Diabetes and Its Effect on Bone and Fracture Healing

Jiao, Hong-Li; Xiao, E.; Graves, Dana T.

doi:10.1007/s11914-015-0286-8

Cited by 401 publications

(317 citation statements)

References 106 publications

(127 reference statements)

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“…In vitro experiments were carried out with primary cultures of microvascular endothelial cells to investigate the impact of TNFα and TNFα in combination with high glucose and advanced glycation end-products (AGE) based on evidence that each is elevated by diabetes [24]. TNFα, AGE and high glucose each reduced microvascular endothelial cell DNA synthesis (p<0.05) (Fig.…”

Section: Resultsmentioning

confidence: 99%

TNFα contributes to diabetes impaired angiogenesis in fracture healing

Lim

Mattos

et al. 2017

Bone

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Diabetes increases the likelihood of fracture, interferes with fracture healing and impairs angiogenesis. The latter may be significant due to the critical nature of angiogenesis in fracture healing. Although it is known that diabetes interferes with angiogenesis the mechanisms remain poorly defined. We examined fracture healing in normoglycemic and streptozotocin-induced diabetic mice and quantified the degree of angiogenesis with antibodies to three different vascular markers, CD34, CD31 and Factor VIII. The role of diabetes-enhanced inflammation was investigated by treatment of the TNFα-specific inhibitor, pegsunercept starting 10 days after induction of fractures. Diabetes decreased both angiogenesis and VEGFA expression. The reduced angiogenesis and VEGFA expression in diabetic fractures was rescued by specific inhibition of TNF in vivo. In addition, the TNF inhibitor rescued the negative effect of diabetes on endothelial cell proliferation and endothelial cell apoptosis. The effect of TNFα in vitro was enhanced by high glucose and an advanced glycation endproduct to impair microvascular cell proliferation and stimulate apoptosis. The effect of TNF, high glucose and an AGE was mediated by the transcription factor FOXO1, which increased expression of p21 and caspase-3. These studies indicate that inflammation plays a major role in diabetes-impaired angiogenesis in endochondral bone formation through its effect on microvascular endothelial cells and FOXO1.

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Section: Resultsmentioning

confidence: 99%

TNFα contributes to diabetes impaired angiogenesis in fracture healing

Lim

Mattos

et al. 2017

Bone

Self Cite

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“…Type 2 diabetes (T2D) is a chronic metabolic disease with high blood glucose levels (1), which results from insulin deficiency and/or insulin resistance (2). T2D or metabolic disorder increased fracture risk (3), interfered with bone formation (4), and impaired fracture healing (5).…”

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confidence: 99%

Dietary Calcium and Serum 25OHD Protect Chinese Women from Type 2 Diabetes

Lin

Wang

2017

J Nutr Sci Vitaminol

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Summary The Chinese dietary structure is different from Western and Mediterranean diets. This study aimed to assess the association of dietary calcium, serum 25-hydroxyvitamin D (25OHD), and other macronutrients with type 2 diabetes (T2D) in Chinese patients. This case-control study enrolled 605 patients (males, 337; females, 268) with T2D and 724 healthy subjects (males, 405; females, 319) at Sir Run Run Shaw Hospital from February to April 2014. Dietary calcium, total energy, fat to energy ratio, glucose administration, 2-h postprandial blood glucose, serum total cholesterol and high density lipoprotein (HDL)-cholesterol, and serum 25OHD level were assessed. Logistic regression was used to assess the associations of various parameters with T2D. Total energy, fat, and the fat-to-energy ratio were significantly higher in healthy male and female controls than in T2D patients (p,0.05). In addition, significant differences were obtained between the T2D and control groups in glucose management, 2-h postprandial blood glucose, serum total cholesterol, and HDL-cholesterol (all p,0.05). Interestingly, statistically significant inverse associations of dietary calcium and total energy intake with the risk of T2D were obtained in women; binary logistic regression analysis showed diet calcium and serum 25OHD were protecting factors against T2D (OR50.40, p50.034; OR50.50, p50.019). Dietary calcium and serum 25OHD may independently protect Chinese women from T2D. These findings highlight the importance of vitamin D and calcium in daily diet or supplement in the early period of T2D, meanwhile indicators associated with bone metabolism should be assessed in clinical nutrition. It is possible that dietary education and guidance should be implemented based clinical bone metabolism data.

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“…However, it is the undesirable non‐enzymatic cross‐links that result in the modification of the bone's extracellular matrix resulting in bone brittleness . In diabetes, AGEs are formed when type 1 collagen undergoes non‐enzymatic modification via the Maillard reaction postexposure to aldose sugars . Two prominent AGEs produced in collagen fibres are pentosidine (PEN) and carboxymethyl lysine, and they have a negative impact on bone health through multiple mechanisms: via modification of the bone matrix, by binding to the receptor for AGE (RAGE) and via the production of reactive oxygen intermediates .…”

Section: Bone Defects In Diabetic Patientsmentioning

confidence: 99%

Weak bones in diabetes mellitus – an update on pharmaceutical treatment options

Lin

Dass

2018

Journal of Pharmacy and Pharmacology

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Objectives Diabetes mellitus is often associated with a number of complications such as nephropathy, neuropathy, retinopathy and foot ulcers. However, weak bone is a diabetic complication that is often overlooked. Although the exact mechanism for weak bones within diabetes mellitus is unclear, studies have shown that the mechanism does differ in both type I (T1DM) and type II diabetes (T2DM). This review, however, investigates the application of mesenchymal stem cells, recombinant human bone morphogenetic protein-2, teriparatide, insulin administration and the effectiveness of a peroxisome proliferator-activated receptor-ϒ modulator, netoglitazone in the context of diabetic weak bones. Key findings In T1DM, weak bones may be the result of defective osteoblast activity, the absence of insulin's anabolic effects on bone, the deregulation of the bone-pancreas negative feedback loop and advanced glycation end product (AGE) aggregation within the bone matrix as a result of hyperglycaemia. Interestingly, T2DM patients placed on insulin administration, thiazolidinediones, SGLT2 inhibitors and sulfonylureas have an associated increased fracture risk. T2DM patients are also observed to have high sclerostin levels that impair osteoblast gene transcription, AGE aggregation within bone, which compromises bone strength and a decrease in esRAGE concentration resulting in a negative association with vertebral fractures. Summary Effective treatment options for weak bones in the context of diabetes are currently lacking. There is certainly scope for discovery and development of novel agents that could alleviate this complication in diabetes patients.

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Diabetes and Its Effect on Bone and Fracture Healing

Cited by 401 publications

References 106 publications

TNFα contributes to diabetes impaired angiogenesis in fracture healing

TNFα contributes to diabetes impaired angiogenesis in fracture healing

Dietary Calcium and Serum 25OHD Protect Chinese Women from Type 2 Diabetes

Weak bones in diabetes mellitus – an update on pharmaceutical treatment options

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