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Purpose: The bone strain index (BSI) is a marker of bone deformation based on a finite element analysis inferred from dual X-ray absorptiometry (DXA) scans, that has been proposed as a predictor of fractures in osteoporosis (i.e., higher BSI indicates a lower bone’s resistance to loads with consequent higher risk of fractures). We aimed to investigate the association between lumbar BSI and vertebral fractures (VFs) in acromegaly. Methods: Twenty-three patients with acromegaly (13 males, mean age 58 years; three with active disease) were evaluated for morphometric VFs, trabecular bone score (TBS), bone mineral density (BMD) and BSI at lumbar spine, the latter being corrected for the kyphosis as measured by low-dose X-ray imaging system (EOS®-2D/3D). Results: Lumbar BSI was significantly higher in patients with VFs as compared to those without fractures (2.90 ± 1.46 vs. 1.78 ± 0.33, p = 0.041). BSI was inversely associated with TBS (rho −0.44; p= 0.034), without significant associations with BMD (p= 0.151), age (p= 0.500), BMI (p= 0.957), serum IGF-I (p= 0.889), duration of active disease (p= 0.434) and sex (p= 0.563). Conclusions: Lumbar BSI corrected for kyphosis could be proposed as integrated parameter of spine arthropathy and osteopathy in acromegaly helping the clinicians in identifying patients with skeletal fragility possibly predisposed to VFs.

L’osteoporosi è una condizione patologica dovuta a un’alterazione del fisiologico rimodellamento osseo con conseguente riduzione della resistenza al carico meccanico e aumento del rischio di fratture da fragilità. Per contrastare l’alto rischio fratturativo correlato all’osteoporosi si possono utilizzare farmaci ad azione anti-riassorbitiva in grado di inibire l’attività osteoclastica e farmaci cosiddetti anabolici che sono in grado, invece, di stimolare la neoformazione ossea e di migliorare la microarchitettura trabecolare. Il teriparatide è stato il primo farmaco anabolico approvato in Europa per l’osteoporosi primitiva severa e per quella secondaria a terapia con glucocorticoidi. Negli ultimi anni la ricerca farmacologica ha portato allo sviluppo e all’applicazione clinica un nuovo farmaco anti-osteoporotico anabolico, il romosozumab, che presenta un duplice effetto, sia anti-riassorbitivo che di stimolazione della neoformazione ossea. La presente rassegna si focalizzerà sui meccanismi d’azione e sui dati di efficacia dei farmaci anabolici attualmente disponibili e sul loro utilizzo nella pratica clinica.

Objective: Prediction of fragility fractures in Cushing syndrome (CS) is a challenge since dual energy X-ray absorptiometry (DXA) measurement of bone mineral density (BMD) does not capture all the alterations in bone microstructure induced by glucocorticoid excess. In this study we investigated the relationship between trabecular bone score (TBS), bone marrow fat (BMF) and vertebral fractures (VFs) in endogenous CS. Design: Cross-sectional. Methods: Thirty subjects (7 M and 23 F, mean age 44.8 ± 13.4 yrs, range: 25–71) with active hypercortisolism were evaluated for VFs by quantitative morphometry, BMD and TBS by lumbar spine DXA and BMF by single-voxel magnetic resonance spectroscopy of vertebral body of L3. Results: Subjects with VFs (17 cases; 56.7%) had higher BMF (P= 0.014) and lower BMD T-score (P= 0.012) and TBS (P= 0.004) as compared to those without VFs. Prevalence of VFs resulted to be significantly higher in individuals with impaired TBS as compared to those with normal TBS (77.8% vs. 25.0%; P= 0.008). Among patients with VFs, only 6 (35.3%) had either osteoporosis or “low BMD for age”. In logistic regression analysis, impaired TBS maintained the significant association with VFs [odds ratio (OR) 6.60, 95% C.I. 1.07–40.61; P= 0.042] independently of BMF (OR 1.03, 95% C.I. 0.99–1.08; P= 0.152). Conclusions: TBS might be more accurate than BMF in identifying subjects with active CS and skeletal fragility at risk of VFs. Significance statement: Excess in glucocorticoids is associated with alterations in bone remodeling and metabolism, leading to fragility fractures regardless of bone mineral density, making more challenging for the clinician the identification of high-risk population and the definition of preventing strategies. In this context, instrumental parameters suggestive of bone quality alterations and predictive of increased fracture risk are needed. In this study, we found CS patients to have bone quality alterations as indicated by the decreased trabecular bone score and increased bone marrow fat, as measured by DEXA and MRI respectively. Both parameters were associated with high risk of VFs, and were inversely correlated, although TBS seems to be more accurate than BMF in fractures prediction in this clinical setting.

Skeletal fragility with high risk of vertebral fractures (VFs) is an emerging complication of growth hormone (GH) hypersecretion. VFs often coexist with spine arthropathy and both clinical conditions negatively impact on quality of life of acromegalic subjects. Management of spine osteopathy and arthropathy in acromegaly could be challenging since both complications can persist or even progress after biochemical control of disease. This article analyzes the latest evidence about possible pathophysiological links between VFs and spine arthropathy in active and controlled acromegaly, as well as the diagnostic and therapeutic aspects concerning the holistic management of acromegalic osteo-arthropathy.

Denosumab (Dmab) è un potente farmaco anti-riassorbitivo impiegato per il trattamento dell’osteoporosi al dosaggio di 60 mg sottocute ogni sei 6 mesi. A differenza dei bisfosfonati (BPs), Dmab non si accumula nella matrice ossea e, in caso di ritardo o interruzione delle somministrazioni, è noto un effetto reboundsul turnover osseo, che si traduce in una rapida perdita di Bone Mineral Density(BMD) e in un aumento del rischio di fratture vertebrali, spesso cliniche e multiple. Data la rilevanza clinica di tale fenomeno, si rende quindi necessario per gli specialisti dedicati al trattamento delle patologie osteometaboliche conoscere nel dettaglio quali sono le evidenze attualmente disponibili, nonché le principali raccomandazioni relative alla gestione della terapia anti-osteoporotica con Dmab, con particolare attenzione alla sua interruzione (programmata o accidentale), su cui si focalizzerà la presente Rassegna.

Purpose: Neuroendocrine neoplasms (NENs) are tumors that arise from cells of the endocrine system and are most common in the gastrointestinal tract, the pancreas, and the lungs. Their incidence is rapidly increasing and the therapeutic options available are limited. Methods: Since the immune system can interfere with tumor growth and response to therapy, using flow cytometry we investigated the immunophenotype in samples of peripheral blood leukocytes from patients with pancreatic (Pan-NENs) and pulmonary NENs (Lung-NENs). Moreover, we performed a multiplex analysis of 13 key cytokines and growth factors essential for the immune response in the plasma of NEN patients and controls. Results: Patients presented with a higher percentage of granulocytes, a lower percentage of lymphocytes, and an increase in the granulocytes to lymphocytes ratio compared to healthy donors. These alterations were more marked in patients with metastasis. Somatostatin analogs (SSAs) restored the immunophenotype of patients to that seen in healthy donors. Finally, Pan-NEN patients showed a higher plasma concentration of IP-10, MCP-1, and IL-8 compared to healthy donors, suggesting a potential role for these cytokines as diagnostic biomarkers. Conclusion: This study highlighted differences in the immunophenotype of patients with Pan- and Lung-NENs compared to healthy individuals; these alterations were partially restored by therapy.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjmed.2010.02.028 Byline: Gherardo Mazziotti (a), Ernesto Canalis (b)(c), Andrea Giustina (a) Keywords: Drugs; Fractures; Osteoporosis; Secondary osteoporosis Abstract: Drug-induced osteoporosis is common and has a significant impact on the prognosis of patients suffering from chronic debilitating diseases. Glucocorticoids are the drugs causing osteoporotic fractures most frequently, but osteoporosis with fractures is observed also in women treated with aromatase inhibitors for breast cancer, in men receiving anti-androgen therapy for prostate cancer, in postmenopausal women treated with high doses of thyroxine, and in men and women treated with thiazolinediones for type 2 diabetes mellitus. Bone loss with fractures also occurs in patients treated with drugs targeting the immune system, such as calcineurin inhibitors, antiretroviral drugs, selective inhibitors of serotonin reuptake, anticonvulsants, loop diuretics, heparin, oral anticoagulants, and proton pump inhibitors. Author Affiliation: (a) Department of Medical and Surgical Sciences, University of Brescia, Montichiari, Italy (b) Department of Research, Saint Francis Hospital and Medical Center, Hartford, Conn (c) University of Connecticut School of Medicine, Farmington Article Note: (footnote) Funding: This work was supported by MIUR and Centro di Ricerca sull'Osteoporosi-University of Brescia/EULO (A. Giustina)., Conflict of Interest: Dr. Mazziotti has nothing to declare. Dr. Canalis reports receiving consulting or lecture fees from Eli Lilly, GlaxoSmithKline, Novartis, and Amgen. Dr. Giustina reports receiving consulting or lecture fees from Abiogen, Eli Lilly, GlaxoSmithKline, Merck, Amgen, and Stroder. No pharmaceutical industry funds were received for the preparation of the manuscript or related research., Authorship: Each author has participated in the writing of the manuscript and has seen and approved the submitted version. Further, each author has been involved in the conception and design of the study and the analysis of the data.

Growth hormone (GH) and insulin-like growth factor 1 (IGF1) are important regulators of bone remodelling and metabolism and have an essential role in the achievement and maintenance of bone mass throughout life. Evidence from animal models and human diseases shows that both GH deficiency (GHD) and excess are associated with changes in bone remodelling and cause profound alterations in bone microstructure. The consequence is an increased risk of fractures in individuals with GHD or acromegaly, a condition of GH excess. In addition, functional perturbations of the GH–IGF1 axis, encountered in individuals with anorexia nervosa and during ageing, result in skeletal fragility and osteoporosis. The effect of interventions used to treat GHD and acromegaly on the skeleton is variable and dependent on the duration of the disease, the pre-existing skeletal state, coexistent hormone alterations (such as those occurring in hypogonadism) and length of therapy. This variability could also reflect the irreversibility of the skeletal structural defect occurring during alterations of the GH–IGF1 axis. Moreover, the effects of the treatment of GHD and acromegaly on locally produced IGF1 and IGF binding proteins are uncertain and in need of further study. This Review highlights the pathophysiological, clinical and therapeutic aspects of skeletal fragility associated with perturbations in the GH–IGF1 axis.

L’osteonecrosi delle ossa mascellari farmaco-relata (Medication-Related Osteonecrosis of the Jaw, MR-ONJ) è una complicanza rara associata all’utilizzo di alcuni farmaci, tra cui quelli ad azione anti-riassorbitiva utilizzati nel trattamento delle metastasi ossee e dell’osteoporosi. Tale condizione decorre inizialmente con segni o sintomi aspecifici, per poi manifestarsi in modo conclamato con l’esposizione dell’osso necrotico. I principali fattori predisponenti sono la presenza di processi infettivo-infiammatori a livello dento-parodontale, la terapia prolungata con uno o più farmaci predisponenti e l’esecuzione di procedure odontoiatriche invasive. Considerando il grande impatto che tale patologia ha sulla qualità di vita del paziente, è necessario che il Bone Specialist sia in grado di valutare il rischio di tale complicanza, riconoscere precocemente segni o sintomi di sospetto e agire di concerto con l’odontoiatra per un’appropriata ed efficace prevenzione. In questa rassegna si esamineranno, dunque, le basi fisiopatologiche della MR-ONJ e il ruolo del Bone Specialist nella gestione di tale patologia.

L’infezione da SARS-CoV-2 è rapidamente diventata una pandemia globale, con più di 100 milioni di persone infettate e 2,3 milioni di morti nel mondo. Particolare attenzione è stata posta all’influenza reciproca tra infezione da SARS-CoV-2 e funzione endocrina. In questa rassegna si discuteranno i risultati dei principali studi ad oggi pubblicati che hanno analizzato le alterazioni della funzione tiroidea, dei livelli di vitamina D e il compenso glicometabolico nei pazienti ospedalizzati per polmonite da SARS-CoV-2 e il loro impatto sull’outcome clinico.

Derangement of pituitary hormone axes can induce changes in bone remodeling and metabolism with possible alterations in bone microarchitectural structure and increased susceptibility to fractures. Vertebral fractures (VFs), which are a hallmark of skeletal fragility, have been described in a very large number of patients with pituitary diseases. These fractures are clinically relevant, since they predispose to further fractures and may negatively impact on patients’ quality of life. However, the management of skeletal fragility and VFs in the specific setting of pituitary diseases is a challenge, since the awareness for this disease is still low, prediction of VFs is uncertain, the diagnosis of VFs cannot be solely based on a clinical approach and also needs a radiological and morphometric approach, the risk of fractures may not be decreased via treatment of pituitary hormone disorders, and the effectiveness of bone-active drugs in this setting is not always evidence-based. This review is an update on skeletal fragility in patients with pituitary diseases, with a focus on clinical and therapeutic aspects concerning the management of VFs.

Purpose: To evaluate the post- coronavirus disease-19 (COVID-19) outcome of thyroid function in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related thyrotoxicosis. Methods: This was a single-center prospective study involving 29 patients (11 females, 18 males; median age 64 years, range: 43–85) with thyrotoxicosis diagnosed after hospitalization for COVID-19 and then followed-up for a median period of 90 days (range: 30–120) after hospital discharge. At follow-up, patients were evaluated for serum thyrotropin (TSH), free-thyroxine (FT4), free-triiodiothyronine (FT3), TSH receptor antibodies (TRAb), thyroglobulin antibodies (TgAb), thyroperoxidase antibodies (TPOAb) and ultrasonographic thyroid structure. Results: After recovery of COVID-19, serum TSH values significantly increased (P< 0.001) and FT4 values significantly decreased (P= 0.001), without significant change in serum FT3 (P= 0.572). At follow-up, 28 subjects (96.6%) became euthyroid whereas overt hypothyroidism developed in one case. At the ultrasound evaluation of thyroid gland, hypoecogenicity was found in 10 patients (34.5%) and in these cases serum TSH values tended to be higher than those without thyroid hypoecogenity (P= 0.066). All subjects resulted to be negative for TgAb, TPOAb and TRAb. Conclusion: In a short-term follow-up, thyroid function spontaneously normalized in most subjects with SARS-CoV-2-related thyrotoxicosis. However, thyroid hypoecogenicity was found in a remarkable number of them and future longer-term studies are needed to clarify whether this ultrasonographic alteration may predispose to develop late-onset thyroid dysfunction.

L’osteoporosi e le fratture da fragilità scheletrica rappresentano importanti comorbidità nei pazienti con carcinoma differenziato della tiroide (DTC), con potenziale impatto negativo sulla qualità di vita e sulla sopravvivenza. La terapia TSH-soppressiva rappresenta il principale determinante della fragilità scheletrica nei pazienti con DTC, favorendo il riassorbimento osseo e il deterioramento della microstruttura ossea. Tale effetto negativo può essere amplificato in presenza di metastasi ossee che incrementano ulteriormente il rischio di fratture. L’inquadramento e la gestione della fragilità scheletrica nel DTC sono ancora controverse e i dati sull’efficacia dei farmaci osteo-attivi in questo contesto clinico sono scarsi.

Purpose: The aim of this study was to evaluate the impact of the COVID-19 lockdown occurred in Italy from March 9th to May 18th, 2020 on anthropometric parameters and glycemic control in patients with type 2 diabetes mellitus (T2DM). Methods: One hundred twenty-eight consecutive patients with T2DM (median age 70 years, 74 males) were retrospectively evaluated at the end of the lockdown period. Data on metabolic control were collected at different time: within three months before the lockdown (visit 0) and within the first six weeks after it (visit 1). Results: During the lockdown, a significant increase in body weight (from 79.7 ± 18.7 kg to 81.4 ± 19.4 kg, p< 0.001), body mass index (BMI, from 29.5 ± 6 kg/m2to 30.1 ± 6.3 kg/m2, p< 0.001), waist circumference (from 103.8 ± 13 cm to 105 ± 13.6 cm, p< 0.001), fasting plasma glucose (FPG; from 138.1 ± 29.4 mg/dL to 146.6 ± 36.4 mg/dL) and glycated hemoglobin (HbA1c; from 7 ± 0.8 to 7.3 ± 0.9%, p< 0.001) was observed. Weight gain was directly associated with HbA1c increase (β 0.085, C.I. 95% 0.05–0.121; p< 0.001) while insulin therapy resulted to be the only significant independent predictor of HbA1c worsening at the multivariate logistic regression analysis (OR 2.40, C.I. 1.06–5.45; p= 0.035). Conclusions: The lockdown due to COVID-19 pandemic had a negative impact on body weight and glucose control in T2DM patients, in particular in those on insulin treatment. This finding provides a further rationale to optimize the diabetes management during eventually new period of home confinement.

Purpose: Radium-223 was associated with high incidence of non-vertebral fractures in patients with castration-resistant prostate cancer (CRPC). However, it is still unclear whether radium-223 may induce skeletal fragility regardless of other therapies for CRPC. We aimed at evaluating the prevalence, incidence, and determinants of vertebral fractures (VFs), i.e., the most frequent complication of skeletal fragility, in CRCP patients undergoing radium-223 therapy in the real-life clinical practice. Methods: We retrospectively reviewed 49 CRPC patients with symptomatic bone metastases treated with radium-223. Patients received median number of four radium-223 doses (range: 2–6) and were followed-up for a median period of 11 months (range: 6–44). VFs were assessed by a quantitative morphometry using lateral images of spine 11C-Choline PET/CT, excluding from the analysis the vertebral bodies affected by bone metastases. Results: Before radium-223 administration, 24 patients (49%) had VFs significantly associated with duration of androgen deprivation therapy (ADT; odds ratio 1.29) and previous abiraterone therapy (odds ratio 3.80). During radium-223 therapy, incident VFs occurred in 25% of patients, in relationship with prevalent VFs (hazard ratio 6.89) and change in serum total alkaline phosphatase values (hazard ratio 0.97), whereas the correlations with ADT and abiraterone therapy were lost. Noteworthy, the risk of VFs did not correlate with the therapeutic end points of radium-223. Conclusions: This study provides a first evidence that in real-life clinical practice, radium-223 therapy may induce skeletal fragility with high risk of VFs, likely by inhibition of bone formation and independently of ADT and abiraterone therapy.

Purpose: The evaluation of skeletal fragility in Cushing’s syndrome (CS) is a clinical challenge, since dual-energy X-ray absorptiometry (DXA) does not capture abnormalities in bone microstructure induced by glucocorticoid excess. Hypercortisolism was shown to increase bone marrow adiposity, but it is still unknown whether high bone marrow fat (BMF) as measured by vertebral magnetic resonance spectroscopy may predict fracture risk in this clinical setting. In this cross-sectional study, we evaluated the association between BMF and vertebral fractures (VFs) in patients with CS. Methods: Twenty patients (5 M, age 44 ± 13 years) with active CS were evaluated for morphometric VFs, lumbar spine BMF, and bone mineral density (BMD). Fifteen healthy volunteers (4 M, age 43 ± 12 years) acted as control group for BMF evaluation. Results: BMF was significantly higher in CS patients vs. controls (52.0% vs. 27.0%, p< 0.01), and was directly correlated with patients’ age (p= 0.03), 24-hours urine-free cortisol (p= 0.03), midnight serum cortisol (p= 0.02), and serum CTX (p= 0.01). Patients with VFs (13 cases) showed significantly higher BMF vs. patients without VFs (65.0% vs. 24.0%, p= 0.03). Fractured patients with either normal BMD or osteopenia showed comparable BMF to fractured patients with either osteoporosis or low BMD for age (p= 0.71). When the analysis was restricted to patients with normal BMD or osteopenia, VFs were still significantly associated with higher BMF (p= 0.05). Conclusions: This study provides a first evidence that vertebral adiposity may be a marker of hypercortisolism-induced skeletal fragility and measurement of spine BMF could have a role in the diagnostic work-up for the assessment of fracture risk in CS.

Minimally invasive image-guided thermal ablation has been proposed as alternative to surgery for treatment of benign thyroid nodules and recurrent differentiated thyroid carcinoma. Here, we report for the first time the use of radiofrequency ablation (RFA) in a patient with non-metastatic medullary thyroid carcinoma (MTC) who did not undergo surgery due to high anesthesiological risk. A 64-year-old woman was referred to our institution for a routine endocrinological visit. No thyroid-related symptoms were present. She had a history of metabolic, cardiovascular and neurological diseases. On clinical examination, a nodular lesion of about 10 mm was palpable in the right thyroid lobe; ultrasonography (US) confirmed the presence of a 13 mm thyroid nodule in the lower pole of the right lobe, that was hypoechoic and with regular margins. Serum calcitonin (Ctn) level was significantly high (647 pg/mL). Fine-needle aspiration (FNA) of the thyroid nodule was negative for malignant cells, but the marked increase of Ctn level in the FNA wash-out fluid confirmed the diagnostic suspicion of MTC. Since patient refused surgery due to high anesthesiological risk, percutaneous US-guided RFA in single session was performed. At 6-months follow-up the serum Ctn level decreased from the initial value of 647 pg/mL, reaching near-normal range (15 pg/mL), and neck ultrasound showed a complete necrosis of the tumour. Afterward, serum Ctn slowly increased to 49 pg/mL at 15-month follow-up. The US performed at 6 and 12 months of follow-up revealed fibrotic tissue in place of the thyroid nodule, without evidence of cervical lymph-node metastases. This clinical case suggests that RFA may be effective and safe for treatment of MTC when surgery cannot be performed.

Neuroendocrinology of bone is a new area of research based on the evidence that pituitary hormones may directly modulate bone remodeling and metabolism. Skeletal fragility associated with high risk of fractures is a common complication of several pituitary diseases such as hypopituitarism, Cushing disease, acromegaly, and hyperprolactinemia. As in other forms of secondary osteoporosis, pituitary diseases generally affect bone quality more than bone quantity, and fractures may occur even in the presence of normal or low-normal bone mineral density as measured by dual-energy X-ray absorptiometry, making difficult the prediction of fractures in these clinical settings. Treatment of pituitary hormone excess and deficiency generally improves skeletal health, although some patients remain at high risk of fractures, and treatment with bone-active drugs may become mandatory. The aim of this review is to discuss the physiological, pathophysiological, and clinical insights of bone involvement in pituitary diseases.Skeletal fragility is a frequent complication of pituitary diseases. Vertebral fractures should be proactively investigated. Fracture risk is closely related to disease activity.

Bone loss and nonvertebral fractures have been reported in patients with differentiated thyroid carcinoma (DTC) undergoing thyroid-stimulating hormone (TSH) suppressive therapy. Radiological vertebral fractures (VFs) are an early and clinically crucial marker of bone fragility.

ABSTRACTIntroduction: Neuroendocrine tumors (NETs) harbor somatostatin receptors and there is a strong rationale for using somatostatin analogs (SSAs) for treatment of NETs.Areas covered: This article discusses i) pharmacology of somatostatin and its analogs; ii) antisecretory and anti-proliferative effects of SSAs in NETs; iii) efficacy and safety of emerging therapeutic regimens with first generation SSAs administered at either high doses or in combination with antineoplastic drugs; iv) efficacy and safety of pasireotide and chimeric molecules; v) efficacy of radionuclide therapy of NETs using SSAs.Expert opinion: SSAs are the first-line medical therapy for functioning and non-functioning well-differentiated NETs. In patients not responder to first generation SSAs, the increase of drug dose over the conventional regimens, the combination of SSAs with other biotherapies or molecular targeted therapies, the switch to pasireotide or the use of SSAs in radionuclide therapy may improve the therapeutic success.

This randomized study investigated the efficacy and safety of LANT-ATG at high doses or high frequency in patients with acromegaly partially controlled by SRLs at conventional regimens.

Glucocorticoid-induced osteoporosis is the most frequent form of secondary osteoporosis caused by chronic exposure to glucocorticoid excess. Pathogenesis of glucocorticoid-induced osteoporosis is multifactorial including direct effects of glucocorticoids on bone cells and indirect effects of glucocorticoids on several neuroendocrine and metabolic pathways. Fragility fractures occur early in glucocorticoid-induced osteoporosis and anti-osteoporotic drugs along with calcium and vitamin D should be started soon after exposure to glucocorticoid excess. This paper summarizes some of the main topics discussed during the 9th Glucocorticoid-Induced Osteoporosis Meeting (Rome, April 2016) with a specific focus on the role of growth hormone/insulin-like growth factor-1 and parathyroid hormone/vitamin D axes in the pathogenesis of glucocorticoid-induced osteoporosis and the controversial aspects concerning therapeutic approach to skeletal fragility in this clinical setting.

Bone mineral density (BMD) lacks sensitivity in individual fracture risk assessment in early breast cancer (EBC) patients treated with aromatase inhibitors (AIs). New dual-energy X-ray absorptiometry (DXA) based risk factors are needed.

Vertebral fractures are an emerging complication of acromegaly but their prediction is still difficult occurring even in patients with normal bone mineral density. In this study we evaluated the ability of high-resolution cone-beam computed tomography to provide information on skeletal abnormalities associated with vertebral fractures in acromegaly. 40 patients (24 females, 16 males; median age 57 years, range 25–72) and 21 healthy volunteers (10 females, 11 males; median age 60 years, range: 25–68) were evaluated for trabecular (bone volume/trabecular volume ratio, mean trabecular separation, and mean trabecular thickness) and cortical (thickness and porosity) parameters at distal radius using a high-resolution cone-beam computed tomography system. All acromegaly patients were evaluated for morphometric vertebral fractures and for mineral bone density by dual-energy X-ray absorptiometry at lumbar spine, total hip, femoral neck, and distal radius. Acromegaly patients with vertebral fractures (15 cases) had significantly (p< 0.05) lower bone volume/trabecular volume ratio, greater mean trabecular separation, and higher cortical porosity vs. nonfractured patients, without statistically significant differences in mean trabecular thickness and cortical thickness. Fractured and nonfractured acromegaly patients did not have significant differences in bone density at either skeletal site. Patients with acromegaly showed lower bone volume/trabecular volume ratio (p= 0.003) and mean trabecular thickness (p< 0.001) and greater mean trabecular separation (p= 0.02) as compared to control subjects, without significant differences in cortical thickness and porosity. This study shows for the first time that abnormalities of bone microstructure are associated with radiological vertebral fractures in acromegaly. High-resolution cone-beam computed tomography at the distal radius may be useful to evaluate and predict the effects of acromegaly on bone microstructure.

ABSTRACTIntroduction: Acromegaly is a relatively rare condition of growth hormone (GH) excess associated with significant morbidity and, when left untreated, high mortality. Therapy for acromegaly is targeted at decreasing GH and insulin-like growth hormone 1 levels, ameliorating patients' symptoms and decreasing any local compressive effects of the pituitary adenoma. The therapeutic options for acromegaly include surgery, medical therapies (such as dopamine agonists, somatostatin receptor ligands and the GH receptor antagonist pegvisomant) and radiotherapy. However, despite all these treatments option, approximately 50% of patients are not adequately controlled.Areas covered: In this paper, the authors discuss: 1) efficacy and safety of current medical therapy 2) the efficacy and safety of the new multireceptor-targeted somatostatin ligand pasireotide 3) medical treatments currently under clinical investigation (oral octreotide, ITF2984, ATL1103), and 4) preliminary data on the use of new injectable and transdermal/transmucosal formulations of octreotide.Expert opinion: This expert opinion supports the need for new therapeutic agents and modalities for patients with acromegaly.

Cross-sectional studies showed an elevated prevalence of clinical and morphometric vertebral fractures (VFs) in adult patients with growth hormone deficiency (GHD). However, no data are available on incidence and determinants of radiological VFs in this clinical setting. In this prospective study, we investigated the incidence and risk factors of radiological VFs in adults with GHD. Forty patients with GHD (28 males, 12 females; median age 44 years, range 19–82) were studied for incident VFs using quantitative morphometric approach on spine X-ray at baseline and after 6 years of follow-up. GHD patients were also studied for bone mineral density (BMD) measured by DXA at lumbar spine. After 6 years of follow-up, 12 patients (30 %) experienced incident VFs. Patients with incident VFs had more frequently untreated GHD and prevalent VFs at baseline, as compared to patients who did not experience incident VFs. Untreated GHD patients were significantly older as compared to treated GHD (50 years, range 19–82 vs. 36 years, range 19–75; p= 0.003), but the correlation between high risk of VFs and untreated GHD remained significant even after adjustment for the age of patients (odds ratio 6.8, CI 95 % 1.1–41.8; p= 0.037). In GHD patients experiencing incident VFs, lumbar spine BMD decreased significantly whereas it did not change in patients not developing VFs. This is the first prospective study confirming the hypothesis suggested by cross-sectional studies that untreated GHD may cause high risk of VFs in adult patients and that recombinant human GH treatment may effectively decrease such a risk.

Pituitary hormones have direct and indirect effects on bone remodeling, and skeletal fragility is a frequent complication of pituitary diseases. Fragility fractures may occur in many patients with prolactinomas, acromegaly, Cushing disease, and hypopituitarism. As in other forms of secondary osteoporosis, pituitary diseases generally affect bone quality more than bone quantity, and fractures may occur even in the presence of normal or low-normal bone mineral density, making difficult the prediction of fractures in these settings. Treatment of excess and defective pituitary hormone generally improves skeletal health, although some patients remain at high risk for fractures, necessitating treatment with bone-active drugs.

Introduction:Octreotide long-acting release (LAR) and lanreotide Autogel (ATG) are the two somatostatin analogs currently approved for treatment of acromegaly and neuroendocrine tumors (NETs). The strength of these drugs has been their specificity for somatostatin receptor subtype 2. However, this peculiarity may become a weakness in some patients with tumors harboring somatostatin receptors different from the subtype 2. Another clinically relevant aspect related to the use of octreotide LAR and lanreotide ATG is the burden of injectable drug regimen that may adversely impact the quality of life of patients with acromegaly and NETs.Areas covered:The authors review the recently published evidence on novel drugs targeting somatostatin receptors developed for treating acromegaly and NETs. Within this article, the authors discuss: i) the pharmacology of somatostatin and traditional somatostatin analogs; ii) the efficacy and safety of multireceptor-targeted somatostatin analogs in acromegaly and NETs; iii) the efficacy of chimeric molecules in acromegaly and NETs; iv) the preliminary data on the use of new injectable, oral and transdermal formulations of octreotide in acromegaly.Expert opinion:The development of new somatostatin analogs and new formulations has opened a new scenario for treatment of acromegaly and NETs. That being said, even though there have been big steps taken in the development of new therapies for acromegaly, there are still a number of unresolved issues, while more trials are necessary for the use of somatostatin anaologs in the treatment of NETs.

Introduction:Acromegaly is a rare disorder characterized by excess secretion of growth hormone (GH) generally caused by a pituitary macroadenoma and associated with reduced life expectancy if the disease is untreated. This article covers the recent available evidences published on octreotide, the first somatostatin analog introduced into clinical practice for the medical treatment of acromegaly.Areas covered:This article discusses i) pharmacology of somatostatin and octreotide; ii) biochemical effects of regular octreotide and long-acting repeatable formulation; iii) tumor shrinkage effects of octreotide in acromegaly; iv) impact of octreotide on acromegalic clinical manifestations and chronic complications; v) safety of octreotide and vi) place of octreotide in the guidelines for acromegaly treatment. Full-text articles in the English language were selected from a PubMed search spanning 1984 – 2013, for keywords including ‘octreotide,' ‘acromegaly,' ‘GH,' ‘IGF-I,' and ‘tumor shrinkage.' Reference lists in selected papers were also used to broaden the search.Expert opinion:Octreotide is a mature drug with a consolidated favorable benefit versus risks profile in the treatment of acromegaly.

In this Review, Gherardo Mazziotti and Andrea Giustina discuss the latest advances in our understanding of how glucocorticoids affect the secretion of growth hormone. The implications for diagnosis and treatment of growth hormone deficiency in patients with a lack or excess of glucocorticoids will also be outlined.

Abstract: Age-related co-morbidities including osteoporosis are relevant in patients responding to combination antiretroviral therapy (cART). Vertebral fractures are common osteoporotic fractures and their diagnosis is useful for managing at-risk individuals. However, there are few data from HIV-infected patients. Therefore, the aim of this study was to determine the prevalence of and factors associated with vertebral fractures in a population of HIV-infected males. A cross-sectional study of 160 HIV-infected patients with available chest X-rays was conducted from 1998 to 2010. One hundred and sixty-three males with comparable age and with no history of HIV infection were recruited as controls. Semi-quantitative evaluation of vertebral heights in lateral chest X-rays and quantitative morphometry assessment of centrally digitized images using dedicated morphometry software were utilized to detect prevalent vertebral fractures. The result showed that the vertebral fractures were detected in 43/160 (26.9%) HIV-infected patients and in 21/163 (12.9%) controls (P = 0.002). In HIV-infected patients with fractures, 27 had two or more fractures and ten patients had severe fractures. The prevalence of any fractures and multiple fractures in HIV-infected patients receiving cART (29.6 and 20.0%) was slightly higher than in HIV-infected patients not exposed to cART (17.1 and 5.7%), but significantly higher than control subjects (12.9 and 3.7%). At multivariable analyses, body mass index and diabetes mellitus were independently correlated with vertebral fractures in HIV-infected patients. We concluded that a significant proportion of HIV-infected males receiving cART showed vertebral fractures. Furthermore, proactive diagnosis of vertebral fragility fractures is particularly relevant in patients who are overweight or suffer from diabetes.

Abstract: Acromegaly is frequently complicated by fragility vertebral fractures and diabetes mellitus. Since type 2 diabetes mellitus is a cause of secondary osteoporosis in the general population, in this cross-sectional study we aimed at investigating the association between diabetes mellitus and vertebral fractures in males with acromegaly. Fifty-seven patients (median age 47 years, range: 24–85) with active (21 cases) and controlled (36 cases) acromegaly and 57 control subjects were evaluated for bone mineral density (BMD) by DXA and vertebral fractures by a quantitative morphometric analysis. Diabetes mellitus was found in 18 patients and 18 control subjects. The prevalence of vertebral fractures was higher in acromegalic patients as compared with the control subjects (50.9 vs. 10.5%; χ2: 21.8; P < 0.001). Acromegalic patients with fractures had serum IGF-I values significantly higher (P = 0.009), longer duration of active disease (P < 0.001) and higher prevalence of active acromegaly (P = 0.007) and diabetes mellitus (P = 0.04) as compared to patients who did not fracture. When acromegaly was active, the prevalence of vertebral fractures was high independently of the coexistent diabetes mellitus. On the contrary, when acromegaly was controlled the prevalence of vertebral fractures was significantly higher in patients with diabetes as compared to patients without diabetes (62.6 vs. 28.0%; P = 0.04). In both diabetic and non diabetic patients, vertebral fractures occurred independently of BMD. In conclusion, this study suggests that diabetes mellitus may be associated with an increased prevalence of vertebral fractures in males with acromegaly. However, this effect seems to be relatively attenuated in the presence of persistent GH hypersecretion.

Abstract: Data on osteoporotic fractures in hyperprolactinemia are limited. An increased prevalence of radiological vertebral fractures was recently observed in women with prolactin (PRL)-secreting adenoma, whereas it is unknown whether this observation may reflect a more general increased risk of fractures in this disease and whether the prevalence of fractures in males is affected by gonadal status. Thirty-two males (median age 47 years, range: 22–79) with PRL-secreting pituitary adenoma (10 with microadenoma and 22 with macroadenoma) and 64 control males, with normal PRL values and with comparable age to patients with hyperprolactinemia, were evaluated for vertebral fractures by a morphometric approach and for bone mineral density (BMD) by a dual-energy X-ray absorptiometry at lumbar spine. Vertebral fractures were shown in 12 patients with PRL-secreting adenoma (37.5%) and in 5 controls (7.8%, P < 0.001). Fractured patients had lower BMD T-score (P = 0.007) and longer duration of disease (P < 0.001) as compared to patients who did not fracture. Fractures occurred more frequently (P = 0.03) in patients with untreated hyperprolactinemia versus patients treated with cabergoline whose frequency of vertebral fractures was still higher than control subjects. The prevalence of vertebral fractures was not significantly different between eugonadal and hypogonadal patients (33.3% vs. 38.5%; P = 0.8). Moreover, no significant (P = 0.4) difference in serum testosterone values was found between fractured and not fractured males. Hyperprolactinemia is associated with high prevalence of radiological vertebral fractures in men with PRL-secreting adenoma. These findings would also suggest that PRL excess may produce negative skeletal effects independently of hypogonadism.

Glucocorticoid-induced osteoporosis (GIO) is the most common form of secondary osteoporosis. Fractures occur in 30—50% of patients with GIO. Therefore, treatment of this disease is critical. Although patients should receive supplemental calcium and vitamin D, additional measures are necessary to prevent fractures. Estrogens and androgens may be of value in patients with hypogonadism, but bisphosphonates and teriparatide are the most effective agents in the treatment of GIO. Bisphosphonates prevent the early bone loss that follows exposure to glucocorticoids, and which has been attributed to increased resorption. Teriparatide appears to be more effective than alendronate in established GIO when reduced bone formation is the predominant pathophysiological mechanism. In conclusion, GIO can be prevented and treated with appropriate medical intervention.

GH and IGF-I are important regulators of bone homeostasis and are central to the achievement of normal longitudinal bone growth and bone mass. Although GH may act directly on skeletal cells, most of its effects are mediated by IGF-I, which is present in the systemic circulation and is synthesized by peripheral tissues. The availability of IGF-I is regulated by IGF binding proteins. IGF-I enhances the differentiated function of the osteoblast and bone formation. Adult GH deficiency causes low bone turnover osteoporosis with high risk of vertebral and nonvertebral fractures, and the low bone mass can be partially reversed by GH replacement. Acromegaly is characterized by high bone turnover, which can lead to bone loss and vertebral fractures, particularly in patients with coexistent hypogonadism. GH and IGF-I secretion are decreased in aging individuals, and abnormalities in the GH/IGF-I axis play a role in the pathogenesis of the osteoporosis of anorexia nervosa and after glucocorticoid exposure.