Glucocorticoids are not always deleterious for bone

Lierop, A.H.J.M. Van; Hamdy, Neveen A. T.; Papapoulos, Socrates E.

doi:10.1016/j.bone.2010.04.570

Cited by 4 publications

(4 citation statements)

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“…However, sclerostin may very well be directly involved in the initial phase of bone loss induced by glucocorticoids. This could not be studied in our patients, but we previously showed that treatment of a patient with sclerostin deficiency with prednisone reduced both resorption and formation markers, and we suggested that sclerostin plays an important role in the modulation of bone resorption by glucocorticoids, whereas it does not affect their action on bone formation (18). Furthermore, mice treated with dexamethasone were protected from glucocorticoid-induced bone loss, when they were simultaneously treated with a neutralizing antibody against sclerostin (7).…”

Section: Discussionmentioning

confidence: 76%

Circulating Sclerostin Levels Are Decreased in Patients with Endogenous Hypercortisolism and Increase after Treatment

Lierop

Eerden²,

Hamdy

et al. 2012

The Journal of Clinical Endocrinology & Metabolism

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Section: Discussionmentioning

confidence: 76%

Circulating Sclerostin Levels Are Decreased in Patients with Endogenous Hypercortisolism and Increase after Treatment

Lierop

Eerden²,

Hamdy

et al. 2012

The Journal of Clinical Endocrinology & Metabolism

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“…A clinical case reported that glucocorticoids stop the exaggerated bone gain and reduced the high circulating P1NP in a patient with Van Buchem disease, a condition that results from lack of sclerostin expression and in which continuous bone anabolism causes life-threatening increased intracranial pressure. (54) Prior to glucocorticoid intervention, the patient exhibited annual BMD gains of 4% to 9% in the lumbar spine and of 4% to 24% in the hip. Treatment with prednisone blunted the anabolic effect of Sost deficiency as evidenced by no gain in BMD after 2 years (-0.7% in lumbar spine and 0.4% in the hip).…”

Section: Journal Of Bone and Mineral Researchmentioning

confidence: 98%

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

109

108

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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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“…Following lumbar puncture, symptoms completely resolved in 1 patient, whereas in another they improved over several months with concomitant treatment with acetazolamide. In the third patient a ventricular peritoneal drain had to be placed and treatment with prednisone was given leading to complete resolution of symptoms 14. One patient had sustained a fracture of the wrist on two separate occasions, one at the age of 14 years after falling from a tree, and the other at the age of 17 years after a motorcycle accident.…”

Section: Resultsmentioning

confidence: 99%

Van Buchem disease: Clinical, biochemical, and densitometric features of patients and disease carriers

Lierop

Hamdy

Egmond

et al. 2012

Journal of Bone and Mineral Research

111

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Van Buchem disease (VBD) is a rare bone sclerosing dysplasia caused by the lack of a regulatory element of the SOST gene, which encodes for sclerostin, an osteocyte-derived negative regulator of bone formation. We studied the demographic, clinical, biochemical, and densitometric features of 15 patients with VBD (12 adults and 3 children) and 28 related carriers of the gene mutation. The most common clinical findings in patients were facial palsy (100%) and various degrees of hearing impairment (93%); raised intracranial pressure had been documented in 20%. The clinical course of the disease appeared to stabilize in adulthood, with the majority of patients reporting no progression of symptoms or development of complications with time. Carriers of the disease had none of the clinical features or complications of the disease. Sclerostin could be detected in the serum in all but 1 VBD patients (mean 8.0 pg/mL; 95% confidence interval [CI], 4.9-11.0 pg/mL), and were lower than those of carriers (mean 28.7 pg/mL; 95% CI, 24.5-32.9 pg/mL; p < 0.001) and healthy controls (mean 40.0 pg/mL; 95% CI, 34.5-41.0 pg/mL; p < 0.). Serum procollagen type 1 amino-terminal propeptide (P1NP) levels were also significantly higher in adult patients (mean 96.0; 95% CI, 54.6-137.4 ng/mL versus mean 47.8; 95% CI, 39.4-56.2 ng/mL, p ¼ 0.003 in carriers and mean 37.8; 95% CI, 34.5-41.0 ng/mL, p ¼ 0.028 in healthy controls) and declined with age. Bone mineral density (BMD) was markedly increased in all patients (mean Z-score 8.7 AE 2.1 and 9.5 AE 1.9 at the femoral neck and spine, respectively); BMD of carriers was significantly lower than that of patients but varied widely (mean Z-scores 0.9 AE 1.0 and 1.3 AE 1.5 at the femoral neck and spine, respectively). Serum sclerostin levels were inversely correlated with serum P1NP levels (r ¼ -0.39, p ¼ 0.018) and BMD values (femoral neck r ¼ -0.69, p < 0.001; lumbar spine r ¼ -0.78, p < 0.001). Our results show that there is a gene-dose effect of the VBD deletion on circulating sclerostin and provide further in vivo evidence of the role of sclerostin in bone formation in humans. The small amounts of sclerostin produced by patients with VBD may explain their milder phenotype compared to that of patients with sclerosteosis, in whom serum sclerostin is undetectable. ß

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Glucocorticoids are not always deleterious for bone

Cited by 4 publications

References 0 publications

Circulating Sclerostin Levels Are Decreased in Patients with Endogenous Hypercortisolism and Increase after Treatment

Circulating Sclerostin Levels Are Decreased in Patients with Endogenous Hypercortisolism and Increase after Treatment

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

Van Buchem disease: Clinical, biochemical, and densitometric features of patients and disease carriers

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