Bone health in diabetes and prediabetes

Costantini, Silvia; Conte, Caterina

doi:10.4239/wjd.v10.i8.421

Cited by 62 publications

(55 citation statements)

References 298 publications

(296 reference statements)

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“…Previous studies that assessed circulating osteocalcin in subjects with T2D yielded conflicting findings, with osteocalcin levels either normal or reduced. (32) Measurement of total AGEs in bone showed a significant 1.5-fold increase in T2D compared to nondiabetic subjects. This finding is important, because it reveals that even patients with well-controlled T2D present higher levels of AGEs as compared to nondiabetic subjects.…”

Section: Discussionmentioning

confidence: 90%

Sclerostin Regulation, Microarchitecture, and Advanced Glycation End-Products in the Bone of Elderly Women With Type 2 Diabetes

Piccoli

Cannata

Strollo

et al. 2020

Journal of Bone and Mineral Research

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Increased circulating sclerostin and accumulation of advanced glycation end‐products (AGEs) are two potential mechanisms underlying low bone turnover and increased fracture risk in type 2 diabetes (T2D). Whether the expression of the sclerostin‐encoding SOST gene is altered in T2D, and whether it is associated with AGEs accumulation or regulation of other bone formation‐related genes is unknown. We hypothesized that AGEs accumulate and SOST gene expression is upregulated in bones from subjects with T2D, leading to downregulation of bone forming genes (RUNX2 and osteocalcin) and impaired bone microarchitecture and strength. We obtained bone tissue from femoral heads of 19 T2D postmenopausal women (mean glycated hemoglobin [HbA1c] 6.5%) and 73 age‐ and BMI‐comparable nondiabetic women undergoing hip replacement surgery. Despite similar bone mineral density (BMD) and biomechanical properties, we found a significantly higher SOST (p = .006) and a parallel lower RUNX2 (p = .025) expression in T2D compared with non‐diabetic subjects. Osteocalcin gene expression did not differ between T2D and non‐diabetic subjects, as well as circulating osteocalcin and sclerostin levels. We found a 1.5‐fold increase in total bone AGEs content in T2D compared with non‐diabetic women (364.8 ± 78.2 versus 209.9 ± 34.4 μg quinine/g collagen, respectively; p < .001). AGEs bone content correlated with worse bone microarchitecture, including lower volumetric BMD (r = −0.633; p = .02), BV/TV (r = −0.59; p = .033) and increased trabecular separation/spacing (r = 0.624; p = .023). In conclusion, our data show that even in patients with good glycemic control, T2D affects the expression of genes controlling bone formation (SOST and RUNX2). We also found that accumulation of AGEs is associated with impaired bone microarchitecture. We provide novel insights that may help understand the mechanisms underlying bone fragility in T2D. © 2020 American Society for Bone and Mineral Research (ASBMR).

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Section: Discussionmentioning

confidence: 90%

Sclerostin Regulation, Microarchitecture, and Advanced Glycation End-Products in the Bone of Elderly Women With Type 2 Diabetes

Piccoli

Cannata

Strollo

et al. 2020

Journal of Bone and Mineral Research

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“…PINP is synthesized by osteoblasts as part of Type I collagen formation, and it has been recommended to be used as a reference analyte for bone turnover markers in observational and intervention studies ( 22 ). It has not been clearly established yet how IR or diabetes affects PINP concentration ( 31 ). Similarly to osteocalcin, PINP concentration was lower in the IR group than in the healthy group.…”

Section: Discussionmentioning

confidence: 99%

Bone Marrow Metabolism Is Impaired in Insulin Resistance and Improves After Exercise Training

Ojala

Motiani

Ivaska

et al. 2020

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Exercise training improves bone mineral density, but little is known about the effects of training on bone marrow (BM) metabolism. BM insulin sensitivity has been suggested to play an important role in bone health and whole-body insulin sensitivity. Objective To study the effects of exercise training on BM metabolism. Design Randomized controlled trial Setting Clinical research center Participants Sedentary healthy (n=28, 40-55 years, all males) and insulin resistant subjects (IR) (n=26, 43-55 years, males/females 16/10) Intervention Two weeks of sprint interval training or moderate-intensity continuous training Main outcome measures We measured femoral, lumbar and thoracic BM insulin-stimulated glucose uptake (GU) and fasting free fatty acid uptake (FFAU) using positron-emission tomography and bone turnover markers from plasma. Results At baseline, GU was highest in lumbar, followed by thoracic and lowest in femoral BM (all p<0.0001). FFAU was higher in lumbar and thoracic than femoral BM (both p<0.0001). BM FFAU and femoral BM GU were higher in healthy compared to IR men and in females compared to males (all p<0.05). Training increased femoral BM GU similarly in all groups and decreased lumbar BM FFAU in males (all p<0.05). Osteocalcin and PINP were lower in IR than healthy men and correlated positively with femoral BM GU and glycemic status (all p<0.05). Conclusions BM metabolism differs regarding anatomical location. Short-term training improves BM GU and FFAU in healthy and IR subjects. Bone turnover rate is decreased in insulin resistance and associates positively with BM metabolism and glycemic control.

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“…Possible explanations for such a "paradox of BMD" are the high frequency of obesity in these patients, and the well-known positive association between high BMI and high BMD (23). Additionally, the role of insulin resistance, and consequent high insulin levels, has been postulated, even though some studies failed to find a positive association with BMD independently of BMI (24). On the contrary, altered bone quality has been demonstrated in patients with T2DM, as demonstrated by studies using the high-resolution peripheral quantitative computed tomography (HR-pQCT) (25).…”

Section: Advanced Glycation End-productsmentioning

confidence: 99%

The Interplay Between Bone and Glucose Metabolism

et al. 2020

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The multiple endocrine functions of bone other than those related to mineral metabolism, such as regulation of insulin sensitivity, glucose homeostasis, and energy metabolism, have recently been discovered. In vitro and murine studies investigated the impact of several molecules derived from osteoblasts and osteocytes on glucose metabolism. In addition, the effect of glucose on bone cells suggested a mutual cross-talk between bone and glucose homeostasis. In humans, these mechanisms are the pivotal determinant of the skeletal fragility associated with both type 1 and type 2 diabetes. Metabolic abnormalities associated with diabetes, such as increase in adipose tissue, reduction of lean mass, effects of hyperglycemia per se, production of the advanced glycation end products, diabetes-associated chronic kidney disease, and perturbation of the calcium-PTH-vitamin D metabolism, are the main mechanisms involved. Finally, there have been multiple reports of antidiabetic drugs affecting the skeleton, with differences among basic and clinical research data, as well as of anti-osteoporosis medication influencing glucose metabolism. This review focuses on the aspects linking glucose and bone metabolism by offering insight into the most recent evidence in humans.

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Bone health in diabetes and prediabetes

Cited by 62 publications

References 298 publications

Sclerostin Regulation, Microarchitecture, and Advanced Glycation End-Products in the Bone of Elderly Women With Type 2 Diabetes

Sclerostin Regulation, Microarchitecture, and Advanced Glycation End-Products in the Bone of Elderly Women With Type 2 Diabetes

Bone Marrow Metabolism Is Impaired in Insulin Resistance and Improves After Exercise Training

The Interplay Between Bone and Glucose Metabolism

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