Osteoclastic function is accelerated in male patients with type 2 diabetes mellitus: the preventive role of osteoclastogenesis inhibitory factor/osteoprotegerin (OCIF/OPG) on the decrease of bone mineral density

Suzuki, Kiyoshi; Kurose, Takeshi; Takizawa, Makoto; Maruyama, Masahiro; Ushikawa, Kenji; Kikuyama, Munetsugu; Sugimoto, Chieko; Seino, Yutaka; Nagamatsu, Shinya; Ishida, Hideyuki

doi:10.1016/j.diabres.2004.08.006

Cited by 72 publications

(56 citation statements)

References 35 publications

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“…Furthermore, our findings of similar OPG concentrations at baseline in all groups are in agreement with one earlier study showing no significant differences between plasma OPG in diabetic and non-diabetic individuals (43), but two other studies have described a difference (20,44). As our own study have a limited number of participants, and the studies mentioned included 264, 490, and 86 subjects respectively, this matter needs elucidation through a larger study.…”

Section: Discussionsupporting

confidence: 81%

Acute hyperinsulinemia decreases plasma osteoprotegerin with diminished effect in type 2 diabetes and obesity

Jörgensen

Vind²,

Nybo³

et al. 2009

European Journal of Endocrinology

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Objective: Osteoprotegerin (OPG) is a soluble tumour necrosis factor-receptor-like molecule present in connective tissues, especially bone and vasculature. It is known to accumulate in the arterial wall in diabetes. As its synthesis in vascular cells is decreased by insulin, we wanted to elucidate the acute effects of insulin on plasma OPG concentrations in individuals with type 2 diabetes and obese individuals compared with lean controls. Design: The study population consisted of ten type 2 diabetic, ten obese subjects, and ten lean subjects with no family history of diabetes. Methods: All subjects underwent a 4-h euglycemic-hyperinsulinemic clamp. Plasma OPG, insulin, lactate, HbA1c, cholesterol, triglycerides, free fatty acids (FFA), and glucose disposal rate were measured before and at the end of the clamp. Results: Baseline OPG concentrations did not differ significantly between groups. Insulin infusion decreased plasma OPG concentrations in all groups (P!0.01); however, the fall in OPG was 50% less in obese and type 2 diabetic individuals (PZ0.007). Baseline OPG correlated with fasting insulin, baseline lactate, and low density lipoprotein cholesterol in the diabetic group, and with baseline FFA in the lean group. The relative change of OPG in response to insulin correlated inversely with HbA1c and baseline FFA in the lean group. Conclusions: Acute hyperinsulinemia decreases plasma OPG, but with diminished effect in individuals with type 2 diabetes and obesity. Increased levels of OPG in arteries and plasma in diabetes together with the capability of plasma OPG as a cardiovascular risk predictor may be related to the described effects of insulin.European Journal of Endocrinology 161 95-101

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Section: Discussionsupporting

confidence: 81%

Acute hyperinsulinemia decreases plasma osteoprotegerin with diminished effect in type 2 diabetes and obesity

Jörgensen

Vind²,

Nybo³

et al. 2009

European Journal of Endocrinology

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“…Figure 3. www.bjournal.com.br bone, as reported in other diabetes models (6)(7)(8)(9)(10)(11)(12)(21)(22)(23)(24).…”

Section: Discussionsupporting

confidence: 55%

“…These include reduction in blood supply and angiogenesis (1), a more severe inflammatory response (18,19), a decrease in collagen synthesis (6,20,21), a disturbance in the mineralization process (9,11,12), and an imbalance between bone resorption by osteoclasts and bone deposition by osteoblasts (22)(23)(24). Another contributing factor may be the advanced glycation end products, present in high levels in diabetic individuals, that amplify inflammatory events (25) and delay wound healing (26).…”

Section: Introductionmentioning

confidence: 99%

Alloxan-induced diabetes delays repair in a rat model of closed tibial fracture

Diniz

Amorim

Cavalcante-Neto

et al. 2008

Braz J Med Biol Res

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A closed fracture was performed on the left tibia of 3-month-old Wistar rats weighing 250 to 350 g that were either healthy (N = 24) or made diabetic with alloxan (N = 24) to investigate the effect of alloxan-induced diabetes on the course of bone fracture healing. Histomorphometric analysis of the fracture site was performed at 7, 14, 25, and 35 days. After 7 days, diabetic rats had significantly less cartilage (P = 0.045) and greater fibrous connective (P = 0.006) tissue formation at the fracture site compared to controls. In contrast, marked callus formation was seen in diabetic rats with significant osteogenesis (P = 0.011, P = 0.010, P = 0.010, respectively, for 14, 25, and 35 days) and chondrogenesis (P = 0.028, P = 0.033, P = 0.019) compared to controls. Radiographic analysis revealed a displaced fracture with poor bone fragment alignment and delayed consolidation at these times in the diabetic group. The levels of alkaline phosphatase were significantly higher in diabetic rats at 25 days (P = 0.009). These results suggest that the initial excessive formation of fibrous connective tissue associated with delay in chondrogenesis and osteogenesis may not provide suitable stability of the fractured site, contributing to the inappropriate alignment of fragments and an increase in the volume of callus in later stages of repair. The resulting displaced fracture in diabetic rats requires long periods for remodeling and complete bone consolidation.

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“…Bone histomorphometry and biomechanical modifications are important factors related to the risk of fracture, given that increased morbidity in orthopedic patients with diabetes is well documented (Suzuki et al, 2004;Thrailkill et al, 2005a). In the current study, our histomorphometric analyses showed significant progressive femoral bone loss in premenopausal diabetic rats as compared to controls rats.…”

Section: Discussionmentioning

confidence: 99%

Relationship between oxidative stress and diabetic osteopenia in premenopausal rats

Duarte

Rodrigues

Rezende

et al. 2010

Braz. J. Pharm. Sci.

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The relationship between lipid peroxidation, antioxidant defense and diabetic osteopenia remains unclear. This study evaluated the relationship among lipid peroxidation index, antioxidant defense parameters and bone metabolism in a premenopausal diabetic model using measures including thiobarbituric acidreactive substances concentration (TBARS) and reduced glutathione (GSH) content in brain homogenates, histomorphometric analysis, biomechanical testing and bone mineral density (BMD). Female Wistar rats with regular estrous cycle were divided into two groups: Group 1: control rats (n = 15) and Group 2: diabetic rats (n = 15). Diabetes was induced by alloxan and confirmed by glycemia ≥250 mg/dL. The lipid peroxidation index, measured by TBARS concentration, showed a significant increase (p<0.05) in diabetic animals in comparison to control animals. However, the antioxidant parameter measured by GSH content, was significantly lower (p<0.05) in diabetic animals. Histomorphometric analysis showed a significant increase (p<0.05) in femoral trabecular separation together with a significant decrease (p<0.05) in trabecular thickness, and reduced trabecular bone volume in diabetic rats. Moreover, biomechanical testing and BMD values were significantly lower (p<0.05) in the diabetic group. Thus, our results demonstrated that increased lipid peroxidation and altered antioxidant defense could be related to the development of oxidative stress and diabetic osteopenia in premenopausal rats.Uniterms: Oxidative stress. Lipid peroxidation. Diabetes mellitus. Diabetic osteopenia/experimental study.A relação entre peroxidação lipídica, defesa antioxidante e osteopenia diabética permanece obscura. Este estudo avaliou a associação entre índice de peroxidação lipídica, parâmetro de defesa antioxidante e metabolismo ósseo em um modelo diabético pré-menopausa através de medidas como a concentração de substâncias reativas ao ácido tiobarbitúrico (SRAT) e conteúdo de glutationa reduzida (GSH) no homogenato cerebral, análises histomorfométricas, teste biomecânico e densidade mineral óssea (DMO). Ratos Wistar fêmeas com ciclo estral regular foram distribuídos em dois grupos: Grupo 1 -ratas controle (n = 15) e Grupo 2 -ratas diabéticas (n = 15). O diabetes foi induzido pela aloxana e confirmado pela glicemia ≥250 mg/dL. O índice de peroxidação lipídica, medido pela concentração de SRAT, demonstrou um aumento significativo (p<0.05) nos animais diabéticos, em relação aos animais controle. Entretanto, o parâmetro de defesa antioxidante, mensurado pelo conteúdo de GSH, foi reduzido significativamente (p<0.05) nos animais diabéticos. As análises histomorfométricas mostraram um aumento significativo (p<0.05) da separação trabecular do fêmur, associado à diminuição significativa da espessura trabecular (p<0.05) e volume ósseo trabecular reduzido nas ratas diabéticas. Além disso, o teste biomecânico, V.M.G. Duarte, A. de S. Rodrigues, L.A. de Rezende, A.Ma. de O. Ramos, R.M. de Souza, F.P.F. Neto, A. da C. Medeiros 540 medido pela força máxima, e val...

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Osteoclastic function is accelerated in male patients with type 2 diabetes mellitus: the preventive role of osteoclastogenesis inhibitory factor/osteoprotegerin (OCIF/OPG) on the decrease of bone mineral density

Cited by 72 publications

References 35 publications

Acute hyperinsulinemia decreases plasma osteoprotegerin with diminished effect in type 2 diabetes and obesity

Acute hyperinsulinemia decreases plasma osteoprotegerin with diminished effect in type 2 diabetes and obesity

Alloxan-induced diabetes delays repair in a rat model of closed tibial fracture

Relationship between oxidative stress and diabetic osteopenia in premenopausal rats

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