Synchronous bilateral adrenalectomy in ACTH-dependent hypercortisolism: predictors, biomarkers and outcomes.

INTRODUCTION: Hypercortisolism requires a prompt therapeutic management to reduce the risk of development of a potential fatal emergency. A synchronous bilateral adrenalectomy (SBA) is effective in recovering hypercortisolism. However, specific indications for an SBA are not available. We aimed to evaluate the outcome of patients who underwent an SBA and to identify biomarkers able to predict the requirements of an SBA. PATIENTS AND METHODS: A mono-centric and longitudinal study was conducted on 19 consecutive patients who underwent SBA for ACTH-dependent hypercortisolism between December 2003 and December 2017. This study population was compared to two control groups composed of patients cured after the resection of the ACTH secreting pituitary adenoma (Group A: 44 patients) and of the ACTH-secreting neuroendocrine tumours (Group B: 8 patients). RESULTS: Short- or long-term SBA complications or the recurrence of hypercortisolism did not occur. A single patient experienced Nelson syndrome. Clinical features after SBA showed improvement in the glico-metabolic assessment, hypertension, bone metabolism and the occurrence of hypokalaemia and infections. The younger the age at the time of Cushing's disease diagnosis, the longer the duration of active hypercortisolism, higher values of plasmatic ACTH and Cortisol (1 month after pituitary neurosurgery) and higher values of Ki67 in pituitary adenomas were detected in this study population as compared to Group A. CONCLUSIONS: SBA is an effective and safe treatment for patients with unmanageable ACTH-dependent hypercortisolism. A multidisciplinary team in a referral centre with a high volume of patients is strongly recommended for the management of these patients and the identification of patients, for better surgical timing.

Pancreatic neuroendocrine tumors in MEN1 disease: a mono-centric longitudinal and prognostic study.

PURPOSE: Multiple endocrine neoplasia type 1 (MEN1) is an inherited endocrine neoplastic syndrome associated with a greater risk of endocrine tumor development like pancreatic neuroendocrine tumors (p-NET), with different clinical characteristics from sporadic ones. This paper aims to compare clinical, hystological and morphological aspects of p-NET in patients affected from MEN1 (MEN1+) and not-affected ones (MEN1-). METHODS: We performed a retrospective observational study. Data was collected between December 2010 and December 2015, including patients with a histological diagnosis of p-NET and radiological imaging. We compared clinical, histological, radiological, and prognostic aspects of MEN+ p-NET with MEN-1 p-NET. RESULTS: Of the 45 patients enrolled, 13 MEN1+ and 21 MEN1- cases were analyzed. Frequency of not secreting p-NETs and insulin secreting p-NETs, histopathological grades and Ki67 expression were superimposable between MEN1+ and MEN1- patients. MEN1+ pNETs are more often multicentric compared to MEN1- pNETs. Frequency of liver and nodes metastatic spread was higher in MEN1- p-NET compared to MEN1+ p-NET. Analyzing p-NET according to the disease outcome, we found that recovered and stable p-NETs in MEN1+ patients, compared to MEN1- cases, are diagnosed at lower age (p = 0.04/p = 0.002) and that are more frequently multifocal lesions (p = 0.009/p = 0.002). CONCLUSIONS: In our study pNETs in MEN1+ and pNETs in MEN1- don't significantly differ for prognosis but only for clinical features. p-NET stage disease and prognosis can be positively influenced by early diagnosis and screening in index patients' first-degree relatives.

Prevalence of morphometric vertebral fractures in "difficult" patients with acromegaly with different biochemical outcomes after multimodal treatment.

INTRODUCTION: Skeletal fragility with high risk of vertebral fractures is an emerging complication of acromegaly in close relationship with duration of active disease. The aim of this cross-sectional study was to evaluate the prevalence and determinants of vertebral fractures in males and females with a history of long-standing active acromegaly undergoing treatment with Pegvisomant. SUBJECTS AND METHODS: Thirty-eight patients (25 females, 13 males) with acromegaly under Pegvisomant therapy were evaluated for vertebral fractures and bone mineral density at lumbar spine and femoral neck. Gonadal status, serum IGF1 levels and growth hormone receptor genotype were also assessed. RESULTS: Vertebral fractures were detected in 12 patients (31.6%). Fractured patients had longer duration of active disease (p = 0.01) with higher frequency of active acromegaly (p = 0.04), received higher dose of Pegvisomant (p = 0.008), and were more frequently hypogonadic (p = 0.02) as compared to patients who did not fracture. Stratifying the patients for gender, vertebral fractures were significantly associated with Pegvisomant dose (p = 0.02) and untreated hypogonadism (p = 0.02) in males and with activity of disease (p = 0.03), serum insulin-like growth factor-I values (p = 0.01) and d3GHR polymorphism (p = 0.005) in females. No significant association was found between vertebral fractures and bone mineral density at either skeletal site. CONCLUSION: Vertebral fractures are a frequent complication of long-standing active acromegaly. When patients are treated with Pegvisomant, vertebral fractures may occur in close relationship with active acromegaly and coexistent untreated hypogonadism.

Correction to: Pegvisomant in acromegaly: an update.

Unfortunately, in page 584, second column, the first sentence under the heading "Type of switch" has been published incorrectly. The complete correct sentence is given below.

How to improve effectiveness of pegvisomant treatment in acromegalic patients.

PURPOSE: Pegvisomant (PEGV) treatment in acromegaly patients resistant to somatostatin analogues is less effective in the real life than in clinical trials. This is a multicenter, observational, retrospective, longitudinal study. The aim was to detect characteristics which improve long-term PEGV effectiveness. METHODS: 87 acromegalic patients treated with PEGV have been enrolled in seven referral Italian centres. PEGV was administered for up to 4 years, at doses up titrated until IGF-1 normalization or to ≥ 30 mg/day. The rate of patients who reached IGF-1 normalization at last visit has been calculated. RESULTS: IGF-1 was normalized in 75.9% of patients after 1 year and in 89.6% at last visit. Disease control was associated with lower baseline GH, IGF-1 and IGF-1 xULN and was more frequent when baseline IGF-1 was < 2.7 × ULN (p < 0.02). PEGV dose was dependent on baseline IGF-1 > 2.7 × ULN (p < 0.05) and doses > 1.0 mg/BMI/day were administered more frequently when baseline IGF-1 was > 2.0 × ULN (p = 0.03). PEGV resistance was associated with higher BMI (p = 0.006) and was more frequent when BMI was > 30 kg/m2 (p = 0.07). There were no significant differences between patients treated with monotherapy or combined treatment. IGF-1 normalization, PEGV dose and rate of associated treatment were similar between males and females. PEGV effectiveness was independent from previous management. Diabetic patients needed higher doses of PEGV than non-diabetic ones. CONCLUSIONS: PEGV effectiveness improves when up titration is appropriate. Higher PEGV doses at start and a more rapid up-titration are necessary in patients with obesity and/or IGF-1 > 2.7 × ULN.

DIAGNOSIS OF ENDOCRINE DISEASE: Primary empty sella: a comprehensive review.

Primary empty sella (PES) is characterized by the herniation of the subarachnoid space within the sella, which is often associated with variable degrees of flattening of the pituitary gland in patients without previous pituitary pathologies. PES pathogenetic mechanisms are not well known but seem to be due to a sellar diaphragm incompetence, associated to the occurrence of upper sellar or pituitary factors, as intracranial hypertension and change of pituitary volume. As PES represents in a majority of cases, a neuroradiological findings without any clinical implication, the occurrence of endocrine, neurological and opthalmological symptoms, due to the above describes anatomical alteration, which delineates from the so called PES syndrome. Headache, irregular menses, overweight/obesity and visual disturbances compose the typical picture of PES syndrome and can be the manifestation of an intracranial hypertension, often associated with PES. Although hyperprolactinemia and growth hormone deficit represent the most common endocrine abnormalities, PES syndrome is characterized by heterogeneity both in clinical manifestation and hormonal alterations and can sometime reach severe extremes, as occurrence of papilledema, cerebrospinal fluid rhinorrhea and worsening of visual acuity. Consequently, a multidisciplinary approach, with the integration of endocrine, neurologic and ophthalmologic expertise, is strongly advocated and recommended for a properly diagnosis, management, treatment and follow-up of PES syndrome and all of the related abnormalities.

Pegvisomant in acromegaly: an update.

BACKGROUND: In 2007, we published an opinion document to review the role of pegvisomant (PEG) in the treatment of acromegaly. Since then, new evidence emerged on the biochemical and clinical effects of PEG and on its long-term efficacy and safety. AIM: We here reviewed the emerging aspects of the use of PEG in clinical practice in the light of the most recent literature. RESULTS: The clinical use of PEG is still suboptimal, considering that it remains the most powerful tool to control IGF-I in acromegaly allowing to obtain, with a pharmacological treatment, the most important clinical effects in terms of signs and symptoms, quality of life and comorbidities. The number of patients with acromegaly exposed to PEG worldwide has become quite elevated and the prolonged follow-up allows now to deal quite satisfactorily with many clinical issues including major safety issues, such as the concerns about possible tumour (re)growth under PEG. The positive or neutral impact of PEG on glucose metabolism has been highlighted, and the clinical experience, although limited, with sleep apnoea and pregnancy has been reviewed. Finally, the current concept of somatostatin receptor ligands (SRL) resistance has been addressed, in order to better define the acromegaly patients to whom the PEG option may be offered. CONCLUSIONS: PEG increasingly appears to be an effective and safe medical option for many patients not controlled by SRL but its use still needs to be optimized.

Growth hormone receptor isoforms and fracture risk in adult-onset growth hormone-deficient patients.

INTRODUCTION: Growth hormone deficiency is considered the most important factor determining skeletal fragility in hypopituitary patients. Osteoblasts and chondrocytes express growth hormone (GH) receptor. Two GH receptor isoforms (GHRi) have been identified: they differ for the presence/absence of a protein fragment encoded by exon 3 of GHR gene. Consequently, three genotypes were identified: carriers of both the full-length proteins (flfl-GHR), carriers of one full-length protein and one deleted protein (fld3-GHR) and carriers of both deleted proteins (d3d3-GHR). This polymorphism confers a higher sensitivity to endogenous GH and to recombinant human GH (rhGH); its effect on bone metabolism and skeletal fragility is unknown. The aim of this article was to investigate the role of GHRi in predicting skeletal fragility in adult-onset GHD (AO-GHD) patients. SUBJECTS AND METHODS: A cross-sectional study was conducted to investigate the association between the d3-GHR isoform and the prevalence of morphometric vertebral fractures (VFs) in AO-GHD. Ninety-three AO-GHD were enrolled. Forty-nine patients carried flfl-GHRi (52·7%), and 44 patients (47·3%) carried at least one allele of the d3-GHR isoform. Thirty-two VFs were documented. Fifty-seven patients underwent rhGH replacement therapy. RESULTS: Median age was significantly higher in fractured patients as compared to nonfractured ones; d3-carrier patients showed a lower VF risk as compared to flfl-GHRi (OR: 0·37, 95% IC: 0·24-0·55, P < 0·0001). This finding was also confirmed in AO-GHD undergoing rhGH replacement therapy. CONCLUSION: This study suggests that d3-GHR may protect AO-GHD particularly when treated with rhGH from the risk of VFs.

Clinical management of teratoma, a rare hypothalamic-pituitary neoplasia.

Intracranial teratomas are rare and comprise about 0.5 % of all intracranial tumours. Actually, a total of 15 cases of sellar-suprasellar teratoma have been described in the last 24 years. Although rare, hypothalamic-pituitary teratomas should be taken into account in the differential diagnosis of hypothalamic-pituitary region tumours. The current review focuses on the clinical and therapeutic management of pituitary region teratomas. Teratomas occur more frequently in children and young adults than in the older population and in males as compared to females. Symptoms at diagnosis are usually neurological defects, diabetes insipidus and hypopituitarism. Teratoma diagnosis can be suggested though neuroimaging findings. Magnetic resonance imaging remains the preferred modality for assessment of teratoma. Neuro-radiological findings of mixed-density mass, usually with mixed cystic and solid components or inclusions of teeth, fat and calcification can be suggestive. Tumour markers as beta-HCG and alpha-FP can be useful at teratoma diagnosis for distinguishing immature teratomas, mixed GCTs and mature teratomas with immature or malignant components. Optimal treatment for mature teratoma is neurosurgical excision. Radical excision is advocated as recurrence rate for a mature teratoma is extremely low in cases of complete resection and long-term outcome is excellent. During post-treatment follow-up, in cases of healing, according to tumour marker evaluation and contrasted MRI findings, hormone replacement therapy should be considered, also for secondary hypogonadism and GH deficit, with a more intense follow-up. However, as actually few evidence are available, safety data have to be confirmed also trough a surveillance study.

Understanding the effect of acromegaly on the human skeleton.

INTRODUCTION: Acromegaly, caused in most cases by Growth Hormone (GH)-secreting pituitary adenomas, is characterized by increased skeletal growth and enlargement of the soft tissue, because GH and its effector Insulin-like Growth factor-1 are important regulators of bone homeostasis and have a central role in the longitudinal bone growth and maintenance of bone mass. Areas covered: Despite the anabolic effect of these hormones is well known, as a result of the stimulation of bone turnover and especially of bone formation, many acromegalic patients are suffering from a form of secondary osteoporosis with increased risk of fractures. Expert commentary: In this review, we summarize the pathophysiology, diagnosis, clinical picture, disease course and management of skeletal complications of acromegaly, focusing in particular on secondary osteoporosis and fracture risk in acromegaly.

Does pegvisomant treatment expertise improve control of resistant acromegaly? The Italian ACROSTUDY experience.

OBJECTIVE: GH receptor antagonist pegvisomant is indicated for treatment of patients with resistant acromegaly. We compared safety and treatment outcomes of pegvisomant therapy in patients managed by Italian centers enrolling less or more than 15 cases in ACROSTUDY, a safety surveillance study of long-term pegvisomant treatment of patients with acromegaly. A noninterventional safety surveillance study in which safety and treatment outcomes of pegvisomant were evaluated on the basis of data collected during a 7-year period. METHODS: A total of 204 acromegaly patients treated by seven centers enrolling 16-49 patients each (group A) and 137 subjects by 18 centers following 3-14 cases ( group B). RESULTS: Patients of group A and B were treated for 4.4 ± 2.7 and 4.2 ± 2.2 years, respectively. IGF-1 ULN normalized in 64.4 % (n = 56) and 54.4 % (n = 31) in group A and B, respectively, after 1-year treatment, and in 57.3 % (n = 106) and 72.5 % (n = 87) at last visit. Starting doses were significantly higher in group A. They were progressively increased during treatment in both groups, but were higher in uncontrolled patients than in controlled ones only in group A. Reported adverse events were more frequent, and the prevalence of patients with adverse events was higher in group B. CONCLUSIONS: On the basis of this original study approach, we could speculate that in the centers in which more patients are treated with pegvisomant, less adverse events are reported, but the long-term effectiveness is lower than in centers with less cases, perhaps because of an inadequate patient's selection.

Treatment of hyperprolactinemia in post-menopausal women: pros.

The incidence of hyperprolactinemia in women peaks during the 3rd-4th decade and then greatly decreases after the menopause. Apart from the effects on the hypothalamic-pituitary-gonadal axis, prolactin can act directly on bone metabolism. Hyperprolactinemia is a recognized cause of secondary osteoporosis, and treatment with dopamine agonists can lead to improved BMD. Moreover, hyperprolactinemia has been linked to weight gain and insulin resistance, which can be ameliorated following medical treatment. Although relatively rare, prolactinomas can be observed in post-menopausal women and are frequently large and invasive; dopamine agonists appear to be as effective in these patients as in younger women to induce reduction of prolactin levels and tumour shrinkage. Here, we review data potentially favouring medical treatment with dopamine agonists in post-menopausal women diagnosed with hyperprolactinemia.

ACROSTUDY: the Italian experience.

ACROSTUDY is a world-wide non-interventional, post marketing surveillance study performed to monitor the safety and outcomes of pegvisomant (PEG) in clinical practice. We report data from acromegaly patients who have been included in the Italian ACROSTUDY registry. The data of 341 acromegaly patients (171 males) were available for analysis using data freeze (12/9/2012). Patients were enrolled in 25 Italian endocrine centres. Before and during PEG treatment IGF-I, liver enzymes, metabolic parameters, and pituitary MRI were assessed. Before PEG, 54.3% patients had been treated with medical therapy and surgery, 22.9% medical therapy only, and 15.8% medical plus radiation and surgical therapy. 199 adverse events were reported in 98 patients (28.7%). Serious adverse events were documented in 29 patients (8.5%). 71.1% of patients had no significant change in tumor volume. Central MRI reading was performed in 34 patients; in 7 patients, an increase in tumor volume was found. Hormonal efficacy progressively increased since the start of PEG. After 6 years, normal IGF-I levels were found in 70.9% of patients (mean daily dose 18.1 mg). 87.1% of patients were treated with daily PEG although in 8.8% of patients, it was administered 2-6 times per week and in 3.8% with weekly injections. 74.8% received a PEG dose 10-15 mg/daily. PEG is a drug with a favorable safety profile which is efficacious also considering that in Italy it is currently available as third-line therapy.

Pituitary-tumour-transforming-gene 1 expression in testicular cancer.

Genomic instability is a feature of germ cell tumours. The pituitary-tumour-transforming-gene 1 (PTTG1) is the major effector of chromosome segregation during mitosis, protecting the cell from aneuploidy. The protein expression of this gene has been evaluated in testicular tumours by immunohistochemistry. Formalin-fixed and paraffin-embedded specimens of testicular tissues from 83 patients undergoing therapeutic orchidectomy for seminomas (n = 53), embryonal carcinoma (n = 10), yolk sac tumour (n = 10) and teratoma (n = 10) were examined. Seminoma was associated with in situ carcinoma (CIS) in 23 samples. PTTG1 immunostaining was performed using rabbit anti-PTTG1 as a primary antibody. In CIS, only isolated cells showed nuclear staining for PTTG1. In the peripheral area of seminoma, PTTG1 was mostly detected as localised in the nucleus; in the central area of seminoma, PTTG1 staining was more intense in cytoplasm. PTTG1-positive cells were also present in the areas of seminoma infiltration. On the other hand, in embryonal carcinoma, cells had a diffuse positive immunostaining, mainly cytoplasmatic, while we did not observe an expression of PTTG1 in yolk sac tumour and mature teratoma. We firstly identified the PTTG1 expression pattern in normal testis, CIS and testicular cancer. Further investigation is needed to clarify the functional activity of PTTG1 in testicular oncogenesis.

Association between l-thyroxine treatment, GH deficiency, and radiological vertebral fractures in patients with adult-onset hypopituitarism.

OBJECTIVE: In this study, we aimed at evaluating the association between radiological vertebral fractures and levo-thyroxine (l-T4) replacement doses in adult patients with hypopituitarism. DESIGN: Cross-sectional study. METHODS: We studied 74 adult hypopituitary patients (males, 43; females, 31; mean age, 57 years; and range, 23-79) with central hypothyroidism treated with l-T4 (median daily dose: 1.1  µg/kg). All patients also had severe GH deficiency (GHD) and 38 of them were replaced with recombinant GH. Vertebral fractures were assessed by a quantitative morphometric analysis performed on thoracic and lumbar spine lateral X-ray. RESULTS: Radiological vertebral fractures were found in 23 patients (31.1%) in association with untreated GHD (P=0.02), higher serum free T4 levels (P=0.03), a higher daily dose of l-T4 (P=0.005), and a longer duration of hypopituitarism (P=0.05). When GHD was treated, the prevalence of vertebral fractures was more frequent (P=0.03) in patients receiving high l-T4 doses (third tertile: >1.35  µg/kg per day) as compared with patients who were treated with lower drug doses (first tertile: <0.93  µg/kg per day). Such a difference was not observed in patients with untreated GHD who showed a higher prevalence of vertebral fractures regardless of l-T4 daily doses. Multivariate analysis showed that untreated GHD (odds ratio: 4.27, 95% CI 1.27-14.33; P=0.01) and the daily dose of l-T4 (odds ratio: 4.01, 95% CI 1.16-14.39; P=0.03) maintained a significant and independent association with vertebral fractures in patients with central hypothyroidism. CONCLUSIONS: Our data suggest for the first time that a relative overtreatment with l-T4 may influence the fracture risk in some patients with hypopituitarism.

Vertebral fractures in patients with acromegaly: a 3-year prospective study.

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, mean age 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 approach on spine x-ray, which was performed 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.

Double pituitary adenomas.

Double pituitary adenomas represent up to 2.6 % of pituitary adenomas in large surgical series and up to 3.3 % of patients with Cushing's disease have been found to have double or multiple pituitary adenomas. We report the case of a 60-year-old male patient whose medical history began in 2002 with erectile dysfunction; hyperprolactinemia was found and MRI showed a 6-mm area of delayed enhancement in the lateral portion of the right pituitary lobe. Treatment with cabergoline was started with normalization of prolactin levels; the following MRI, performed in 2005 and 2008, showed shrinkage of the pituitary lesion. In 2005, the patient began to manifest weight gain, hypertension, and facial plethora, but no further evaluations were done. In January 2010, the patient came to our attention and underwent multiple tests that suggested Cushing's disease. A new MRI was negative. Bilateral inferior petrosal sinus sampling showed significant pituitary-to-peripheral ratio and, in May 2010, the patient underwent exploratory pituitary surgery with evidence of a 1-2-mm white-coloured midline area compatible with pituitary adenoma that was surgically removed. Post-operatively, the patient's clinical conditions improved with onset of secondary hypoadrenalism. The histologic examination confirmed a pituitary adenoma (immunostaining was found to be positive for ACTH and negative for prolactin). We report the case of an ACTH-producing microadenoma metachronous to a prolactin secreting microadenoma although not confirmed histologically, shrunk by medical treatment. A review of data in the literature regarding double or multiple pituitary adenomas has also been done.

Clinical predictors of vertebral osteoporotic fractures in post-menopausal women: a cross-sectional analysis.

BACKGROUND: Osteoporosis is a very common bone disorder and accounts for 1.4 million vertebral compression fractures (VCFs) per year, mostly in post-menopausal women. AIM: The aim of this study was to develop a risk scoring system to identify and gauge the risk of osteoporotic VCFs in post-menopausal women. MATERIALS AND METHODS: We conducted a retrospective cross-sectional study on 477 post-menopausal women consecutively visited at our institution. We studied 15 different clinical variables, i.e. age, body mass index (BMI), weight, L1-L4 lumbar T-Score, L1-L4 lumbar Z-Score, L1-L4 lumbar bone mineral density (BMD), femoral neck T-Score, femoral neck Z-Score, femoral neck BMD, smoking habit, alcohol consumption, 25-OH-vitamin D, total alkaline phosphatase, bone alkaline phosphatase, and L4 vertebral volume. Study population was split in a derivation and a validation cohort. A logistic regression model was used to develop a predictive score of osteoporotic VCFs in the derivation cohort, finally the performance of the score was tested in the validation cohort. RESULTS: Age, L1-L4 lumbar T-Score, femoral neck T-Score, L4 vertebral volume, and smoking habit were found to be predictors of VCFs. To each variable a score from 0 to +12 was assigned to the magnitude of regression coefficient. A score ≥ 22 identified VCFs with a sensitivity of 87%/89% and a specificity of 87%/90% in the derivation and validation cohorts, respectively. CONCLUSIONS: Our findings indicate that a simple score derived from clinical history and routine diagnostic workout can be usefully employed to gauge the risk of fragility VCFs in post-menopausal women.