Search

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) exert physiological actions on the skeleton throughout life, by stimulating longitudinal bone growth in children, the acquisition of bone mass during adolescence and the maintenance of skeletal architecture in adults. When GH and IGF-I are secreted in excess, bone remodeling is enhanced leading to deterioration of bone microstructure and impairment of bone strength. Indeed, acromegaly causes skeletal fragility, and vertebral fractures are reported in a remarkable number of subjects exposed to GH and IGF-I excess. The management of skeletal fragility in acromegaly is a challenge, since the awareness of this complication is low, the prediction of fracture risk is difficult to ascertain, the risk of fractures remains after the control of acromegaly and the effectiveness of bone-active drugs is unknown. This review is an update on bone disorders associated with acromegaly and provides a perspective of possible therapeutic approaches based on emerging pathophysiological and clinical information. [ABSTRACT FROM AUTHOR]

Background: Bone health management in premenopausal women with breast cancer (BC) under hormone-deprivation therapies (HDTs) is often challenging, and the effectiveness of bone-active drugs is still unknown., Methods: This retrospective multicenter study included 306 premenopausal women with early BC undergoing HDTs. Bone mineral density (BMD) and morphometric vertebral fractures (VFs) were assessed 12 months after HDT initiation and then after at least 24 months., Results: After initial assessment, bone-active drugs were prescribed in 77.5% of women (151 denosumab 60 mg/6 months, 86 bisphosphonates). After 47.0 ± 20.1 months, new VFs were found in 16 women (5.2%). Vertebral fracture risk was significantly associated with obesity (odds ratio [OR] 3.87, P = .028), family history of hip fractures or VFs (OR 3.21, P = .040], chemotherapy-induced menopause (OR 6.48, P < .001), preexisting VFs (OR 25.36, P < .001), baseline T-score less than or equal to -2.5 standard deviation (SD) at any skeletal site (OR 4.14, P = .036), and changes at lumbar and total hip BMD (OR 0.94, P = .038 and OR 0.88, P < .001, respectively). New VFs occurred more frequently in women untreated compared to those treated with bone-active drugs (14/69, 20.8% vs 2/237, 0.8%; P < .001) and the anti-fracture effectiveness remained significant after correction for BMI (OR 0.03; P < .001), family history of fractures (OR 0.03; P < .001), chemotherapy-induced menopause (OR 0.04; P < .001), and preexisting VFs (OR 0.01; P < .001)., Conclusions: Premenopausal women under HDTs are at high risk of VFs in relationship with high BMI, densitometric diagnosis of osteoporosis, preexisting VFs, and family history of osteoporotic fractures. Vertebral fractures in this setting might be effectively prevented by bisphosphonates or denosumab., Competing Interests: Conflict of interest: R.P. received consultancy fees from Roche, Novartis, Eli Lilly, Daiichi Sankyo, Gilead, Eisai, and Accord, outside the submitted work. A.P. reports lecture fees from Amgen, Theramex, and UCB, outside the submitted work. A.N. reports lecture fees from Theramex, outside the submitted work. G.T. reports lectures fees from Theramex and Abiogen, outside the submitted work. R.T. received research grants from Pfizer, consultancy fees from MSD, and lecture fees from Pfizer, Eli Lilly, Eisai, and Genomic Health outside the submitted work. A.Z. received consultancy fees from Roche, Novartis, Pfizer, Eli Lilly & Co., AstraZeneca, and Genomic Health outside the submitted work. L.C. received consultancy fees from UCB and lecture fees from Abiogen Pharma and Bruno Farmaceutici, outside the submitted work. A.C. Bossi reports research grants from Bayer SA, Lilly Italia SpA, MSD USA, and Novo Nordisk Italia SpA and personal fees from Sanofi Italia SpA, Boehringer Ingelheim Italia SpA, and AstraZeneca Italia SpA, outside the submitted work. A.L. received grants from Pfizer and lecture fees from Recordati, outside the submitted work. A.B. reports receiving grants and personal fees from Janssen Cilag, grants and personal fees from Astellas, and personal fees from Bayer outside the submitted work. G.M. received consultancy fees and preceptorship from Amgen–UCB and Sanofi and lectures fees from Theramex and Recordati. The other authors have nothing to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: In this study we performed single-cell analysis of the intracellular cytokine expression in peripheral CD4+ and CD8+ lymphocytes from patients with Hashimoto's thyroiditis (HT) to investigate the type-1 response separately for the two lymphocyte sub-populations., Design and Methods: Twenty-nine patients affected by HT and 20 healthy subjects, matched for sex and age, were enrolled. After the analysis of the lymphocyte sub-populations, the intracellular content of interferon-gamma (IFN-gamma) in phorbolmyristate acetate (PMA)-stimulated CD4+ and CD8+ lymphocytes was assayed. Moreover, the CD4+ lymphocytes were also evaluated for the intracellular expression of IL-4., Results: No significant differences in CD3+, CD4+ and CD8+ lymphocytes were found between HT patients and control subjects. However, the HT patients showed higher numbers of CD4+ IFN-gamma+, CD4+ IL-4+ and CD8+ IFN-gamma+ (t-test, P< or =0.001) cells than the control subjects. Analysing the intracellular expression of IFN-gamma and IL-4 in relation to thyroid function, we found that the euthyroid patients (18 cases) showed more expression of IL-4 in CD4+ lymphocytes than the control subjects, without any significant modification of IFN-gamma expression in CD4+ and CD8+ lymphocytes. However, the hypothyroid patients (11 cases) showed an increase of IFN-gamma expression in both CD4+ and CD8+ lymphocytes with respect to the control subjects and the euthyroid patients. Moreover, the expression of IL-4 in CD4+ cells from hypothyroid patients was significantly lower than that seen in the euthyroid cases and comparable to that found in the control subjects., Conclusions: Our study has demonstrated that the peripheral CD4+ and CD8+ T lymphocytes from the HT patients show a type-1 activation strictly correlated to the occurrence of hypothyroidism. Further studies will be needed to clarify the exact role of peripheral lymphocytes in HT and whether they could provide a reliable marker of thyroid immune involvement.