Serum Sclerostin Concentrations Research Articles

Effects of running a marathon on sclerostin and parathyroid hormone concentration in males aged over 50.

The aim of our study was to verify whether running a marathon (32nd Wroclaw Marathon) was associated with changes in sclerostin and intact PTH (iPTH) concentration in middle-aged males. We enrolled 33 males who completed the marathon race. Blood samples were taken 60 minutes before (V1), immediately after (V2), and 7 days after the run (V3). The mean serum sclerostin concentration was 42.4 ± 10.8 pmol/L at V1, increased to 62.9 ± 12.6 pmol/L at V2 (t= -11.206; p < 0.001) and returned to baseline in V3 (t = 8.344; p < 0.001, V3 vs. V2). A similar trend was recorded for iPTH (t= -7.440; p < 0.001, for V2 vs. V1; t = 6.229; p < 0.001, for V3 vs. V2), at V3, iPTH levels remained significantly higher than V1 (t= -2.759; p = 0.010). The results of our study suggest that, in middle-aged males, running a marathon affects skeletal metabolism by activating two counteracting mechanisms, although temporarily overlapping: first, by a sudden inhibition of bone formation, through induction sclerostin expression and, secondly, by a long-lasting induction of PTH, which also guarantees the maintenance of adequate circulating levels of calcium. The net effect would be the maintenance of adequately high levels of circulating calcium to be used for neuromuscular activity and muscle contraction.

Influence of Muscle Mass and Strength on Bone Mineralisation with Consideration of Sclerostin Concentration.

Osteoporosis is a disease characterised by a reduction in bone strength due to increased porosity and impaired mineralisation. In our study, we investigated whether muscle strength and mass exert a significant effect on bone mineral density in young adult women. We also tested whether sclerostin can be used as an indicator in the assessment of bone mineralisation. The study included 111 patients. All patients had their bone mineral density determined in the L1-L4 section of the lumbar spine and in the whole skeleton. The parameters of fat mass (FM), lean body mass (LBM) and visceral fat mass (VF) were also determined. Metabolic activity of osteocytes was assessed by measuring the serum sclerostin concentration. There was a statistically significant association of both hands' muscle strength with all parameters expressing bone mineralisation. A statistically significant relationship was also obtained between BMD L1-L4 and the body mass components (FM, LBM). Sclerostin levels in the study did not differ between groups with normal and reduced bone mineral density. Muscle strength assessment may be a potential exponent of reduced bone mineral density, also used clinically in young adult women. The utility of sclerostin in the clinical assessment of bone mineralisation has not been demonstrated.

Serum Osteocalcin, Sclerostin and Lipocalin-2 Levels in Adolescent Boys with Obesity over a 12-Week Sprint Interval Training.

The aim of the study was to examine the effects of supervised cycling sprint interval training (SIT) on serum osteocalcin, lipocalin-2 and sclerostin levels, and bone mineral characteristics among obese adolescent boys. Untrained obese adolescent boys aged 13.4 ± 0.3 were assigned to either a 12-week SIT group (3 sessions/week), or a non-exercising control group who continued with their habitual everyday life. Serum osteocalcin, lipocalin-2 and sclerostin concentrations, and bone mineral values were assessed before and after intervention. After 12-week intervention, where 14 boys in both groups ended the study, there were no significant differences in serum osteokine levels between the groups after 12 weeks, while whole body bone mineral content and lower limb bone mineral density increased in the SIT group (p < 0.05). Change in body mass index was negatively correlated with the change in osteocalcin (r = -0.57; p = 0.034), and positively correlated with the change in lipocalin-2 levels (r = 0.57; p = 0.035) in the SIT group. Supervised 12-week SIT intervention improved bone mineral characteristics, but did not change osteocalcin, lipocalin-2 or sclerostin levels in adolescent boys with obesity.

Human Placental LRP5 and Sclerostin are Increased in Gestational Diabetes Mellitus Pregnancies.

The low-density lipoprotein receptor-related protein 5 (LRP5) and its inhibitor sclerostin, are key components of bone metabolism and potential contributors to type 2 diabetes mellitus susceptibility. This study aims at evaluating the expression of placental LRP5 and sclerostin in pregnancies with gestational diabetes mellitus (GDM) and investigate possible associations with umbilical sclerostin concentrations and clinical outcomes in mothers and their neonates. Twenty-six GDM-mothers and 34 non-GDM mothers of Caucasian origin and their neonates admitted in a gynecology and obstetrics department of a university hospital were included in this study. Demographic data and maternal fasting glucose concentrations (24-28 weeks of gestation) were retrieved from the patients' medical records. Placental LRP5 was determined by immunohistochemistry (IHC) and Western blotting analysis; placental sclerostin was determined by IHC. Umbilical serum sclerostin concentrations were measured by ELISA. Placental sclerostin IHC intensity values were positively correlated with LRP5 values as detected either by IHC (r = 0.529; P < .001) or Western blotting (r = 0.398; P = .008), with pregestational maternal body mass index values (r = 0.299; P = .043) and with maternal fasting glucose concentrations (r = 0.475; P = .009). Placental sclerostin and LRP5 were significantly greater in GDM compared with non-GDM placentas (histo-score: 65.08 ± 17.09 vs 11.45 ± 2.33, P < .001; 145.53 ± 43.74 vs 202.88 ± 58.65, P < .001; respectively). Sclerostin and LRP5 were detected in human placentas. The overexpression of placental sclerostin and LRP5 values in GDM compared with non-GDM pregnancies, as well as the positive association of placental sclerostin values with pregestational maternal body mass index and maternal fasting glucose concentrations may indicate the development of an adaptive mechanism in face of maternal hyperglycemia.

Relationship Between Sclerostin Levels and Coronary Artery Calcification and Plaque Composition.

The primary function of sclerostin is the regulation of bone metabolism. Research investigating the cardiovascular effects of sclerostin had conflicting results. We aimed to study serum sclerostin levels in coronary artery plaque types. Coronary calcium scores of 175 patients were evaluated. Patients with normal coronary arteries and calcium score of greater than zero constituted control (n = 47) and study groups (n = 83), respectively. Patients' plaques were further categorized as non-calcified plaque, calcified plaque, or mixed plaque (n = 45, n = 40, and n = 43, respectively). The study group had increased serum sclerostin levels than that of controls. Moreover, sclerostin levels were significantly higher in patients with calcified or mixed plaques compared to those without plaque or non-calcified plaque (median 248.5, 60.7-790.4) pg/mL and 1085.8 (185.8-3902.2) pg/mL versus 68.7 (34.0-141.3) pg/mL, and 67.7 (48.6-94.9) pg/mL, P < 0.001, respectively). Sclerostin showed a high correlation with coronary calcium scores (r = 0.95, P < 0.001). Serum sclerostin concentration of 106.27 pg/mL had 97.5% sensitivity and 67.4% specificity for the prediction of calcific plaque, whereas the level of 308.55 pg/mL had 95.3% sensitivity and 90.9% specificity for the prediction of mixed plaque. Coronary calcium scores, serum sclerostin, and C-reactive protein levels were significant predictors of 1-year major adverse cardiac events. Increased serum sclerostin level is a marker of coronary atherosclerosis burden and has a value for the prediction of 1-year major adverse cardiac events.

Trabecular bone score and sclerostin concentrations in patients with primary adrenal insufficiency

Patients with primary adrenal insufficiency need lifelong replacement therapy with glucocorticoids and mineralocorticoids, which may influence their bone quality. The aim of the study was to evaluate densitometry parameters, trabecular bone score and sclerostin concentrations in patients with primary adrenal insufficiency in comparison to control group. We included 29 patients (62% females) with diagnose of autoimmune primary adrenal insufficiency (mean age 49.7 ± 11.7 years, mean duration of the disease 13.2± 13.6 years) and 33 healthy subjects (adjusted with age, sex and body mass index). Bone mineral density at the femoral neck, lumbar spine, total body and trabecular bone score were evaluated. Serum sclerostin concentrations were measured. There were no significant differences in densitometry parameters (T-score, Z-score, bone mineral density in all locations) as well as in trabecular bone score in patients with adrenal insufficiency in comparison to control group. Mean serum sclerostin concentration was significantly higher in patients with adrenal insufficiency than in control group (44.7 ± 23.5 vs 30.7 ± 10.4 pmol/l, p=0.006). There was a negative correlation between trabecular bone score and the duration of adrenal insufficiency and age, also a negative correlation between femoral neck and total densitometry parameters and 24-hour urine cortisol as a marker of hydrocortisone daily dose in patients with adrenal insufficiency. The bone status in patients with primary adrenal insufficiency was not impaired in comparison to control group, while sclerostin concentration was higher. The duration of the disease and higher hydrocortisone doses may affect negatively bone status.

Role of sclrostin (SOST) to predisposing for osteoporosis in β- thalassemia major patients

Sclrostin is a biomarker interrupted in bone resorption process by binding to LRP5 and/or LRP6 family, and prevent Wingless-type signaling (Wnt) which is important to both bone development and the maintain of bone mass. Sixty (60) patients with thalassemia major were enrolled from the period 2/5/2021 to 1/9/2021 in summer to assessment role of sclrostin to predisposing for osteoporosis in β-thalassemia major patients (β-TM). Patients ages were from (2-40 year) males and females they divided to children and adults had osteoporosis and/or osteopenia."All patients diagnosed by Hb electrophoresis and were receiving regular blood transfusions for anemia and chelation therapy for prevention of iron overload related complications. Detailed history and examination including height and weight were recorded on pre-designed questionnaire and blood samples were taken for measurement of serum"sclrostin level. The results showed non-significant differences (P˃0.05) of serum sclerostin (SOST) concentration between osteoporosis of beta thalassemia patients (β-TM) and osteopenia of beta thalassemia patients for both gender, but appeared increased significant (P˃0.05) in male adults of osteopenia with progressive aged.

Serum Sclerostin Is Associated with Peripheral and Central Systolic Blood Pressure in Pediatric Patients with Primary Hypertension.

Recent studies showed the significance of the canonical Wnt/beta-catenin pathway and its inhibitor—sclerostin, in the formation of arterial damage, cardiovascular morbidity, and mortality. The study aimed to assess serum sclerostin concentration and its relationship with blood pressure, arterial damage, and calcium-phosphate metabolism in children and adolescents with primary hypertension (PH). Serum sclerostin concentration (pmol/L) was evaluated in 60 pediatric patients with PH and 20 healthy children. In the study group, we also assessed calcium-phosphate metabolism, office peripheral and central blood pressure, 24 h ambulatory blood pressure, and parameters of arterial damage. Serum sclerostin did not differ significantly between patients with PH and the control group (36.6 ± 10.6 vs. 41.0 ± 11.9 (pmol/L), p = 0.119). In the whole study group, sclerostin concentration correlated positively with height Z-score, phosphate, and alkaline phosphatase, and negatively with age, peripheral systolic and mean blood pressure, and central systolic and mean blood pressure. In multivariate analysis, systolic blood pressure (SBP) and height expressed as Z-scores were the significant determinants of serum sclerostin in the studied children: height Z-score (β = 0.224, (95%CI, 0.017–0.430)), SBP Z-score (β = −0.216, (95%CI, −0.417 to −0.016)). In conclusion, our results suggest a significant association between sclerostin and blood pressure in the pediatric population.

Sclerostin and Dickkopf-1 Characteristics According to Age and Physical Activity Levels in Premenopausal Women

We aimed to compare serum concentrations of sclerostin and DKK-1 in young (20-30 yrs, n = 25) and middle-aged (35-45 yrs, n = 25) premenopausal women and based on physical activity (PA) status. PA status was assessed by the International Physical Activity Questionnaire (low-moderate (≤ 2999 MET-min/week) and high (≥ 3000 MET-min/week). Serum sclerostin and DKK-1 levels were measured in fasting morning blood samples by ELISA. Areal bone mineral density (aBMD) was measured by DXA, and non-dominant tibia bone characteristics were assessed by pQCT. After adjusting for total body aBMD, middle-aged women had significantly (p < 0.001) higher (0.54 ± 0.01 ng/mL) serum sclerostin than young women (0.41 ± 0.01 ng/mL), and sclerostin was positively correlated with age (rs = 0.065, p ≤ 0.001) and total PA score (rs = 0.33, p = 0.021). Young women had higher left trochanter aBMD (p = 0.036) than middle-aged women and aBMD variables were higher (all p ≤ 0.043) in the high active group. Middle-aged women had higher 38% cortical vBMD than young women (p = 0.021), otherwise young women had higher values for pQCT variables (all p ≤ 0.036). Sclerostin showed significant correlations (r = 0.32 to 0.58, all p ≤ 0.026) with spine aBMD for the entire cohort and for each age group. Middle-aged women had significant correlations between sclerostin and hip aBMD sites (r = 0.043 to 0.56, all p ≤ 0.031). Sclerostin and cortical vBMD were positively correlated in the entire cohort (r = 0.35 to 0.50; both p < 0.013); split by age group, middle-aged women had positive correlations (r = 0.45 to 0.61 age and, all p ≤ 0.021) between sclerostin and pQCT variables. No significant differences for physical activity were observed for serum DKK-1 concentrations. Serum sclerostin concentrations were positively associated with age and bone characteristics in premenopausal women; however, these findings were not evident for circulating DKK-1. Further research is needed to elucidate the mechanisms for the discordant results in these Wnt inhibitors.

PTH-Independent Hypercalcemia in Undiagnosed Adrenal Insufficiency

In contrast to PTH-dependent hypercalcemia, the differential diagnosis of PTH-independent hypercalcemia is extensive. Thorough history and physical examination can help direct the clinician in the right direction and avoid extensive and unnecessary work up.A 27-year-old-female with a medical history significant only for untreated subclinical hypothyroidism was admitted to the hospital for hypercalcemia and acute kidney injury after presenting with dizziness, nausea, vomiting, dyspnea, and multiple syncopal episodes prior to admission. Serum calcium on presentation was elevated to 15.9 (8.5–10.2 mg/dL) with an intact parathyroid hormone level of 3.6 (8.5–75 pg/mL). On initial presentation, she was hypotensive, tachycardic, and was noted to be underweight with a body mass index of 17 kg/m2. The patient’s skin was diffusely hyperpigmented, with increased pigmentation in the creases of her hands and on the sides of her fingers. Further lab evaluation was remarkable for hyponatremia and hyperkalemia as well as an undetectable 8 AM cortisol of <1.0 (7–25 µg/dL), adrenocorticotropic hormone (ACTH) level significantly elevated to >1,250 (6–58 pg/mL), aldosterone <4 (<21 ng/dL), and plasma renin activity elevated to 18 (<0.6–3 ng/mL/h). Antibodies to 21-alpha hydroxylase were positive, confirming a diagnosis of Addison’s disease. Prior to the workup confirming an elevated ACTH and low cortisol levels, the patient was treated with aggressive intravenous fluid repletion and calcitonin with overnight improvement in calcium to 11.4 mg/dL. After the diagnosis of primary adrenal insufficiency was confirmed, she was treated with stress doses of intravenous hydrocortisone then gradually tapered to physiologic doses of oral hydrocortisone and fludrocortisone with resolution of her hypercalcemia by the fourth day of hospitalization.Adrenal insufficiency is a known but uncommon cause of PTH-independent hypercalcemia, but the exact mechanism is unknown. Hypercalcemia is thought to result from a combination of a hypovolemic state seen in adrenal insufficiency which leads to decreased urinary calcium excretion as well as increased bone resorption, which may result from increased serum sclerostin concentrations.Adrenal insufficiency should be considered in the differential of PTH-independent hypercalcemia. This case highlights the improvement in hypercalcemia that is seen with correction of glucocorticoid deficiency, and supports delaying additional work up for other PTH-independent causes until appropriate treatment has been given.

Serum sclerostin concentration is associated with specific adipose, muscle and bone tissue markers in lean adolescent females with increased physical activity.

Sclerostin is an important regulator of bone mass involving the Wnt/β-catenin signalling pathway. Relatively few studies have investigated the relationships of circulating sclerostin levels with adiposity-related and muscle-related biochemical factors in individuals with increased energy metabolism. The aim of this study was to investigate the associations of circulating sclerostin with adipokines, myokines, osteokines and body composition values in lean adolescent females with increased physical activity. A total of 73 adolescent females who were physically active and aged 14-18 years old participated in the study. Sclerostin, leptin, resistin, tumour necrosis factor (TNF)-α, interleukin (IL)-6, irisin, osteocalcin, C-terminal telopeptide of type I collagen (CTx), insulin-like growth factor (IGF)-1 and insulin were obtained from fasting blood samples. Body composition was measured by dual-energy X-ray absorptiometry (DXA) and analyzed for body fat mass, lean body mass, bone mineral content and muscle mass. Serum sclerostin (117.9±60.3pg/mL) was correlated with age, age at menarche, body fat, muscle mass, training activity, leptin, TNF-α, irisin, osteocalcin, CTx and IGF-1. Multivariate linear regression analysis demonstrated that fat mass (β = 0.434; p = 0.001), leptin (β =-0.308; p = 0.015), irisin (β = 0.227; p = 0.024) and CTx (β = 0.290; p = 0.031) were the most important predictors of serum sclerostin concentration. Bone-derived sclerostin is associated with specific adipokine, myokine and osteokine values in lean adolescent females with increased physical activity. These results suggest that the interactions between bone, adipose and muscle tissues could also be associated with circulating sclerostin concentrations.

Relationship Between Maternal Bone Biomarkers and Fetal Adiposity Through Normal Pregnancy.

To examine the association of maternal bone markers [sclerostin, soluble receptor activator of nuclear factor-κB ligand (sRANKL), osteocalcin, 25-hydroxyvitamin D3] with fetal intra-abdominal and subcutaneous adipose tissue deposition and birthweight during normal pregnancy. One hundred pregnant women (aged 30.4 ± 5.6 years, mean ± SD) with prepregnancy body mass index = 24.1 ± 4.6 kg/m2 were seen prospectively during each trimester. At each visit they were submitted to anthropometric measurements, a fasting blood sampling, a 75-g oral glucose tolerance test, and a fetal ultrasonogram. At birth, neonates had birth weight measurement. In the second trimester, maternal sclerostin concentrations correlated positively with fetal abdominal circumference and birth weight; maternal sRANKL concentrations correlated positively with fetal abdominal subcutaneous fat thickness, sagittal abdominal diameter, and abdominal circumference. Fetuses born to mothers with greater (>254 ng/mL), compared to fetuses born to mothers with lower (≤254ng/mL), sRANKL concentrations had greater abdominal circumference, sagittal diameter, and abdominal subcutaneous fat thickness. Maternal serum sclerostin concentrations were the best positive predictors of birth weight. In the third trimester maternal sclerostin concentrations correlated positively with fetal sagittal abdominal diameter; maternal sRANKL concentrations positively correlated with fetal abdominal circumference and fetal abdominal sagittal diameter. Maternal bone markers sclerostin and sRANKL may relate to fetal intra-abdominal adipose tissue deposition through as yet unknown direct or indirect mechanisms, thus contributing to birthweight.

The Impact of Sclerostin Levels on Long-Term Prognosis in Patients Undergoing Coronary Angiography: A Personalized Approach with 9-Year Follow-Up.

Sclerostin might play a role in atherosclerosis development. This study aimed to analyze the impact of baseline sclerostin levels on 9-year outcomes in patients without significant renal function impairment and undergoing coronary angiography. The primary study endpoint was the rate of major cardiovascular events (MACE), defined as a combined rate of myocardial infarction (MI), stroke, or death at 9 years. We included 205 patients with a mean age of 62.9 ± 0.6 years and 70.2% male. Median serum sclerostin concentration was 133.22 pg/mL (IQR 64.0–276.17). At 9 years, in the whole population, the rate of MACE was 34.1% (n = 70), MI: 11.2% (n = 23), stroke: 2.4% (n = 5), and death: 20.5% (n = 42). In the high sclerostin (>median) group, we observed statistically significant higher rates of MACE and death: 25.2% vs. 43.1% (HR 1.75, 95% CI 1.1–2.10, p = 0.02) and 14.6% vs. 26.5% (HR 1.86, 95% CI 1.02–3.41, p = 0.049), respectively. Similar relationships were observed in patients with chronic coronary syndrome and SYNTAX 0–22 subgroups. Our results suggest that sclerostin assessment might be useful in risk stratification, and subjects with higher sclerostin levels might have a worse prognosis.

Serum sclerostin is negatively associated with insulin sensitivity in obese but not lean women.

ObjectiveThe mechanisms underlying the development of peripheral insulin resistance are complex. Several studies have linked sclerostin, an osteocyte-derived inhibitor of the Wnt/β-catenin pathway, to obesity and insulin resistance. The aim of this study was to investigate (1) whether serum sclerostin is associated with insulin sensitivity in lean and/or obese women; and (2) whether hyperinsulinaemia affects serum sclerostin concentrations.DesignA cross-sectional study.MethodsInsulin sensitivity was measured in lean (BMI < 25 kg/m2) and obese (BMI > 30 kg/m2) women using a hyperinsulinaemic–euglycaemic clamp. Serum sclerostin was measured at baseline and during the clamp procedure.ResultsWe studied 21 lean and 22 obese women with a median age of 40 and 43 years and a median BMI of 22.4 and 33.5 kg/m2, respectively. Obese women had higher serum sclerostin than lean women (122 ± 33 vs 93 ± 33 nmol/L, P < 0.01). Higher serum sclerostin was associated with lower insulin sensitivity in obese, but not in lean individuals (difference in M-value between highest and lowest quartile: −7.02 mg/kg/min, P = 0.03 and 1.59 mg/kg/min, P = 0.50, respectively). Hyperinsulinaemia did not affect serum sclerostin in lean nor obese women (P > 0.5).ConclusionSerum sclerostin is negatively associated with insulin sensitivity as measured with the hyperinsulinaemic–euglycaemic clamp in obese, but not lean women. This indicates a potential role of the Wnt/β-catenin pathway in regulating insulin sensitivity particularly in obese individuals. Our findings remain hypothesis-generating and should be confirmed by additional studies.

Serum sclerostın levels ın chronıc otıtıs medıa wıth and wıthout cholesteatoma.

OBJECTIVE Sclerostin is a glycoprotein that plays a catabolic role in bone and is involved in the regulation of bone metabolism by increasing the osteoclastic bone resorption. In this study, serum sclerostin levels were measured in chronic otitis media (COM) with and without cholesteatoma, assuming that it might have a role in the aetiopathogenesis of bone resorption. METHODS A total of 44 patients with cholesteatomatous COM (cCOM) (n = 22) and non-cholesteatomatous COM (ncCOM) (n = 22) were included in this study, and 26 healthy volunteers without any chronic ear disease problem(s) constituted the control group (n = 26). RESULTS No significant difference was not found in terms of serum iPTH, ALP, and vitamin D levels between ncCOM, cCOM, and the control groups. A significant difference was found in terms of serum sclerostin, Ca, and P levels between ncCOM, cCOM, and the control groups (p<0.05). Serum sclerostin levels in the study groups were significantly higher but their serum Ca and P levels were significantly lower compared to the control group. CONCLUSION We think that serum sclerostin concentrations, which were significantly higher in patients with cCOM and ncCOM compared to healthy controls are associated with bone erosion. There is a need for further studies with larger samples in order to determine the relationship between sclerostin and bone erosion in cholesteatoma to help in establishing preventive measures against cholesteatoma and set new targets for the development of non-surgical treatments.

Short-Term Glucocorticoid Treatment Reduces Circulating Sclerostin Concentrations in Healthy Young Men: A Randomized, Placebo-Controlled, Double-Blind Study.

ABSTRACTGlucocorticoid use is the most common cause of osteoporosis in young individuals. In the current study, we investigated the effects of glucocorticoid treatment on circulating sclerostin concentrations and serum bone turnover markers in healthy young men. We performed additional measurements in two combined randomized, placebo‐controlled, double‐blind, dose–response intervention studies: 64 healthy men (age: 22 ± 2 years; BMI: 22.1 ± 1.7 kg/m2) were allocated to receive placebo (n = 16), prednisolone 7.5 mg once daily (n = 24), or prednisolone 30 mg once daily (n = 24) for 2 weeks using block randomization. Primary outcome variables were serum sclerostin and serum bone turnover markers (CTx and P1NP), before and after the intervention. Baseline characteristics and variables did not differ between intervention groups. Compared with placebo, prednisolone high‐dose decreased serum sclerostin concentrations (−8.5 [−28.0 to 7.3] versus 1.5 [−6.5 to 20.0] pg/mL, p = 0.048), decreased P1NP concentrations (−28.0 [−39.3 to −18.3] versus –1.5 [−15.3 to 11.3] μg/L, p < 0.001) and increased CTx concentrations (108.0 [55.0 to 177.0] versus 64.0 [−24.3 to 120.0] ng/L, p = 0.038). Compared with placebo, prednisolone low‐dose did not alter sclerostin concentrations (p = 0.5) or CTx concentrations (p = 0.7), but tended to decrease P1NP concentrations (−9.0 [−24.0 to −1.3] versus –1.5 [−15.3 to 11.3] μg/L, p = 0.095). At baseline concentrations of sclerostin were positively correlated with concentrations of CTx (Spearman's rank correlation coefficient ρ = +0.409, p = 0.001), but not with P1NP. No significant correlations were observed between changes in outcome variables during the interventions. Short‐term high‐dose, but not low‐dose, prednisolone treatment reduces serum sclerostin concentrations in healthy young men. Whether this reflects a counter regulatory mechanism to compensate glucocorticoid‐induced negative effects through other mechanisms remains to be elucidated. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Body Composition, Serum Sclerostin and Physical Function After Bariatric Surgery: Performance of Dual-Energy X-ray Absorptiometry and Multifrequency Bioelectrical Impedance Analysis.

The aim of this study was to determine the effects of bariatric surgery and weight loss on body composition, serum sclerostin and physical performance. Seventy-three consecutive patients (36 non-surgical controls and 37 who underwent bariatric surgery) were evaluated by means of laboratory tests, multifrequency bioelectrical impedance analysis (BIA), total-body dual-energy X-ray absorptiometry (DXA), gait speed and handgrip strength. The differences between non-surgical and surgical patients were as follows: body mass index (BMI) 42.9 ± 5.7 vs 34.8 ± 6.0kg/m2 (p < 0.001); handgrip strength 31.3 ± 7.0 vs 27.1 ± 9.3kg (p < 0.033); skeletal muscle mass index (SMI)-BIA 12.3 ± 1.2 vs 10.6 ± 1.2kg/m2; fat-free mass index (FFMI)-BIA 21.9 ± 1.9 vs 18.9 ± 2.1k/m2 (p < 0.001 for all comparisons); Baumgartner-DXA 10.8 ± 1.5 vs 9.0 ± 1.4kg/m2 (p < 0.001); fat mass BIA 55.4 ± 12.5 vs 36.8 ± 9.6; fat mass DXA 54.3 ± 12.38 vs 35.1 ± 7.5kg (p < 0.001 for both comparisons) and serum sclerostin 30.9 ± 31.9 vs 26.9 ± 21.1pmol/L (p = 0.516). Positive correlation was found between BIA and DXA: SMI × Baumgartner (r = 0.842; p < 0.001) and fat mass (r = 0.970; p < 0.001). Gait speed was relatively preserved in sleeve gastrectomy (SG) compared with Roux-en-Y gastric bypass (RYGB) (1.2 ± 0.3 and 0.9 ± 0.1m/s; p = 0.038). Bariatric surgery leads to lower values of lean and fat mass and of handgrip strength with no differences in serum sclerostin concentrations. There was a positive correlation between BIA and DXA for fat and lean mass parameters. Physical performance was better after SG than in RYGB.

The association of circulating sclerostin level with markers of bone metabolism in patients with thyroid dysfunction.

The aim of this study was to compare serum sclerostin concentrations in patients with thyroid dysfunction with euthyroid control subjects and to assess the relationship between sclerostin and markers of bone metabolism (osteocalcin and beta-cross-laps). The study included 30 patients with thyroid dysfunction (hypothyroidism, hyperthyroidism and subclinical hyperthyroidism) and ten euthyroid controls. Free thyroxine (FT4) was measured by radioimmunoassay, while thyroid stimulating hormone (TSH) concentration was determined immunoradiometrically. We used an ELISA kit to determine the sclerostin level. The electrochemiluminescence method was applied for measuring the bone markers. Sclerostin levels were significantly lower in hypothyroid patients (p=0.009) and significantly elevated in hyperthyroid patients (p=0.008) compared to control values. Hyperthyroid patients also had higher sclerostin than patients with subclinical hyperthyroidism (p=0.013). Sclerostin concentrations were negatively correlated with TSH levels (r=-0.746, p<0.001), but positively with FT4 (r=0.696, p < 0.001). Moreover, sclerostin was positively associated with osteocalcin (r=0.605, p=0.005) and beta-cross-laps levels (r=0.573, p=0.008) in all thyroid patients. Serum sclerostin is significantly affected in subjects with thyroid dysfunction. Both sclerostin and thyroid status affect bone homeostasis, which is reflected through the significant correlations with osteocalcin and beta-cross-laps.

534-P: Serum Sclerostin, Body Composition, and Sarcopenia in Hemodialysis Patients with Diabetes

Sclerostin (Scl) is an osteoblast inhibiting glycoprotein secreted mainly by osteocytes which is regulated by hormonal changes and skeletal loading. Decreased physical function and high serum Scl concentrations have been reported in chronic renal failure patients but little is known about the differences among diabetic and nondiabetic patients on hemodyalisis who are susceptible to both sarcopenia and bone fragility. Objective: To determine the prevalence of sarcopenia and its association with serum sclerostin concentrations and metabolic parameters in 92 patients on hemodyalisis. Anthropometric data and physical performance were evaluated. Blood sample were collected for sclerostin, glucose, cholesterol, triglycerides, calcium, phosphate, PTH e 25OH-vitamin D measurements. Lean mass was evaluated using multifrequency electro-bioimpedance at a “dry weight” time (after dialysis session). Results: Mean age was 63.3±13.6 years, 63% were male and 44.6% had diabetes. Mean BMI was higher in diabetics (26.6±5.2 vs. 24.1±3.7; p=0.01) and there were no differences in gait speed and hand grip strength between diabetic and nondiabetic subjects. A low skeletal muscle mass index (SMI) was identified in 65.2% of the participants, and among them 76.7% were men and 36.7% diabetics. Mean serum sclerostin was 86.9 ± 39.0 pmol/L, which was higher in men (94.6 ± 41.7; p = 0.017), in individuals with low SMI (94.9 ± 40.7; p &amp;lt; 0.001) and in diabetics (97.2 ± 46.6; p &amp;lt; 0.003). After multivariate analysis and adjustments for potential confounders, high serum sclerostin was independently associated with low SMI and with the presence of diabetes. The following variables correlated positively with diabetes: blood pressure, body mass index (BMI) waist circumference, waist/hip ratio, plasma glucose, serum sclerostin and fat mass. Conclusions: We found higher serum sclerostin concentrations in hemodialysis patients with diabetes which were inversely related to muscle mass. Disclosure F. Bandeira: None. M.W. Medeiros: None. M.H. Junior: None. N.R. Silva: None. M. Bandeira Farias: None. L. Farias: None. Funding Arab Society for Paediatric Endocrinology and Diabetes

Serum Sclerostin and Bone Morphogenetic Protein-2 Levels in Patients with Ankylosing Spondylitis: A Meta-Analysis.

Various studies have investigated the serum sclerostin and bone morphogenetic protein-2 (BMP-2) levels in patients with ankylosing spondylitis (AS), but the results were inconsistent. The aim of this meta-analysis was to synthetically assess the associations of serum levels of sclerostin and BMP-2 with AS. Multiple electronic databases were searched to locate relevant articles published before November 2018. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by the random-effect model. Totally, 21 studies were included. Meta-analysis results showed no significant difference between AS group and control group in serum sclerostin levels (SMD = 0.098, 95% CI - 0.395 to 0.591, p = 0.697). Nevertheless, serum BMP-2 levels in AS patients were higher than that in controls (SMD = 1.184, 95% CI 0.209 to 2.159, p = 0.017). Subgroup analysis demonstrated that European and South American AS patients had lower serum levels of sclerostin than controls. AS patients with age ≥ 40 years, erythrocyte sedimentation rate (ESR) ≤ 20mm/h and Bath Ankylosing Spondylitis Functional Index (BASFI) < 4 had statistically significant lower serum sclerostin concentrations compared to controls. Chinese and Korean AS patients as well as patients with lower CRP had higher serum BMP-2 levels than controls, and country may be a source of heterogeneity across the studies. No publication bias existed and sensitivity analysis confirmed the stability of results. Serum BMP-2, but not sclerostin levels may be closely related to the development of AS.