Multifactorial effects of hyperglycaemia, hyperinsulinemia and inflammation on bone remodelling in type 2 diabetes mellitus

Shahen, Victor A.; Gerbaix, Maude; Koeppenkastrop, S.; Lim, Soo-min; McFarlane, K.E.; Nguyen, Amanda; Peng, Xiujuan; Weiss, N.B.; Brennan‐Speranza, Tara C.

doi:10.1016/j.cytogfr.2020.04.001

Cited by 30 publications

(17 citation statements)

References 155 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been showed that proinflammatory cytokines affected hematopoiesis [ 34 ]. IL-6 has been reported to promote osteoclast differentiation and activation [ 35 ]. In addition, hs-CRP levels have been associated with BMD in several studies [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

Hemoglobin level and osteoporosis in Chinese elders with type 2 diabetes mellitus

Xiu

Sun

et al. 2022

Nutr. Diabetes

View full text Add to dashboard Cite

Objectives Several studies demonstrated a positive relationship between hemoglobin level and bone mineral density (BMD). Thus, the association between hemoglobin concentration and osteoporosis in elders with type 2 diabetes mellitus (T2DM) was explored in this study. Methods Totally, 573 elders with T2DM were included in the study. BMD was measured by dual-energy X-ray absorptiometry. Hemoglobin levels were tested. The association between the hemoglobin level and osteoporosis was subjected to logistic regression analysis. Results For men, the hemoglobin levels were significantly lower in osteoporosis group than that in non-osteoporosis group (135.98 ± 16.20 vs. 142.84 ± 13.78 g/L, P = 0.002). Hemoglobin levels were positively related with BMD of total hip and femoral neck in men (r = 0.170, P = 0.004; r = 0.148, P = 0.012, respectively). After adjusting for age, body mass index (BMI), hemoglobin A1c (HbA1c), estimated glomerular filtration rate (eGFR) and 25-hydroxyvitamin D3 [25(OH) D3], the hemoglobin level was related with a 0.97-fold lower risk of osteoporosis (odds ratio (OR): 0.97; 95% confidence interval (CI): 0.95–0.99; P = 0.004) in men, but no such association was found in women. Conclusion Higher levels of hemoglobin play a protective role against osteoporosis in older men with T2DM.

show abstract

Section: Discussionmentioning

confidence: 99%

Hemoglobin level and osteoporosis in Chinese elders with type 2 diabetes mellitus

Xiu

Sun

et al. 2022

Nutr. Diabetes

View full text Add to dashboard Cite

show abstract

“…Previous findings support a link between the hyperglycaemic, hyperinsulinemic and inflammatory environments in metabolic diseases such as glucose intolerance and T2DM with impaired bone remodelling. This has been comprehensively reviewed recently in Shahen et al, 2020 [ 55 ]. Thus, one limitation of our current study is that we have not investigated changes in inflammatory markers and direct links with the compromised bone quality we observed in our high fat fed mice.…”

Section: Discussionmentioning

confidence: 99%

Distinct Effects of a High Fat Diet on Bone in Skeletally Mature and Developing Male C57BL/6J Mice

et al. 2021

View full text Add to dashboard Cite

Increased risks of skeletal fractures are common in patients with impaired glucose handling and type 2 diabetes mellitus (T2DM). The pathogenesis of skeletal fragility in these patients remains ill-defined as patients present with normal to high bone mineral density. With increasing cases of glucose intolerance and T2DM it is imperative that we develop an accurate rodent model for further investigation. We hypothesized that a high fat diet (60%) administered to developing male C57BL/6J mice that had not reached skeletal maturity would over represent bone microarchitectural implications, and that skeletally mature mice would better represent adult-onset glucose intolerance and the pre-diabetes phenotype. Two groups of developing (8 week) and mature (12 week) male C57BL/6J mice were placed onto either a normal chow (NC) or high fat diet (HFD) for 10 weeks. Oral glucose tolerance tests were performed throughout the study period. Long bones were excised and analysed for ex vivo biomechanical testing, micro-computed tomography, 2D histomorphometry and gene/protein expression analyses. The HFD increased fasting blood glucose and significantly reduced glucose tolerance in both age groups by week 7 of the diets. The HFD reduced biomechanical strength, both cortical and trabecular indices in the developing mice, but only affected cortical outcomes in the mature mice. Similar results were reflected in the 2D histomorphometry. Tibial gene expression revealed decreased bone formation in the HFD mice of both age groups, i.e., decreased osteocalcin expression and increased sclerostin RNA expression. In the mature mice only, while the HFD led to a non-significant reduction in runt-related transcription factor 2 (Runx2) RNA expression, this decrease became significant at the protein level in the femora. Our mature HFD mouse model more accurately represents late-onset impaired glucose tolerance/pre-T2DM cases in humans and can be used to uncover potential insights into reduced bone formation as a mechanism of skeletal fragility in these patients.

show abstract

“…Osteoporosis as well as osteoarthritis are present in obesity, where the release of adipokines from bone marrow fat can alter bone trophism, even though the role of these substances is still controversial [ 89 ]. An increased risk of fracture has been reported mainly in obese patients with type 2 diabetes mellitus, in whom the levels of the same cytokines are enhanced [ 90 ]. Similarly, a mineral bone disorder is evident in CKD, a pathology in which high levels of cytokines, including transforming growth factor-beta in addition to the others mentioned above, are correlated with the disease progression [ 91 ].…”

Section: Role Of Purine Enzymes In Bone Inflammatory Conditionsmentioning

confidence: 99%

In Search of a Role for Extracellular Purine Enzymes in Bone Function

et al. 2021

View full text Add to dashboard Cite

Bone is one of the major tissues that undergoes continuous remodeling throughout life, thus ensuring both organic body growth during development and protection of internal organs as well as repair of trauma during adulthood. Many endogenous substances contribute to bone homeostasis, including purines. Their role has increasingly emerged in recent decades as compounds which, by interacting with specific receptors, can help determine adequate responses of bone cells to physiological or pathological stimuli. Equally, it is recognized that the activity of purines is closely dependent on their interconversion or metabolic degradation ensured by a series of enzymes present at extracellular level as predominantly bound to the cell membrane or, also, as soluble isoforms. While the effects of purines mediated by their receptor interactions have sufficiently, even though not entirely, been characterized in many tissues including bone, those promoted by the extracellular enzymes providing for purine metabolism have not been. In this review, we will try to circumstantiate the presence and the role of these enzymes in bone to define their close relationship with purine activities in maintaining bone homeostasis in normal or pathological conditions.

show abstract

Multifactorial effects of hyperglycaemia, hyperinsulinemia and inflammation on bone remodelling in type 2 diabetes mellitus

Cited by 30 publications

References 155 publications

Hemoglobin level and osteoporosis in Chinese elders with type 2 diabetes mellitus

Hemoglobin level and osteoporosis in Chinese elders with type 2 diabetes mellitus

Distinct Effects of a High Fat Diet on Bone in Skeletally Mature and Developing Male C57BL/6J Mice

In Search of a Role for Extracellular Purine Enzymes in Bone Function

Contact Info

Product

Resources

About