Bone histomorphometry in Cushing’s syndrome

Borelli, A; Leite, Marco; Corrêa, Pedro Henrique Silveira; Jorgetti, Vanda; Marcondes, José Antônio Miguel; Batalha, Joao R. F.; Cintra, A.; Wajchenberg, B. L.

doi:10.1007/bf03348804

Cited by 16 publications

(10 citation statements)

References 19 publications

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“…This finding was interesting because, as aforementioned, GIO in humans generally results in more pronounced changes in the BMD of trabecular bone compared to cortical bone. However, in line with the CRH‐Tg model, several studies have shown significant decreases in cortical thickness with Cushing's syndrome; and a very recent study using high‐resolution quantitative CT showed that patients with Cushing's syndrome exhibited deleterious effects primarily on cortical bone microstructure (lower cortical areas, thicknesses, and vBMD) when compared to age‐ and sex‐matched controls . The decreased trabecular thickness observed in CRH‐Tg mice is also in agreement with several studies that have shown exogenous administration of GC drugs causes trabecular thinning (reviewed in Dalle Carbonare and colleagues).…”

Section: Discussionsupporting

confidence: 83%

“…In line with this, there is a higher incidence of fractures in the femoral neck and vertebrae; compartments that have a higher percentage of trabecular bone . However, cortical bone is also significantly affected by GCs, and a recent study of Cushing's syndrome patients using micro–computed tomography (μCT) for analysis revealed a dominant effect of GCs on cortical bone microstructure . It is therefore important to consider all parameters in parallel when studying the effects of GCs on the skeleton.…”

Section: Introductionmentioning

confidence: 99%

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The CRH‐Transgenic Cushingoid Mouse Is a Model of Glucocorticoid‐Induced Osteoporosis

et al. 2017

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Glucocorticoids (GCs) have unparalleled anti‐inflammatory and immunosuppressive properties, which accounts for their widespread prescription and use. Unfortunately, a limitation to GC therapy is a wide range of negative side effects including Cushing's syndrome, a disease characterized by metabolic abnormalities including muscle wasting and osteoporosis. GC‐induced osteoporosis occurs in 30% to 50% of patients on GC therapy and thus, represents an important area of study. Herein, we characterize the molecular and physiologic effects of GC‐induced osteoporosis using the Cushing's mouse model, the corticotropin releasing hormone (CRH) transgenic mouse (CRH‐Tg). The humeri, femurs, and tibias from wild‐type (WT) and CRH‐Tg male mice, aged 13 to 14 weeks old were subjected to multiple bone tests including, micro–computed tomography (μCT), static and dynamic histomorphometry, strength testing, and gene expression analyses. The CRH‐Tg mice had a 38% decrease in cortical bone area, a 35% decrease in cortical thickness, a 16% decrease in trabecular thickness, a sixfold increase in bone adiposity, a 27% reduction in osteoid width, a 75% increase in bone‐resorbing osteoclast number/bone surface, a 34% decrease in bone formation rate, and a 40% decrease in bone strength compared to WT mice. At the gene expression level, CRH‐Tg bone showed significantly increased osteoclast markers and decreased osteoblast markers, whereas CRH‐Tg muscle had increased muscle atrophy gene markers compared to WT mice. Overall, the CRH‐Tg mouse model aged to 14 weeks recapitulated many features of osteoporosis in Cushing's syndrome and thus, represents a useful model to study GC‐induced osteoporosis and interventions that target the effects of GCs on the skeleton. © 2017 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

The CRH‐Transgenic Cushingoid Mouse Is a Model of Glucocorticoid‐Induced Osteoporosis

et al. 2017

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“…GCs exert complex effects on the skeleton, either inhibiting or enhancing, which are dependant on the species under investigation, the developmental stage as well as the concentration and duration of GC exposure [22]. In vitro, a low concentration of GCs induces cells of the osteoblast lineage to differentiate into mature OBs [23][24][25][26][27][28], whereas GCs at high concentrations dramatically decrease OB number and bone formation rate [29][30][31].…”

Section: Cellular Effects Of Gcsmentioning

confidence: 99%

Glucocorticoid-Induced Osteoporosis: A Review

Bouvard

Legrand

Audran

et al. 2009

Clinic Rev Bone Miner Metab

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Glucocorticoid (GC)-induced osteoporosis is the main cause of secondary osteoporosis. Fractures, which are often asymptomatic, can occur in as many as 50% of patients receiving chronic GC therapy. GCs have direct and indirect effects on bone cells (osteoblasts, osteocytes, and osteoclasts) with a suppression of bone formation and an increased bone resorption. The management of patients exposed to GCs should include the use of the minimal effective dose of GC, general health measures, and adequate intakes of calcium and vitamin D. Bisphosphonates are nowadays largely used in GC-induced osteoporosis and teriparatide has proved its efficiency as well.

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“…Glucocorticoids decrease bone formation and stimulate bone resorption, the latter partly secondary to reduced intestinal calcium absorption (1). In accord, histomorphometric studies in steroid-induced osteopenia have shown decreased bone formation rate and signs of increased bone resorption (2)(3)(4). Bone mineral content (BMC) and density (BMD) are markedly decreased in untreated CS, with significant improvement following treatment (5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 97%

Decreased bone area, bone mineral content, formative markers, and increased bone resorptive markers in endogenous Cushing's syndrome

Godang

Ueland

Bollerslev

1999

European Journal of Endocrinology

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It is well established that chronic excess of glucocorticoids has negative effects on bone and collagen turnover, and that secondary osteoporosis is a known clinical complication of endogenous Cushing's syndrome (CS). The aim of the present study was to evaluate bone dimension and bone mineral content in relation to biochemical markers of bone and collagen turnover, in a consecutive series of 23 patients with endogenous CS (18 with pituitary adenoma and 5 with adrenal tumor; 17 women, 6 men; mean age 39.7 Ϯ 2.8 (S.E.M.) and 44.3 Ϯ 3.1 years respectively), compared with 23 age-, sex-and body mass index-matched healthy controls.Bone mineral densities were uniformly reduced in the different regions analyzed: lumbar spine (16.1%, P < 0.001), femoral neck (15.2%, P < 0.001), total body (11.5%, P < 0.001), and the subregions of arms (8.4%, P < 0.05), legs (10.1%, P < 0.05) and trunk (15.8%, P < 0.001). Similar results were observed for bone mineral content, although these were less prominent. The calculated area was significantly decreased in trunk (13.8%, P < 0.01) and total body (11.6%, P < 0.05).Serum levels of osteocalcin were significantly decreased (28%, P < 0.03) in patients with CS. No significant differences were observed for the formative markers carboxyterminal propeptide of type I procollagen and aminoterminal propeptide of type I procollagen. Markers of bone resorption, serum Crosslaps and carboxyterminal cross-linked telopeptide of type I collagen were increased in patients compared with controls, although only significantly for Crosslaps (P < 0.02). No correlations between formative and resorptive markers were found in the patients, but in controls, the formative markers were positively correlated with resorptive markers.In conclusion, bone dimension and bone mineral content of the entire skeleton are found to be decreased in endogenous CS. As judged by biochemical markers of bone remodeling, this is caused by decreased bone formation and an increased bone resorption.

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Bone histomorphometry in Cushing’s syndrome

Cited by 16 publications

References 19 publications

The CRH‐Transgenic Cushingoid Mouse Is a Model of Glucocorticoid‐Induced Osteoporosis

The CRH‐Transgenic Cushingoid Mouse Is a Model of Glucocorticoid‐Induced Osteoporosis

Glucocorticoid-Induced Osteoporosis: A Review

Decreased bone area, bone mineral content, formative markers, and increased bone resorptive markers in endogenous Cushing's syndrome

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