Experimental techniques for screening of antiosteoporotic activity in postmenopausal osteoporosis

Author(s):  
Swaha Satpathy ◽  
Arjun Patra ◽  
Bharti Ahirwar

AbstractPostmenopausal osteoporosis, a silent epidemic, has become a major health hazard, afflicting about 50% of postmenopausal women worldwide and is thought to be a disease with one of the highest incidences in senile people. It is a chronic, progressive condition associated with micro-architectural deterioration of bone tissue that results in low bone mass, decreased bone strength that predisposes to an increased risk of fracture. Women are more likely to develop osteoporosis than men due to reduction in estrogen during menopause which leads to decline in bone formation and increase in bone resorption activity. Estrogen is able to suppress the production of proinflammatory cytokines like interleukin (IL)-1, IL-6, IL-7 and tumor necrosis factor (TNF-α). This is why these cytokines are elevated in postmenopausal women. In this review article we have made an attempt to collate the various methods and parameters most frequently used for screening of antiosteoporotic activity in postmenopausal osteoporosis. Pertaining to ovariectomized animal model, this is the most appropriate model for studying the efficacy of different drugs to prevent bone loss in postmenopausal osteoporosis.

Author(s):  
Lindsey S Lawrence ◽  
Amer Heider ◽  
Andrew A M Singer ◽  
Haley C Neef ◽  
Jeremy Adler

Abstract Background Granulomatous intestinal inflammation may be associated with aggressive Crohn’s disease (CD) behavior. However, this has not been confirmed, and it is unknown if associated disease complications are preventable. Methods This is a retrospective cohort of patients younger than 21 years at CD diagnosis (November 1, 2005 to November 11, 2015). Clinical information was abstracted, including dates of starting medications and the timing of perianal fistula or stricture development, if any. Diagnostic pathology reports were reviewed, and a subset of biopsy slides were evaluated by a blinded pathologist. Patients were excluded if perianal fistula or stricture developed within 30 days after CD diagnosis. Medications were included in analyses only if started >90 days before development of perianal fistula or stricture. Results In total, 198 patients were included. Half (54%) had granulomas at diagnosis. Granulomas were associated with a greater than 3-fold increased risk of perianal fistula (hazard ration [HR] = 3.24; 95% confidence interval CI], 1.40–7.48). Immunomodulator and anti-tumor necrosis factor-α (anti-TNF) therapy were associated with 90% (HR, = 0.10; 95% CI, 0.03–0.42) and 98% (HR, = 0.02; 95% CI, 0.01–0.10) reduced risk of perianal fistula, respectively. Patients with granulomatous inflammation preferentially responded to anti-TNF therapy with reduced risk of perianal fistula. The presence of granulomas was not associated with risk of stricture. Immunomodulator and anti-TNF therapy were associated with 96% (HR, = 0.04; 95% CI, 0.01–0.22) and 94% (HR, = 0.06; 95% CI, 0.02–0.20) reduced risk of stricture, respectively. Conclusions Granulomas are associated with increased risk of perianal fistula but not stricture. Steroid sparing therapies seem to reduce the risk of both perianal fistula and stricture. For those with granulomas, anti-TNF-α therapy greatly reduced the risk of perianal fistula development, whereas immunomodulators did not.


2019 ◽  
Vol 10 (10) ◽  
pp. 6556-6567 ◽  
Author(s):  
Haiming Jin ◽  
Zhenxuan Shao ◽  
Qingqing Wang ◽  
Jiansen Miao ◽  
Xueqin Bai ◽  
...  

Postmenopausal osteoporosis (PMO) is a progressive disease occurring in elderly postmenopausal women that is characterized by low bone mass and impaired bone quality.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dong Wang ◽  
Liqun He ◽  
Xiaotian Zhang

AbstractMany studies tried to assess the relationship between -308G/A polymorphism of tumor necrosis factor alpha (TNF-α) gene and risk of metabolic syndrome (MS), but their results were contradictory. This meta-analysis aimed to precisely evaluate this association. A systematic literature search was performed in Pubmed database and WanFang Med Online, STATA software 14.0 was used for the meta-analysis. Eleven independent studies containing 3277 cases and 3312 controls were included in our meta-analysis. In overall analysis, significant association was found between -308G/A polymorphism of TNF-α and MS in both allele model (OR 1.47, 95% CI 1.09–1.98, P 0.013) and dominant model (OR 1.77, 95% CI 1.21–2.58, P 0.003). In the subgroup analysis, the A allele was associated with increased risk of MS in Asia group (allele model: OR 1.82 95% CI 1.31–2.53, P < 0.001; dominant model: OR 2.30, 95% CI 1.64–3.21 P < 0.001; homozygous model: OR 2.29, 95% CI 1.31–4.01, P 0.004), and decreased risk of MS in Europe group (dominant model: OR 0.83, 95% CI 0.70–0.99, P < 0.001; recessive model: OR 0.51, 95% CI 0.28–0.92, P 0.025; homozygous model: OR 0.49 95% CI 0.27–0.89, P 0.02). The A allele also appeared to linked to increased risk of MS in CDS group and IDF groups. No significant association was observed in NCEPATPIII group. Our results suggested that -308G/A of TNF-α gene was a risk factor for MS, but it may played different roles in different ethnics, further studies with larger sample size and more other ethnics should be performed to confirm our conclusions.


2008 ◽  
Vol 40 (6) ◽  
pp. 273-279 ◽  
Author(s):  
Simona Mencej ◽  
Omar M E Albagha ◽  
Janez Preželj ◽  
Tomaž Kocjan ◽  
Janja Marc

Tumour necrosis factor superfamily member 11 (TNFSF11) gene, that codes for receptor activator of nuclear factor-κB ligand, is one of the candidate genes for the genetic susceptibility to osteoporosis. As variations in the TNFSF11 gene promoter could alter its expression, the aim of the study was to evaluate the functional influence of three polymorphisms in the promoter and to investigate their association with bone mineral density (BMD) and biochemical markers in postmenopausal women. A total of 404 postmenopausal women were genotyped for the presence of TNFSF11 gene promoter polymorphisms −290C>T, −643C>T and −693G>C. Two common haplotypes, CCG and TTC, which occur in 44.3 and 49.3% of subjects respectively, were subjected to functional analysis. Amplified fragments were cloned into pGL3-basic reporter plasmid, which was co-transfected with pRL-TK plasmid into HEK293 cells. Dual luciferase reporter assay was performed. BMD and biochemical markers were measured. Reporter gene analysis showed significantly higher luciferase activity in CCG than in TTC haplotype (P=0.018). Both showed association with lumbar spine BMD (BMD-ls; P=0.005 and 0.007 for TTC and CCG respectively), whereas in femoral neck there was no association with BMD. In postmenopausal osteoporosis, association with BMD-ls was established in −290C>T, −643C>T and −693G>C (P values: 0.001, 0.041 and 0.013 respectively). Association with femoral neck BMD was shown in −693G>C (P=0.049). No association was found with biochemical markers in any of the groups. Our results suggest that in postmenopausal osteoporosis, TNFSF11 gene promoter polymorphisms −290C>T, −643C>T and −693G>C play a functional role in the genetic regulation of BMD.


2015 ◽  
Vol 18 (1) ◽  
pp. 3-6
Author(s):  
S V Yureneva ◽  
A E Donnikov ◽  
E V Bordakova ◽  
O V Yakushevskaya ◽  
A A Smetnik ◽  
...  

Aim. To identify gene polymorphisms (OPG, RANKL, VDR, SOST) and evaluate their relationship with bone mineral density (BMD) and fractures for further optimization of diagnosis and treatment of postmenopausal osteoporosis (PMO). Materials and methods. The study included 236 postmenopausal women living in Moscow and the Moscow region. The main group (I) consisted of 174 patients, aged 50 to 83 years, with BMD < - 2.5 SD for the T-score. The comparison group (II) consisted of 62 postmenopausal women with BMD within the normal range and the lack of previous fractures, aged 50 to 77 years. Molecular genetic analysis of polymorphisms of VDR (rs10735810, rs1544410), RANKL (rs9594738, rs9594759) and OPG (rs3102735, rs3102735 and rs4355801), SOST (rs1230399) was performed by polymerase chain reaction in all subjects with PMO and in the control group. Results. In the presence of the T allele of the gene RANKL (rs9594759 and rs9594738) risk of reduced BMD at L1-L4 was increased by 2 times. Women with genotype C/C gene polymorphism of OPG (rs3102735) the risk of fractures of the distal radius (PR) was increased by 17 times, regardless of BMD. Genotype G/G rs1544410 polymorphism of VDR gene in patients with PMO is associated with an increased risk of fractures of the distal radius by three times. In patients with PMO genotype C/C in gene SOST (rs1230399) only cause differences in body mass index. According to an autosomal recessive pattern, homozygous genotype C/C was significantly associated with obesity in the PMO. Conclusions. Polymorphisms of genes RANKL (rs9594759 and rs9594738), OPG (rs3102735) and VDR (rs1544410) are associated with the risk of fractures and PMO. Gene SOST (rs1230399) had no statistically significant effect on BMD and fracture risk.


Author(s):  
Selva Kumari T. R. Thanga ◽  
S. Sujan ◽  
Janhavi Patharkar ◽  
Mansi Modi

Osteoporosis is a major international health problem, accentuated by increasing longevity. Osteoporosis as “a systemic skeletal disease characterized by low bone mass and bone architectural leading to increased risk”. Menopause is the normal process but now a day it becoming the major health problem in developing countries like India.   In Ayurveda Menopause deals with jarapakvaavasta of the body Jara and Rajonivritti are manifested due to the progressive reduction in the functional ability of Agnis, which results in an inadequate tissue nutrition. This nutritional imbalance triggers the irreversible degenerative changes in „Sapta Dhatus‟. The disease Osteoporosis is somewhat similar to the description of Asthi Kshaya in which metabolism of Asthi Dhatu is disturbed. Rasayana therapy has proved efficacious in managing and preventing many chronic conditions till date. As Postmenopausal Osteoporosis is a disease related to aging, Rasayana can provide the better alternative to increasing quality of life. Here, the drug Lashuna also one of the Rasayana guna dravya.  


Blood ◽  
2008 ◽  
Vol 112 (10) ◽  
pp. 4276-4283 ◽  
Author(s):  
Sarah H. Atkinson ◽  
Kirk A. Rockett ◽  
Gareth Morgan ◽  
Philip A. Bejon ◽  
Giorgio Sirugo ◽  
...  

Abstract Plasma levels of tumor necrosis factor-α (TNF-α) are significantly raised in malaria infection and TNF-α is thought to inhibit intestinal iron absorption and macrophage iron release. This study investigated putative functional single nucleotide polymorphisms (SNPs) and haplotypes across the major histocompatibility complex (MHC) class III region, including TNF and its immediate neighbors nuclear factor of κ light polypeptide gene enhancer in B cells (lκBL), inhibitor-like 1 and lymphotoxin alpha (LTA), in relation to nutritional iron status and anemia, in a cohort of 780 children across a malaria season. The prevalence of iron deficiency anemia (IDA) increased over the malaria season (P < .001). The TNF−308 AA genotype was associated with an increased risk of iron deficiency (adjusted OR 8.1; P = .001) and IDA (adjusted OR 5.1; P = .01) at the end of the malaria season. No genotypes were associated with IDA before the malaria season. Thus, TNF appears to be a risk factor for iron deficiency and IDA in children in a malaria-endemic environment and this is likely to be due to a TNF-α–induced block in iron absorption.


QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
M H ElSayed ◽  
S E Ahmed ◽  
K Ali ◽  
N N ElKhazragy ◽  
M S Attia

Abstract Background Psoriasis is known as chronic immune-mediated inflammatory skin disease affecting about 3% of the world’s population. Cytokine gene polymorphism attracted considerable interest as they have been found to alter gene transcription thereby influencing inflammatory processes in response to various diseases. Subjects A total of 50 psoraitic patients and 50 controls were genotyped for TNF–α −238G/A polymorphism by using polymerase chain reaction. ECG and lipid profile were done to assess cardiovascular risk. Results Polymorphism of TNF–α −238 was not found to be associated with an increased risk for psoriasis (p value 0.98). There is significant difference between cases and controls as regard systolic and diastolic blood pressure . Conclusion Our findings suggest that there is no association between TNF alpha polymorphism and risk of psoriasis in Egyptian psoraitic patients.


2013 ◽  
Vol 1 (1) ◽  
pp. 127-134
Author(s):  
Zorica Nanovic ◽  
Milena Petrovska

Aim: To establish a review in the current literature and to analyze the relation Legionnaires’ disease – TNF-α inhibitors, in order to estimate the real indications for such connection.Material and Methods: The electronic data for PubMed and Google Scholar have been searched, according to the vocabulary: legionellosis, epidemiology, outbreak, diagnosis, pathogenesis, therapy, TNF-α inhibitors, indications, side effects, risk of infection. The obtained studies have been selected in English, according to the relevance by the topic.Results: Selected papers, consisted of ten studies and eight case reports, yielded 35 cases of Legionnaires' disease associated with the use of TNF- α inhibitor treatment.Discussion: There is a prevailing conclusion for increased risk of serious infections while using TNF-α inhibitors and also a deficiency of studies for an association of Legionnaires’ disease with the use of TNF-α inhibitors. Sub-diagnosing and no-existence of screening before the anti-TNF-α therapy blur the factual profile for the researched relation. The possibility for latent infection has not been sufficiently researched.Conclusion: There are indications that Legionnaires’ disease in the therapy with TNF-α inhibitors is indeed a forthcoming problem. Additional target researches are required in order to establish the position of Legionnaires’ disease in the mosaic of anti - TNF-α therapy.


Healthcare ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 985
Author(s):  
Beom-Jun Ku ◽  
Kangeun Ko ◽  
Ki-Ok Shin ◽  
Ju-Yong Bae

We aimed to investigate the effect of a 12-week Taekwondo self-defense training course on oxidative stress and inflammation in postmenopausal women. Sixteen middle-aged women participated and were randomized into two groups: a control group (CG, n = 8) and a Taekwondo self-defense training group (TSDG, n = 8). The TSDG was trained for 60 min, four times per week, for 12 weeks. Following the Taekwondo training intervention, side-step was significantly higher in the TSDG than in the CG (p < 0.001). Malondialdehyde levels were significantly lower after the intervention than before in the TSDG (p < 0.01). Superoxide dismutase (SOD) levels were also significantly higher after the intervention than before in the TSDG (p < 0.001). After the Taekwondo training intervention, SOD levels were significantly higher in the TSDG than in the CG (p < 0.01). Tumor necrosis factor α (TNF-α) levels were significantly lower after the intervention than before in the TSDG (p < 0.05). After the Taekwondo training intervention, TNF-α levels were significantly lower in the TSDG than in the CG (p < 0.05). The results of this study suggest that Taekwondo self-defense training is an effective exercise that improves agility, oxidative stress, and inflammatory responses in postmenopausal women.


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