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Mazziotti G.,Endocrine and Bone Unit | Giustina A.,University of Brescia
Nature Reviews Endocrinology | Year: 2013

Glucocorticoids modulate the secretion of growth hormone (GH) by various and competing effects on the hypothalamus and pituitary gland. The final effects of this modulation depend on hormone concentrations and the duration of exposure. The traditional hypothesis is that chronically raised levels of glucocorticoids suppress the secretion of GH. However, a functional impairment of the GH reserve might also be observed in patients with low levels of glucocorticoids, such as those with secondary hypoadrenalism, which is consistent with the model of biphasic dose-dependent effects of glucocorticoids on the somatotropic axis. This Review updates our current understanding of the mechanisms underlying the effects of glucocorticoids on the secretion of GH and the clinical implications of the dual action of glucocorticoids on the GH reserve in humans. This Review will also address the potential diagnostic and therapeutic implications of GH for patients with a deficiency or excess of glucocorticoids.© 2013 Macmillan Publishers Limited. All rights reserved.

Mazziotti G.,University of Brescia | Mazziotti G.,Endocrine and Bone Unit | Bilezikian J.,Columbia University | Canalis E.,Saint Francis Medical Center College of Nursing | And 3 more authors.
Endocrine | Year: 2012

To summarize promising areas of investigation in osteoporosis and to stimulate further research in this area, as discussed in a recent international conference. Over the recent years, there has been an improvement in the knowledge of molecular pathways involved in bone formation and resorption with the development of new drugs to treat osteoporosis. Intact parathyroid hormone, teriparatide, and anti-sclerostin monoclonal antibody are anabolic drugs, whereas denosumab and odanacatib are anti-resorptive drugs with more reversible effects as compared to bisphosphonates. Anabolic and anti-resorptive agents have different effects on bone, and research in this area includes the efficacy of combination and sequential therapies with them. New insights in the molecular pathways of bone remodeling have clarified the mechanisms responsible for skeletal fragility in several forms of secondary osteoporosis, such as that occurring in type 2 diabetes, following drug exposure and systemic inflammatory diseases. Future research is needed to address the efficacy of anti-osteoporotic drugs in these more recently recognized conditions of skeletal fragility. Osteoporosis continues to be an important field of biomedical research. © Springer Science+Business Media, LLC 2011.

Mazziotti G.,University of Brescia | Mazziotti G.,Endocrine and Bone Unit | Bianchi A.,Catholic University of Rome | Porcelli T.,University of Brescia | And 6 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Context: Cross-sectional studies showed an elevated prevalence of vertebral fractures in acromegaly. However, no data are available on incident vertebral fractures in this clinical setting. Objective: The objective of the study was to investigate the incidence and risk factors of vertebral fractures in patients with acromegaly. Design: This was a 3-year prospective study. Setting: The study was conducted at referral centers. Subjects: Eighty-eight patients with acromegaly (33 females, 55 males; mean age 50 years, range 21-85 years) and 106 control subjects, matched for sex and age (43 females and 63 males, meanage 55 years, range 33-79 years), attending outpatient bone clinics participated in the study. Main Measures: Patients and control subjects were evaluated for the incidence of vertebral fractures using a quantitative morphometric approachonspine x-ray, whichwasperformed at baseline and after 3 years of follow-up. At the same time points, patients with acromegaly were also evaluated for bone mineral density with dual-energy X-ray absorptiometry at lumbar spine and femoral neck. Results: After a 3-year follow-up, 37 patients with acromegaly (42.0%) and 4 control subjects (3.8%) experienced incident vertebral fractures (P<.001). The incidence of vertebral fractures was significantly higher in patients with active disease as compared with those who had controlled/ cured acromegaly at the study entry (62.5% vs 25.0%; P < .001). The risk of incident vertebral fractures was significantly associated with hypogonadism, a change in the femoral neck bone mineral density, and prevalent vertebral fractures at the study entry only in patients with controlled/ cured acromegaly, whereas in patients with active disease, the fracture risk was not influenced by the above-mentioned clinical factors, but it was significantly associated with the duration of active acromegaly. Conclusions: This prospective study demonstrates a high rate of incident vertebral fractures both in patients with active and controlled acromegaly. Copyright © 2013 by The Endocrine Society.

Mazziotti G.,University of Brescia | Mazziotti G.,Endocrine and Bone Unit | Baracca M.,Endocrine and Bone Unit | Doga M.,University of Brescia | And 3 more authors.
European Journal of Endocrinology | Year: 2012

Objective: Heart failure (HF) has been associated with increased risk of fragility fractures. Indeed, most literature data on fractures were based on an historical and clinical approach focused on the identification of peripheral fractures, whereas the risk of vertebral fractures in this clinical setting is still unclear. Design: Cross-sectional study. Aim: To evaluate the prevalence and determinants of radiological thoracic vertebral fractures in patients with HF. Methods: The study includes 1031 elderly hospitalized patients (491 females and 540 males; median age, 75 years; range, 65-90; 430 patients with HF) who were evaluated for the presence of thoracic vertebral fractures by quantitative morphometric analysis, using chest X-ray routinely performed in the diagnostic work-up of HF. Results:Vertebral fractures were found in166 patients (16.1%), the prevalence being significantly higher in patients with HF as compared with those without HF, both in females (30.9 vs 15.8%; P<0.001) and in males (16.4vs 7.4%; P=0.001). The association between HF and vertebral fractures remained statistically significant (odds ratio, 2.14; 95% CI, 1.25-3.66; P=0.01) even after adjustment for age, sex, loop diuretic therapy, anticoagulant therapy, proton pump therapy, coexistent chronic obstructive pulmonary disease, diabetes mellitus, renal insufficiency, and chronic liver diseases. In patients with HF, vertebral fractures were positively correlated with female sex, duration of HF, ischemic heart disease, cigarette smoking, and treatment with anti-osteoporotic drugs, and inversely correlated with left ventricular ejection fraction. Conclusions: Hospitalized patients suffering from HF are at higher risk of vertebral fractures than patients without HF in the same clinical context. © 2012 European Society of Endocrinology.

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