Diabetic Osteopenia Research Articles

Osteoblast-intrinsic defect in glucose metabolism impairs bone formation in type II diabetic male mice.

Skeletal fragility is associated with type 2 diabetes mellitus (T2D), but the underlying mechanism is not well understood. Here, in a mouse model for youth-onset T2D, we show that both trabecular and cortical bone mass is reduced due to diminished osteoblast activity. Stable isotope tracing in vivo with 13C-glucose demonstrates that both glycolysis and glucose fueling of the TCA cycle are impaired in diabetic bones. Similarly, Seahorse assays show suppression of both glycolysis and oxidative phosphorylation by diabetes in bone marrow mesenchymal cells as a whole, whereas single-cell RNA sequencing reveals distinct modes of metabolic dysregulation among the subpopulations. Metformin not only promotes glycolysis and osteoblast differentiation in vitro, but also improves bone mass in diabetic mice. Finally, osteoblast-specific overexpression of either Hif1a, a general inducer of glycolysis, or Pfkfb3 which stimulates a specific step in glycolysis, averts bone loss in T2D mice. The study identifies osteoblast-intrinsic defects in glucose metabolism as an underlying cause of diabetic osteopenia, which may be targeted therapeutically.

Mapping Knowledge Landscapes and Emerging Trends of the Links Between Bone Metabolism and Diabetes Mellitus: A Bibliometric Analysis From 2000 to 2021.

BackgroundDiabetes mellitus (DM) have become seriously threatens to human health and life quality worldwide. As a systemic metabolic disease, multiple studies have revealed that DM is related to metabolic bone diseases and always induces higher risk of fracture. In view of this, the links between bone metabolism (BM) and DM (BMDM) have gained much attention and numerous related papers have been published. Nevertheless, no prior studies have yet been performed to analyze the field of BMDM research through bibliometric approach. To fill this knowledge gap, we performed a comprehensive bibliometric analysis of the global scientific publications in this field.MethodsArticles and reviews regarding BMDM published between 2000 and 2021 were obtained from the Web of Science after manually screening. VOSviewer 1.6.16, CiteSpace V 5.8.R3, Bibliometrix, and two online analysis platforms were used to conduct the bibliometric and visualization analyses.ResultsA total of 2,525 documents including 2,255 articles and 270 reviews were retrieved. Our analysis demonstrated a steady increasing trend in the number of publications over the past 22 years (R2 = 0.989). The United States has occupied the leading position with the largest outputs and highest H-index. University of California San Francisco contributed the most publications, and Schwartz AV was the most influential author. Collaboration among institutions from different countries was relatively few. The journals that published the most BMDM-related papers were Bone and Osteoporosis International. Osteoporosis and related fractures are the main bone metabolic diseases of greatest concern in this field. According to co-cited references result, “high glucose environment,” “glycation end-product” and “sodium-glucose co-transporter” have been recognized as the current research focus in this domain. The keywords co-occurrence analysis indicated that “diabetic osteoporosis,” “osteoarthritis,” “fracture risk,” “meta-analysis,” “osteogenic differentiation,” “bone regeneration,” “osteogenesis,” and “trabecular bone score” might remain the research hotspots and frontiers in the near future.ConclusionAs a cross-discipline research field, the links between bone metabolism and diabetes mellitus are attracting increased attention. Osteoporosis and related fractures are the main bone metabolic diseases of greatest concern in this field. These insights may be helpful for clinicians to recognize diabetic osteopenia and provide more attention and support to such patients.

The increase of neuropathic symptoms in diabetic patients is related with osteopenia.

To investigate the relationship between the intensity of neuropathic pain and the severity of osteopenia in type 2 diabetic patients with painful diabetic peripheral neuropathy (painful DPN). In 220 patients with type 2 diabetes included in the screening, the presence of neuropathic pain was evaluated using the Douleur Neuropathique 4 Questions (DN4) scoring system. One hundred forty-five patients with painful DPN were identified and included in the study. Socio-demographic and laboratory evaluations were made and bone mineral density (BMD) of these patients was evaluated by the dual-energy x-ray absorptiometry (DEXA) method. There was a significant correlation between the neuropathic pain score and the total T scores of the lumbar spine and femur in patients with painful DPN. According to the regression analysis (standard coefficients), the DN4 score (0.498); the level of vitamin D (- 0.246) and the female sex (0.236) for the lumbar spine region; age (0.387); DN4 score (0.261); and vitamin D level (- 0.155) for the femur region were independently influencing factors on the development of osteoporosis. When osteoporosis (T score ≤ - 2.5) of the lumbar spine was analyzed by binary logistic regression, the risk of osteoporosis in women was 4.4 times higher, and the risk increased with increasing DN4 score. The increase of neuropathic symptoms in patients with DPN is an effective and important factor in the development of diabetic osteopenia.

Phlorotannins Remarkably Suppress the Formation of Nε-(Carboxymethyl)lysine in a Collagen-Glyoxal Environment

N ε-(Carboxymethyl)lysine (CML), which is formed by the glycation of collagen, is a skin-accumulating advanced glycation end product and has been shown to be deeply involved in diabetic osteopenia and skin aging. In this study, we prepared the phlorotannins of marine algal polyphenols from Japanese Lessoniaceae ( Ecklonia cava, Ecklonia kurome, cultured E. kurome, Ecklonia stolonifera, Eisenia nipponica, and Eisenia bicyclis) and evaluated their inhibitory activities against CML formation in a collagen-glyoxal environment. The level of CML formed from the glycation of collagen by glyoxal was detected using an enzyme-linked immunosorbent assay. Except for E. stolonifera, the level of CML formation in the treatment with crude phlorotannins at 0.16 µg/mL was found to be comparable to that in the treatment with 0.40 mM aminoguanidine hydrochloride (AG) which is a typical antiglycation agent. In the test using phloroglucinol and isolated eckols (eckol, fucofuroeckol A, phlorofucofuroeckol A, dieckol, and 8,8’-bieckol) at a concentration of 0.80 µg/mL, the level of CML formed was lower for each compound, except for phlorofucofuroeckol A, than the data obtained with the addition of 2.0 mM AG. The mass concentration of 0.80 µg/mL was converted to 6.3 µM for phloroglucinol, 2.2 µM for eckol, 1.7 µM for fucofuroeckol A, 1.3 µM for phlorofucofuroeckol A, and 1.1 µM for dieckol and 8,8’-bieckol. From a comparison of the molar concentrations, it was found that phloroglucinol and the eckols inhibited the formation of CML resulting from glycation of collagen by glyoxal at concentrations of approximately 317 to 1818 times lower than AG.

Possible therapeutic potential of berberine in the treatment of STZ plus HFD-induced diabetic osteoporosis.

Diabetic osteoporosis is a complication of diabetes mellitus, and can result in an increased incidence of bone fractures and a delay in fracture healing. Berberine is one of the most widely distributed isoquinoline alkaloid in plants and possesses antioxidant properties. These properties can reduce the high glucose mediated in the dysfunction of human bone marrow stem cells. Therefore, the present study was designed to investigate the apparent beneficial effect of berberine on bone characteristics in streptozotocin plus HFD-induced diabetic rats. Rats were selected at random and divided into four groups: (A) control group (CG) (n = 10); (B) diabetic group (DG) (n = 10); (C) diabetic group with 50 mg kg-1day-1 of berberine (Brb-50) (n = 10); and (D) diabetic group with 100 mg kg-1day-1 of berberine (Brb-100) (n = 10). After 12 weeks of being treated with berberine, the femora from all rats were assessed and other blood biochemistries evaluated. Berberine at 50 mg/kg showed little effect and significance on diabetic osteopenia, while berberine at 100 mg/kg was significantly increased in diabetic rats. The same group also displayed a significantly decreased serum osteocalcin and serum alkaline phosphatase activity in diabetic rats. The impaired micro-architecture of the femurs in diabetic rats could partially be prevented by berberine with 100 mg/kg. In addition, berberine could to an extent restore the decreased bone formation and reabsorption of the femurs in diabetic rats through the histomorphometric analysis. Berberine could not only significantly lower the oxidative level of DNA damage, but also up-regulate the activity of serum antioxidants. According to our investigations and discoveries, we have found, that berberine may be a potential drug for controlling bone loss in diabetic osteoporosis.

Dental health of osteopenia diabetes mellitus male patients

Objective: The aim of the study was to examine the oral health of osteopenia diabetes mellitus (DM) male, which includes condition of the teeth, the periodontal tissue, and the temporomandibular joint (TMJ). Materials and Methods: The basis of the absolute value and t-score, only 42 diabetic osteopenia male patients were included in this study. The examination used only male patients with DM osteopenia, aged between 30 and 70 years; they were divided into two groups according to the type of DM. The following clinical parameters used in this study determined the conditions of periodontal tissues involved: Carious of the teeth, gingivitis, periodontitis bleeding on probing, mobility of the teeth, and number of the teeth and the TMJ included TMJ tenderness, TMJ clicking, limitation in opening, drifting to one side, and statement of teeth like the presence of attrition. Results: The results of this study for the osteopenia DM patients found that the carious teeth and gingivitis occurred in all ages in both groups of DM. TMJ tender, clicking, limiting of mouth opening percentage increased with increasing the age in both groups of DM, the older age more suspected to, periodontitis, bleeding on probing, number of the teeth, and mobility of the teeth also attrition increased with increasing the age in both groups of DM. Conclusion: The oral health for the diabetic osteopenia male patients more effected, the percentage of carious teeth, gingivitis, attrition mobility of the teeth, bleeding on probing periodontitis, and number of the teeth were increased with increasing the age in both the groups of DM.

EFFICACY OF QUERCETIN ON ALVEOLAR BONE STRUCTURE OF RATS WITH INDUCED DIABETES

INTRODUCTION: Diabetic osteopenia is the sixth classic complication of Diabetes mellitus. High glucose level is capable of triggering increased oxidative stress which induce osteoblast apoptosis. Quercetin, a powerful natural antioxidant, can protect many organs against oxidative damage, including bone. OBJECTIVES: The present study is designed to investigate the effect of quercetin administration on the alveolar bone in rats with induced diabetes. MATERIALS AND METHODS: Twenty-four adult male rats were divided into three equal groups (8 rats each) as follows: Group I: Control group, Group II: diabetic group (with no treatment), Group III: quercetin treated group (induction of diabetes with oral administration of quercetin dose 100mg/ kg/ day for 12 weeks). Diabetes was induced in group II and group III by a single intraperitoneal injection of Streptozotocin (STZ). After 12 weeks all rats were sacrificed and the mandibles were dissected out and prepared for histological analysis using scanning electron microscope (SEM), and energy dispersive x-ray microanalysis (EDX). RESULTS: In diabetic group, there was significant increase in blood sugar level. Bone surface revealed irregular surface with multiple resorptive pits. Moreover, there was significant decrease in calcium level and increase in phosphorous level while in quercetin group. Both blood sugar level and alveolar bone surface relatively returned back to normal. Also there was slight decrease in calcium and increase in phosphorous in comparison to control group. CONCLUSIONS: Quercetin exerts protective effects on STZ-induced oxidative stress in diabetic rats restoring the architecture of bone. KEYWORDS: Quercetin, Streptozotocin, Diabetes, Alveolar bone.

Long term bone alterations in aged rats suffering type 1 diabetes

Increasing duration of type 1 diabetes mellitus alters bone metabolism. Clinical studies and experimental studies in long bones of rats with experimentally induced diabetes have reported a decrease in bone density. Few studies have explored this diabetes related alteration in the maxillae. Given that this finding could indicate the possible development of osteopenia in the maxilla in the long term, the present study sought to analyze alterations in alveolar bone in aged rats, 12, 18, and 24weeks after inducing diabetes, and compare alveolar bone response to that of tibial subchondral bone at the same experimental times. Thirty-six male Wistar rats, 130g body weight, were divided into 2 groups: an experimental group (E) receiving a single i.p. 60mg/kg dose of streptozotocin, and a control group (C). Both the control and experimental groups were divided into 3 sub-sets, according to the time of euthanasia: 12, 18 and 24weeks. The alveolar bone and tibiae were examined histologically and histomorphometrically. The results were analyzed using Student's t-test; a value of p<0.05 was considered statistically significant. Results: Subchondral bone volume and bone activity/remodeling, mainly bone rest, were significantly lower in diabetic animals compared to controls, at both 12 and 18weeks. No differences in alveolar bone parameters were observed between diabetic and control animals at either of the experimental times. Animals surviving at 24weeks showed few trabeculae at rest and severe destruction of dental and periodontal tissues. The results of the present study show that diabetic osteopenia is evident in the tibia at 12 and at 18weeks, whereas its effects on the maxilla can be seen at 24weeks, with substantial destruction of alveolar bone and of the remaining periodontal and dental tissues. All the above observations highlight the need for preventive oral care in diabetic patients, before irreversible damage to dental and periodontal tissues occurs.

High glucose-associated osmolality promotes adipocytogenic differentiation of primary rat osteoblasts in a protein kinase A and phosphatidylinositol 3-kinase/Akt-dependent manner

AbstractIncreased risk of osteoporosis in patients with diabetes mellitus may be related to hyperglycemia. However, the potential mechanisms accounting for diabetic bone disorder remain unresolved. The present study investigated the effects of high glucose-associated osmolality on differentiation of primary rat calvarial osteoblasts. Osteoblastogenic differentiation was determined by bone nodule staining for mineralization assay, enzyme-linked immunosorbent assay for type I collagen production and real-time polymerase chain reaction (PCR) for osteoblastogenic marker gene expression. Adipocytogenic differentiation was assessed by oil red O staining for lipid accumulation and real-time PCR for adipocytogenic marker gene expression. The phosphorylations of protein kinase A (PKA) and Akt were measured with or without specific inhibitors to confirm osmolality involved signalling pathways. The results showed that high glucose-associated osmolality significantly promoted adipocytogenic differentiation, manifested by increased lipid droplet formation and gene expression of adipocytogenic markers including adipocyte fatty acid binding protein (aP2), adipsin and peroxisome proliferator-activated receptor gamma (PPARγ). Meanwhile, high glucose-associated osmolality inhibited osteoblastogenic differentiation, characterized by decreased collagen I protein production and cell mineralization, as well as gene expression of osteoblastogenic markers including collagen I, osteocalcin and runt-related transcription factor 2 (Runx2). More importantly, we demonstrated for the first time that high glucose-associated osmolality induced adipocytogenic differentiation and suppressed osteoblastogenic differentiation in a PKA and phosphatidylinositol 3-kinase (PI3K)/Akt-dependent manner. These results indicated that osmolality was involved in high glucose-induced osteoblast trans-differentiation into adipocyte-like cell and suppression of cellular osmolality could provide novel therapeutic approach for diabetic osteopenia.

The Effect of Systemic Delivery of Aminoguanidine versus Doxycycline on the Resorptive Phase of Alveolar Bone Following modified Widman Flap in Diabetic Rats: A Histopathological and Scanning Electron Microscope (SEM) study.

Aminoguanidine (guanylhydrazinehydrochloride) is a drug that prevents many of the classical systemic complications of diabetes including diabetic osteopenia through its inhibitory activity on the accumulation of advanced glycation end -products (AGEs). The aim of the present study was to evaluate the effectiveness of aminoguanidine versus doxycycline in reducing alveolar bone resorption following mucoperiosteal flap in diabetic rats, using the conventional histopathology and scanning electron microscope (SEM). Twenty-seven male albino rats were used in this study. Periodontal defects were induced experimentally on lower anterior teeth. All rats were subjected to induction of diabetes, by IV injection of the pancreatic B-cells toxin alloxan monohydrate. After eight weeks following the establishment of periodontal defects in all rats, the ligation was removed and 3 rats were scarified as negative control (group 1). The remaining animals were divided into three group based on treatment applied following mucoperiosteal flap surgery. Group 2 received saline treatment only, group 3 received doxycycline periostat (1.5 mg/kg/day) for 3 weeks, and group 4 received aminoguanidine (7.3 mmol/kg) for 3 weeks. The fasting glucose level was measured weekly post operatively. After 21 days all rats were sacrificed. Three anterior parts of the mandible of each group was prepared for histopathological examination and two parts were prepared for SEM. Aminoguanidine treated group (group 4) showed statistically significant increased new bone formation, higher number of osteoblasts and decrease osteoclasts number, resorptive lacunae and existing inflammatory cell infiltration as compared to positive control group (group 2) (P<0.05). Doxycycline was also effective in reducing bone loss as documental by histopathological study. The present study showed that aminoguanidine was significantly effective in reducing alveolar bone loss and can modify the detrimental effects of diabetes in alveolar bone resorption.

Diabetic osteopenia by decreased β-catenin signaling is partly induced by epigenetic derepression of sFRP-4 gene.

In diabetics, methylglyoxal (MG), a glucose-derived metabolite, plays a noxious role by inducing oxidative stress, which causes and exacerbates a series of complications including low-turnover osteoporosis. In the present study, while MG treatment of mouse bone marrow stroma-derived ST2 cells rapidly suppressed the expression of osteotrophic Wnt-targeted genes, including that of osteoprotegerin (OPG, a decoy receptor of the receptor activator of NF-kappaB ligand (RANKL)), it significantly enhanced that of secreted Frizzled-related protein 4 (sFRP-4, a soluble inhibitor of Wnts). On the assumption that upregulated sFRP-4 is a trigger that downregulates Wnt-related genes, we sought out the molecular mechanism whereby oxidative stress enhanced the sFRP-4 gene. Sodium bisulfite sequencing revealed that the sFRP-4 gene was highly methylated around the sFRP-4 gene basic promoter region, but was not altered by MG treatment. Electrophoretic gel motility shift assay showed that two continuous CpG loci located five bases upstream of the TATA-box were, when methylated, a target of methyl CpG binding protein 2 (MeCP2) that was sequestered upon induction of 8-hydroxy-2-deoxyguanosine, a biomarker of oxidative damage to DNA. These in vitro data suggest that MG-derived oxidative stress (not CpG demethylation) epigenetically and rapidly derepress sFRP-4 gene expression. We speculate that under persistent oxidative stress, as in diabetes and during aging, osteopenia and ultimately low-turnover osteoporosis become evident partly due to osteoblastic inactivation by suppressed Wnt signaling of mainly canonical pathways through the derepression of sFRP-4 gene expression.

Medicinal and edible fungi as an alternative medicine for treating age-related disease.

Medicinal and edible fungi as an alternative medicine for treating age-related disease.

Collagen advanced glycation inhibits its Discoidin Domain Receptor 2 (DDR2)-mediated induction of lysyl oxidase in osteoblasts

Diabetes increases the risk of bone fracture. Organic and inorganic bone extracellular matrix components determine bone strength. Previous studies indicate that in diabetes, glycation of collagen causes abnormal arrangements of collagen molecules and fragile bones. Diabetic bone fragility is additionally attributed to reduced levels of lysyl oxidase enzyme-dependent collagen cross-links. The mechanism underlying the presence of lower enzymatic collagen cross-links in diabetic bone has not been directly investigated. Here we determine in primary osteoblast cultures the regulation of lysyl oxidase protein by type I collagen and collagen modified by carboxymethylation (CML-collagen), a form of advanced glycation endproducts. Data indicate that non-glycated collagen up-regulates lysyl oxidase levels both in primary non-differentiated and in differentiating mouse and rat osteoblast cultures, while CML-collagen fails to regulate lysyl oxidase in these cells. Collagen binding to Discoidin Domain Receptor-2 (DDR2) mediates lysyl oxidase increases, determined in DDR2 shRNA knockdown studies. DDR2 binding and activation were disrupted by collagen glycation, pointing to a mechanism for the diminished levels of lysyl oxidase and consequently low lysyl oxidase-derived cross-links in diabetic bone. Our studies indicate that collagen–integrin interactions may not play a major role in up-regulating lysyl oxidase. Furthermore, non-collagenous ligands for the receptor for advanced glycation end products (RAGE) failed to alter lysyl oxidase levels. Taken together with published studies a new understanding emerges in which diabetes- and age-dependent inhibition of normal collagen-stimulated DDR2- and integrin-signaling, and independent advanced glycation-stimulated RAGE-signaling, each contributes to different aspects of diabetic osteopenia.

Activation of the PI3K/Akt pathway by oxidative stress mediates high glucose-induced increase of adipogenic differentiation in primary rat osteoblasts

Diabetes mellitus is associated with increased risk of osteopenia and bone fracture that may be related to hyperglycemia. However, the mechanisms accounting for diabetic bone disorder are unclear. Here, we showed that high glucose significantly promoted the production of reactive oxygen species (ROS) in rat primary osteoblasts. Most importantly, we reported for the first time that ROS induced by high glucose increased alkaline phosphatase activity, inhibited type I collagen (collagen I) protein level and cell mineralization, as well as gene expression of osteogenic markers including runt-related transcription factor 2 (Runx2), collagen I, and osteocalcin, but promoted lipid droplet formation and gene expression of adipogenic markers including peroxisome proliferator-activated receptor gamma, adipocyte fatty acid binding protein (aP2), and adipsin, which were restored by pretreatment with N-acetyl-L-cysteine (NAC), a ROS scavenger. Moreover, high glucose-induced oxidative stress activated PI3K/Akt pathway to inhibited osteogenic differentiation but stimulated adipogenic differentiation. In contrast, NAC and a PI3K inhibitor, LY-294002, reversed the down-regulation of osteogenic markers and the up-regulation of adipogenic markers as well as the activation of Akt under high glucose. These results indicated that oxidative stress played a key role in high glucose-induced increase of adipogenic differentiation, which contributed to the inhibition of osteogenic differentiation. This process was mediated by PI3K/Akt pathway in rat primary osteoblasts. Hence, suppression of oxidative stress could be a potential therapeutic approach for diabetic osteopenia.

Alleviating effects of morin against experimentally-induced diabetic osteopenia

BackgroundPlant flavonoids are emerging as potent therapeutic drugs effective against a wide range of aging diseases particularly bone metabolic disorders. Morin (3,5,7,20,40-pentahydroxyflavone), a member of flavonols, is an important bioactive compound by interacting with nucleic acids, enzymes and protein. The present study was designed to investigate the putative beneficial effect of morin on diabetic osteopenia in rats.MethodsStreptozotocin (STZ)-induced diabetic model was used by considering 300 mg/dl fasting glucose level as diabetic. Morin (15 and 30 mg/kg) was treated for five consecutive weeks to diabetic rats. Serum levels of glucose, insulin, deoxypyridinoline cross links (DPD), osteocalcin (OC), bone specific alkaline phosphatase (BALP), telopeptides of collagen type I (CTX), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), thiobarbituric acid reactive substance (TBARS) and reduced glutathione (GSH) were estimated. Femoral bones were taken for micro CT scan to measure trabecular bone mineral density (BMD) and other morphometric parameters.ResultsSignificant bone loss was documented as the level of bone turnover parameters including DPD, OC, BALP and CTX were increased in serum of diabetic rats. Morin treatment significantly attenuated these elevated levels. Bone micro-CT scan of diabetic rats showed a significant impairment in trabecular bone microarchitecture, density and other morphometric parameters. These impairments were significantly ameliorated by morin administration. Serum levels of glucose, TBARS, IL-1β, IL-6 and TNF-α were significantly elevated, while the level of insulin and GSH was decreased in diabetic rats. These serum changes in diabetic rats were bring back to normal values after 5 weeks morin treatment.ConclusionThese findings revealed the protective effect of morin against diabetic induced osteopenia. We believed that this effect is through its both the anti-inflammatory and antioxidant properties.

The Protective Effect of Cordymin, a Peptide Purified from the Medicinal Mushroom Cordyceps sinensis, on Diabetic Osteopenia in Alloxan-Induced Diabetic Rats.

The aim of this study was to investigate the protective effect of cordymin on diabetic osteopenia in alloxan-induced diabetic rats and the possible mechanisms involved. The diabetic rats received daily intraperitoneal injection with cordymin (20, 50, and 100 mg/kg/day) for 5 weeks. Cordymin could restore the circulating blood glucose, glycosylated hemoglobin (HbA1c), serum alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRAP), and insulin levels in a dose-dependent manner. Also, the treatment of diabetic rats with cordymin could partially reverse the β cells death and decrease the total antioxidant status (TAOS) in the diabetic rats. The results may directly and indirectly account for the possible mechanism of the beneficial effect of cordymin on diabetic osteopenia, which was confirmed with the increased bone mineral content (BMC) and bone mineral density (BMD) in diabetic rats (P < 0.05). All those findings indicate that cordymin may play a protective role in diabetic osteoporosis.

Amylin exerts osteogenic actions with different efficacy depending on the diabetic status

Amylin displays osteogenic features, but its role in diabetic osteopenia is unclear. We examined the possible osteogenic action of amylin infusion for 3days into fructose-induced insulin-resistant (IR) and streptozotocin-induced type 2 diabetic (T2D) and normal (N) rats. Amylin failed to affect glycaemia or parathyroid hormone levels in any group, but reduced hyperinsulinemia in IR rats. In N rats, amylin increased bone formation rate and reduced osteoclast surface and erosive surface in the femoral metaphysis, and increased osteoprotegerin (OPG)/receptor activator of NFκB ligand (RANKL) mRNA ratio in the tibia. In T2D rats, amylin normalized trabecular structure parameters and increased osteoblast number and osteocalcin (OC) expression in long bones. In contrast, in IR rats, no apparent osteogenic effect of amylin in the femur was observed, although both OC and OPG/RANKL ratio were increased in the tibia. Our findings demonstrate a different osteogenic efficacy of amylin in two diabetic settings.

1673 Osteopathy in Insulin-Dependant Diabetes Mellitus; A Neglected Complication

The main aim of management of insulin dependent diabetes (IDDM) is to prevent the acute as well as the long term complications, Recent studies suggest that IDDM in children is...

Characteristics of Diabetic Osteopenia in KK-Ay Diabetic Mice

We examined the bone mineral density (BMD) of the proximal region and the mid-diaphysis of the femur using dual energy X-ray absorption (DXA), the blood osteocalcin level and the blood glucose level every five weeks from 8 to 23 weeks old in KK-Ay diabetic mice. The BMD of the proximal region after 18 weeks old was significantly lower when compared with that at 8 weeks old (p<0.05), whereas there was no significant difference in the BMD of the mid-diaphysis at each week. The BMD of the proximal region at 18 weeks old was significantly lower than that in ddY mice, used as controls (p<0.05). The blood osteocalcin level at 18 weeks old was significantly lower than that at 8 weeks old and that in 18-week-old ddY mice (p<0.05). There was significant negative correlation between the blood glucose level and the BMD of the proximal region (r=-0.64, p<0.05). These results suggest that type 2 diabetes exerts an influence only on spongy bone, not on cortical bone, and that the BMD in the proximal region of the femur seems to be affected by blood glucose level, parallel with the progression of diabetes, through the blood osteocalcin level. In the present study, we show the characteristics of diabetic osteopenia in KK-Ay mice, an animal model of type 2 diabetes.

Oral administration of quercetin inhibits bone loss in rat model of diabetic osteopenia

Diabetic osteopenia can result in an increased incidence of bone fracture and a delay in fracture healing. Quercetin, one of the most widely distributed flavonoids in plants, possesses antioxidant property and beneficial effect on osteoporosis in ovariectomized mice. All these properties make quercetin a potential candidate for controlling the development of diabetic osteopenia. Therefore, the present study was designed to investigate the putative beneficial effect of quercetin on diabetic osteopenia in rats. Diabetes mellitus was induced by streptozotocin. The diabetic rats received daily oral administration of quercetin (5mg/kg, 30 mg/kg and 50mg/kg) for 8 weeks, which was started at 4 weeks after streptozotocin injection. Quercetin at 5mg/kg showed little effect on diabetic osteopenia, while quercetin at 30 mg/kg and 50mg/kg could increase the decreased serum osteocalcin, serum alkaline phosphatase activity, and urinary deoxypyridinoline in diabetic rats. In addition, quercetin (30 mg/kg and 50mg/kg) could partially reverse the decreased biomechanical quality and the impaired micro-architecture of the femurs in diabetic rats. Histomorphometric analysis showed that both decreased bone formation and resorption were observed in diabetic rats, which was partially restored by quercetin (30 mg/kg and 50mg/kg). Further investigations showed that quercetin significantly lowered the oxidative DNA damage level, up-regulated the total serum antioxidant capability and the activity of serum antioxidants in diabetic rats. All those findings indicate the beneficial effect of quercetin on diabetic osteopenia in rats, and raise the possibility of developing quercetin as potential drugs or an ingredient in diet for controlling diabetic osteopenia.