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Pedersini R.,University of Brescia | Pedersini R.,Spedali Civili Hospital | Monteverdi S.,University of Brescia | Monteverdi S.,Spedali Civili Hospital | And 14 more authors.
Bone | Year: 2017

Background The impact of long-term adjuvant therapy with aromatase inhibitors (AIs) on vertebral fracture (VF) risk is still unclear. Objective In this cross-sectional study, we explored the prevalence and determinants of VFs in breast cancer (BC) patients before and during AI therapy. Each woman underwent a dual-energy X-ray absorptiometry (DXA) to evaluate bone mineral density (BMD) and identify VFs by a quantitative morphometric approach. Blood samples were collected to measure serum hormone and calcium levels. Results We consecutively included 263 postmenopausal women with hormone receptor-positive early BC. One-hundred-sixty-nine women were AI-naïve, and 94 were AI-treated. AI-treated patients had lower BMD at total hip (p = 0.01) and lumbar spine (p = 0.03), higher serum vitamin D (p < 0.001) and parathyroid hormone (p = 0.006) values as compared to AI-naïve patients. The prevalence of VFs was 18.9% in AI-naïve patients, and 31.2% in those assessed during AI therapy (odds ratio 1.90, 95% CI 1.1–3.5, p = 0.03). In AI-naïve patients, VFs were associated with older age (p = 0.002) and lower BMD values at femoral neck (p = 0.04) and total hip (p = 0.007), whereas VFs occurred without association with any parameter analyzed in AI-treated patients. In AI-treated group, the prevalence of VFs was not significantly different between patients with osteoporosis and those with normal BMD (36.7% vs. 20.0%; p = 0.31). Conclusions In women with early BC, AI therapy is associated with high prevalence of radiological VFs, which were shown to be independent of BMD values during the adjuvant treatment. These findings may be clinically relevant since they may lead to a change in management of AI-induced skeletal fragility. Specifically, the results of this study provide a rationale for performing a morphometric evaluation of VFs in all women undergoing treatment with AIs. © 2017 Elsevier Inc.


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.,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.


PubMed | Spedali Civili Hospital, Vita-Salute San Raffaele University, Endocrine and Bone Unit and University of Brescia
Type: | Journal: Bone | Year: 2017

The impact of long-term adjuvant therapy with aromatase inhibitors (AIs) on vertebral fracture (VF) risk is still unclear.In this cross-sectional study, we explored the prevalence and determinants of VFs in breast cancer (BC) patients before and during AI therapy. Each woman underwent a dual-energy X-ray absorptiometry (DXA) to evaluate bone mineral density (BMD) and identify VFs by a quantitative morphometric approach. Blood samples were collected to measure serum hormone and calcium levels.We consecutively included 263 postmenopausal women with hormone receptor-positive early BC. One-hundred-sixty-nine women were AI-nave, and 94 were AI-treated. AI-treated patients had lower BMD at total hip (p=0.01) and lumbar spine (p=0.03), higher serum vitamin D (p<0.001) and parathyroid hormone (p=0.006) values as compared to AI-nave patients. The prevalence of VFs was 18.9% in AI-nave patients, and 31.2% in those assessed during AI therapy (odds ratio 1.90, 95% CI 1.1-3.5, p=0.03). In AI-nave patients, VFs were associated with older age (p=0.002) and lower BMD values at femoral neck (p=0.04) and total hip (p=0.007), whereas VFs occurred without association with any parameter analyzed in AI-treated patients. In AI-treated group, the prevalence of VFs was not significantly different between patients with osteoporosis and those with normal BMD (36.7% vs. 20.0%; p=0.31).In women with early BC, AI therapy is associated with high prevalence of radiological VFs, which were shown to be independent of BMD values during the adjuvant treatment. These findings may be clinically relevant since they may lead to a change in management of AI-induced skeletal fragility. Specifically, the results of this study provide a rationale for performing a morphometric evaluation of VFs in all women undergoing treatment with AIs.

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