Role of sclerostin and dkk1 in bone remodeling in type 2 diabetic patients

Wang, Na; Xue, Peng; Wu, Xuelun; Ma, Jianxia; Wang, Yan; Li, Yukun

doi:10.1080/07435800.2017.1373662

Cited by 28 publications

(24 citation statements)

References 47 publications

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“…We found that serum sclerostin was higher in patients with combined T2DM and osteoporosis than osteoporosis only; the biomarker was positively correlated with higher degrees of osteoporosis-as indicated by BMD-as well as markers of insulin resistance and glycemic control. Similar to our ndings, Wang and colleagues (33) showed that the combination of T2DM and osteoporosis led to higher increase in serum sclerostin than osteoporosis alone; moreover, serum sclerostin correlated with BMD parameters, HbA1c, and serum glucose level. Likewise, García-Martín and colleagues (34) found positive correlation between with higher severity of osteoporosis, HOMA-IR, and serum insulin.…”

Section: Discussionsupporting

confidence: 89%

The Impact of Type 2 Diabetes Mellitus on the Markers of Osteoporosis (Sclerostin and CTRP3) in Postmenopausal Women: A Comparative, Observational, Study

Ahmad

Wakeel

Elhamed

et al. 2020

Preprint

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Background In the present study, our goal was to assess the impact of type 2 diabetes mellites (T2DM) on osteoporosis markers (sclerostin and CTRP3) among postmenopausal women, and whether sclerostin and CTRP3 can be used as early biomarkers of osteoporosis/osteopenia in T2DM patients. Methods In a comparative, observation, study, a total of 30 postmenopausal women with osteoporosis/osteopenia and T2DM were included, as well as 30 non-diabetic women with osteoporosis/osteopenia. Thirty age and sex-matched healthy women were included as control groups. The enzyme-linked immunosorbent assay (ELISA) was used to assess the serum levels of sclerostin and CTRP3. Results A total of 90 women were included in the present study (30 patients per group). The serum CTRP3 was significantly lower in the DM-OST (3.45 ± 3.5 ng/dL) and OST (9.15 ± 3.65 ng/dL) groups than the control group (16.80 ± 0.55 ng/dL; p < 0.001); likewise, the serum sclerostin was higher in the DM-OST (109.95 ± 28.96 pmol/L) and OST (51.52 ± 23.18 pmol/L) than the control group (11.22 ± 1.21 pmol/L; p < 0.001). Notably, the serum CTRP3 was significantly lower and sclerostin was significantly higher in the DM-OST group than the OST group (p < 0.001)). In the DM + OST and OST groups, the serum CTRP3 correlated positively with BMD of lumbar spines, left femur, and left forearm. Serum CTRP3 was associated with lower risk of osteoporosis (OR) and diabetes (OR) in postmenopausal women. In addition, the serum sclerostin was associated with higher risk of osteoporosis (OR) and diabetes (OR) in postmenopausal women. Conclusion The present study provides a novel evidence about the impact of T2DM on osteoporosis biomarkers, serum CTRP3 and sclerostin. The results indicated that women with combined T2DM and osteoporosis/osteopenia exhibited more dysregulation in both biomarkers than women with osteoporosis/osteopenia. alone. Thus, serum CTRP3 and sclerostin can be used as biomarkers for early detection of osteoporosis in diabetic patients.

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Section: Discussionsupporting

confidence: 89%

The Impact of Type 2 Diabetes Mellitus on the Markers of Osteoporosis (Sclerostin and CTRP3) in Postmenopausal Women: A Comparative, Observational, Study

Ahmad

Wakeel

Elhamed

et al. 2020

Preprint

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“…Recently, we and others demonstrated that serum and skeletal levels of DKK1, but not SOST, are elevated in obese mice and in patients with type 2 diabetes mellitus . As DKK1 is a potent suppressor of bone formation and bone mass, we hypothesized that elevated DKK1 levels may drive obesity‐induced bone loss in mice.…”

Section: Introductionmentioning

confidence: 92%

Contributions of Dickkopf‐1 to Obesity‐Induced Bone Loss and Marrow Adiposity

et al. 2020

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Low bone strength in overweight individuals is a significant medical problem. One important determinant of mesenchymal stem cell fate into osteoblasts or adipocytes is the Wnt signaling pathway. We recently showed that Dickkopf‐1 (DKK1), a potent Wnt inhibitor, is upregulated in obese mice. In this study, we investigated the role of DKK1 in the pathogenesis of obesity‐induced bone loss using global and tissue‐specific KO mice. Obesity was induced in 8‐week‐old male mice with an inducible global (Rosa26‐CreERT2) or osteoprogenitor‐ (Osx–Cre‐) specific deletion of Dkk1 with a high‐fat diet (HFD) containing 60% fat. After 12 weeks, body weight, bone volume, bone fat mass, and bone turnover were assessed. Dkk1 fl/fl;Rosa26‐CreERT2 mice experienced a similar increase in body weight and white fat pads as control mice. A HFD significantly reduced trabecular bone mass and the bone formation rate in Cre‐ mice and Dkk1 fl/fl;Rosa26‐CreERT2 mice. Interestingly, Dkk1 fl/fl;Rosa26‐CreERT2 mice were protected from HFD‐induced cortical bone loss. Furthermore, a HFD was associated with increased bone marrow fat in the femur, which was less pronounced in Dkk1 fl/fl;Rosa26‐CreERT2 mice. Mice with an osteoprogenitor‐specific Dkk1 deletion showed similar results as the global knockout, showing a protection against HFD‐induced cortical bone loss and an accumulation of bone marrow fat, but a similar decrease in trabecular bone volume. In summary, DKK1 appears to contribute distinctly to cortical, but not trabecular bone loss in obesity. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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“…In our meta-analysis we also found increased levels of circulating sclerostin in patients with T2D compared with controls [ 25 ]. Circulating levels of sclerostin have previously been associated with low BMD and also correlated negatively with circulating levels of PINP in patients with T2D [ 30 ]. Sclerostin is produced by the osteocytes and regulate bone turnover by being an antagonist of the Wnt pathway [ 31 ].…”

Section: Low Bone Turnover In 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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Role of sclerostin and dkk1 in bone remodeling in type 2 diabetic patients

Cited by 28 publications

References 47 publications

The Impact of Type 2 Diabetes Mellitus on the Markers of Osteoporosis (Sclerostin and CTRP3) in Postmenopausal Women: A Comparative, Observational, Study

The Impact of Type 2 Diabetes Mellitus on the Markers of Osteoporosis (Sclerostin and CTRP3) in Postmenopausal Women: A Comparative, Observational, Study

Contributions of Dickkopf‐1 to Obesity‐Induced Bone Loss and Marrow Adiposity

Skeletal Fragility in Type 2 Diabetes Mellitus

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