scholarly journals EFFECT OF LOVASTATIN NANO DRUG DELIVERY SYSTEM ON BONE MINERAL DENSITY (BMD) AND BIOMECHANICAL PROPERTIES OF TIBIA BONES OF WISTAR RATS

2019 ◽  
pp. 42-48
Author(s):  
RAMANDEEP KAUR ◽  
Makula Ajitha
Keyword(s):  
Wistar Rats ◽  
Type I Collagen ◽  
Biomechanical Properties ◽  
Type I ◽  
Mineral Density ◽  
Bone Specific Alkaline Phosphatase ◽  
Type I Procollagen ◽  
Nanoemulsion Gel ◽  
Male Wistar Rats

Objective: In the present study, transdermal nanoemulsion (NE) gel of lovastatin was investigated for its anti-osteoporosis effect on the long bones of rat i.e. tibia. Methods: Male wistar rats (n=30, weighing 180-200g) were taken for this study and grouped as: 1) control (normal saline daily), 2) Dex (dexamethasone sodium; 25 mg/kg subcutaneously twice a week), 3) Dex+LNG5 (lovastatin nanoemulsion gel; 5 mg/kg/d transdermally daily), 4) Dex+LNG10 (lovastatin nanoemulsion gel; 10 mg/kg/d transdermally daily), and 5) Dex+ALN (alendronate sodium; 0.03 mg/kg/d orally daily). All the treatments were carried out for 60 d. At the end of the experiment, all animals were anesthetized using diethyl ether and collected blood samples from retro-orbital venous plexus of rats in dry eppendorf tubes followed by the sacrifice of animals by cervical dislocation method and collected tibia bones of both the legs for analysis. Results: Bone formation biomarkers (OC: osteocalcin, b-ALP: bone-specific alkaline phosphatase, PINP: N-terminal propeptides of type I procollagen) were significantly improved and resorption biomarkers (CTx: C-terminal cross-linking telopeptides of type-I collagen, TRAcP5b: isoform 5b of tartarate resistant acid phosphatase) were significantly reduced in the LNG5 (p<0.05) and LNG10 (p<0.05) treatment groups when compared to Dex. In vivo anti-osteoporotic results demonstrated the formation of new bone in osteoporotic rat tibias. Biomechanical strength testing demonstrated increased load-bearing capacity of rat tibias in the treated animals in comparison with the osteoporotic group (p<0.05 for LNG5 and p<0.01 for LNG10). Conclusion: Thus, the transdermal NE gel formulation of lovastatin demonstrated the greater potential for the treatment of osteoporosis.

scholarly journals Reduced Bone Mineral Density and Increased Bone Metabolism Rate in Young Adult Patients with 21-Hydroxylase Deficiency

2006 ◽  
Vol 91 (11) ◽  
pp. 4453-4458 ◽  
Author(s):  
Mariateresa Sciannamblo ◽  
Gianni Russo ◽  
Debora Cuccato ◽  
Giuseppe Chiumello ◽  
Stefano Mora
Keyword(s):  
Bone Mineral Density ◽  
Alkaline Phosphatase ◽  
Bone Metabolism ◽  
Type I Collagen ◽  
Whole Body ◽  
Type I ◽  
Healthy Controls ◽  
Mineral Density ◽  
Specific Alkaline Phosphatase ◽  
Bone Specific Alkaline Phosphatase

Abstract Context: Patients with congenital adrenal hyperplasia (CAH) receive glucocorticoids as replacement therapy. Glucocorticoid therapy is the most frequent cause of drug-induced osteoporosis. Objective: The objective of the study was to evaluate bone mineral density (BMD) and bone metabolism in CAH patients. Design: This was a cross-sectional observational study. Setting: The study was conducted at a referral center for pediatric endocrinology. Patients and Other Participants: Thirty young patients with the classical form of CAH (aged 16.4–29.7 yr) treated with glucocorticoid from diagnosis (duration of treatment 16.4–29.5 yr) and 138 healthy controls (aged 16.0–30.0 yr) were enrolled. Main Outcome Measures: BMD was measured in the lumbar spine and whole body by dual-energy x-ray absorptiometry. Bone formation and resorption rates were estimated by serum measurements of bone-specific alkaline phosphatase and C-terminal telopeptide of type I collagen, respectively. Results: CAH patients were shorter than controls (women −6.8 and men −13.3 cm). Therefore, several methods were used to account for the effect of this difference on bone measurements. Whole-body BMD measurements were significantly lower, compared with controls (P &lt; 0.03), after controlling for height (on average −2.5% in females and −9.3% in male patients). No differences were found in lumbar spine measurements. Bone-specific alkaline phosphatase and C-terminal telopeptide of type I collagen serum concentrations were higher in CAH patients than control subjects (P &lt; 0.04). BMD measurements and bone metabolism markers did not correlate with the actual glucocorticoid dose or mean dose over the previous 7 yr. Conclusions: Young adult patients with the classical form of CAH have decreased bone density values, compared with healthy controls. This may put them at risk of developing osteoporosis early in life.

scholarly journals Treatment of Glucocorticoid-Induced Osteoporosis with Bisphosphonates Alone, Vitamin D Alone or a Combination Treatment in Eastern Asians: A Meta-Analysis

2019 ◽  
Vol 25 (14) ◽  
pp. 1653-1662
Author(s):  
Junjie Wang ◽  
Hongzhuo Li
Keyword(s):  
Vitamin D ◽  
Femoral Neck ◽  
Combination Treatment ◽  
Type I Collagen ◽  
Meta Analysis ◽  
Type I ◽  
Mineral Density ◽  
Bone Specific Alkaline Phosphatase ◽  
Asian Populations ◽  
Significant Difference

Background: Glucocorticoid (GC)-induced osteoporosis and fractures have become a serious problem for Eastern Asians. Bisphosphonates (BPs), vitamin D and a combination treatment are effective methods to prevent and treat GC-induced osteoporosis. Objective: The study aimed to compare the efficacy of BPs, vitamin D and a combination treatment for preventing and managing GC-induced osteoporosis in Eastern Asians. Methods: A comprehensive search in the PubMed, EMBASE, Web of Science and Cochrane CENTRAL databases was undertaken for randomized controlled trials (RCTs) on the effect of BPs, vitamin D and the combination treatment on GCs-induced osteoporosis in Eastern Asian populations. Primary outcome measures were the change in bone mineral density (BMD) and bone turnover markers. The final search was performed in March 2019. Results: Nine RCTs were included. A total of 545 patients met the inclusion criteria. Compared with vitamin D, BPs and the combination treatment significantly alleviated osteoporosis of the spine and femoral neck in Eastern Asians with GC-induced osteoporosis. At the same time, the change in serum bone-specific alkaline phosphatase (BAP) and serum C-telopeptide of type I collagen (CTX) levels was observed to be significantly less with BPs and the combination treatment with vitamin D alone. No significant difference was found between BPs and the combination treatment in the markers mentioned above. Conclusion: Compared with vitamin D alone, BPs alone and the combination treatment were significantly effective on Eastern Asians with GC-induced osteoporosis. Compared with the combination treatment, BPs alone were observed to be effective enough to increase the BMDs of the spine and femoral neck on both sides and thus prevent GC-induced osteoporosis in Eastern Asians.

scholarly journals SAT-021 Effects of E2/P4 Oral Capsules on Bone Turnover in Women with Vasomotor Symptoms

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Ginger Constantine ◽  
Michael R McClung ◽  
Risa Kagan ◽  
Shelli Graham ◽  
Brian Bernick ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Type I Collagen ◽  
Osteoporotic Fractures ◽  
Vasomotor Symptoms ◽  
Type I ◽  
Bone Specific Alkaline Phosphatase ◽  
Type I Procollagen ◽  
Turnover Markers ◽  
Mean Differences ◽  
Post Hoc

Abstract Menopausal hormone therapy slows bone turnover and reduces the risk of osteoporotic fractures. The objective of this post hoc analysis was to evaluate bone turnover markers (BTM) in the phase 3 REPLENISH trial, which evaluated vasomotor symptoms (VMS) with an oral estradiol/progesterone (E2/P4) in postmenopausal women with a uterus. Eligible women for this analysis had ≥50 moderate to severe VMS/week, &lt;5 years since last menstrual period, and BTM measurements at baseline, and months 6 and 12. Percent changes for 3 BTM (bone specific alkaline phosphatase [BSAP], C-terminal telopeptide of type I collagen [CTX-1], and N-terminal propeptide of type I procollagen [PINP]) assessed by immunoassay methods were evaluated from baseline to months 6 and 12 for the 1/100, 0.5/100 and placebo groups. A total of 157 women (40–61 years, 69% White) were analyzed (56 for each 1/100 and 0.5/100; 45 for placebo). Mean baseline values ranged from 14.0–14.3 U/L for BSAP, 0.34–0.39 ng/mL for CTX-1, and 76.9–79.3 ng/mL for PINP. Mean differences in percent change from baseline versus placebo significantly decreased with both E2/P4 doses for all 3 BTM at months 6 and 12. Mean differences from placebo for E2/P4 at months 6/12 ranged from -8.1% to -17.8% for BSAP (all, P≤0.02), -30% to -41% for CTX-1 (all, P≤0.001), and -14% to -29% for PINP (all, P≤0.007). REPLENISH data provide support for a potential skeletal benefit of E2/P4 when used for the treatment of moderate to severe VMS.

scholarly journals Effects of amlodipine on bone metabolism in male albino Wistar rats

2011 ◽  
Vol 80 (4) ◽  
pp. 391-396 ◽  
Author(s):  
Iveta Gradošová ◽  
Helena Živná ◽  
Klára Švejkovská ◽  
Vladimír Palička ◽  
Aleš Tichý ◽  
...  
Keyword(s):  
Body Weight ◽  
Bone Metabolism ◽  
Wistar Rats ◽  
Type I Collagen ◽  
Bone Alkaline Phosphatase ◽  
Bone Morphogenetic Protein 2 ◽  
Control Group ◽  
Type I ◽  
Mineral Density ◽  
Procollagen Type

Amlodipine (dihydropyridine-type calcium channel blocker) is a widely used agent for the treatment of hypertension in human and veterinary medicine but detailed information about its effects on bone metabolism are missing. Therefore, the aim of our study was to investigate the effect of amlodipine on bone metabolism in male albino Wistar rats. Amlodipine (0.3 mg/100 g body weight; gavage) was administered to 8 rats for 8 weeks. Control group (n = 8) received aqua pro inj. (0.2 ml/100 g body weight; gavage). Bone marker concentrations of carboxy-terminal cross-linking telopeptide of type I collagen (CTX-I) and aminoterminal propeptide of procollagen type I in serum, and of bone alkaline phosphatase (BALP) in both serum and bone homogenate were measured by enzyme immunoassay. We investigated the expression of bone morphogenetic protein 2 (BMP-2) in proximal tibia using Western blotting, and bone mineral density was measured by Dual-energy X-ray Absorptiometry in lumbar and caudal vertebrae and in femoral areas. Mechanical properties of the femurs were measured by three-point bending of the shaft and compression testing of the femoral neck. After 8 weeks of amlodipine administration there was a significant decrease in serum concentrations of BALP (p = 0.0009) and CTX-I (p = 0.003), and the content of BALP in bone homogenate (p = 0.026) compared to the control. In addition, Western blot analysis indicated increased BMP-2 protein concentration after amlodipine administration. Our findings suggest that amlodipine has a retarding influence on bone metabolism in rats by decreasing bone turnover, which probably in consequence increases expression of BMP-2.

scholarly journals Binding of soluble type I collagen to fibroblasts: specificities for native collagen types, triple helical structure, telopeptides, propeptides, and cyanogen bromide-derived peptides.

1982 ◽  
Vol 95 (3) ◽  
pp. 752-756 ◽  
Author(s):  
B D Goldberg ◽  
R E Burgeson
Keyword(s):  
Cyanogen Bromide ◽  
Type I Collagen ◽  
Helical Structure ◽  
Type I ◽  
Collagen Types ◽  
Surface Receptors ◽  
Type I Procollagen ◽  
Competitive Inhibitors ◽  
A Minor

Unlabeled collagenous proteins were quantified as inhibitors of binding of native, soluble, radioiodinated type I collagen to the fibroblast surface. Collagen types IV, V a minor cartilage isotype (1 alpha 2 alpha 3 alpha), and the collagenlike tail of acetylcholinesterase did not inhibit binding. Collagen types II and III behaved as competitive inhibitors of type I binding. Denaturation of native collagenous molecules exposed cryptic inhibitory determinants in the separated constituent alpha chains. Inhibition of binding by unlabeled type I collagen was not changed by enzymatic removal of the telopeptides. Inhibitory determinants were detected in cyanogen bromide-derived peptides from various regions of helical alpha 1 (I) and alpha 1(III) chains. The aminoterminal propeptide of chick pro alpha 1(I) was inhibitory for binding, whereas the carboxyterminal three-chain propeptide fragment of human type I procollagen was not. The data are discussed in terms of the proposal that binding to surface receptors initiates the assembly of periodic collagen fibrils in vivo.

scholarly journals Oxidative Stress and Bone Resorption Interplay as a Possible Trigger for Postmenopausal Osteoporosis

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Carlo Cervellati ◽  
Gloria Bonaccorsi ◽  
Eleonora Cremonini ◽  
Arianna Romani ◽  
Enrica Fila ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lumbar Spine ◽  
Bone Resorption ◽  
Postmenopausal Osteoporosis ◽  
Type I Collagen ◽  
Serum Levels ◽  
Type I ◽  
Bone Homeostasis ◽  
Mineral Density ◽  
Bone Specific Alkaline Phosphatase

The underlying mechanism in postmenopausal osteoporosis (PO) is an imbalance between bone resorption and formation. This study was conducted to investigate whether oxidative stress (OxS) might have a role in this derangement of bone homeostasis. In a sample of 167 postmenopausal women, we found that increased serum levels of a lipid peroxidation marker, hydroperoxides, were negatively and independently associated with decreasedbone mineral density(BMD) in total body (r=-0.192,P<0.05), lumbar spine (r=-0.282,P<0.01), and total hip (r=-0.282,P<0.05), as well as with increased bone resorption rate (r=0.233,P<0.05), as assessed by the serum concentration of C-terminal telopeptide of type I collagen (CTX-1). On the contrary, the OxS marker failed to be correlated with the serum levels of bone-specific alkaline phosphatase (BAP), that is, elective marker of bone formation. Importantly, multiple regression analysis revealed that hydroperoxides is a determinant factor for the statistical association between lumbar spine BMD and CTX-1 levels. Taken together, our data suggest that OxS might mediate, by enhancing bone resorption, the uncoupling of bone turnover that underlies PO development.

scholarly journals The Therapeutic Effectiveness of the Coadministration of Weekly Risedronate and Proton Pump Inhibitor in Osteoporosis Treatment

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Mizue Tanaka ◽  
Soichiro Itoh ◽  
Taro Yoshioka ◽  
Kimihiro Yamashita
Keyword(s):  
Proton Pump Inhibitor ◽  
Proton Pump ◽  
Type I Collagen ◽  
Bodily Pain ◽  
Osteoporosis Treatment ◽  
Physical Parameters ◽  
Type I ◽  
Long Term Effects ◽  
Mineral Density ◽  
Bone Specific Alkaline Phosphatase

This trial was conducted to investigate the long-term effects of proton pump inhibitor (PPI) coadministration on the efficacy of weekly risedronate treatment for osteoporosis. Ninety-six women over 50 years old with low bone mineral density (BMD) participated in this trial. Subjects were randomly divided into 2 groups: a 17.5 mg dose of sodium risedronate was administered weekly, with or without a daily 10 mg dose of sodium rabeprazole (n=49and 47 in the BP + PPI and BP groups, resp.). The following biomarkers were measured at the baseline and every 3 months: bone-specific alkaline phosphatase, N-terminal telopeptide of type I collagen corrected for creatinine, parathyroid hormone, BMD of the lumbar spine, and physical parameters evaluated according to the SF-36v2 Health Survey. Statistical comparisons of these parameters were performed after 6, 12, 18, and 24 months. The Δ values of improvement in physical functioning after 12 months and bodily pain after 6 and 12 months in the BP + PPI group were significantly larger than those in the BP group. These results suggest that PPI does not adversely affect bone metabolism. Alternatively, approved bone formation by concomitant PPI treatment may have had favorable effects on the improvement of bodily pain and physical functions.

scholarly journals Mallotus Feretianus Extract Inhibits Ethanol-induced Activation of Hepatic Stellate Cell via PI3K-Akt and cAMP-PKA Pathways (P06-065-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Isao Matsui-Yuasa ◽  
Eri Yoshikawa ◽  
Xuedan Huang ◽  
Yoshinori Kobayashi ◽  
Akiko Kojima-Yuasa
Keyword(s):  
Liver Fibrosis ◽  
Wistar Rats ◽  
Type I Collagen ◽  
Liver Steatosis ◽  
The Other ◽  
Main Role ◽  
Type I ◽  
Other Hand ◽  
Phosphorylated Akt ◽  
Male Wistar Rats

Abstract Objectives Chronic and excessive alcohol consumption is a significant cause of liver fibrosis. The development of alcohol induced liver fibrosis may progress to hepatic decompensation and hepatocellular carcinoma. Therefore, liver fibrosis is associated with severe morbidity and mortality. Mallotus furetianus (MF) is a tropical plant in Hainan Island of China. The extract of its leaves is used as a folk medicine. In this study, we examined the effects of MF extract on the development of liver fibrosis in an in vivo ethanol-carbon tetrachloride (CCl4)-induced cirrhosis model and in vitro alcohol-injury model of hepatic stellate cells (HSCs). Methods Male Wistar rats were fed a diet that included 0.012% or 0.04% MF extract or no MF extract. For a period of 3 weeks, the animals were given drinking water containing 5% ethanol and were also treated with CCl4 (0.1 ml/kg of body weight). HSCs were isolated from male Wistar rats and were incubated with ethanol with or without MF extract. Results Plasma ALT and AST activities in rats treated with the ethanol plus CCl4 and MF extract (0.012% or 0.04%) were significantly reduced from the those in rats treated with the ethanol plus CCl4. The protective effect of MF extract was dose dependently. Histological analysis observed lipid and collagen accumulations in the liver of the ethanol plus CCl4-treated rats. On the other hand, MF extract treatment fully protected rats against ethanol plus CCl4-induced liver steatosis and fibrosis. HSCs play a main role in liver fibrosis because they are a primary producer of the extracellular matrix such as type I collagen and α-SMA. MF extract treatment suppressed the ethanol-induced increases in type I and α-SMA expression to near control levels in HSCs. The treatments with MF extract suppressed the increase in the levels of phosphorylated Akt in ethanol-treated HSCs. Furthermore, the treatment of LY194002, an inhibitor of PI3K, suppressed the ethanol-induced increase in the expression of type I collagen in HSCs. On the other hand, the addition of H-89, an inhibitor of PKA, inhibited the suppression of the synthesis of type I collagen in MF extract-treated HSCs. Conclusions MF extract may be a candidate for preventing ethanol-induced liver injury via regulating liver steatosis and fibrosis in PI3K-Akt and cAMP-PKA manners. Funding Sources This study was supported by JSPS KAKENHI Grant Numbers JP24500987, JP15K00832.

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