Dataset Information

Integrative Analysis for Elucidating Transcriptomics Landscapes of Glucocorticoid-Induced Osteoporosis.

ABSTRACT: Osteoporosis is the most common bone metabolic disease, characterized by bone mass loss and bone microstructure changes due to unbalanced bone conversion, which increases bone fragility and fracture risk. Glucocorticoids are clinically used to treat a variety of diseases, including inflammation, cancer and autoimmune diseases. However, excess glucocorticoids can cause osteoporosis. Herein we performed an integrated analysis of two glucocorticoid-related microarray datasets. The WGCNA analysis identified 3 and 4 glucocorticoid-related gene modules, respectively. Differential expression analysis revealed 1047 and 844 differentially expressed genes in the two datasets. After integrating differentially expressed glucocorticoid-related genes, we found that most of the robust differentially expressed genes were up-regulated. Through protein-protein interaction analysis, we obtained 158 glucocorticoid-related candidate genes. Enrichment analysis showed that these genes are significantly enriched in the osteoporosis related pathways. Our results provided new insights into glucocorticoid-induced osteoporosis and potential candidate markers of osteoporosis.

SUBMITTER: Ying X

PROVIDER: S-EPMC7176994 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Integrative Analysis for Elucidating Transcriptomics Landscapes of Glucocorticoid-Induced Osteoporosis.

Ying Xiaoxia X Jin Xiyun X Wang Pingping P He Yuzhu Y Zhang Haomiao H Ren Xiang X Chai Songling S Fu Wenqi W Zhao Pengcheng P Chen Chen C Ma Guowu G Liu Huiying H

Frontiers in cell and developmental biology 20200416

Osteoporosis is the most common bone metabolic disease, characterized by bone mass loss and bone microstructure changes due to unbalanced bone conversion, which increases bone fragility and fracture risk. Glucocorticoids are clinically used to treat a variety of diseases, including inflammation, cancer and autoimmune diseases. However, excess glucocorticoids can cause osteoporosis. Herein we performed an integrated analysis of two glucocorticoid-related microarray datasets. The WGCNA analysis id ...[more]

PMID: 32373610

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Project description:Glucocorticoids (GC) are an important risk factor for bone fragility in children with serious illnesses, largely due to their direct adverse effects on skeletal metabolism. To better appreciate the natural history of fractures in this setting, over a decade ago the Canadian STeroid-associated Osteoporosis in the Pediatric Population ("STOPP") Consortium launched a 6 year, multi-center observational cohort study in GC-treated children. This study unveiled numerous key clinical-biological principles about GC-induced osteoporosis (GIO), many of which are unique to the growing skeleton. This was important, because most GIO recommendations to date have been guided by adult studies, and therefore do not acknowledge the pediatric-specific principles that inform monitoring, diagnosis and treatment strategies in the young. Some of the most informative observations from the STOPP study were that vertebral fractures are the hallmark of pediatric GIO, they occur early in the GC treatment course, and they are frequently asymptomatic (thereby undetected in the absence of routine monitoring). At the same time, some children have the unique, growth-mediated ability to restore normal vertebral body dimensions following vertebral fractures. This is an important index of recovery, since spontaneous vertebral body reshaping may preclude the need for osteoporosis therapy. Furthermore, we now better understand that children with poor growth, older children with less residual growth potential, and children with ongoing bone health threats have less potential for vertebral body reshaping following spine fractures, which can result in permanent vertebral deformity if treatment is not initiated in a timely fashion. Therefore, pediatric GIO management is now predicated upon early identification of vertebral fractures in those at risk, and timely intervention when there is limited potential for spontaneous recovery. A single, low-trauma long bone fracture can also signal an osteoporotic event, and a need for treatment. Intravenous bisphosphonates are currently the recommended therapy for pediatric GC-induced bone fragility, typically prescribed to children with limited potential for medication-unassisted recovery. It is recognized, however, that even early identification of bone fragility, combined with timely introduction of intravenous bisphosphonate therapy, may not completely rescue the osteoporosis in those with the most aggressive forms, opening the door to novel strategies.

Project description:Glucocorticoid-induced osteoporosis (GIOP) is a serious problem for patients with rheumatic diseases requiring long-term glucocorticoid treatment. Alendronate, a bisphosphonate, has been recommended in the prevention of GIOP. However, the efficacy and safety of alendronate in preventing GIOP remains controversial. We performed a meta-analysis to investigate the efficacy and safety of alendronate in preventing GIOP in patients with rheumatic diseases.We retrieved randomized controlled trials from PubMed, EMBASE, and the Cochrane Library. Two reviewers extracted the data and evaluated the risk of bias and quality of the evidence. We calculated the risk ratio (RR) with a 95% confidence interval (CI) for dichotomous outcomes, and the mean difference (MD) with a 95% CI for continuous outcomes using Review Manager, version 5.3.A total of 339 studies were found, and 9 studies (1134 patients) were included. Alendronate was not able to reduce the incidence of vertebral fractures (RR = 0.63, 95% CI: 0.10-4.04, P = 0.62) and nonvertebral fractures (RR = 0.40, 95% CI: 0.15-1.12, P = 0.08). Alendronate significantly increased the percent change in bone mineral density (BMD) at the lumbar spine (MD = 3.66, 95% CI: 2.58-4.74, P < 0.05), total hip (MD = 2.08, 95% CI: 0.41-3.74, P < 0.05), and trochanter (MD = 1.68, 95% CI: 0.75-2.61, P < 0.05). Significant differences were not observed in the percent change in BMD at the femoral neck (MD = -0.33, 95% CI: -2.79 to 2.13, P = 0.79) and total body (MD = 0.64, 95% CI: -0.06 to 1.34, P = 0.07). No significant differences in the adverse events were observed in patients treated with alendronate versus the controls (RR = 1.00, 95% CI: 0.94-1.07, P = 0.89). The odds of gastrointestinal adverse events were significantly reduced (RR = 0.77, 95% CI: 0.62-0.97, P < 0.05).Our analysis suggests that alendronate can increase the percent change in BMD at the lumbar spine, total hip, and trochanter, and is not associated with an increased incidence of gastrointestinal adverse events; however, the vertebral and nonvertebral fractures cannot be reduced. However, the results should be interpreted with caution due to the poor statistical power.

Dataset Information

Integrative Analysis for Elucidating Transcriptomics Landscapes of Glucocorticoid-Induced Osteoporosis.

Publications

Integrative Analysis for Elucidating Transcriptomics Landscapes of Glucocorticoid-Induced Osteoporosis.

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