Increased sclerostin and bone turnover after diet-induced weight loss in type 2 diabetes: a post hoc analysis of the MADIAB trial

Strollo, Rocky; Soare, Andreea; Khazrai, Yeganeh Manon; Mauro, A. Di; Palermo, Andrea; Toro, Rossella Del; Fallucca, Sara; Belluomo, Maria Giovanna; Dugo, Laura; Pianesi, Mario; Pozzilli, Paolo; Napoli, Nicola

doi:10.1007/s12020-016-1171-7

Cited by 9 publications

(6 citation statements)

References 37 publications

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“…Sclerostin has been studied in association with other features of MetS, such as body weight, providing mixed results. A positive correlation with body weight or BMI has been shown in a report (7), while others have reported no association (6,9) such as in the present study, or even increased levels in response to weight loss, as also recently shown by our group (36).…”

Section: Discussionsupporting

confidence: 84%

Serum Sclerostin and Bone Turnover in Latent Autoimmune Diabetes in Adults

Napoli

Strollo

Defeudis

et al. 2018

The Journal of Clinical Endocrinology &Amp; Metabolism

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Section: Discussionsupporting

confidence: 84%

Serum Sclerostin and Bone Turnover in Latent Autoimmune Diabetes in Adults

Napoli

Strollo

Defeudis

et al. 2018

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…In patients with T2D, a weight loss of 20% or more leads to increased risk of fragility fractures compared to a weight loss of less than 10% [ 82 ]. Thus, changes in body composition may influence fracture risk and a rapid diet-induced weight loss is accompanied by increased circulating levels of sclerostin and CTX in patients with T2D [ 83 ]. Microangiopathy in diabetes is proposed to increase fracture risk by increasing cortical porosity [ 84 ] and diabetes complications may also influence fracture risk as peripheral neuropathy [ 85 86 ], and retinopathy [ 9 87 ] is associated with an increased risk of fracture in T2D .…”

Section: Detection Of Diabetic Bone Diseasementioning

confidence: 99%

Skeletal Fragility in Type 2 Diabetes Mellitus

2018

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Type 2 diabetes (T2D) is associated with an increased risk of fracture, which has been reported in several epidemiological studies. However, bone mineral density in T2D is increased and underestimates the fracture risk. Common risk factors for fracture do not fully explain the increased fracture risk observed in patients with T2D. We propose that the pathogenesis of increased fracture risk in T2D is due to low bone turnover caused by osteocyte dysfunction resulting in bone microcracks and fractures. Increased levels of sclerostin may mediate the low bone turnover and may be a novel marker of increased fracture risk, although further research is needed. An impaired incretin response in T2D may also affect bone turnover. Accumulation of advanced glycosylation endproducts may also impair bone strength. Concerning antidiabetic medication, the glitazones are detrimental to bone health and associated with increased fracture risk, and the sulphonylureas may increase fracture risk by causing hypoglycemia. So far, the results on the effect of other antidiabetics are ambiguous. No specific guideline for the management of bone disease in T2D is available and current evidence on the effects of antiosteoporotic medication in T2D is sparse. The aim of this review is to collate current evidence of the pathogenesis, detection and treatment of diabetic bone disease.

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“…In the present study, at baseline a significant positive correlation was found between serum sclerostin with CTx, but not with P1NP concentrations. Results in other studies regarding correlations between sclerostin concentrations and concentrations of bone turnover markers are contrasting . Sclerostin is thought to act predominantly as an inhibitor of bone formation.…”

Section: Discussionmentioning

confidence: 91%

“…Results in other studies regarding correlations between sclerostin concentrations and concentrations of bone turnover markers are contrasting. (27)(28)(29) Sclerostin is thought to act predominantly as an inhibitor of bone formation. However, in mice, the Wnt/β-catenin signaling pathway predominantly anabolic for bone, is switched to anticatabolic in situations of glucocorticoid excess.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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Glucocorticoid 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.

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Increased sclerostin and bone turnover after diet-induced weight loss in type 2 diabetes: a post hoc analysis of the MADIAB trial

Abstract: Diet-induced weight loss may induce significant and rapid changes in bone turnover and sclerostin levels. These changes may further impair bone health in subjects with type 2 diabetes.

Cited by 9 publications

References 37 publications

Serum Sclerostin and Bone Turnover in Latent Autoimmune Diabetes in Adults

Serum Sclerostin and Bone Turnover in Latent Autoimmune Diabetes in Adults

Skeletal Fragility in Type 2 Diabetes Mellitus

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

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