scholarly journals Scopoletin and Coumarin Attenuate Aberrant Bone Remodeling in Glucose-exposed Osteoblasts and Osteoclasts (P06-062-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Eun-jung Lee ◽  
Young-Hee Kang
Keyword(s):  
Bone Remodeling ◽  
High Bone Mineral Density ◽  
Diabetic Patients ◽  
Tartrate Resistant Acid Phosphatase ◽  
Raw 264.7 ◽  
Mineral Density ◽  
Trap Activity ◽  
Alp Activity ◽  
Increased Risk ◽  
Diabetic Osteoporosis

Abstract Objectives Diabetes mellitus is a complex disease with harmful effects on the osteoblast and osteoclast activity. Type 2 diabetic patients have normal or high bone mineral density but associated with an increased risk of fractures. Coumarins (1-benzopyran-2-one) are chemical compounds in the benzopyrone class of organic compounds found in many plants. The purpose of this study was to identify that hyperglycemia resulted in impaired bone remodeling and to examine whether coumarins were capable of preventing diabetic osteoporosis. Methods The in vitro study employed osteoblastic MC3T3-E1 cells that were exposed to 33 mM glucose for 6 days in the presence of 20 μM coumarins of scopoletin, aesculetin and coumarin. Alkaline phosphatase (ALP) activity was quantitatively determined in osteoblastic MC3T3-E1 cells by using stable p-nitrophenyl phosphate. In addition, murine macrophage Raw 264.7 cells were differentiated with receptor activator of nuclear factor-κΒ ligand (RANKL) in 33 mM glucose and 20 μM coumarins for 5 days. Tartrate-resistant acid phosphatase (TRAP) activity was measured using an assay kit. Results High glucose attenuated the ALP activity of osteoblastic MC3T3-E1 cells, which was enhanced by treating scopoletin, aesculetin and coumarin to cells. In addition, 33 mM glucose diminished TRAP activity in RANKL-differentiated Raw 264.7 macrophages, indicating that bone remodeling was impaired in diabetic osteoclasts. In contrast, scopoletin and coumarin elevated osteoclastic differentiation and activation. Interestingly, coumarin was highly effective in balancing bone turnover of osteoblasts and osteoclasts. Conclusions These results demonstrate that glucose evoked abnormal bone remodeling leading to diabetic bone disorder. In addition, coumarins such as scopoletin and coumarin ameliorated bone remodeling impaired in diabetic osteoblasts and osteoclasts. These findings suggest the possibility that coumarins might be a potential agent for the treatment of diabetic osteoporosis. Funding Sources This work (Grants No. C0501612) was supported by project for Cooperative R&D between Industry, Academy, and Research Institute funded Korea Ministry of SMEs and Startups in 20.

scholarly journals Coumarin Boosts Optimal Bone Remodeling Through Blocking AGE-RAGE Interaction in Diabetic Osteoblasts and Osteoclasts

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 395-395
Author(s):  
Lee Eun-Jung ◽  
Young-Hee Kang
Keyword(s):  
Bone Mineral Density ◽  
Bone Remodeling ◽  
Bone Mineral ◽  
Bone Fragility ◽  
Osteoblastic Cells ◽  
Raw 264.7 Cells ◽  
High Bone Mineral Density ◽  
Mineral Density ◽  
Alp Activity ◽  
Diabetic Osteoporosis

Abstract Objectives Accumulating evidence has shown that the risk of osteoporotic fractures is increased in patients with diabetes mellitus despite normal or high bone mineral density. Thus, diabetes-induced bone fragility has been recently recognized as a diabetic complication. Because the fracture risk is independent of the reduction in bone mineral density, deterioration of the bone quality may be the main cause of bone fragility. Coumarin is naturally found in many plants as phenylpropanoids and present in tonka beans at notably high concentrations. The purpose of this study was to identify that hyperglycemia-mediated advanced glycation end-product (AGE) resulted in impaired bone remodeling and to examine whether coumarin was capable of preventing diabetic osteoporosis through boosting bone remodeling. Methods The in vitro study employed osteoblastic MC3T3-E1 cells that were exposed to 33 mM glucose for 6 days in the presence of 1–20 μM coumarin. Alkaline phosphatase (ALP) activity was quantitatively determined in osteoblastic cells by using stable p-nitrophenyl phosphate. In addition, murine macrophage Raw 264.7 cells were differentiated to multi-nucleated osteoclasts with receptor activator of nuclear factor-κΒ ligand (RANKL) in 33 mM glucose and 1–20 μM coumarin for 5 days. Results High glucose attenuated the ALP activity of osteoblastic cells, which was enhanced by treating 1–20 μM coumarin to cells. On the other hand, 33 mM glucose diminished TRAP and bone resorption activity in RANKL-differentiated osteoclasts, indicating that osteoclast activation was impaired under diabetic conditions. On the contrary, coumarin elevated osteoclastic differentiation and activation. In addition, coumarin ameliorated aberrant bone remodeling in osteoblasts and osteoclasts evoked by AGE. Together, coumarin improved bone remodeling impaired in diabetic osteoblasts and osteoclasts though suppressing interaction of AGE and its receptor. Conclusions These findings suggest the possibility that coumarin might be a potential agent for the treatment of diabetic osteoporosis. Funding Sources This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2019R1A2C1003218).

Keel-bone fractures are associated with bone quality differences in laying hens

2021 ◽  
Vol 30 (1) ◽  
pp. 71-80
Author(s):  
HD Wei ◽  
YJ Chen ◽  
XY Zeng ◽  
YJ Bi ◽  
YN Wang ◽  
...  
Keyword(s):  
Bone Quality ◽  
Laying Hens ◽  
Bone Fractures ◽  
Quality Parameters ◽  
Bone Volume ◽  
Tartrate Resistant Acid Phosphatase ◽  
Bone Surface ◽  
Mineral Density ◽  
Trabecular Thickness ◽  
Trap Activity

This study aimed to investigate the relationship between bone quality in terms of metabolism, homeostasis of elements, bone mineral density (BMD), and microstructure and keel-bone fractures in laying hens (Gallusgallusdomesticus). One hundred and twenty 17 week old Lohmann White laying hens with normal keel bones were individually housed in furnished cages for 25 weeks. Birds were then euthanased and dissected to assess keel-bone status at 42 weeks. Serum and keel-bone samples from normal keel (NK) and fractured keel (FK) hens were collected to determine the previously mentioned bone quality parameters. The results showed FK hens to have higher levels of the components of osteocalcin, greater alkaline phosphatase activity in serum and keel bones, and greater tartrate-resistant acid phosphatase (TRAP) activity in keel bones, compared to NK hens. Additionally, FK hens also had higher concentrations of Li, B, K, Cu, As, Se, Sn, Hg, and Pb, but lower concentrations of Na, P, and Ca. Moreover, FK hens showed decreased bone microstructural parameters including bone volume/tissue volume, trabecular number, degree of anisotropy, connectivity density, and BMD, but increased trabecular separation. Meanwhile, no differences were detected in serum TRAP activity, trabecular thickness, bone surface, or bone surface/bone volume. Results showed laying hens with keel-bone fractures to have differences in bone metabolism, elements of homeostasis, bone microstructure parameters, and BMD. These results suggest that keel-bone fractures may be associated with bone quality.

Edgeworthia papyrifera Regulates Osteoblast and Osteoclast Differentiation In Vitro and Exhibits Anti-osteoporosis Activity in Animal Models of Osteoporosis

Planta Medica ◽  
2019 ◽  
Vol 85 (09/10) ◽  
pp. 766-773 ◽  
Author(s):  
Pansoo Kim ◽  
Yeon-Ju Nam ◽  
Woo Jung Kim ◽  
Jin Kyu Kim ◽  
Gyeongbeen Lee ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Animal Models ◽  
Osteoclast Differentiation ◽  
Raw 264.7 Cells ◽  
Tartrate Resistant Acid Phosphatase ◽  
Raw 264.7 ◽  
Treatment Of Osteoporosis ◽  
Increased Risk ◽  
Interesting Candidate

AbstractOsteoporosis is a clinical condition characterized by low bone strength that leads to an increased risk of fracture. Strategies for the treatment of osteoporosis involve inhibition of bone resorption by osteoclasts and an increase of bone formation by osteoblasts. Here, we identified the extract derived from the stem part of Edgeworthia papyrifera that enhanced differentiation of MC3T3-E1 cells to osteoblast-like cells and inhibited osteoclast differentiation of RAW 264.7 cells in vitro. In support of our observation, rutin and daphnoretin, which were previously reported to inhibit osteoclast differentiation, were identified in E. papyrifera extract. In an animal model of osteoporosis, the ovariectomy-induced increases in bone resorption biomarkers such as pyridinoline and tartrate-resistant acid phosphatase were significantly reduced by E. papyrifera extract administration at 25.6 and 48.1%, respectively. Furthermore, the ovariectomy-induced bone loss in animal models of osteoporosis was significantly prevented by the administration of E. papyrifera in our study. Taking these observations into account, we suggest that E. papyrifera is an interesting candidate for further exploration as an anti-osteoporotic agent.

scholarly journals Does type 2 diabetic osteoporotic patients present more periodontal risks than non-osteoporotic patients? An evaluation with mandibular cortical index (Klemetti)

2018 ◽  
Vol 17 ◽  
pp. e181211
Author(s):  
Wladimir Gushiken de Campos ◽  
Gonzalo André Montesinos ◽  
Rosa Cristina Peinado Agudo ◽  
Kaisermann Costa ◽  
Luciana Munhoz ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bone Loss ◽  
Periodontal Disease ◽  
Diabetic Patients ◽  
Mineral Density ◽  
Cortical Index ◽  
Increased Risk ◽  
Type 2 Diabetic ◽  
Mandibular Cortical Index

Aim: This study aim was to evaluate if patients with type 2 diabetes and osteoporosis have an increased risk of periodontal disease (horizontal and vertical bone loss) when compared to diabetic patients without osteoporosis. Additionally, to assess if patients with diabetes and osteoporosis have a greater risk of reduction of bone mineral density in the mandible, expressed by mandibular cortical index (MCI) when compared to diabetic patients without osteoporosis. Methods: 59 patients (39 diagnosed with type 2 diabetes and osteoporosis; 20 diagnosed with type 2 diabetes and without osteoporosis) were selected. Type 2 diabetes was previously diagnosed by glycated hemoglobin examination and osteoporosis by peripheral dual-energy x-ray absorptiometry. Mandibular cortical index, as well as the presence of vertical and horizontal bone loss was verified on panoramic radiographs. Adjusted odds ratio analyses were performed on presence of periodontal disease and MCI considering the effect of osteoporosis. Results: Absence of statistical significance between variables was found. Conclusions: There is no difference between the risk of periodontal disease or low MCI among osteoporotic and non-osteoporotic type 2 diabetic patients.

scholarly journals Effect of Intermittent Fasting on Glucose Homeostasis and Bone Remodeling in Glucocorticoid-Induced Osteoporosis Rat Model

2021 ◽  
Vol 28 (4) ◽  
pp. 307-316
Author(s):  
Majed G. Alrowaili ◽  
Abdelaziz M. Hussein ◽  
Elsayed A. Eid ◽  
Mohamed S. Serria ◽  
Hussein Abdellatif ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Bone Mineral ◽  
Serum Levels ◽  
Male Rats ◽  
Control Group ◽  
Intermittent Fasting ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Mineral Density ◽  
Trap 5B

Background: The present study examined the effect of intermittent fasting (IF) on bone mineral content (BMC) and bone mineral density (BMD) and the markers of bone remodeling in a glucocorticoid-induced osteoporosis (GIO) rat model.Methods: Forty male rats were allocated to 4 groups (N=10 per group): control group of normal rats; control+IF group (normal rats subjected to IF for 16-18 hr daily for 90 days); dexamethasone (DEX) group: (DEX [0.5 mg i.p.] for 90 days); and DEX+IF group (DEX and IF for 90 days). By the end of the experiment, BMD and BMC in the right tibia were measured. Serum levels of the following were measured: glucose; insulin; triglycerides (TGs); total cholesterol; parathyroid hormone (PTH); osteoprotegerin (OPG); receptor activator of nuclear factor-κB (RANK); bone-resorbing cytokines, including bone deoxypyridinoline (DPD), N-terminal telopeptide of collagen type I (NTX-1), and tartrate-resistant acid phosphatase 5b (TRAP-5b); and bone-forming cytokines, including alkaline phosphatase (ALP) and osteocalcin (OC).Results: DEX administration for 90 days resulted in significantly increased serum levels of glucose, insulin, TGs, cholesterol, PTH, OPG, DPD, NTX-1, and TRAP-5b and significantly decreased BMD, BMC, and serum levels of RANK, OC, and ALP (all P<0.05). IF for 90 days significantly improved all these parameters (all P<0.05).Conclusions: IF corrected GIO in rats by inhibiting osteoclastogenesis and PTH secretion and stimulating osteoblast activity.

scholarly journals Interspecies Comparison of Alveolar Bone Biology, Part I: Morphology and Physiology of Pristine Bone

2020 ◽  
pp. 238008442093697
Author(s):  
I. Pilawski ◽  
U.S. Tulu ◽  
P. Ticha ◽  
P. Schüpbach ◽  
H. Traxler ◽  
...  
Keyword(s):  
Animal Models ◽  
Bone Remodeling ◽  
Alveolar Bone ◽  
State Of The Art ◽  
Tartrate Resistant Acid Phosphatase ◽  
Knowledge Gap ◽  
Bone Biology ◽  
Mineral Density ◽  
Surgical Interventions

Introduction: Few interspecies comparisons of alveolar bone have been documented, and this knowledge gap raises questions about which animal models most accurately represent human dental conditions or responses to surgical interventions. Objectives: The objective of this study was to employ state-of-the-art quantitative metrics to directly assess and compare the structural and functional characteristics of alveolar bone among humans, mini pigs, rats, and mice. Methods: The same anatomic location (i.e., the posterior maxillae) was analyzed in all species via micro–computed tomographic imaging, followed by quantitative analyses, coupled with histology and immunohistochemistry. Bone remodeling was evaluated with alkaline phosphatase activity and tartrate-resistant acid phosphatase staining to identify osteoblast and osteoclast activities. In vivo fluorochrome labeling was used as a means to assess mineral apposition rates. Results: Collectively, these analyses demonstrated that bone volume differed among the species, while bone mineral density was equal. All species showed a similar density of alveolar osteocytes, with a highly conserved pattern of collagen organization. Collagen maturation was equal among mouse, rat, and mini pig. Bone remodeling was a shared feature among the species, with morphologically indistinguishable hemiosteonal appearances, osteocytic perilacunar remodeling, and similar mineral apposition rates in alveolar bone. Conclusions: Our analyses demonstrated equivalencies among the 4 species in a plurality of the biological features of alveolar bone. Despite contradictory results from older studies, we found no evidence for the superiority of pig models over rodent models in representing human bone biology. Knowledge Transfer Statement: Animal models are extensively used to evaluate bone tissue engineering strategies, yet there are few state-of-the-art studies that rigorously compare and quantify the factors influencing selection of a given animal model. Consequently, there is an urgent need to assess preclinical animal models for their predictive value to dental research. Our article addresses this knowledge gap and, in doing so, provides a foundation for more effective standardization among animal models commonly used in dentistry.

scholarly journals Methoxsalen and Bergapten Prevent Diabetes-Induced Osteoporosis by the Suppression of Osteoclastogenic Gene Expression in Mice

2019 ◽  
Vol 20 (6) ◽  
pp. 1298 ◽  
Author(s):  
Ju Ham ◽  
Ra-Yeong Choi ◽  
Hae-In Lee ◽  
Mi-Kyung Lee
Keyword(s):  
Underlying Mechanism ◽  
Volume Density ◽  
Diabetic Control ◽  
Bone Alkaline Phosphatase ◽  
Control Group ◽  
Tartrate Resistant Acid Phosphatase ◽  
Diabetic Mice ◽  
Mineral Density ◽  
Activated T Cells ◽  
Diabetic Osteoporosis

This study evaluated whether bergapten and methoxsalen could prevent diabetes-induced osteoporosis and its underlying mechanism. For 10 weeks, bergapten or methoxsalen (0.02%, w/w) was applied to diabetic mice that were provided with a high-fat diet and streptozotocin. Bone mineral density (BMD) and microarchitecture quality were significantly reduced in the diabetic control group; however, both bergapten and methoxsalen reversed serum osteocalcin, bone-alkaline phosphatase and femur BMD. These coumarin derivatives significantly increased bone volume density and trabecular number, whereas they decreased the structure model index of femur tissue in diabetic mice. Conversely, tartrate-resistant acid phosphatase 5 (TRAP) staining revealed that these derivatives reduced osteoclast numbers and formation in diabetic bone tissue. Additionally, both bergapten and methoxsalen tended to downregulate the expression of osteoclast-related genes such as receptor activator of nuclear factor kappa-B ligand (RANKL), nuclear of activated T-cells, cytoplasmic 1 (NFATc1) and TRAP in diabetic femurs, with NFATc1 and TRAP expression showing significant reductions. Our data suggest that both bergapten and methoxsalen prevent diabetic osteoporosis by suppressing bone resorption.

The effect of monthly ibandronate on bone mineral density and bone turnover markers in patients with haemophilia A and B and increased risk for fracture

2013 ◽  
Vol 110 (08) ◽  
pp. 257-263 ◽  
Author(s):  
Timoleon-Achilleas Vyzantiadis ◽  
Maria Charizopoulou ◽  
Fotini Adamidou ◽  
Spyridon Karras ◽  
Dimitrios Goulis ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Resorption ◽  
Bone Formation ◽  
Bone Mineral ◽  
Tartrate Resistant Acid Phosphatase ◽  
Haemophilia A ◽  
Mineral Density ◽  
Risk Of Fracture ◽  
Increased Risk ◽  
Turnover Markers

SummaryHaemophilia A and B have been associated with increased prevalence of low bone mineral density (BMD). However, no study has so far evaluated the effects of anti-osteoporotic therapy on BMD in haemophilia. The primary endpoint of this prospective study was to estimate the effect of 12-month therapy of oral ibandronate 150 mg/ month on BMD in patients with haemophilia A and B. Secondary endpoint was its effect on turnover markers (BTM) of bone resorption [serum C-terminal telopeptide of type 1 collagen (sCTX), tartrate-resistant acid phosphatase band 5b] and bone formation (osteocalcin and bone-specific alkaline phosphatase. Ten adult patients with T-score < −2.5 SD or Z-score < −2 and/or increased risk of fracture according to FRAX model were included. All received 1,000 mg/day calcium carbonate with 800 IU/d cholecalciferol. Males with haemophilia A (n=7) or B (n=3) (mean age 43.5 ± 13.5 years) were studied. Ibandronate resulted in an increase in lumbar BMD (from 0.886 ± 0.169 to 0.927 ± 0.176 g/cm2, 4.7%, p=0.004). No change in BMD of total hip (from 0.717 ± 0.128 to 0.729 ± 0.153 g/cm2, p=0.963) or femoral neck (0.741 ± 0.135 to 0.761 ± 0.146 g/cm2, p=0.952) was noticed. Ibandronate led to a decrease in sCTX (from 0.520 ± 0.243 to 0.347 ± 0.230 ng/ml, −29.9%, p=0.042). No change was observed in other BTM. Ibandronate was generally well-tolerated. In conclusion, ibandronate significantly improved BMD in lumbar spine and reduced bone resorption in adults with haemophilia at increased risk of fracture. Its effect on hip BMD and bone formation markers was not significant.

scholarly journals Is there an association of bone mineral density and risk of breast cancer in postmenopausal Saudi women?

2021 ◽  
Vol 6 (2) ◽  
Keyword(s):  
Breast Cancer ◽  
Bone Mineral Density ◽  
Lumbar Spine ◽  
Bone Mineral ◽  
High Bone Mineral Density ◽  
Mineral Density ◽  
Saudi Women ◽  
T Score ◽  
Increased Risk ◽  
Significant Difference

Several studies revealed an association between high bone mineral density (BMD) and the increased risk for developing breast cancer (BC). Aim: Explore if there is an association between BMD and BC risk in postmenopausal Saudi (PMS) women. Material and Method: In a retrospective cohort study of 1145 PMS women age range from 46 – 85 year (mean = 55 year). The average time period of menopause 4 years.We reviewed BMD of all patients performed between October 2012 and November 2018. All patients had BMD measurements of lumbar spine L2-L4 and right femoral neck in gm/cm². Results: The T-score was used for analysis of the results. Among the total patient studied 195 (17%) were found to have BC group 1 (G1) while 950 (93%) without BC group 2(G2). Analysis of lumbar spine T-score in G1 showed that: 29 % had osteoporosis, 37% osteopenia and 34% had normal BMD and in G2 40% had osteoporosis, 31% osteopenia and 29 had normal values. Results showed prevalence of osteoporosis in G1 was significantly lower than in G2 (p =0.002) while there was no significant difference between the two groups with osteopenia and normal BMD results (p = 0.06 and 0.205 respectively). Conclusion: PMS women with BC had higher BMD at time of diagnosis compared to their counterpart without BC.

scholarly journals Risk Factors for Fracture in Diabetes: The Canadian Multicentre Osteoporosis Study

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Lisa-Ann Fraser ◽  
Alexandra Papaioannou ◽  
Jonathan D. Adachi ◽  
Jinhui Ma ◽  
Lehana Thabane
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Family History ◽  
Female Gender ◽  
Diabetic Patients ◽  
Mineral Density ◽  
Cross Sectional ◽  
Increased Risk ◽  
Traumatic Fracture ◽  
History Of

Objective. Individuals with diabetes have been found to be at increased risk of nontraumatic fracture. However, within the diabetic population, how to distinguish who is at the highest risk and warranting therapy has remained elusive. Design. Cross-sectional analysis of a national population-based cohort study. Patients. Men and women over the age of 50 with diabetes from across Canada. Measurements. Logistic regression analysis to identify diabetes specific factors associated with a history of one or more non-traumatic fractures. Results. Six hundred and six individuals with diabetes with a mean age of 69 years were examined. Thirty percent had a history of non-traumatic fracture. Macrovascular diseases in the form of stroke or TIA, as well as hypertension, were found to be independently associated with fragility fracture. Other, more traditional, clinical risk factors were also associated with fracture, including increased age, female gender, rheumatoid arthritis, family history of osteoporosis, and decreased bone mineral density. Conclusions. In this cohort of Canadians with diabetes, those with rheumatoid arthritis, a family history of osteoporosis, female gender, increased age, decreased BMD, cerebrovascular disease, or hypertension were more likely to have had a non-traumatic fracture. These risk factors may be important to clinicians when identifying which of their diabetic patients are at highest risk of fracture and in need of preventative therapies.

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