scholarly journals Icariin Prevents Diabetes-Induced Bone Loss in Rats by Reducing Blood Glucose and Suppressing Bone Turnover

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1871 ◽  
Author(s):  
Shanshan Qi ◽  
Jia He ◽  
Hongxing Zheng ◽  
Chen Chen ◽  
Shiqiang Lan

Diabetic Osteoporosis (DOP) is a common metabolic bone disease, characterized by decreased bone mineral density (BMD) and destruction of bone microstructure. It has been reported that icariin is beneficial for estrogen deficiency-induced osteoporosis, and alcohol-induced osteoporosis; whether icariin has protective effects on diabetes-induced osteoporosis has not been reported. In this study, a rat model of diabetic osteoporosis was established by streptozotocin injection, the bone protective effects and potential mechanism of icariin on diabetes-induced bone loss was observed. Thirty 8-week-old female Sprague Dawley rats were divided into control group (vehicle treatment), T1DM (diabetic) group and T1DM-icariin (ICA) group (diabetic rats treated with icariin), 10 rats in each group. The bone histomorphometry parameters, bone mineral density (BMD), serum bone turnover markers, and bone marrow adipogenesis were analyzed after 8 weeks of icariin administration. The results showed consumption of icariin at a doses of 100 mg kg−1 decreased blood glucose, and increased the BMD of diabetic rats. Icariin effectively decreased serum bone turnover marker levels, including CTX-1, ALP, TRACP 5b, osteocalcin, and PINP. Meanwhile, the bone histomorphometry parameters, the number of osteoclasts per bone perimeter were turned to be normal level, and the icariin treatment suppressed bone marrow adipogenesis. The runt-related transcription factor 2 (RUNX 2), as well as the osteoprotegerin (OPG)/receptor activator of nuclear factor-κ B ligand (RANKL) ratio in serum and bone tissues were increased significantly after icariin treatment in diabetic rats. All of the above indicate that oral administration of icariin can prevent diabetic osteoporosis; the effect is mainly related to its ability to reduce blood glucose, inhibit bone turnover and bone marrow adipogenesis, as well as up-regulate bone RUNX 2, and OPG expression.

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Tae-Ho Kim ◽  
Eui Kyun Park ◽  
Man-Il Huh ◽  
Hong Kyun Kim ◽  
Shin-Yoon Kim ◽  
...  

Inhibition of osteoclast differentiation and bone resorption is a therapeutic strategy for the management of postmenopausal bone loss. This study investigated the effects ofRhus javanica(R. javanica) extracts on bone marrow cultures to develop agents from natural sources that may prevent osteoclastogenesis. Extracts ofR. javanica(eGr) cocoons spun byRhus javanica(Bell.) Baker inhibited the osteoclast differentiation and bone resorption. The effects of aqueous extract (aeGr) or 100% ethanolic extract (eeGr) on ovariectomy- (OVX-) induced bone loss were investigated by various biochemical assays. Furthermore, microcomputed tomography (µCT) was performed to study bone remodeling. Oral administration of eGr (30 mg or 100 mg/kg/day for 6 weeks) augmented the inhibition of femoral bone mineral density (BMD), bone mineral content (BMC), and other factors involved in bone remodeling when compared to OVX controls. Additionally, eGr slightly decreased bone turnover markers that were increased by OVX. Therefore, it may be suggested that the protective effects of eGr could have originated from the suppression of OVX-induced increase in bone turnover. Collectively, the findings of this study indicate that eGr has potential to activate bone remodeling by inhibiting osteoclast differentiation and bone loss.


Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2398 ◽  
Author(s):  
Hongxing Zheng ◽  
Shanshan Qi ◽  
Chen Chen

Postmenopausal diabetic women have a high risk of fractures. Salidroside has preventive effects on estrogen deficiency-induced osteoporosis and has hypoglycemic effects on diabetes in rats. However, whether salidroside inhibits bone loss in postmenopausal diabetic patients is still unknown. Here, we established a rat model of osteoporosis to investigate the protective effects of salidroside on bone loss induced by ovariectomy combined with diabetes, also investigating the underlying mechanisms. Two-month-old female Sprague-Dawley rats were divided into three equal groups (10 rats in each group): control group (with sham operation, treated with drug vehicle); OVX/T1DM group (ovariectomized diabetic rats); OVX/T1DM-SAL group, comprising ovariectomized diabetic rats treated with salidroside (20 mg/kg body weight) by gavage. The results showed that after 60 consecutive days of treatment, the bone mineral density (BMD) of OVX/T1DM-SAL increased significantly compared with the OVX/T1DM group (p < 0.01). The level of serum bone turnover markers, including alkaline phosphatase (ALP), cross linked c-telopeptide of type I collagen (CTX-1), osteocalcin, N-terminal propeptide of type I procollagen (PINP), and tartrate-resistant acid phosphatase 5b (TRACP 5b) were all increased in the OVX/T1DM group compared with the control (p < 0.01), and those were decreased by salidroside treatment. Meanwhile, the bone histopathological changes were also attenuated, and the bone marrow adipogenesis was inhibited in salidroside treated rats. Moreover, protein and mRNA ratio of bone osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) was upregulated in ovariectomized diabetic rats by salidroside treatment. The results above indicated that the protective effect of salidroside on bone loss induced by ovariectomy and diabetes was mainly due to its ability to suppress bone turnover, inhibit bone marrow adipogenesis, and up-regulate the OPG/RANKL ratio.


2020 ◽  
Author(s):  
Lungwani Muungo

Although it is well established that estrogen deficiencycauses osteoporosis among the postmenopausalwomen, the involvement of estrogen receptor (ER) in itspathogenesis still remains uncertain. In the presentstudy, we have generated rats harboring a dominantnegative ERa, which inhibits the actions of not only ERabut also recently identified ERb. Contrary to our expectation,the bone mineral density (BMD) of the resultingtransgenic female rats was maintained at the same levelwith that of the wild-type littermates when sham-operated.In addition, ovariectomy-induced bone loss wasobserved almost equally in both groups. Strikingly, however,the BMD of the transgenic female rats, after ovariectomized,remained decreased even if 17b-estradiol(E2) was administrated, whereas, in contrast, the decreaseof littermate BMD was completely prevented byE2. Moreover, bone histomorphometrical analysis ofovariectomized transgenic rats revealed that the higherrates of bone turnover still remained after treatmentwith E2. These results demonstrate that the preventionfrom the ovariectomy-induced bone loss by estrogen ismediated by ER pathways and that the maintenanceof BMD before ovariectomy might be compensatedby other mechanisms distinct from ERa and ERbpathways.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Bahram Arjmandi ◽  
Neda Akhavan ◽  
Joseph Munoz ◽  
Kelli George ◽  
Elizabeth Foley ◽  
...  

Abstract Objectives Osteoporosis may result in fracture with dire consequences. For instance, 40% of people with their second hip fracture die within two years. Aside from pharmaceutical interventions, that are not free of side effects, identifying edible and safe foods to prevent bone loss is of importance. We and others have shown that dried plum (DP) prevents loss of bone both in ovariectomized (Ovx) rat models as well as postmenopausal women. Hence, the purpose of this study was to examine the bone protective mechanism of action of DP, a rich source of phenolic and flavonoid compounds, in preventing bone loss using a rat model of ovarian hormone deficiency. Methods Forty-eight 90-day old female Sprague-Dawley rats were divided into four groups: sham-operated (Sham), Ovx, Ovx + 5% DP (low-dose, LD), and Ovx + 25% DP (high-dose, HD). Treatments started immediately after surgery and continued for 45 days. Animals were either fed a semi-purified diet, or a similar diet in which 5% or 25% of the diet (w/w) consisted of DP. All diets were made isocaloric and isonitrogenous containing 0.4% calcium and 0.3% phosphorus. Food intake, bone mineral density, bone mineral content, body/organ weight, blood biomarkers of bone metabolism, and static bone histomorphometry were assessed. Results The right femoral and the 4th lumbar vertebrae density were significantly (P < 0.05) lower in the Ovx control rats compared to Sham. The loss of density in both bones were completely prevented by HD-DP (P < 0.05). The HD-DP increased insulin-like growth factor-1 (IGF-1) significantly (P < 0.05) from 110 ± 4 ηmol/L to 135 ± 4 ηmol/L. In terms of bone histomorphometry, % bone area was significantly (P < 0.05) decreased as a result of Ovx and HD-DP nearly prevented this decrease (P > 0.05). Although the endosteal perimeter (mm2) was not statistically different from other groups, the endosteal perimeter of the HD-DP group was 13.6% lower than that of the Ovx group. Conclusions The bone protective effects of DP may, in part, be explained by an increase in IGF-1, which is strongly correlated with bone formation, and a decrease in the endosteal perimeter, which is increased in ovarian hormone deficiency and postmenopausal women. Future studies should examine radiolabeling compounds in DP to see how they contribute to its bone protective effects. Funding Sources There have been no funding sources.


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Laurentiu Badescu ◽  
Oana Badulescu ◽  
Magda Badescu ◽  
Manuela Ciocoiu

The effects of polyphenols extracted fromSambucus nigrafruit were studied in streptozotocin- (STZ-) induced hyperglycemic rats to evaluate its possible antioxidant, anti-inflammatory, antiglycosylation activity, and antiosteoporosis effects in diabetes. DEXA bone mineral density tests were performed in order to determine bone mineral density (BMD), bone mineral content (BMC), and fat (%Fat) in control and diabetic animals, before and after polyphenol delivery. As compared to the normoglycemic group, the rats treated with STZ (60 mg/kg body weight) revealed a significant malondialdehyde (MDA) increase, as an index of the lipid peroxidation level, by 69%, while the total antioxidant activity (TAS) dropped by 36%, with a consistently significant decrease () in the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPX). Also, the treatment of rats with STZ revealed a significant increase of IL-6, glycosylated haemoglobin (HbA1c), and osteopenia detected by DEXA bone mineral density tests. The recorded results highlight a significant improvement () in the antioxidative capacity of the serum in diabetic rats treated with natural polyphenols, bringing back to normal the concentration of reduced glutathione (GSH), as well as an important decrease in the serum concentration of MDA, with improved osteoporosis status. Knowing the effects of polyphenols could lead to the use of the polyphenolic extract ofSambucus nigraas a dietary supplement in diabetic osteoporosis.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3813-3813
Author(s):  
Ersi Voskaridou ◽  
Dimitrios Christoulas ◽  
Lito Antoniadou ◽  
Panagiotis Tsaftaridis ◽  
Eleni Plata ◽  
...  

Abstract Osteoporosis represents an important cause of morbidity in adult patients with thalassemia. Its pathogenesis is multifactorial, and includes mainly bone marrow expansion, endocrine dysfunction and iron overload. Patients with thalassaemia intermedia (TI) seem to have a more expanded bone marrow with pressure on cortical bone, which causes pain and bone loss in several cases. The measurement of soluble transferrin receptor (sTfR) and erythropoietin (Epo) in the serum is considered as accurate marker of erythropoietic activity in thalassemia. Bisphosphonates are potent inhibitors of osteoclast activity and have been used for the management of thalassemia-induced osteoporosis. The aim of this study was to evaluate the effect of zoledronic acid, the most potent aminobisphosphonate, on bone mineral density (BMD) of patients with TI and explore possible correlations with bone marrow expansion and erythropoietic activity. Thirty-five patients with TI and osteopenia or osteoporosis (13M/22F, median age 45 years) were evaluated. Twenty-three were randomized to receive zoledronic acid, 4 mg, IV, every 3 months (n=12) or every 6 months (n=11) for one year, while 12 patients received placebo every 3 months. There was no difference in terms of the presence of gonadal dysfunction between the three studied groups. BMD of the lumbar spine (L), femoral neck and forearm was determined in all patients, using DEXA, before and 12 months after treatment. Bone marrow expansion was assessed by the measurement of sTfR and Epo serum levels, using an ELISA methodology (R&D Systems, Minneapolis, MN, USA), before and 12 months post zoledronic acid or placebo administration. In all patients markers of bone remodelling, such as C-telopeptide of collagen type-I (CTX) and bone specific alkaline phosphatase (bALP) were also measured by ELISA (Nordic Bioscience Diagnostics, Herlev, Denmark, and Quidel, San Diego, CA, USA, respectively). Patients were asked to quantify their degree of bone pain on Huskisson’s visual analogue scale and the McGill-Melzack scoring system before and 12 months post-therapy. All patients had increased values of sTfR, Epo, CTX, and bALP compared with 40 controls of similar age and gender (p&lt;0.001). Patients who received zoledronic acid showed a significant increase in their L-BMD (p=0.01), which was accompanied by a dramatic reduction in CTX and bALP values ((p&lt;0.001). There was no difference in terms of L-BMD changes between zoledronic acid groups. Placebo group showed an aggravation of L-BMD (p=0.041) and markers of bone remodelling at 12 months. No other changes were observed in the BMD of other sites. Zoledronic acid reduced bone pain, which remained stable in placebo group during the study period. There was only weak correlation between baseline sTfR levels and L-BMD, while there was no correlation between Epo or hemolytic parameters (indirect bilirubin, reticulocytes counts, and LDH) with BMD of all studied sites. Serum sTfR and Epo values showed a significant elevation after 12 months of therapy in all studied groups (p&lt;0.01, p&lt;0.02, and p&lt;0.01, respectively); this elevation was irrespective of the L-BMD changes. This study suggests that the increase of BMD produced by zoledronic acid in TI is irrespective of the continuous increase of bone marrow expansion, which is considered a major cause of bone loss in this hemoglobinopathy.


Nephrology ◽  
2019 ◽  
Vol 25 (2) ◽  
pp. 163-171
Author(s):  
Suthanit Laowalert ◽  
Tanatorn Khotavivattana ◽  
Lalita Wattanachanya ◽  
Pobe Luangjarmekorn ◽  
Suwasin Udomkarnjananun ◽  
...  

Obesity Facts ◽  
2021 ◽  
pp. 1-12
Author(s):  
Cheng Huang ◽  
Qiong Wang ◽  
Qin Zhang ◽  
Biao Zhou ◽  
Jun Lin ◽  
...  

Background: While bariatric surgery could result in weight loss as well as glycaemia improvement, the short-term impact on bone health in a high glycemic environment following Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) remains intriguing. Objective: The aim of this study was to compare the short-term effects of RYGB and SG procedures on bone health in Zucker diabetic fatty (ZDFfa/fa) rats. Methods: Thirty age-matched male ZDFfa/fa rats were randomized into RYGB, SG, and sham groups after establishment of the diabetic model. Body weight, blood glucose, bone mineral density (BMD), the level of bone turnover markers (BTM), vitamin D, and serum calcium and phosphorus were measured 4 weeks after the operation. Results: The RYGB procedure brought about lower blood glucose, BMD, serum calcium and phosphorus levels, as well as a relatively higher bone turnover rate and 1,25(OH)2VD level, compared to the SG and sham groups, while the influences of the SG procedure were not significant. 25(OH)VD demonstrated no significant difference among the 3 groups. Conclusions: Despite its excellent ability to provide short-term glycemic control, the RYGB procedure could led to more severe impairment of bone health compared to the SG procedure. Bone health should be procured after bariatric surgery, especially with the RYGB procedure. Early detection of BMD and BTM may help to avoid deterioration of bone.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9517-9517
Author(s):  
D. Lin ◽  
M. R. Smith ◽  
R. A. Morton ◽  
M. S. Steiner

9517 Background: Androgen deprivation therapy (ADT) decreases bone mineral density by reducing estrogens to castrate levels and, as a result, increases fracture risk. We recently completed a two-year trial in 1382 men in which we examined the ability of toremifene to reduce fracture risk in men on ADT. Herein we describe analyses of the placebo group to assess the baseline characteristics associated with new fractures. Methods: We conducted a randomized double blind placebo controlled trial in 1382 men with histologically confirmed prostate cancer on ADT. Entry criteria included age ≥ 50 years, continous ADT for 6 months or longer or intermittent ADT for 12 months or longer. Subjects on intermittent ADT at enrollment had to remain on continuous ADT for their duration on study. Subjects were randomized to receive either 80mg toremifene citrate daily or matching placebo. The primary end point was the incidence of new morphometric vertebral fractures. Secondary endpoints included bone mineral density, clinical fragility fractures, bone turnover markers, lipid profile, hot flashes, and gynecomastia. Results: The modified intent to treat (MITT) population included subjects who took study medication and had an on-study radiograph. There were 467 subjects in the placebo MITT population. To identify factors associated with fracture risk in men on ADT we compared placebo subjects who suffered a fracture or during the first year on study suffered 7% or greater bone loss with those placebo subjects who did not. Baseline characteristics included: BMD (spine, hip, femoral neck), Age, history of fracture, ADT duration, bone turnover markers, and race. Logistic regression models of the probability of fracture/bone loss as a function of country showed that each of BMD at all sites, age, race, CTX, and history of previous fracture independently predicted fracture/7% bone loss. When all characteristics were analyzed in a multivariable model lower spine BMD (p=0.006) and older age (p=0.018) were significantly associated with incident fractures. Conclusions: In prostate cancer patients on ADT older age and lower baseline spine BMD were associated with a greater risk of fracture in untreated patients. [Table: see text]


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