scholarly journals Identification of a key gene module associated with glucocorticoid- induced derangement in bone mineral density in patients with asthma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Suh-Young Lee ◽  
Ha-Kyeong Won ◽  
Byung-Keun Kim ◽  
Sae-Hoon Kim ◽  
Yoon-Seok Chang ◽  
...  

AbstractDerangement in bone mineral density (BMD) caused by glucocorticoid is well-known. The present study aimed to find key biological pathways associated with low BMD after glucocorticoid treatment in asthmatics using gene expression profiles of peripheral blood cells. We utilized immortalized B cells (IBCs) from 32 childhood asthmatics after multiple oral glucocorticoid bursts and peripheral blood mononuclear cells (PBMCs) from 17 adult asthmatics after a long-term use of oral glucocorticoid. We searched co-expressed gene modules significantly related with the BMD Z score in childhood asthmatics and tested if these gene modules were preserved and significantly associated with the BMD Z score in adult asthmatics as well. We identified a gene module composed of 199 genes significantly associated with low BMD in both childhood and adult asthmatics. The structure of this module was preserved across gene expression profiles. We found that the cellular metabolic pathway was significantly enriched in this module. Among 18 hub genes in this module, we postulated that 2 genes, CREBBP and EP300, contributed to low BMD following a literature review. A novel biologic pathway identified in this study highlighted a gene module and several genes as playing possible roles in the pathogenesis of glucocorticoid- induced derangement in BMD.

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_5) ◽  
Author(s):  
Radwa Helmy Shalaby ◽  
Elham Mohamed Kassem ◽  
Nagat Mohamed El-Gazzar ◽  
Sahar Ahmed Fathy Hammoudah ◽  
Amal Mohamed El-Barbary

Abstract Background Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic arthropathy of childhood and is associated with low bone mass, and may hasten the onset of osteoporosis later in life1. Bone loss occurs because of an imbalance between osteoclasts-activating factors like receptor activator of nuclear factor-κB ligand (RANKL) and its inhibitor osteoprotegerin (OPG) 2. Dual energy X-ray absorptiometry (DXA) is the preferred method for measuring bone mineral density (BMD) in children and to identify and follow individuals at risk for fracture 3. The objective is the Evaluation of serum levels of osteoprotegerin and RANKL and their correlation with BMD in JIA patients. Methods Forty JIA patients (according to the revised classification criteria of ILAR) and 40 healthy children individually matched for age, sex and race were included in this study. Children excluded from the study were those with primary and secondary causes of osteoporosis (such as chronic illness). All patients were assessed clinically by: age, sex, body mass index, type of JIA, disease duration and disease activity (by Juvenile Arthritis Disease Activity Score; JADAS 10). The functional disability was assessed by the Childhood Health Assessment Questionnaire (CHAQ). Blood samples were collected from JIA patients and healthy controls to determine serum levels of OPG and RANKL by ELISA. DXA scans were done using GE Healthcare Lunar DPX, Madison, Wisconsin. Bone mineral density of the L1-L4 lumbar spine and total body less head (TBLH) was evaluated in g/cm2 and expressed as Z score for age, sex according to the reference data given for this equipment. Results The study included 40 patients (25 females) with a mean age of 11.14 years and median disease duration of 2.5 years. As regard JIA type, 45% of patients were oligoarticular, 32.5% were polyarticular, and 22.5% were systemic JIA. Median JADAS 10 was 13.95. Patients (especially polyarticular JIA) had significantly higher serum RANKL levels and lower serum OPG and OPG/RANKL ratio when compared with controls (with p-value <0.001, 0.032 and <0.001 respectively). A diagnosis of low BMD (BMD Z-score ≤ -2) was given in 25% of patients (15% polyarticular and 10% systemic) by DXA of lumbar spine, and 20% (10% polyarticular and 10% systemic) by DXA of TBLH. On the other hand, no patient was given a diagnosis of osteoporosis (BMD Z-score ≤ -2 and a significant fracture history). Low BMD at lumbar spine and TBLH was negatively correlated with serum RANKL while positively correlated with OPG/RANKL ratio. Moreover, low BMD at lumbar spine was positively correlated with serum OPG level Conclusion High RANKL and low OPG levels appear to be associated with low bone mass in JIA patients. Patients with JIA (especially polyarticular and systemic subtype) are at increased risk of low bone mineral mass. Disclosure of Interests None declared


2016 ◽  
Vol 8 ◽  
pp. 2016004 ◽  
Author(s):  
Seham Ragab

Background:Osteoporosis is a major problem in beta thalassemia major (TM) patients. Increased oxidative stress and its controlling genes were linked to osteoporosis. Glutathione S-transferase P1 (GSTP1),Ile105 Val variant  is a functional  mutation with  reduced ant-oxidative property  .No data are available about this variant  or its association with osteoporosis  among thalassemia patients yet. Objectives: The aim of this study was to investigate Ile105Val polymorphism and its possible association with bone mineral density (BMD) values in a group of TM  children. Methods:Thirty five TM patients and 30 age and sex matched healthy controls were included. Liver and renal functions, serum ferritin, calcium, phosphorous, alkaline phosphatase and osteocalcin were assayed. BMD was determined by DXA with calculation of  Z-scores at lumbar spine (Ls) and femoral neck (Fn).Height for age z- score (HAZ) adjusted BMD Z-scores were considered . GSTP1 Ile105Val polymorphism was studied by polymerase chain reaction-restriction fragment length polymorphism. Results:The relative frequency of 105 Val allele was significantly higher in TM patients than the controls (P<0.0001). Significant association between genotype subgroups and BMD parameters was detected. Mutant homozygotes had significant lower BMD , Z –score and haz -adjusted BMD  Z-score at both Ls and Fn compared to wild homozygotes ( Ps =0.029, 0.008, 0.011, 0.001,0.02, 0.001) with significant higher osteocalcin level compared to heterozygotes and wild homozygotes (P=0.012 and P=0.013,respectively). Conclusion:  The results indicated that 105Val allele was frequent among TM patients and could increase their susceptibility to osteoporosis. Large sample studies are required to confirm these findings.  


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yuri Battaglia ◽  
Michele Provenzano ◽  
Francesco Tondolo ◽  
Antonio Bellasi ◽  
Pasquale Esposito ◽  
...  

Abstract Background and Aims In the medical literature, several studies have linked bone mineral density (BMD) with vitamin D deficiency in kidney transplant patients (KTRs). However, in spite of the fact that ergocalciferol, cholecalciferol and calcifediol reduce parathyroid hormone (PTH) and improves calcium levels, their effects on the bone mineral density (BMD) in KTRs remain undefined. In consideration of the lack of data available, we aim at investigating the effect of inactive form of vitamin D supplementation on the BMD over a follow-up period up to 2 year, in a real-life cohort of long-term kidney transplant(KT). Method This study was carried out in KTRs who were followed up in a Nephrology Unit. Exclusion criteria were parathyroidectomy, therapy with bisphosphonate, previous history of bone fractures. Demographic, clinical and immunosuppressive agents were collected. Based on 25-OH-D levels, KTRs were classified as suffering from deficiency (&lt; 30 ng/mL). BMD was evaluated at lumbar vertebral bodies (LV) and right femoral hip (FH) by a single operator, using a standard dual energy X-ray absorptiometry. According to WHO criteria, results were expressed as T-score (standard deviation [SD] relative to young healthy adults), and Z-score (SD relative to age-matched controls). Osteoporosis and osteopenia were defined as T score ≤ −2.5 SD and T score &lt; −1 and &gt; −2.5 SD, respectively. Laboratory data, 25-OH-D, and BMD were measured at baseline and after 24 months of supplementation therapy. Vitamin D deficiency was corrected using standard treatment strategy recommended for general population. Continuous variables were expressed as mean ± SD whereas categorical variables as percentage. The Student’s t test and chi-square test were used to compare to compare continuous and categorical variables, respectively. For before and after comparisons of continuous variables, the paired t-test or one-sample Wilcoxon signed rank test were used based on variable’s distribution. Results Data pertaining to 111 out of 133 consecutive outpatients were collected, of whom most were males (69.4%), no-smokers (89.1%) and treated with glucocorticoids (84%). The mean age was 53.9±11.6 years and months after transplant was 161.6±128.3. No statistical differences were found among patients with normal BMD, osteopenia or osteoporosis at LV and FH in terms of age at transplant, gender distribution, time on dialysis, BMI and eGFR, serum calcium, serum phosphate, 25-OH-D and iPTH. At baseline, 25-OH-D was 13.9±7.2 ng/ml and the prevalence of osteopenia/osteoporosis was 40.9% (T-Score -1.69±0.37; Z-score -1.16±1.09) and 21.8 % (T-Score -3.15±0.50; Z-score -2.27±0.58) at LV; 55.3 % (T-Score -1.8±0.46; Z-score -0.84±0.633) and 14 % (T-Score -2.83±0.39; Z-score -1.65±0.49) at FH. After 27.6±3.7 months of therapy with cholecalciferol at mean dose of 13.396±7.537 UI at week, 25-OH-D values increased to 29.4±9.4 ng/ml (p&lt;0.0001) while no statistically significant changes were found in Z-score and T-score at both sites, except for a mild improvement in lumbar vertebral Z-score, reaching −0.82± 0.7 (p = 0.06) in KTRs with osteopenia Conclusion Our study showed BMD remained stable after up to 2 years of inactive vitamin D therapy in long-term kidney transplant with vitamin D deficiency. A mild increase in Z-score was observed in the L-spine. Further designated studies should be conducted to demonstrate the effect of vitamin D on BMD.


2016 ◽  
Vol 77 (9) ◽  
pp. 961-968 ◽  
Author(s):  
Shohei Ogawa ◽  
Mie Okutani ◽  
Takamitsu Tsukahara ◽  
Nobuo Nakanishi ◽  
Yoshihiro Kato ◽  
...  

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