin ELISA kits (Biomedica, Vienna, BI-20492) were used to measure serum α-Klotho, FGF23 and sclerostin levels in the certified laboratory at the Sechenov University according to the manufacturers' protocols.All patients underwent echocardiography to evaluate left ventricular mass index (LVMI), left ventricular ejection fraction by Simpson method, and cardiac (valve) calcification score by a semi-quantitative point scale. Lateral abdominal radiography by Kauppila method was used to estimate calcificationof the abdominal aorta.Cox multivariate regression and receiver-operating characteristic curve (ROC)-analysis were used to evaluate risk factors for death and their cut-off values. Primary and secondary endpoints were reached in 15 (20%) and 9 (12%) patients, respectively. Median α-Klotho levels in deceased and surviving patients were 344 and 484pg/ml, respectively (p = 0.002). In a multivariate Cox regression model, baseline α-Klotho levels (HR 0.99, 95% CI 0.98-1.00, p = 0.023), aortic calcification (HR 1.18, 95% CI 1.02-1.36, p = 0.029) and left ventricular mass index (LVMI) (HR 1.04, 95% CI 1.00-1.08, p = 0.033) were associated with the primary endpoint, whereas α-Klotho (HR 0.99, 95% CI 0.98-1.00, p = 0.029), aortic calcification (HR 1.23, 95% CI 1.07-1.42, p = 0.003) and LVMI (HR 1.04, 95% CI 1.00-1.08, p = 0.021) were associated with the secondary endpoint. α-Klotho levels had the highest area under the curve (AUC)by ROC analysis, that is, 0.766 (95% CI 0.70-0.82) for the primary endpoint and 0.842 (95% CI 0.79-0.90) for the secondary endpoint with cut-off values of 412pg/ml (HR 3.06, 95% CI 1.36-6.89, p = 0.007) and 368pg/ml (HR 4.84, 95% CI 1.59-14.73, p = 0.005), respectively. In pre-dialysis CKD patients, α-Klotho levels areassociated with all-cause and cardiovascular mortality and may be considered an early prognostic marker.

Correlation between Body Composition and Bone Mineral Density Differs by Sex and Skeletal Site in Overweight and Obese Chinese Subjects

Previous studies have yielded inconsistent results regarding the relationship between obesity and bone mineral density (BMD). The aim of this study was to determine the influence of body composition on BMD and the serum sclerostin level in overweight and obese adults. The study had a cross-sectional design and included 90 men and 118 women with a body mass index ≥25. Fat mass, lean mass, and spinal and pelvic BMD were measured using dual-emission X-ray absorptiometry. Subcutaneous fat, visceral fat, and lean mass were measured between L2 and L3 by 16-slice spiral computed tomography. The serum sclerostin level was determined by enzyme-linked immunosorbent assay. Pearson analysis showed that fat mass and appendicular lean mass were positively correlated with spinal BMD in both sexes. A positive association of both fat mass and lean mass with pelvic BMD, which was stronger in women, was also found. Partial correlation analysis showed the positive association between fat mass and BMD was significantly attenuated but the positive association between lean mass and pelvic BMD remained after adjustment for age and body weight. A negative correlation was observed between visceral fat and spinal and pelvic BMD only in women, and the positive association between lean mass with pelvic BMD was more obvious in women than in men, indicating body composition seemed to have a greater impact on the BMD in women. The serum sclerostin level was positively associated with BMD but not with body composition. These findings suggest that the correlation between body composition and BMD is influenced by sex and skeletal site.

Bone turnover biomarkers reflect radiation-induced bone injuries in women with non-metastatic rectal cancer.

Preoperative radiotherapy (RT) for non-metastatic rectal cancer reduces local recurrence rates but can cause pelvic insufficiency fractures. Despite the high morbidity from RT-induced skeletal injuries, predictive and preventive measures are lacking. How these injuries are reflected by bone biomarkers are largely unknown. The aim was to assess longitudinal changes in bone biomarkers and their relation to RT-related bone injuries in women with rectal cancer. This longitudinal cohort study includes 47 women with non-metastatic rectal cancer treated with surgery ± preoperative RT with or without chemotherapy. Sclerostin, bioactive sclerostin, C-terminal telopeptide cross-links of collagen type I (CTX), bone-specific alkaline phosphatase (BALP), and type I procollagen intact N-terminal propeptide (PINP) were measured at baseline, after RT, and 1 yr postoperatively. Pelvic magnetic resonance imaging was used for detection of skeletal injury. Sixteen of 36 (44%) irradiated women had radiation-induced bone injuries and were compared to 11 women (RT-) and 20 women (RT+) without bone injuries. Serum CTX, BALP, and PINP increased during the first year after RT in women with radiation-induced bone injuries. The difference in mean change of CTX (p=.037) and BALP (p=.042) was conferred by longitudinal regression analyses adjusted for serum estradiol. Serum sclerostin and bioactive sclerostin remained stable over time. Taken together, bone markers may be of interest for future research on fracture prediction or preventive measures in women susceptible to radiation-induced bone injury. Due to few measure points, the full pattern cannot be captured regarding the relation over time between bone biomarkers and skeletal injury from irradiation.

Efficacy and safety of zoledronic acid in the treatment of osteoporosis: A meta-analysis of randomized controlled trials

PurposeZoledronic acid can inhibit the activity of osteoclasts, and thus, may slow or inhibit bone loss. The purpose of this study was to systematically evaluate the efficacy and safety of zoledronic acid in the treatment of osteoporosis. MethodsFour databases, PubMed, Embase, Cochrane Library, and Web of Science, were systematically searched up to December 26, 2022. The primary outcomes included bone mineral density (BMD), carboxy-terminal cross-linked telopeptide of type 1 collagen (CTX), bone-specific alkaline phosphatase (BSAP), procollagen type 1 N-terminal prope-ptide (P1NP), adverse events, and fracture. Secondary outcomes included serum sclerostin level, Visual Analogue Scale (VAS) score, and Oswestry Disability Index (ODI). ResultsA total of 22 randomized controlled trials were included in this meta-analysis. Meta-analysis results showed that zoledronic acid was effective in increasing BMD of the lumbar spine, femoral neck, trochanter and serum sclerostin level; and reduced CTX, BSAP, P1NP, VAS score, and ODI in patients with osteoporosis. Regarding safety, zoledronic acid could reduce the incidence of fractures but had relatively more adverse events. ConclusionZoledronic acid can significantly improve BMD of the lumbar spine, femoral neck and trochanter, and effectively reduce incidence of fracture in patients with osteoporosis, thereby significantly improving patients' quality of life. However, the incidence of adverse events was higher than that of patients treated with placebo.

Short-term effects of dapagliflozin on biomarkers of bone and mineral metabolism in patients with diabetic kidney disease: A prospective observational study

BackgroundThere is still a lack of information regarding the impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on bone and mineral metabolism in patients with diabetes and chronic kidney disease (CKD). Therefore, we aimed to investigate the effects of SGLT2i in a cohort of patients suffering from diabetic kidney disease (DKD). MethodsIn this prospective observational study, patients with type 2 diabetes and biopsy-proven diabetic nephropathy or presumptive DKD with eGFR levels ≥20 ml/min/1.73m2 and 25-OH vitamin D levels ≥20 ng/dl were included. 41 used SGLT2i (study group) and 39 continued their current treatment regimens (control group). Serum FGF-23, sclerostin, osteoprotegerin (OPG), and hydroxyproline levels were measured at baseline, 1 month and 3 months after treatment. ResultsMean age of all patients was 67±9.3 years, and 48 (60%) were female. All patients in the study group used dapagliflozin. Taking into account the renal functions at the commencement of the study, the eGFR values for the study group and the control group were 51.2±15.6 and 44.6±16.9ml/min/1.73m2, respectively (p=0.01). After three months, these values were observed to be 47.4±16.7 and 44.3±18.8 ml/min/1.73m2 (p=0.43), respectively. At baseline, OPG levels were higher in the study group (p=0.025) but there were no differences between the groups in terms of FGF-23 and sclerostin levels (p=0.670 and p=0.467, respectively). Levels of OPG, FGF-23, and sclerostin significantly decreased throughout 3 months of treatment with dapagliflozin (p<0.001 for all). Hydroxyproline levels also declined but did not reach to statistical significance (p=0.075). Multiple linear regression models revealed that treatment with SGLT2i was associated with the change in levels of sclerostin (β=0.303, p=0.011) and OPG (β=0.210, p=0.010), but not with FGF-23 (β=0.089, p=0.150). ConclusionsFGF-23, sclerostin and OPG levels significantly declined after treatment with dapagliflozin for 3 months.

Serum sclerostin as a biomarker of disease activity in ankylosing spondylitis in correlation with radiographic imaging

BackgroundThe wingless signaling pathway of bone development is inhibited by sclerostin, which may contribute to the etiology of ankylosing spondylitis.AimThe study aimed to evaluate serum sclerostin levels in ankylosing spondylitis patients and investigate how it correlated with radiographic damage using the Spondylo-arthritis Research Consortium of Canada index (SPARCC), disease activity, and functional impairment.ResultsThis cross-sectional case–control study revealed a significantly lower mean serum sclerostin (11.28 ng/ml) in AS patients compared with controls (101.25 ng/ml). Serum sclerostin levels showed a significant negative correlation with each of Bath Ankylosing Spondylitis Metrology Index (BASMI) (p = 0.043), sacroiliac joints SPARCC, spine SPARCC, and overall SPARCC scores (p = 0.012, p = 0.036, and p = 0.007). The detection of AS, serum sclerostin levels ≤ 20 ng/ml showed 100% sensitivity and specificity.ConclusionSerum sclerostin had good discriminating power between ankylosing spondylitis cases and healthy control individuals and was correlated with subclinical activity status on magnetic resonance imaging.

Analysis of factors influencing vascular calcification in peritoneal dialysis patients and their impact on long-term prognosis

BackgroundThis study aims to investigate the influencing factors of vascular calcification in peritoneal dialysis (PD) patients and its relationship with long-term prognosis.MethodsThis retrospective cohort study included chronic kidney disease patients undergoing peritoneal dialysis at the Peritoneal Dialysis Center of Beijing Luhu Hospital, Capital Medical University, from January 2019 to March 2019. Demographic and clinical laboratory data, including serum sclerostin (SOST), calcium (Ca), phosphate (P), serum albumin (ALB), and intact parathyroid hormone (iPTH) levels, were collected. Abdominal aortic calcification (AAC) was assessed using abdominal lateral X-ray examination to determine the occurrence of vascular calcification, and patients were divided into the AAC group and Non-AAC group based on the results.ResultsA total of 91 patients were included in the study. The AAC group consisted of 46 patients, while the Non-AAC group consisted of 45 patients. The AAC group had significantly older patients compared to the non-AAC group (P < 0.001) and longer dialysis time (P = 0.004). Multivariable logistic regression analysis indicated that risk factors for vascular calcification in PD patients included dialysis time, diabetes, hypertension, and SOST. Kaplan–Meier survival analysis showed that the AAC group had a significantly higher mortality rate than the non-AAC group (χ2 = 35.993, P < 0.001). Multivariable Cox regression analysis revealed that dialysis time, diabetes and AAC were risk factors for all-cause mortality in peritoneal dialysis patients.ConclusionLonger dialysis time, comorbid diabetes, comorbid hypertension, and SOST are risk factors for vascular calcification in PD patients. Additionally, AAC, longer dialysis time, and comorbid diabetes are associated with increased risk of all-cause mortality in peritoneal dialysis patients.

Association of serum sclerostin levels with marrow adiposity in postmenopausal women with glucocorticoid-induced osteoporosis

BackgroundGlucocorticoids and sclerostin act as inhibitors of the Wnt signaling pathway, thereby hindering bone formation. Given the pathway's intricate association with mesenchymal stem cells, the hypothesis suggests that heightened sclerostin levels may be intricately linked to an augmentation in marrow adiposity induced by glucocorticoids. This study endeavored to delve into the nuanced relationship between circulating sclerostin and bone marrow adipose tissue in postmenopausal women grappling with glucocorticoid-induced osteoporosis (GIO).MethodsIn this cross-sectional study, 103 patients with autoimmune-associated diseases underwent glucocorticoid treatment, boasting an average age of 61.3 years (standard deviation 7.1 years). The investigation encompassed a thorough assessment, incorporating medical history, anthropometric data, biochemical analysis, and dual-energy X-ray absorptiometry measurements of lumbar and femoral bone mineral density (BMD). Osteoporosis criteria were established at a T-score of -2.5 or lower. Additionally, MR spectroscopy quantified the vertebral marrow fat fraction.ResultsBMD at the femoral neck, total hip, and lumbar spine showcased an inverse correlation with marrow fat fraction (r = –0.511 to – 0.647, P < 0.001). Serum sclerostin levels exhibited a positive correlation with BMD at various skeletal sites (r = 0.476 to 0.589, P < 0.001). A noteworthy correlation emerged between circulating sclerostin and marrow fat fraction at the lumbar spine (r = –0.731, 95% CI, –0.810 to –0.627, P < 0.001). Multivariate analysis brought to light that vertebral marrow fat fraction significantly contributed to sclerostin serum concentrations (standardized regression coefficient ß = 0.462, P < 0.001). Even after adjusting for age, body mass index, physical activity, renal function, BMD, and the duration and doses of glucocorticoid treatment, serum sclerostin levels maintained a significant correlation with marrow fat fraction.ConclusionsCirculating sclerostin levels exhibited a noteworthy association with marrow adiposity in postmenopausal women grappling with GIO.

Serum sclerostin levels as a diagnostic marker for osteoporosis.

Osteoporosis is asymptomatic, in which low bone-mass and micro-architectural deterioration of bone tissue leads to increasing bone fragility and fracture. Vertebral and hip fractures lead to increased mortality, resulting in enormous health care costs. BMD testing by DEXA is used in diagnosis of osteoporosis. However, low-and middle-income populations are unable to conduct periodic examinations of bone mineral status. Thus, current study is mainly aimed at finding a cost-effective diagnostic-marker for osteoporosis. 170 participants, of whom 51 had osteoporosis, 62 had osteopenia and 57 had normal bone-mass. Selection of individuals was based on DEXA scan BMD. Sclerostin was determined by ELISA. The variables were compared using ANOVA test and ROC analysis was performed. Sclerostin levels were significantly decreased in osteoporosis (4.62 ± 1.6 ng/mL) and osteopenia (4.92 ± 1.4 ng/mL) compared with controls (5.74 ± 1.3 ng/mL), (p < 0.0001). Sclerostin level 5.6 ng/mL is the cut-off value for diagnostic purpose, according to good sensitivity and specificity. In patients with osteopenia and osteoporosis, decreased sclerostin levels were associated with an increased disease risk. These relationships were independent of BMD and bone turnover, suggesting that Sclerostin levels may reflect disease-severity in osteoporosis. Sclerostin measurements could become a useful clinical index for diagnosis of osteoporosis.

Factors associated with low bone mineral density in Turner syndrome: a multicenter prospective observational study.

Turner syndrome (TS) is associated with a high risk of fracture due to low bone mineral density (BMD). While hypogonadism is known to play a role in decreasing BMD, other factors have not been studied well. Focusing on diet, exercise, and bone metabolism markers, the present, multicentric, prospective, observational study aimed to identify factors contributing to decreased BMD in TS. In total, 48 patients with TS aged between 5 and 49 years comprising a pre-pubertal group (n = 9), a cyclical menstruation group (n = 6), and a hormone replacement therapy (HRT) group (n = 33) were enrolled. The cyclical menstruation group and the HRT group were referred to collectively as the post-pubertal group. The bone mineral apparent density (BMAD) Z-score was higher in the pre-pubertal group than in the post-pubertal group (-0.3 SD vs. -1.8 SD; p = 0.014). Within the post-pubertal group, the median BMAD Z-score was -0.2 SD in the cyclical menstruation group and -2.3 SD in the HRT group (p = 0.016). Spearman's rank correlation revealed no correlation between the BMAD Z-score and bone metabolism markers. No significant relationship was observed between the BMAD Z-score and either the vitamin D sufficiency rate or the step sufficiency rate. A negative correlation was found between BMAD Z-score and serum sclerostin in the pre-pubertal group and serum FSH in the post-pubertal group. In conclusion, the present study found no relationship between the vertebral BMAD Z-score and diet or exercise habits in TS, indicating that estrogen deficiency is the chief reason for low BMD in TS.

Dual role of sclerostin and other parameters in postmenopausal women with osteoporosis

Background &amp; objective: Osteoporosis is a chronic progressive disease, characterized by decreased bone mass and damage to the microstructure of bone tissue, leading to decreased bone strength and increased risk of fractures. The main serious consequence of osteoporosis is fragility fracture. This case-control study was conducted to know the prevalence of osteoporosis in Iraqi postmenopausal women. Methodology: One hundred female patients visiting Al-Sader Teaching Hospital in Al-Najaf province of Iraq, were included in the study. To determine the percentage of their bone density we used a dual energy x-ray absorptiometry (DEXA). Blood samples were taken after diagnosing the disease. In addition, serum estrogen and vitamin D3 were measured by enzyme linked immune sorbent assay (ELISA), while alkaline phosphatase was measured by spectrophotometer. Data were gathered by direct interviews with the women. The study excluded those who had chronic diseases. Results: This study showed a significant increase (P &lt; 0.05) in the concentration of sclerostin and alkaline phosphatase and non-significant differences in vitamin D3 concentrations between patients and healthy group. Conclusion: Increased serum sclerostin and alkaline phosphatase levels in postmenopausal women with osteoporosis play an important role in the development of primary osteoporosis. Key word: Osteoporosis; Sclerostin; DEXA Citation: Ahmed NH, Jaffat HS, Alrufaie MM. Dual role of sclerostin and other parameters in postmenopausal women with osteoporosis. Anaesth. pain intensive care 2023;27(6):745−749; DOI: 10.35975/apic.v27i6.2349 Received: August 22, 2023; Revised: August 29, 2023; Accepted: September 11, 2023

Association Between Plasma Sclerostin Levels and Body Mass Index in Women With Polycystic Ovary Syndrome.

Background Polycystic ovary syndrome (PCOS) is recognized as one of the most common endocrine pathologies in females of reproductive age worldwide. This study investigated the relationship between serum sclerostin levels and body mass index (BMI) in women with PCOS. Methods Women aged 18-40 years who presented to our clinic between January 1, 2019, and January 1, 2020, and were diagnosed with PCOS were included in this study. The patients' clinical and laboratory data were recorded, and waist circumference, hip circumference, and BMI values were calculated. The patients with a BMI of >25 kg/m2 were evaluated as Group I, those with a BMI of <18.5 kg/m2 as Group II, and those with a BMI of 18.5-25 kg/m2 as Group III. Serum sclerostin levels were compared between the BMI groups. Results The study included 90 patients. The mean BMI values were 32.2±2.1, 17.0±0.9, and 22.9±2.1 kg/m2 for Groups I, II, and III, respectively. We detected a statistically significant difference in serum sclerostin levels between Group II and Group I (p<0.005). There was a significant, positive correlation between the sclerostin level and BMI (r=0.258, p=0.014), weight (r=0.237, p=0.044), waist measurement (r=0.225, p=0.045), and hip measurement (r=0.225, p=0.033). Conclusion This study revealed that abnormal body composition in PCOS could alter circulating sclerostin levels.

Cardioprotective function of sclerostin by reducing calcium deposition, proliferation, and apoptosis in human vascular smooth muscle cells

BackgroundSclerostin is an inhibitor of the Wnt/b-catenin pathway, which regulates bone formation, and can be expressed in vascular smooth muscle cells (VSMCs). Type 2 diabetes (T2D) is associated with an increased risk of cardiovascular disease (CVD) and increased serum and tissue expression of sclerostin. However, whether the role of sclerostin is detrimental or protective in the development of CVD is unknown. Therefore, our aims are to determine the level of sclerostin in T2D patients with/without CVD and in controls, both at serum and vascular tissue, and to analyze the role of sclerostin in VSMCs under calcified environments.MethodsCross-sectional study including 121 controls and 139 T2D patients with/without CVD (48/91). Sclerostin levels in serum were determined by ELISA, and sclerostin expression was analyzed by RT-qPCR and immunohistochemistry in calcified and non-calcified artery of lower limb from T2D patients (n = 7) and controls (n = 3). In vitro experiments were performed in VSMCs (mock and sclerostin overexpression) under calcifying conditions analyzing the sclerostin function by determination of calcium and phosphate concentrations, and quantification of calcium deposits by Alizarin Red. Proliferation and apoptosis were analyzed by MTT assay and flow cytometry, respectively. The regulation of the expression of genes involved in bone metabolism was determined by RT-qPCR.ResultsA significant increase in serum sclerostin levels in T2D patients with CVD compared to T2D patients without CVD and controls (p < 0.001) was observed. Moreover, higher circulating sclerostin levels were independently associated with CVD in T2D patients. Increased sclerostin expression was observed in calcified arteries of T2D patients compared to non-calcified arteries of controls (p = 0.003). In vitro experiments using VSMCs under calcified conditions, revealed that sclerostin overexpression reduced intracellular calcium (p = 0.001), calcium deposits (p < 0.001), cell proliferation (p < 0.001) and promoted cell survival (p = 0.015). Furthermore, sclerostin overexpression exhibited up-regulation of ALPL (p = 0.009), RUNX2 (p = 0.001) and COX2 (p = 0.003) and down-regulation of inflammatory genes, such as, IL1β (p = 0.005), IL6 (p = 0.001) and IL8 (p = 0.003).ConclusionsSclerostin could play a protective role in the development of atherosclerosis in T2D patients by reducing calcium deposits, decreasing proliferation and inflammation, and promoting cell survival in VSMCs under calcifying conditions. Therefore, considering the bone-vascular axis, treatment with anti-sclerostin for bone disease should be used with caution.Graphical

Serum sclerostin is associated with recurrent kidney stone formation independent of hypercalciuria.

Kidney stones are frequent in industrialized countries with a lifetime risk of 10 to 15%. A high percentage of individuals experience recurrence. Calcium-containing stones account for more than 80% of kidney stones. Diet, environmental factors, behavior, and genetic variants contribute to the development of kidney stones. Osteocytes excrete the 21kDa glycoprotein sclerostin, which inhibits bone formation by osteoblasts. Animal data suggests that sclerostin might directly or indirectly regulate calcium excretion via the kidney. As hypercalciuria is one of the most relevant risk factors for kidney stones, sclerostin might possess pathogenic relevance in nephrolithiasis. We performed a prospective cross-sectional observational controlled study in 150 recurrent kidney stone formers (rKSF) to analyse the association of sclerostin with known stone risk factors and important modulators of calcium-phosphate metabolism. Serum sclerostin levels were determined at the first visit. As controls, we used 388 non-stone formers from a large Swiss epidemiological cohort. Sclerostin was mildly increased in rKSF in comparison to controls. This finding was more pronounced in women compared to men. Logistic regression indicated an association of serum sclerostin with rKSF status. In hypercalciuric individuals, sclerostin levels were not different from normocalciuric patients. In Spearman correlation analysis we found a positive correlation between sclerostin, age, and BMI and a negative correlation with eGFR. There was a weak correlation with iPTH and intact FGF 23. In contrast, serum sclerostin levels were not associated with 25-OH Vitamin D3, 1,25-dihydroxy-Vitamin D3, urinary calcium and phosphate or other urinary lithogenic risk factors. This is the first prospective controlled study investigating serum sclerostin in rKSF. Sclerostin levels were increased in rKSF independent of hypercalciuria and significantly associated with the status as rKSF. It appears that mechanisms other than hypercalciuria may be involved and thus further studies are required to elucidate underlying pathways.