Prevention and Treatment of Glucocorticoid-Induced Osteoporosis in Adults: Consensus Recommendations From the Belgian Bone Club

Laurent, Michaël; Goemaere, Stefan; Verroken, Charlotte; Bergmann, Pierre; Body, Jean‐Jacques; Bruyère, Olivier; Cavalier, Étienne; Rozenberg, Serge; Lapauw, Bruno; Gielen, Evelien

doi:10.3389/fendo.2022.908727

Cited by 44 publications

(28 citation statements)

References 199 publications

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“…It is well established that glucocorticoids have detrimental effects on bone; glucocorticoid-induced osteoporosis generally is regarded as the most frequent secondary cause of osteoporosis [ 61 ]. In contrast to other autoimmune diseases (such as systemic lupus erythematosus), there is controversy concerning RA, concerning whether glucocorticoids (that inhibit inflammatory processes) indeed harm bone.…”

Section: Human Association Studiesmentioning

confidence: 99%

Mechanisms of Systemic Osteoporosis in Rheumatoid Arthritis

Pietschmann

Butylina

Kerschan‐Schindl

et al. 2022

IJMS

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Rheumatoid arthritis (RA), an autoimmune disease, is characterized by the presence of symmetric polyarthritis predominantly of the small joints that leads to severe cartilage and bone destruction. Based on animal and human data, the pathophysiology of osteoporosis, a frequent comorbidity in conjunction with RA, was delineated. Autoimmune inflammatory processes, which lead to a systemic upregulation of inflammatory and osteoclastogenic cytokines, the production of autoantibodies, and Th cell senescence with a presumed disability to control the systemic immune system’s and osteoclastogenic status, may play important roles in the pathophysiology of osteoporosis in RA. Consequently, osteoclast activity increases, osteoblast function decreases and bone metabolic and mechanical properties deteriorate. Although a number of disease-modifying drugs to treat joint inflammation are available, data on the ability of these drugs to prevent fragility fractures are limited. Thus, specific treatment of osteoporosis should be considered in patients with RA and an associated increased risk of fragility fractures.

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Section: Human Association Studiesmentioning

confidence: 99%

Mechanisms of Systemic Osteoporosis in Rheumatoid Arthritis

Pietschmann

Butylina

Kerschan‐Schindl

et al. 2022

IJMS

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“…However, long-term use of GCs is associated with delayed negative side effects at the molecular, cellular, and clinical level [ 20 , 21 , 22 ], such as undesirable metabolic complications, including the development of type 2 diabetes mellitus [ 23 ] and insulin resistance [ 24 ], accelerated generalized bone loss and increased vertebral and non-vertebral fracture risk [ 25 , 26 ], and predisposition to cardiovascular diseases [ 27 ]. This has become especially important recently due to the active use of GCs during the COVID-19 pandemic and seems to be realized through numerous molecular pathways and mechanisms, including effects of GCs on various cell types and the extracellular matrix (ECM) of any tissue or organ.…”

Section: Introductionmentioning

confidence: 99%

Glucocorticoid Effects on Proteoglycans and Glycosaminoglycans

Grigorieva

2022

IJMS

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Glucocorticoids are steroid hormones that play diverse roles in numerous normal and pathological processes. They are actively used to treat a wide variety of diseases, including neurodegenerative and inflammatory diseases, cancers, and COVID-19, among others. However, the long-term use of glucocorticoids is associated with numerous side effects. Molecular mechanisms of these negative side effects are not completely understood. Recently, arguments have been made that one such mechanisms may be related to the influence of glucocorticoids on O-glycosylated components of the cell surface and extracellular matrix, in particular on proteoglycans and glycosaminoglycans. The potential toxic effects of glucocorticoids on these glycosylated macromolecules are particularly meaningful for brain physiology because proteoglycans/glycosaminoglycans are the main extracellular components of brain tissue. Here, we aim to review the known effects of glucocorticoids on proteoglycan expression and glycosaminoglycan content in different tissues, with a specific focus on the brain.

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“…It is known that a decrease in osteoreparative processes and an increase in osteoresorption are often associated with a violation of steroid hormone metabolism. In this regard, the main risk factors for the development of osteoporosis are the postmenopausal period and long-term therapy with glucocorticoids (Laurent et al 2022). Therefore, one of the most obvious directions for the search for molecular predictors and new targets for pharmacotherapy of osteoporosis is the system of tissue metabolism of steroid hormones.…”

Section: Introductionmentioning

confidence: 99%

Characteristics of the state of bone tissue in genetically modified mice with impaired enzymatic regulation of steroid hormone metabolism

Корокин¹,

Гудырев²,

Lebedev³

et al. 2022

RRP

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Introduction: The aim was to evaluate the structural and functional changes of bone tissue in mice with null expression of 11β-HSD2 or both 11β-HSD2 and Apolipoprotein E. Materials and methods: The experimental study was performed in 60 male mice, weighting 24–30 g. The animals were kept in accordance with the rules of laboratory practice for preclinical studies on the territory of the Russian Federation. Mice lacking 11β-HSD2 (Hsd2-/-) and male mice lacking 11β-HSD2 and Apolipoprotein E (Hsd2-/-/Apoe-/-) were used in the study. We studied and characterized the state of bone tissue, indicators of bone density, microcirculation in bone tissue, endothelial dysfunction coefficient, width of bone trabeculae, as well as serum concentrations of bone alkaline phosphatase, hydroxyproline, deoxyprinoline and expression levels of p53, Bcl2, Bax, eNOS genes. Results and discussion: We showed that mice with the Hsd2-/- genotype with no expression of 11ß-HSD2 by the 6th month of life showed a statistically significant decrease in bone density, which progresses to the 7th and 8th months of life. At the 8th month of animal life, a decrease in bone density is accompanied by a statistically significant decrease in the level of microcirculation in the bone and an increase in the coefficient of endothelial dysfunction. Taking into account the relationship of endothelial dysfunction, atherogenesis and disorders in the processes of bone remodeling, in the framework of this study, we also assessed the state of bone tissue in double transgenes with the genotype Hsd2-/-/Apoe-/-, which lack the expression of both 11ß-HSD2 and Apolipoprotein E. In this study, we also saw increased activation of processes leading to disruption of bone remodeling processes. In the group of the animals with the genotype Hsd2-/-/Apoe-/-, we found statistically significant differences from the mice with no expression of 11ß-HSD2 in bone density and microcirculation, and the width of bone trabeculae. Also, a statistically significant increase in hydroxyproline and deoxyprinoline was found in the group of double transgenes, in the absence of significant changes in the concentration of bone alkaline phosphatase. This fact indicates a pronounced activation of bone resorption processes in the absence of activation of osteosynthesis processes, which leads to the detected violation of bone remodeling processes. Conclusion: Thus, we have shown that a violation of the metabolic regulation of steroid hormone metabolism in animals with null expression of the 11ß-HSD2 (Hsd2-/- genotype) leads to the development of signs of osteoporosis – bone density decreases, which is accompanied by a decrease in the width of bone trabeculae, the level of microcirculation in bone tissue decreases simultaneously with an increase in the coefficient of endothelial dysfunction. The additional null expression of ApoE gene in double transgenes with the genotype Hsd2-/-/Apoe-/- leads to an increase in the severity of changes associated with a violation of bone remodeling processes and, in addition to a more pronounced change in bone tissue density, bone trabecular width, microcirculation and the coefficient of endothelial dysfunction leads to an increase in the concentration of biochemical markers of bone resorption. These changes indicate the important role of the enzyme 11ß-hydroxysteroid dehydrogenase type 2 in the processes of bone remodeling disorders. Graphical abstract

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Prevention and Treatment of Glucocorticoid-Induced Osteoporosis in Adults: Consensus Recommendations From the Belgian Bone Club

Cited by 44 publications

References 199 publications

Mechanisms of Systemic Osteoporosis in Rheumatoid Arthritis

Mechanisms of Systemic Osteoporosis in Rheumatoid Arthritis

Glucocorticoid Effects on Proteoglycans and Glycosaminoglycans

Characteristics of the state of bone tissue in genetically modified mice with impaired enzymatic regulation of steroid hormone metabolism

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