[Adrenal pheochromocytoma associated with "tako-tsubo" syndrome]. / Un caso di feocromocitoma surrenalico manifestatosi con un quadro di cardiomiopatia tipo "tako-tsubo".

"Tako-tsubo" cardiomyopathy is a condition characterized by a transitory left ventricular asinergia, induced by physical and emotional stress. In literature there are few cases of association between cardiomyopathy and pheochromocytoma. We described a case of a 72 year-old woman admitted in Emergency Room for chest pain associated with high blood pressure: the ECG showed non-ST elevation in leads III, AVF and V1. An echocardiogram showed global reduction in contractility (EF 40%) with apical akinesia. The coronary angiography showed coronary without stenosis while left ventriculography showed an average apical akinesia of the anterior wall with enhanced contractility of basal segments. Subsequently, the patient continued to present episodes of tremors associated with high blood pressure and therefore was made the determination of urinary metanephrines and urinary vanilmandelic acid that were both high. A subsequent abdomen MRI showed a 32 mm left adrenal lesion with arterial phase impregnation. The diagnosis of left adrenal pheochromocytoma was made and the tumor, after appropriate preoperative pharmacological preparation with α-blockers, was removed surgically. In conclusion, the unexplained transitory left ventricular asinergia alert the clinician of an underlying disorder, such as pheochromocytoma, the early detection of which is crucial to the prognosis.

Neurofibromatosis type 1 (NF1) and pheochromocytoma: prevalence, clinical and cardiovascular aspects.

The aim of the study was to evaluate the prevalence of pheochromocytoma (PHEO) in patients with neurofibromatosis type 1 (NF1), and to analyze the behavior of some anthropometric and cardiovascular parameters. In 48 consecutive NF1 patients, urinary metanephrines and vanillylmandelic acid excretion were assessed. The body mass index (BMI), waist circumference (WC), ambulatory blood pressure monitoring (ABPM), echocardiography and ultrasound carotid arterial wall evaluation were performed. In NF1 patients, 11 (29.3%) had arterial hypertension, 7 (14.6%) had a PHEO. Four (57%) NF1 patients with PHEO were symptomatic at the diagnosis. In PHEO-NF1 patients, we revealed a lower BMI and WC values with respect to NF1 patients without PHEO and normal subjects (NSs) (p < 0.05), respectively. The nocturnal non-dipping pattern at the ABPM was present in 40.4% of NF1 patients, and in particular this phenomenon was present in PHEO-NF1 patients (71.4%). Left ventricular mass index and intima media thickness were significantly higher in NF1 patients as compared to NS (p < 0.05), particularly in NF1-PHEO patients (p < 0.05). In conclusions, these findings revealed high prevalence of PHEO in NF1 patients and suggest that, in addition to blood pressure, humoral factors (increased sympathetic activity or neurofibromin), influence the pathogenesis of remodeling of cardiovascular system.

Adipokines and cardiometabolic profile in primary hyperaldosteronism.

CONTEXT: Primary aldosteronism (PA) has been recently associated with an unfavorable cardiometabolic profile. However, whether pro- and antiinflammatory adipokines levels can vary in PA is unknown. OBJECTIVE: We evaluated the circulating levels of resistin, leptin, and adiponectin, echocardiographic left ventricle (LV) parameters, and the prevalence of metabolic syndrome (SM) in subjects with PA. PATIENTS: Seventy-five subjects with established diagnosis of PA and 232 consecutive individuals with known or suspected hypertension were enrolled. MAIN OUTCOME MEASURES: Plasma adipokine levels and echocardiographic parameters were calculated. Prevalence of SM was also estimated. RESULTS: Among the 75 PA subjects, 37 patients were affected by aldosterone-producing adenoma and 38 by idiopathic hyperaldosteronism; 40 subjects were affected by essential hypertension (EH) and SM (EH SM+); 152 subjects were affected by EH without SM (EH SM-); and 40 subjects were normotensive (NT). Subjects with PA had the highest plasma resistin levels among the four groups (P < 0.01). Plasma resistin concentration was significantly higher in PA subjects when compared with EH SM+ individuals (P < 0.01) and EH SM- subjects (P < 0.01). PA subjects showed the higher LV mass and left atrium than EH individuals, irrespectively of the presence of SM (P < 0.01 for both). Plasma resistin levels was significantly correlated with ejection fraction and LV end-diastolic volume. The prevalence of SM was higher in PA subjects than in those with EH (25.4 vs. 20.3%). CONCLUSIONS: Our data suggest that elevated aldosterone levels is associated with elevated circulating resistin levels and cardiac morphological changes independently of the presence of SM.

Gastrointestinal and retroperitoneal manifestations of type 1 neurofibromatosis.

BACKGROUND: Type 1 neurofibromatosis (NF1) is a genetic disease characterized by neoplastic and not neoplastic disorders, involving tissues of neuroectodermal or mesenchymal origin. The mainly involved districts are skin, central nervous system, and eye, and there is a wide range of severity of clinical presentations. DATA SOURCES: Abdominal manifestations of NF1 comprehend five categories of tumors: neurogenic with neurofibromas, malignant peripheral nerve sheath tumors and ganglioneuromas, neuroendocrine with pheochromocytomas and carcinoids, non-neurogenic gastrointestinal stromal tumors, i.e., GISTs, and embryonal tumors and miscellaneous. CONCLUSIONS: Early diagnosis of these abdominal manifestations is very important given the risk of malignancy, organic complications such as in the case of pheochromocytomas or hemorrhagic-obstructive complications such as in the case of the tumors of the gastrointestinal tract (GISTs and neurofibromas). The importance of an annual clinical evaluation on the part of a multidisciplinary pool of clinicians in highly specialized centers allows early detection of complications and of neoplastic transformation.

Role of growth factors on human parathyroid adenoma cell proliferation.

INTRODUCTION: Primary hyperparathyroidism (pHPT) is caused by a single monoclonal adenoma in more than 80% of patients. Biomolecular mechanisms causing pHPT are still not completely known, even if a great amount of studies have been developed recently, mainly regarding angiogenesis and growth factors. Among the latter, insulin-like growth factor 1 (IGF-1), basic fibroblastic growth factor (bFGF), vascular endothelial growth factor (VEGF), and transforming growth factor beta 1 (TGF-beta1) and their effects have been extensively evaluated in different kinds of endocrine disease. METHODS: Parathyroid cell cultures were prepared from six human adenomatous parathyroid glands that were surgically removed. After 7 days of culture, the cells were refed with DMEM supplemented with 2% FCS alone (control group), or containing hrTGFbeta1, or hrIGF-I, or hrbFGF, or hrVEGF. Then, after 48-hour incubation, cell count was performed by a particle count and size analyzer, and prevalence of cell cycle was analyzed by using a flow cytometer. RESULTS: Cell count (x10000) in the control group was 3.73 +/- 0.32. Low-dose TGF-beta1 stimulation resulted in 5.25 +/- 0.38 cells, and high-dose TGF-beta1 stimulation resulted in 2.35 +/- 0.37 cells. IGF-1 stimulation resulted in 5.4 +/- 0.65 cells, bFGF stimulation in 5.68 +/- 0.86 cells, and VEGF stimulation resulted in 6.03 +/- 1.03 cells. Statistical analysis revealed significant differences in the control group compared with the growth factor-stimulated groups. Cytometry showed different results in the percentage of cells in S-phase, in particular 22.65 +/- 4.98% of IGF-1-stimulated cells were found in S-phase compared with 7.55 +/- 3.2% of control group cells (p < 0.0001). CONCLUSIONS: Growth factors seem to play an important role in parathyroid adenoma cell proliferation; IGF-1, bFGF, VEGF, and low-dose TGF-beta1 promote cell proliferation, whereas high-dose TGF-beta1 inhibits these phenomena.

Late recurrence after surgical resection of a pancreatic tumor in von Hippel-Lindau disease.

CONTEXT: Patients with von Hippel-Lindau syndrome, a dominantly inherited familial cancer syndrome, develop a variety of tumors in different organ systems which make the clinical management of these patients complex. CASE REPORT: The long clinical history of a 45-year-old woman started at 22 years of age when she had surgery for a right adrenal pheochromocytoma. Two years later, a pancreaticoduodenectomy was performed to remove a pancreatic mass which turned out to be a pancreatic neuroendocrine tumor. After a long period of relative wellness, 21 years after the surgical resection of her primary pancreatic neuroendocrine tumor, abdominal lymph node metastases of pancreatic neuroendocrine origin occurred. In fact, three abdominal nodules were removed by laparoscopic surgery, and the histological examination showed well-differentiated neuroendocrine tumors with similar immunohistochemical characteristics and Ki67 below 1%. Considering the patient's clinical history, an inherited cause was postulated and multiple endocrine neoplasia type 1 was first investigated, but the result was negative. Then, a missense mutation in exon 3 of the VHL gene (ACT>ATT; Thr157Ile) was found. CONCLUSION: Although no local and/or distant tumor recurrences are usually reported in radically operated on von Hippel-Lindau pancreatic neuroendocrine tumor patients after a median time of five years of follow-up, the present patient had a recurrence after a very long period of time, suggesting that a pancreatic neuroendocrine tumor associated with von Hippel-Lindau syndrome may behave more aggressively than that has previously been described, thus requiring a life-long follow-up.

Clinical experience with pheochromocytoma in a single centre over 16 years.

BACKGROUND: Pheochromocytoma and paraganglioma are rare tumours of neuroectodermal origin. Pheochromocytoma occurs in 0.1-2% of people with hypertension, while the incidence rises to 4-5% in patients with incidental adrenal mass. AIM: To analyse the presentation, diagnosis and localization, pathology, molecular genetic aspects, surgical management and long-term outcome of a large series of patients with pheochromocytoma referred to a single centre. METHODS: From 1992 to 2008, we observed 91 patients with pheochromocytoma, 70 (77%) with the sporadic form and 21 (23%) with the hereditary form. In the group with the hereditary form, the mean age at diagnosis was significantly lower than the mean age of the group with the sporadic form (38 vs 48 years; p < 0.001). RESULTS: Eighty (88%) patients with pheochromocytoma were symptomatic and the classical triad of palpitations, headache and diaphoresis was present in 30% of patients. In 12% of patients, the pheochromocytoma was discovered during radiological images (adrenal incidentaloma). The unilateral adrenal localization was observed in 78% of patients, bilateral in 15% and extra-adrenal in 7% of patients. All pheochromocytoma patients underwent surgical procedure and the laparotomic approach was used in 49 (53%) patients, while the laparoscopic approach was performed in 42 (47%) patients. Pheochromocytoma was benign in 86 patients (93%) [mean size was 4.3 cm] and the malignant form was found in five patients (7%) [mean size was 10 cm]. CONCLUSIONS: These data from a large cohort of patients are consistent with those reported in the literature and show that pheochromocytoma is an in important challenge for clinicians.

A Case of Acute Aortic Dissection Type B Associated with Cushing's Syndrome.

UNLABELLED: We report a case of a 63-year-old man, with a previous history of hypertension and glucose intolerance associated troncular obesity that was emergently admitted to our Institution for evaluation of a severe, constant posterior chest pain which radiated anteriorly and dyspnoea with a suspected diagnosis of acute aortic dissection. A CT scan of thorax and abdomen demonstrated a dissection starting just below left succlavian artery and extending downward to the left renal artery, involving the celiac tripod and superior mesenteric artery. The dissection was classified as Stanford B, De Bakey III. Moreover, CT scan of abdomen revealed incidentally a left adrenal tumor of 25 mm of diameter. An emergent prosthetic graft was placed just below the origin of the left succlavian artery up-to the diaphragmatic hiatus. Furthermore, a diagnostic evaluation of the mass revealed an increase of cortisol production, and a diagnosis of Cushing's syndrome was done and the patient underwent an adrenalectomy via laparotomic approach. We report an association of acute aortic dissection of acute aortic dissection type B associated to Cushing's syndrome. KEYWORDS: Cushing's syndrome; Adrenocortical adenoma; Aortic dissection type B.

Multiple catecholamine-secreting paragangliomas: diagnosis after hemorrhagic stroke in a young woman.

OBJECTIVE: To describe a case of multiple catecholamine-secreting paragangliomas, with a hemorrhagic stroke as the main clinical manifestation. METHODS: We present a case report with clinical, laboratory, histologic, and genetic details. RESULTS: A 23-year-old woman with a history of hypertension treated with orally administered medications presented to our emergency department because of sudden onset of hemiplegia of the left side of the body. A computed tomographic scan of the brain showed a right frontoparietal hematoma, and her blood pressure was 185/115 mm Hg. She was admitted to the Department of Neurosurgery, and an external drain was inserted to evacuate the hematoma. She was then referred to the Department of Clinical Sciences, where a search for possible secondary causes of hypertension was undertaken. Substantially elevated urinary levels of vanillylmandelic acid and metanephrines were found, and a pheochromocytoma was suspected. Abdominal computed tomographic scans revealed a large retroperitoneal mass (3.6 by 4 cm) and similar smaller lesions in the right adrenal gland, between the aorta and the vena cava, and in the left paraaortic area. Iodine I 123 metaiodobenzylguanidine scintigraphy showed high uptake in those same areas, consistent with the diagnosis of multiple catecholamine-secreting paragangliomas. After adequate control of the patient's hypertension was achieved with an alpha1-adrenergic receptor blocker, a Ca2+ antagonist, and a beta-adrenergic blocking agent, the tumors were excised in the Department of Surgery. The histopathologic findings confirmed the diagnosis of multiple paragangliomas. The genetic analysis demonstrated an exon 4 mutation in codon 109 (CAA>TAA, Gln>Stop) of the SDHD gene. CONCLUSION: Although cerebral hemorrhage is an unusual complication of pheochromocytomas or paragangliomas, early recognition of the characteristic symptoms of headache, palpitations, and diaphoresis in a patient with hypertension and prompt appropriate intervention can minimize the morbidity associated with such tumors and prevent a potentially fatal outcome.

Ambulatory blood pressure monitoring in secondary arterial hypertension due to adrenal diseases.

The aim of this study was to evaluate ambulatory blood pressure monitoring in patients with essential hypertension and hypertension caused by adrenal pathology. Sixty-six patients with primary aldosteronism, 37 with pheochromocytomas, and 45 with adrenal incidentalomas were included. These patients were compared with 152 essential hypertensive patients and 64 normotensive subjects. Ambulatory blood pressure monitoring evaluated daytime and nighttime systolic and diastolic blood pressure and heart rate. The authors found that the "nondipper" phenomenon was present in 51.5% of patients with primary aldosteronism, 43.2% with pheochromocytomas, 42.2% with incidentalomas, 34.2% with hypertension, and 15% of subjects who were normotensive. In 58% of primary aldosteronism patients with idiopathic adrenal hyperplasia, there was an absence of the physiologic blood pressure nocturnal fall (nondipper), which was statistically significant (P<.001) compared with nondipper primary aldosteronism patients with adrenocortical adenoma (38%). In conclusion, the prevalence of the nondipping pattern was higher in patients with adrenal hypertension compared with patients with essential hypertension, suggesting an independent cardiovascular risk factor.

An unusual association of cerebral meningioma, parathyroid adenoma and thyroid papillary carcinoma.

The case of a 50-year-old woman with cerebral meningioma and concomitant parathyroid adenoma and papillary thyroid carcinoma is presented. She complained of neurological symptoms characterized by right hemiparesis and dysarthria. Cerebral CT and MRI scans revealed a left voluminous frontal parasagittal lesion with the characteristics of a meningioma. Routine laboratory analysis revealed altered values of calcium-phosphorus metabolism. Intravenous infusion of saline solution at 0.9% of NaCl resulted in a reduction of serum ionized calcium. A left craniotomy was performed and a fibroblastic meningioma of 5 cm in diameter was removed. Even though the patient's clinical condition was good, a calcium-phosphorus metabolism test confirmed high plasma levels of ionized calcium and parathyroid hormone. Thyroid and parathyroid ultrasonography revealed multinodular goiter and a parathyroid lesion confirmed by 99mTc-TCO4 / 99mTc-MIBI scintigraphy. A left superior parathyroidectomy and total thyroidectomy were performed. Histological examination revealed a parathyroid adenoma and a small papillary carcinoma of 0.4 cm in the right thyroid lobe. As far as we know, this patient is the third case of meningioma associated with parathyroid adenoma and papillary thyroid carcinoma described in the literature.

[High prevalence of thyroid disfunction in primary hyperaldosteronism]. / Alta prevalenza di disfunzioni della tiroide nell'iperaldosteronismo primario.

Primary hyperaldosteronism is associated with other endocrinology pathologies, like pheochromocytoma, Cushing's syndrome, hyperprolactinemia, primary hyperparathyroidism and a type of multiple endocrine neoplasia. Furthermore, association between hyperaldosteronism and thyroid diseases were already pointed out. Aim of the study was to value the prevalence of some thyroid diseases in a series of patients with primary hyperaldosteronism. We studied 105 consecutive patients with primary hyperaldosteronism, 43 (40.95%) with adrenal adenoma, 62 (50.05%) with bilateral adrenal hyperplasia and a control group of 223 patients with essential arterial hypertension. In all patients we tested thyroid function (FT3, FT4, TSH), thyroid antibodies (AbTPO, AbTG) and, sometimes, thyroid morphology by ultrasonography (US scan). The results of the study show that thyroid disfunction occur in 28.6% of patients with primary hyperaldosteronism and in 16.6% of patients with essential hypertension, with a statistically significative difference (chi2 = 0.012). At present, the relationship between primary hyperaldosteronism and thyroid diseases is unclear, but it can be hypothesized that there are common pathogenetic mechanisms, like an imbalance between various growth factors. Further studies are necessary to confirm the results of our study.

High plasma levels of human chromogranin A and adrenomedullin in patients with pheochromocytoma.

AIMS AND BACKGROUND: The aim of our study was to investigate the plasma chromogranin A (CgA) and adrenomedullin (AM) levels in patients with pheochromocytomas. METHODS AND STUDY DESIGN: We collected blood samples for measurement of plasma CgA and AM in 21 patients with pheochromocytomas, 43 healthy subjects and 26 patients with solid non-functioning adrenocortical adenomas. In 11 patients with pheochromocytomas plasma CgA and AM were measured again four weeks after tumor removal. CgA and AM were measured by means of a novel solid-phase two-site immunoradiometric assay based on monoclonal antibodies (CgA-RIA CT, CIS bio international) and by a specific radioimmunoassay (RIA, Phoenix Pharm. Inc.), respectively. RESULTS: The mean plasma CgA level (+/- SD) in patients with pheochromocytomas (204 +/- 147.9 ng/mL) was significantly higher (P < 0.001) than that in healthy subjects (41.6 +/- 10.7 ng/mL) and in patients with non-functioning adrenocortical adenomas (47.3 +/- 17.6 ng/mL). The mean plasma AM concentration (+/- SD) in patients with pheochromocytomas (27.5 +/- 10.4 pg/mL) was significantly higher (P < 0.001) than that in HS (13.8 +/- 4.5 pg/mL) and in patients with non-functioning adrenocortical adenomas (16.6 +/- 7.3 pg/mL). Plasma CgA levels correlated with plasma AM levels (r = 0.501; P < 0.02) and with plasma metanephrine levels (r = 0.738; P < 0.0001) in patients with pheochromocytomas. In 11 patients with pheochromocytomas plasma CgA and AM concentrations significantly decreased after tumor removal (P < 0.001 for both). Circulating CgA and AM had a sensitivity of 76.2% and 81%, a specificity of 97.7% and 90.7%, and an accuracy of 91% and 88%, respectively. CONCLUSION: This study demonstrates that circulating CgA and AM levels are increased in pheochromocytoma patients compared with healthy subjects and patients with non-functioning adrenocortical adenomas. Moreover, at the time of diagnosis plasma CgA levels correlated with plasma AM levels and with plasma metanephrine levels in all patients with pheochromocytomas. In conclusion, plasma CgA and AM concentrations may represent additional biochemical parameters for clinical monitoring of patients with pheochromocytomas.

[Turnover of bone metabolism and prevalence of vertebral fractures in adrenal incidentalomas]. / Valutazione del turnover osseo e delle fratture vertebrali in incidentalomi surrenalici.

Aim of the study was to evaluate, in a homogeneous group of patients with adrenal incidentalomas (AI), calcium-phosphorus metabolism alterations, bone mineral density (BMD) and the prevalence of vertebral fractures. We selected 46 patients with adrenal incidentalomas (26M, 20F; age: M = 61 +/- 14, F = 65 +/- 10 years, BMI: M = 26.2 +/- 4 Kg/m2, F = 28.8 +/- 4 Kg/m2) compared with 84 normal subjects (NS) (44M, 40F; age: M = 60 +/- 10, F = 62 +/- 8 years; BMI: M = 27 +/- 2 Kg/m2, F = 28.1 +/- 4.5 Kg/m2). In all subjects we estimated calcium-phosphorus parameters. Our results showed that in 46 patients with AI there were a significant reduction of BMD-LS (0.915 +/- 0.176 g/cm2; p = 0.01) and of BMD-FN (0.710 +/- 0.129; p = 0.034) respect to those of NS (respectively: 0.994 +/- 0.14 9 g/cm2; 0.758 +/- 0.117 g/cm2). BMD-LS of the 20 women with AI (0.864 +/- 0.157 g/cm2, p = 0.01) was significantly reduced compared with the 40 female normal subjects (0.904 +/- 0.148 g/cm2); BMD-LS of the 26 men with AI (0.967 +/- 0.187 g/cm2; p = 0.048) was significantly reduced compared with the male normal subjects (1.048 +/- 0.133 r/cm2; p = 0.048). The MXA showed vertebral fractures in 15 (75%) of 20 patients with AI (2 patients were osteoporotic, 9 osteopenic and 4 normal at the MXA scans). In 20 women with AI, compared with female NS, we found a significant reduction of serum 25 OH D3 (p = 0.024) levels and a significant increase of plasma i-PTH (P = 0.04) value; and we found a negative correlation between plasma i-PTH and 25 OH D3 values (r = -0.451; p > 0.045). In conclusion, we demonstrated that patients with non-functioning adrenal incidentalomas present calcium-phosphorus metabolism alterations, associated at a reduction of BMD and an increase of vertebral fractures.

[The use of parenteral clodronate in elderly women with postmenopausal osteoporosis: compliance, effects on bone mineral density and on bone turnover]. / L'uso del clodronato per via parenterale in donne anziane affette da osteoporosi postmenopausale: compliance, effetti sulla densità minerale ossea e sul turnover scheletrico.

The aim of the study was to evaluate parenteral clodronate (CLD) compliance in patients with postmenopausal osteoporosis and intolerance to aminobisphosphonates. Moreover, we have also assessed the effects of CLD on bone mineral density (BMD) and bone turnover. Eighty-four consecutive postmenopausal women with osteoporosis (range 62-74 years) were enrolled and randomly allocated to three groups: group A included 26 women who received CLD i.v., 300 mg/2 weeks and oral supplemental calcium carbonate (500 mg x 2/day) and vitamin D3 (400 IU x 2/day); group B included 28 women who received CLD i.m., 100 mg/week, and the same dose of calcium and vitamin D3 administered to group A; group C, the control group, included 30 women receiving only calcium and vitamin D3 at the same doses as the other two groups. The lumbar spine (L1-L4) and femoral neck (FN) BMD were measured by dual energy X-ray absorbiometry at time 0 (T0) and after 6 (T6), 12 (T12), 18 (T18) and 24 (T24) months. At the same time, the serum bone specific alkaline phosphatase and amino-terminal telopeptide of type I collagen normalized by creatinine (NTx/cr) were determined at T0, T6, T12, T18, and T24. Eighty (95.2%) women completed the study, 24 in group A, 27 in group B and 29 in group C. In groups A and B, after 6 months of treatment we found a significantly greater (p < 0.05) increase in the L1-L4 BMD with respect to group C. After 12 months of therapy, in group A the L1-L4 BMD (1.8 +/- 0.5%) was significantly higher (p < 0.05) than that in group B (0.9 +/- 0.3%). At the end of the study, in groups A (1.2 +/- 0.5%) and B (1.1 +/- 0.4%) the percentage increase in the FN BMD was significantly greater (p < 0.05) than in group C (0.6 +/- 0.5%). After 24 months of therapy, there was no difference in the FN BMD between groups A and B. Since the sixth month, both the bone specific alkaline phosphatase and NTx/cr were found to be more markedly and significantly decreased (p < 0.05) in groups A and B with respect to group C. After 18 months, in group A (NTx/cr -16.7 +/- 0.8%) we observed a significantly reduced (p < 0.05) bone resorption with respect to group B (NTx/cr -11.0 +/- 0.5%). In group B, only 3 patients (11.2%) referred pain at the site of drug administration. Our data demonstrate that compliance to parenteral CLD is satisfactory and that this drug reduces bone turnover, increases the L1-L4 BMD and decreases the FN BMD loss. Parenteral CLD administration can represent an effective alternative treatment for postmenopausal women with osteoporosis, especially those who do not tolerate oral aminobisphosphonates.