Metformin attenuates diabetes-induced osteopenia in rats is associated with down-regulation of the RAGE-JAK2-STAT1 signal axis

Lin, Rui; Xu, Bin; Ye, Zhiqiang; Yin, Guangwen; Fang, H. S.; Song, Jintong; Liang, Dahong; Liu, Lingna; Hu, Zhiying; Zhang, Min; Wei, Jinsong; Deng, Feifu; Zhong, Xiangxin; Cui, Liao; Liu, Yan Zhi

doi:10.1016/j.jot.2023.05.002

Cited by 5 publications

(1 citation statement)

References 63 publications

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“…The exact mechanisms of interfering with glucose homeostasis are still unclear, but experimental studies on β-cells showed that the monoclonal antibody that blocks the RANK/RANKL pathway might protect the pancreatic cell against dysfunction and apoptosis induced by diabetes-induced inflammatory cytokines and reactive oxygen species [130]. Additionally, we mention further topics to explore such as the results of murine experiments showing linagliptin and metformin protective effects against bone loss [131] (one of the pathogenic traits being metformin-induced down regulation of RAGE-JAK2-STAT1 signal transduction pathway) [132]. Also, the metabolic components other than the anomalies of glucose profile, such as obesity, chronic steatosis, and abnormal lipid status might add a supplementary influence on bone damage that may be additional to insulin resistance, hyperinsulinemia, and increased blood glycemia together with the potential impairment of mineral metabolism [133][134][135].…”

Section: Integrating Tbs To the Panel Of Bone Status Assessment In T2dmmentioning

confidence: 99%

Trabecular Bone Score (TBS) in Individuals with Type 2 Diabetes Mellitus: An Updated Review

Trandafir,

Sima,

Gheorghe

et al. 2023

JCM

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Bone fragility is a complication of type 2 diabetes mellitus (T2DM) that has been identified in recent decades. Trabecular bone score (TBS) appears to be more accurate than bone mineral density (BMD) in diabetic bone disease, particularly in menopausal women with T2DM, to independently capture the fracture risk. Our purpose was to provide the most recent overview on TBS-associated clinical data in T2DM. The core of this narrative review is based on original studies (PubMed-indexed journals, full-length, English articles). The sample-based analysis (n = 11, N = 4653) confirmed the use of TBS in T2DM particularly in females (females/males ratio of 1.9), with ages varying between 35 and 91 (mean 65.34) years. With concern to the study design, apart from the transversal studies, two others were prospective, while another two were case-control. These early-post-pandemic data included studies of various sample sizes, such as: males and females (N of 245, 361, 511, and 2294), only women (N of 80, 96, 104, 243, 493, and 887), and only men (N = 169). Overall, this 21-month study on published data confirmed the prior profile of BMD-TBS in T2DM, while the issue of whether checking the fracture risk is mandatory in adults with uncontrolled T2DM remains to be proven or whether, on the other hand, a reduced TBS might function as a surrogate marker of complicated/uncontrolled T2DM. The interventional approach with bisphosphonates for treating T2DM-associated osteoporosis remains a standard one (n = 2). One control study on 4 mg zoledronic acid showed after 1 year a statistically significant increase of lumbar BMD in both diabetic and non-diabetic groups (+3.6%, p = 0.01 and +6.2%, p = 0.01, respectively). Further studies will pinpoint additive benefits on glucose status of anti-osteoporotic drugs or will confirm if certain glucose-lowering regimes are supplementarily beneficial for fracture risk reduction. The novelty of this literature research: these insights showed once again that the patients with T2DM often have a lower TBS than those without diabetes or with normal glucose levels. Therefore, the decline in TBS may reflect an early stage of bone health impairment in T2DM. The novelty of the TBS as a handy, non-invasive method that proved to be an index of bone microarchitecture confirms its practicality as an easily applicable tool for assessing bone fragility in T2DM.

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Section: Integrating Tbs To the Panel Of Bone Status Assessment In T2dmmentioning

confidence: 99%

Trabecular Bone Score (TBS) in Individuals with Type 2 Diabetes Mellitus: An Updated Review

Trandafir,

Sima,

Gheorghe

et al. 2023

JCM

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Localized delivery of metformin via 3D printed GelMA-Nanoclay hydrogel scaffold for enhanced treatment of diabetic bone defects

Li,

Mao,

Zhong

et al. 2024

Journal of Orthopaedic Translation

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Low bone turnover is associated with advanced glycation end‐products, oxidative stress, and inflammation induced by type 2 diabetes mellitus

Shi,

Gong,

Lyu

et al. 2024

The FASEB Journal

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Type 2 diabetes mellitus (T2DM) can lead to multiple complications. T2DM‐related bone damage has been linked to abnormal bone turnover, but it cannot fully explain the mechanisms of T2DM bone disease. This study attempts to elucidate the underlying mechanisms of poor bone quality in T2DM. Hence, T2DM model was induced by a high‐fat diet combined with a single streptozotocin injection in 7‐week‐old male SD rats. Osteoblasts derived from SD rats were cultured in high glucose to mimic hyperglycemia. Low bone turnover was observed in T2DM bone with elevated levels of advanced glycation end‐products (AGEs) and receptor for AGEs (RAGE). Additionally, higher levels of oxidative stress and inflammatory factors were found in T2DM bone. AGEs content in bone was pairwise correlated with RAGE, hydrogen peroxide, and inflammatory factors. Serum levels of RAGE, oxidative stress, and inflammatory factors were higher in T2DM, while AGEs content tended to be lower. Besides, 35 differentially expressed metabolites were screened in T2DM serum. Osteoblasts exposed to high glucose displayed analogous abnormal changes in these biomarkers. Thus, low bone turnover in T2DM might be partially due to excess oxidative stress and inflammation induced by AGE‐RAGE signaling. Furthermore, these biomarker levels in serum were mostly consistent with bone, demonstrating their possibility for predicting bone quality in T2DM.

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Metformin attenuates diabetes-induced osteopenia in rats is associated with down-regulation of the RAGE-JAK2-STAT1 signal axis

Cited by 5 publications

References 63 publications

Trabecular Bone Score (TBS) in Individuals with Type 2 Diabetes Mellitus: An Updated Review

Trabecular Bone Score (TBS) in Individuals with Type 2 Diabetes Mellitus: An Updated Review

Localized delivery of metformin via 3D printed GelMA-Nanoclay hydrogel scaffold for enhanced treatment of diabetic bone defects

Low bone turnover is associated with advanced glycation end‐products, oxidative stress, and inflammation induced by type 2 diabetes mellitus

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