Practical Guidance for Prevention and Management of Glucocorticoid-Induced Osteoporosis for the Allergist/Immunologist

Weare-Regales, Natalia; Hudey, S.; Lockey, Richard F.

doi:10.1016/j.jaip.2020.12.050

Cited by 11 publications

(17 citation statements)

References 81 publications

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“…The principal treatment for MPP is anti-infective treatment, combined with general and symptomatic treatment. Macrolide antibiotics are currently the drug of choice for MPP treatment in children (3,11,12). The general and symptomatic treatment of MPP does not differ from that for CAP in other children (3,9).…”

Section: Discussionmentioning

confidence: 99%

A prediction study of IL-18 and IFN-γ in glucocorticoid treatment response in infants and young children with severe Mycoplasma pneumoniae pneumonia

et al. 2022

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Background: In infants and young children, the clinical decision to apply glucocorticoids to severe Mycoplasma pneumoniae pneumonia (SMPP) is more an empirical choice with reference to clinical symptoms, but the effect is not satisfying. We aimed to explore and identify early predictive indicators of ideal response to glucocorticoids treatment in SMPP in infants and young children. Methods:We retrospectively reviewed the data of 59 patients, which met the age range and diagnostic criteria, admitted to Department of Pediatrics, the Sixth People's Hospital Affiliated to Shanghai Jiaotong University, from January to December 2017. Patients were divided into a glucocorticoid treatment group and a normal treatment group according to whether glucocorticoid treatment was used, and the difference in therapeutic effectiveness was compared between two groups. The glucocorticoid treatment group was further subdivided into effective versus ineffective treatment groups dependent on the difference of glucocorticoid treatment effect in main clinical symptoms improvement. We obtained the test value of biomarkers by ELISA, and identified several specific indicators with significantly different expressions in the early stage by independent sample t-tests and calculated their cut-off values by ROC curve.Results: Thirty-one SMPP patients who received glucocorticoid treatment were divided into effective and ineffective treatment groups according to the clinical improvements shown on different days of glucocorticoid use. The expression of two markers, interleukin-18 (IL-18) and interferon-γ (IFN-γ), were significantly different in cases showing improvement in the early stage of SMPP (P<0.05), and the cutoff values for IL-18 (218.19 pg/mL, AUC =0.581, sensitivity =0.909, 1-specificity =0.786) and IFN-γ (11.24 pg/mL, AUC =0.566, sensitivity =0.905, 1-specificity =0.795) were identified. Conclusions:The expressions of IL-18 and IFN-γ in the early stage of SMPP might suggest their predictive effect of early application of glucocorticoid for effective treatment of SMPP in infants and young children. Further study with larger sample size will be carried on in the future.

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Section: Discussionmentioning

confidence: 99%

A prediction study of IL-18 and IFN-γ in glucocorticoid treatment response in infants and young children with severe Mycoplasma pneumoniae pneumonia

et al. 2022

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“…GIOP is a systemic bone disease secondary to glucocorticoid intake, which is the most common secondary osteoporosis [28]. Although numerous protein-coding genes have been identi ed to be GIOP-related genes [29], these genes could not give a good interpretation to the onset and development of GIOP.…”

Section: Discussionmentioning

confidence: 99%

Zuogui Pill Ameliorates Glucocorticoid-Induced Osteoporosis through ZNF702P-Based ceRNA Network: Bioinformatics Analysis and Experimental Validation

Zhang

Chen

Shang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Glucocorticoid-induced osteoporosis (GIOP) is a musculoskeletal disease with increased fracture risk caused by long-term application of glucocorticoid, but there exist few effective interventions. Zuogui Pill (ZGP) has achieved clinical improvement for GIOP as an ancient classical formula, but its molecular mechanisms remain unclear due to scanty relevant studies. This study aimed to excavate the effective compounds and underlying mechanism of ZGP in treating GIOP and construct relative ceRNA network by using integrated analysis of bioinformatics analysis and experimental validation. Results show that ZNF702P is significantly upregulated in GIOP than normal cases based on gene chip sequencing analysis. Totally, 102 ingredients and 535 targets of ZGP as well as 480 GIOP-related targets were selected, including 122 common targets and 8 intersection targets with the predicted mRNAs. The ceRNA network contains one lncRNA (ZNF702P), 6 miRNAs, and 8 mRNAs. Four hub targets including JUN, CCND1, MAPK1, and MAPK14 were identified in the PPI network. Six ceRNA interaction axes including ZNF702P-hsa-miR-429-JUN, ZNF702P-hsa-miR-17-5p/hsa-miR-20b-5p-CCND1, ZNF702P-hsa-miR-17-5p/hsa-miR-20b-5p-MAPK1, and ZNF702P-hsa-miR-24-3p-MAPK14 were obtained. By means of molecular docking, we found that all the hub targets could be effectively combined with related ingredients. GO enrichment analysis showed 649 biological processes, involving response to estrogen, response to steroid hormone, inflammatory response, macrophage activation, and osteoclast differentiation, and KEGG analysis revealed 102 entries with 36 relative signaling pathways, which mainly contained IL-17 signaling pathway, T cell receptor signaling pathway, FoxO signaling pathway, the PD-L1 expression and PD-1 checkpoint pathway, MAPK signaling pathway, TNF signaling pathway, Estrogen signaling pathway, and Wnt signaling pathway. Our experiments confirmed that ZNF702P exhibited gradually increasing expression levels during osteoclast differentiation of human peripheral blood monocytes (HPBMs) induced by RANKL, while ZGP could inhibit osteoclast differentiation of HPBMs induced by RANKL in a concentration-dependent manner. Therefore, by regulating inflammatory response, osteoclast differentiation, and hormone metabolism, ZGP may treat GIOP by regulating hub target genes, such as JUN, CCND1, MAPK1, and MAPK14, and acting on numerous key pathways, which involve the ZNF702P-based ceRNA network.

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“…Although an in-depth discussion of interventions to prevent systemic CS-related toxicities is beyond the scope of this article, the adverse skeletal effects of these agents deserve special mention because of the high prevalence of bone disorders in patients with severe asthma ( Weare-Regales et al, 2021 ). Bone-related adverse effects are the result of OCS action in osteoblasts, osteocytes, and osteoclasts.…”

Section: Introductionmentioning

confidence: 99%

Potential impact of mepolizumab in stepping down anti-osteporotic treatment in corticosteroid-dependent asthma

et al. 2023

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Oral corticosteroids (OCS) are commonly used for the acute management of severe asthma exacerbations or as maintenance therapy; however, chronic use is associated with significant toxicities, e.g., osteoporosis. In the REal worlD Effectiveness and Safety (REDES) study of mepolizumab in a multicentric Spanish cohort of asthma patients, mepolizumab effectively reduced clinically severe asthma exacerbations and decreased OCS dependence. This post-hoc analysis further evaluates mepolizumab’s de-escalation effect on OCS dose. Patients enrolled in REDES who had OCS consumption data available for 12 months pre- and post-mepolizumab treatment were included in this analysis. Primary outcomes were to determine the change in the proportion of patients eligible for anti-osteoporotic treatment due to the changes in OCS consumption before and after 1 year of mepolizumab treatment. All analyses are descriptive. Approximately one-third (98/318; 30.8%) of patients in REDES were on maintenance OCS at the time of mepolizumab treatment initiation. In REDES, mean cumulative OCS exposure decreased by 54.3% after 1 year of treatment. The proportion of patients on high-dose OCS (≥7.5 mg/day) fell from 57.1% at baseline to 28.9% after 12 months of mepolizumab treatment. Thus, 53.6% of OCS-dependent asthma patients treated with mepolizumab would cease to be candidates for anti-osteoporotic treatment according to guidelines thresholds.

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Practical Guidance for Prevention and Management of Glucocorticoid-Induced Osteoporosis for the Allergist/Immunologist

Cited by 11 publications

References 81 publications

A prediction study of IL-18 and IFN-γ in glucocorticoid treatment response in infants and young children with severe Mycoplasma pneumoniae pneumonia

A prediction study of IL-18 and IFN-γ in glucocorticoid treatment response in infants and young children with severe Mycoplasma pneumoniae pneumonia

Zuogui Pill Ameliorates Glucocorticoid-Induced Osteoporosis through ZNF702P-Based ceRNA Network: Bioinformatics Analysis and Experimental Validation

Potential impact of mepolizumab in stepping down anti-osteporotic treatment in corticosteroid-dependent asthma

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