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

Lauterlein, Jens Jacob Lindegaard; Hermann, Pernille; Konrad, Thomas R.; Wolf, Peter; Nilsson, Peter M.; Sánchez, Rafael; Ferrannini, Ele; Balkau, Beverley; Højlund, Kurt; Frost, Morten

doi:10.1016/j.bone.2020.115681

Cited by 4 publications

(2 citation statements)

References 40 publications

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“…Sclerostin is secreted by osteocytes and inhibits osteoblast activity as part of bone's adaptative response to mechanical loading ( 110 ). Serum sclerostin has been positively associated with fasting blood glucose and declines in response to acute hyperinsulinemia ( 111 , 112 ). On the contrary, fasting blood glucose level or glucose variability did not contribute to serum sclerostin level, while other BTMs such as serum CTX and PINP were significantly affected by blood glucose levels ( 113 ).…”

Section: Methodsmentioning

confidence: 99%

Biochemical Markers of Bone Fragility in Patients With Diabetes

Meier

Eastell

Pierroz³

et al. 2023

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context The risk of fragility fractures is increased in both type 1 and type 2 diabetes. Numerous biochemical markers reflecting bone and/or glucose metabolism have been evaluated in this context. This review summarizes current data on biochemical markers in relation to bone fragility and fracture risk in diabetes. Methods Literature review by a group of experts from the International Osteoporosis Foundation (IOF) and European Calcified Tissue Society (ECTS) focusing on biochemical markers, diabetes, diabetes treatments and bone in adults. Results Although bone resorption and bone formation markers are low and poorly predictive of fracture risk in diabetes, osteoporosis drugs seem to change bone turnover markers in diabetics similarly to non-diabetics, with similar reductions in fracture risk. Several other biochemical markers related to bone and glucose metabolism have been correlated with BMD and/or fracture risk in diabetes, including osteocyte-related markers such as sclerostin, HbA1c and advanced glycation end products (AGEs), inflammatory markers and adipokines, as well as IGF-1 and calciotropic hormones. Conclusion Several biochemical markers and hormonal levels related to bone and/or glucose metabolism have been associated with skeletal parameters in diabetes. Currently, only HbA1c levels seem to provide a reliable estimate of fracture risk, while bone turnover markers could be used to monitor the effects of anti-osteoporosis therapy.

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Section: Methodsmentioning

confidence: 99%

Biochemical Markers of Bone Fragility in Patients With Diabetes

Meier

Eastell

Pierroz³

et al. 2023

The Journal of Clinical Endocrinology &Amp; Metabolism

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show abstract

“…After mechanical unloading, osteocytes secrete sclerostin, which inhibits bone formation by blocking Wnt signaling. ( 15 ) Although serum sclerostin levels and insulin sensitivity were not associated in healthy and prediabetic men, ( 16 ) sclerostin levels are increased in overt T2D. ( 17 ) This indicates that hyperglycemia changes the function of osteocytes and the lacunocanalicular network, which may lead to lower bone remodeling and higher cortical porosity in T2D.…”

Section: Introductionmentioning

confidence: 99%

Microvascular Disease Associates with Larger Osteocyte Lacunae in Cortical Bone in Type 2 Diabetes Mellitus

Zanner,

Goff,

Ghatan

et al. 2023

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Clinical studies indicate that microvascular disease (MVD) affects bone microstructure and decreases bone strength in type 2 diabetes mellitus (T2D). Osteocytes are housed in small voids within the bone matrix and lacunae and act as sensors of mechanical forces in bone. These cells regulate osteoclastic bone resorption and osteoblastic bone formation as well as osteocytic perilacunar remodeling. We hypothesized that MVD changes morphometric osteocyte lacunar parameters in individuals with T2D. We collected iliac crest bone biopsies from 35 individuals (10 female, 25 male) with T2D with MVD (15%) or without MVD (21%) with a median age of 67 years (interquartile range [IQR] 62–72 years). The participants were included based on c‐peptide levels >700 pmol L−1, absence of anti‐GAD65 antibodies, and glycated hemoglobin (HbA1c) levels between 40 and 82 mmol mol−1 or 5.8% and 9.7%, respectively. We assessed osteocyte lacunar morphometric parameters in trabecular and cortical bone regions using micro‐computed tomography (micro‐CT) at a nominal resolution of 1.2 μm voxel size. The cortical osteocyte lacunar volume (Lc.V) was 7.7% larger (p = 0.05) and more spherical (Lc.Sr, p < 0.01) in the T2D + MVD group. Using linear regression, we found that lacunar density (Lc.N/BV) in trabecular but not cortical bone was associated with HbA1c (p < 0.05, R2 = 0.067) independently of MVD. Furthermore, Lc.V was larger and Lc.Sr higher in the center than in the periphery of the trabecular and cortical bone regions (p < 0.05). In conclusion, these data imply that MVD may impair skeletal integrity, possibly contributing to increased skeletal fragility in T2D complicated by MVD. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

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New Emerging Biomarkers for Bone Disease: Sclerostin and Dickkopf-1 (DKK1)

Dinçel

Jørgensen

2022

Calcif Tissue Int

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

Cited by 4 publications

References 40 publications

Biochemical Markers of Bone Fragility in Patients With Diabetes

Biochemical Markers of Bone Fragility in Patients With Diabetes

Microvascular Disease Associates with Larger Osteocyte Lacunae in Cortical Bone in Type 2 Diabetes Mellitus

New Emerging Biomarkers for Bone Disease: Sclerostin and Dickkopf-1 (DKK1)

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