Decreased osteoclastogenesis, osteoblastogenesis and low bone mass in a mouse model of type 2 diabetes

Xu, Fei; Dong, Yonghui; Huang, Xin; Li, Mi; Qin, Liang; Ren, Ye; Guo, Fengjing; Chen, Anmin; Huang, Shu

doi:10.3892/mmr.2014.2430

Cited by 19 publications

(17 citation statements)

References 21 publications

(17 reference statements)

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“…In humans, biochemical markers and bone histomorphometry reveal a low bone turnover in T2DM (9, 10, 11, 12, 13). In animals, however, low bone formation is also a characteristic of T2DM, while bone resorption parameters are usually increased (14, 15, 16, 17, 18). At a structural level, the accumulation of advanced glycation end (AGE) products under diabetic conditions has been proposed to alter collagen structure and contribute to impaired material properties.…”

Section: Introductionmentioning

confidence: 99%

Update on the impact of type 2 diabetes mellitus on bone metabolism and material properties

Picke

Campbell

Napoli

et al. 2019

Endocrine Connections

100

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The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide, especially as a result of our aging society, high caloric intake and sedentary lifestyle. Besides the well-known complications of T2DM on the cardiovascular system, the eyes, kidneys and nerves, bone strength is also impaired in diabetic patients. Patients with T2DM have a 40–70% increased risk for fractures, despite having a normal to increased bone mineral density, suggesting that other factors besides bone quantity must account for increased bone fragility. This review summarizes the current knowledge on the complex effects of T2DM on bone including effects on bone cells, bone material properties and other endocrine systems that subsequently affect bone, discusses the effects of T2DM medications on bone and concludes with a model identifying factors that may contribute to poor bone quality and increased bone fragility in T2DM.

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Section: Introductionmentioning

confidence: 99%

Update on the impact of type 2 diabetes mellitus on bone metabolism and material properties

Picke

Campbell

Napoli

et al. 2019

Endocrine Connections

100

View full text Add to dashboard Cite

show abstract

“…Nevertheless, how T2DM affects bone is still controversial. Several mechanisms may be involved, such as direct effects of insulin resistance and hyperglycemia on the bone and bone marrow microenvironment, advanced glycation end products of bone matrix proteins, abnormal cytokine production, and impaired neuromuscular/skeletal interactions [ 4 , 5 ]. Obesity associated with T2DM may be a confounder due to its controversial effect on bone per se (see Dolan et al, 2017 for a comprehensive review) [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Type 2 diabetes affects bone cells precursors and bone turnover

Sassi¹,

Buondonno²,

Luppi³

et al. 2018

BMC Endocr Disord

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BackgroundHere we study the effect of type 2 diabetes (T2DM) on bone cell precursors, turnover and cytokines involved in the control of bone cell formation and activity.MethodsWe enrolled in the study 21 T2DM women and 21 non diabetic controls matched for age and body mass index (BMI). In each subject we measured bone cell precursors, Receptor Activator of Nuclear Factor κB (RANKL), Osteoprotegerin (OPG), Sclerostin (SCL) and Dickoppf-1 (DKK-1) as cytokines involved in the control of osteoblast and osteoclast formation and activity, bone density (BMD) and quality trough trabecular bone score (TBS) and bone turnover. T2DM patients and controls were compared for the analyzed variables by one way ANOVA for Gaussian ones and by Mann-Whitney or Kruskal-Wallis test for non-Gaussian variables.ResultsRANKL was decreased and DKK-1 increased in T2DM. Accordingly, patients with T2DM have lower bone turnover compared to controls. BMD and TBS were not significantly different from healthy controls. Bone precursor cells were more immature in T2DM. However the number of osteoclast precursors was increased and that of osteoblasts decreased.ConclusionsPatients with T2DM have more immature bone cells precursors, with increased number of osteoclasts and decreased osteoblasts, confirming low bone turnover and reduced cytokines such as RANKL and DKK-1. BMD and TBS are not significantly altered in T2DM although, in contrast with other studies, this may be due to the match of patients and controls for BMI rather than age.

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“…When compared to non-diabetic male ddY mice, male KK-A y mice had lower areal BMD at the proximal femur, not at the mid-shaft, by 18 weeks of age [32]. However, when using non-diabetic C57BL/6 for controls, Xu et al observed lower volumetric BMD and lower structural strength in bending of the tibia mid-shaft for the diabetic KK-A y mice [33]. Yet another study comparing male KK-A y to male C57BL/6 mice observed higher areal BMD of the whole femur, lower volumetric BMD of trabecular bone in the distal femur, and higher volumetric BMD of cortical bone in the distal femur [34].…”

Section: Introductionmentioning

confidence: 99%

Low bone toughness in the TallyHO model of juvenile type 2 diabetes does not worsen with age

Creecy

Uppuganti

Ünal

et al. 2018

Bone

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Fracture risk increases as type 2 diabetes (T2D) progresses. With the rising incidence of T2D, in particular early-onset T2D, a representative pre-clinical model is needed to study mechanisms for treating or preventing diabetic bone disease. Towards that goal, we hypothesized that fracture resistance of bone from diabetic TallyHO mice decreases as the duration of diabetes increases. Femurs and lumbar vertebrae were harvested from male, TallyHO mice and male, non-diabetic SWR/J mice at 16weeks (n≥12 per strain) and 34weeks (n≥13 per strain) of age. As is characteristic of this model of juvenile T2D, the TallyHO mice were obese and hyperglycemic at an early age (5weeks and 10weeks of age, respectively). The femur mid-shaft of TallyHO mice had higher tissue mineral density and larger cortical area, as determined by micro-computed tomography, compared to the femur mid-shaft of SWR/J mice, irrespective of age. As such, the diabetic rodent bone was structurally stronger than the non-diabetic rodent bone, but the higher peak force endured by the diaphysis during three-point (3pt) bending was not independent of the difference in body weight. Upon accounting for the structure of the femur diaphysis, the estimated toughness at 16weeks and 34weeks was lower for the diabetic mice than for non-diabetic controls, but neither toughness nor estimated material strength and resistance to crack growth (3pt bending of contralateral notched femur) decreased as the duration of hyperglycemia increased. With respect to trabecular bone, there were no differences in the compressive strength of the L6 vertebral strength between diabetic and non-diabetic mice at both ages despite a lower trabecular bone volume for the TallyHO than for the SWR/J mice at 34weeks. Amide I sub-peak ratios as determined by Raman Spectroscopy analysis of the femur diaphysis suggested a difference in collagen structure between diabetic and non-diabetic mice, although there was not a significant difference in matrix pentosidine between the groups. Overall, the fracture resistance of bone in the TallyHO model of T2D did not progressively decrease with increasing duration of hyperglycemia. However, given the variability in hyperglycemia in this model, there were correlations between blood glucose levels and certain structural properties including peak force.

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Decreased osteoclastogenesis, osteoblastogenesis and low bone mass in a mouse model of type 2 diabetes

Cited by 19 publications

References 21 publications

Update on the impact of type 2 diabetes mellitus on bone metabolism and material properties

Update on the impact of type 2 diabetes mellitus on bone metabolism and material properties

Type 2 diabetes affects bone cells precursors and bone turnover

Low bone toughness in the TallyHO model of juvenile type 2 diabetes does not worsen with age

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