Glucocorticoid-induced osteoporosis: an update

Mazziotti, Gherardo; Angeli, Alberto; Bilezikian, John P.; Canalis, Ernesto; Giustina, Andrea

doi:10.1016/j.tem.2006.03.009

Cited by 315 publications

(266 citation statements)

References 66 publications

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“…(15,33) The findings of the present study suggest that bone microarchitecture is also reduced in patients with subclinical cortisol excess in relation with disease activity. Moreover, the present data confirm and reinforce our previous finding that in SHþ patients, SDI, a proposed surrogate index of damaged bone microarchitecture, (15)(16)(17) is augmented, increases over time, and is associated with disease activity and incident vertebral fractures regardless of BMD.…”

Section: Discussionmentioning

confidence: 55%

Bone quality, as measured by trabecular bone score in patients with adrenal incidentalomas with and without subclinical hypercortisolism

Eller-Vainicher

Morelli

Ulivieri

et al. 2012

Journal of Bone and Mineral Research

126

108

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Patients with adrenal incidentalomas (AIs) and subclinical hypercortisolism (SH) have increased risk of fracture independent of bone mineral density (BMD) and possibly due to reduced bone quality. The trabecular bone score (TBS) has been proposed as a index of bone microarchitecture. The aim of the study was to investigate TBS in AI. In 102 AI patients, SH was diagnosed in the presence of at least two of the following: (1) urinary free cortisol >70 mg/24 h (193.1 nmol/L); (2) cortisol after 1-mg dexamethasone suppression test (1-mg DST) >3.0 mg/dL (82.8 nmol/L); or (3) adrenocorticotropic hormone (ACTH) <10 pg/mL (<2.2 pmol/L). In patients and in 70 matched controls, BMD was measured at lumbar spine (LS) and femur (neck [FN] and total [FT]) by dual X-ray absorptiometry and TBS was assessed in the region of LS-BMD; BMD and TBS data were reported as Z-scores. In patients, vertebral deformities were assessed by radiograph. Patients with SH (n ¼ 34) had lower LS-BMD (À0.31 AE 1.17), FT-BMD (À0.29 AE 0.91), and TBS (À3.18 AE 1.21) than patients without SH (n ¼ 68, 0.31 AE 1.42, p ¼ 0.03; 0.19 AE 0.97, p ¼ 0.01; À1.70 AE 1.54, p < 0.0001, respectively) and controls (0.42 AE 1.52, p ¼ 0.02; 0.14 AE 0.76, p ¼ 0.02; À1.19 AE 0.99, p < 0.0001, respectively). TBS was inversely correlated with 1-mg DST (b ¼ À0.26, t ¼ À2.79, p ¼ 0.006) regardless of age, LS-BMD, body mass index (BMI), and gender. The presence of fracture was associated with low TBS alone (odds ratio [OR], 4.8; 95% confidence interval [CI], 1.85-12.42, p ¼ 0.001) and with the cluster low TBS plus low LS-BMD (OR, 4.37; 95% CI, 1.71-11.4, p ¼ 0.002), after adjustment for age, BMI, and gender. Low TBS plus low LS-BMD showed a good specificity (79%) for predicting fractures, whereas normal TBS (ie, > À1.5) plus normal LS-BMD high specificity (88.1%) for excluding fractures. Finally, TBS predicted the occurrence of a new fracture in 40 patients followed for 24 months (OR, 11.2; 95%CI, 1.71-71.41, p ¼ 0.012) regardless of LS-BMD, BMI, and age. In SH, bone quality, as measured by TBS, is altered. TBS is useful in detecting AI patients at risk of fractures. ß

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Section: Discussionmentioning

confidence: 55%

Bone quality, as measured by trabecular bone score in patients with adrenal incidentalomas with and without subclinical hypercortisolism

Eller-Vainicher

Morelli

Ulivieri

et al. 2012

Journal of Bone and Mineral Research

126

108

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“…(4)(5)(6)(7)(8) Prolonged treatment with glucocorticoids leads to a dramatic loss of bone mineral and strength in cortical and cancellous bone, and increases atraumatic fractures in approximately 30% to 50% of patients. (9)(10)(11)(12)(13)(14) Excess glucocorticoids also causes muscle weakness with the consequent loss of body balance and increased falls, which in turn contribute to elevate the risk of bone fractures. (8) It is estimated that 4.4 million individuals in the United States and the United Kingdom are chronically treated with oral glucocorticoids, (8,15) and the use of these agents extends worldwide.…”

Section: Introductionmentioning

confidence: 99%

Protection From Glucocorticoid-Induced Osteoporosis by Anti-Catabolic Signaling in the Absence of Sost/Sclerostin

Sato

Cregor

Delgado‐Calle

et al. 2016

Journal of Bone and Mineral Research

100

107

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Excess of glucocorticoids, either due to disease or iatrogenic, increases bone resorption and decreases bone formation and is a leading cause of osteoporosis and bone fractures worldwide. Improved therapeutic strategies are sorely needed. We investigated whether activating Wnt/b-catenin signaling protects against the skeletal actions of glucocorticoids, using female mice lacking the Wnt/b-catenin antagonist and bone formation inhibitor Sost. Glucocorticoids decreased the mass, deteriorated the microarchitecture, and reduced the structural and material strength of bone in wild-type (WT), but not in Sost -/-mice. The high bone mass exhibited by Sost -/-mice is due to increased bone formation with unchanged resorption. However, unexpectedly, preservation of bone mass and strength in Sost -/-mice was due to prevention of glucocorticoid-induced bone resorption and not to restoration of bone formation. In WT mice, glucocorticoids increased the expression of Sost and the number of sclerostin-positive osteocytes, and altered the molecular signature of the Wnt/b-catenin pathway by decreasing the expression of genes associated with both anticatabolism, including osteoprotegerin (OPG), and anabolism/survival, such as cyclin D1. In contrast in Sost -/-mice, glucocorticoids did not decrease OPG but still reduced cyclin D1. Thus, in the context of glucocorticoid excess, activation of Wnt/b-catenin signaling by Sost/sclerostin deficiency sustains bone integrity by opposing bone catabolism despite markedly reduced bone formation and increased apoptosis. This crosstalk between glucocorticoids and Wnt/b-catenin signaling could be exploited therapeutically to halt resorption and bone loss induced by glucocorticoids and to inhibit the exaggerated bone formation in diseases of unwanted hyperactivation of Wnt/b-catenin signaling.

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“…Glucocorticoids influence bone metabolism by suppressing osteoblast activity, promoting increased bone resorption by osteoclasts, and interfering with calcium absorption from the gastrointestinal tract [63]. Thus, the need for chronic glucocorticoid therapy leads to concerns regarding bone density for individuals with CAH.…”

Section: Bone Mineral Densitymentioning

confidence: 99%

Non-classic congenital adrenal hyperplasia

Witchel

2013

Steroids

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Nonclassic congenital adrenal hyperplasia (NCAH) due to P450c21 (21-hydroxylase deficiency) is a common autosomal recessive disorder. This disorder is due to mutations in the CYP21A2 gene which is located at chromosome 6p21. The clinical features predominantly reflect androgen excess rather than adrenal insufficiency leading to an ascertainment bias favoring diagnosis in females. Treatment goals include normal linear growth velocity and "on-time" puberty in affected children. For adolescent and adult women, treatment goals include regularization of menses, prevention of progression of hirsutism, and fertility. This paper will review key aspects regarding pathophysiology, diagnosis, and treatment of NCAH.

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Glucocorticoid-induced osteoporosis: an update

Cited by 315 publications

References 66 publications

Bone quality, as measured by trabecular bone score in patients with adrenal incidentalomas with and without subclinical hypercortisolism

Bone quality, as measured by trabecular bone score in patients with adrenal incidentalomas with and without subclinical hypercortisolism

Protection From Glucocorticoid-Induced Osteoporosis by Anti-Catabolic Signaling in the Absence of Sost/Sclerostin

Non-classic congenital adrenal hyperplasia

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