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Eller-Vainicher C.,University of Milan | Filopanti M.,University of Milan | Palmieri S.,University of Milan | Ulivieri F.M.,University of Milan | And 10 more authors.
European Journal of Endocrinology | Year: 2013

Objective: In primary hyperparathyroidism (PHPT), vertebral fractures (VFx) occur regardless of bone mineral density (BMD) and may depend on decreased bone quality. Trabecular bone score (TBS) is a texture measurement acquired during a spinal dual-energy X-ray absorptiometry (DXA). Recently, TBS has been proposed as an index of bone micro-architecture. Design:We studied 92 PHPT patients (74 females, age 62.1±9.7 years) and 98 control subjects. In all patients at baseline, in 20 surgically treated patients and in 10 conservatively treated patients after 24 months, TBS, spinal (lumbar spine (LS)) and femoral (total hip (TH) and femoral neck (FN)) BMD were assessed by DXA and VFx by spinal radiograph. Results: PHPT patients had lower TBS (K2.39±1.8) and higher VFx prevalence (43.5%) than controls (K0.98±1.07 and 8.2% respectively, both P!0.0001). TBS was associated with VFx (odds ratio 1.4, 95% CI 1.1-1.9, PZ0.02), regardless of LS-BMD, age, BMI and gender, and showed a better compromise between sensitivity (75%) and specificity (61.5%) for detecting VFx than LS-BMD, TH-BMD and FN-BMD (31 and 75%, 72 and 44.2%, and 64 and 65% respectively). In surgically treated patients, TBS, LS-BMD, TH-BMD and FN-BMD increased (C47±44.8,C29.2 ±34.1,C49.4G48.7 and C30.2±39.3% respectively, all P!0.0001). Among patients treated conservatively, TBS decreased significantly in those (nZ3) with incident VFx (K1.3±0.3) compared with those without (K0.01±0.9, PZ0.048), while BMD changes were not statistically different (LS 0.3G1.2 vs K0.8G0.9 respectively, PZ0.19; TH 0.4G0.8 vs K0.8±1.4 respectively, PZ0.13 and FN 0.4±0.9 vs K0.8±1.4 respectively, PZ0.14). Conclusions: In PHPT, bone quality, as measured by TBS, is reduced and associated with VFx and improves after surgery. © 2013 European Society of Endocrinology.

Fintini D.,Endocrinology and Diabetology Unit | Chinali M.,Bambino Gesu Childrens Hospital IRCCS | Cafiero G.,Sport Medicine Unit | Esposito C.,Bambino Gesu Childrens Hospital IRCCS | And 5 more authors.
Nutrition, Metabolism and Cardiovascular Diseases | Year: 2014

Background and aims: Although it is generally accepted that non alcoholic fatty liver disease (NAFLD) is linked to increased risk of cardiovascular disease, the presence of abnormalities in cardiac function among NAFLD children is limited and controversial. Aim of the study was to detect cardiac abnormalities/dysfunction in a paediatric population of NAFLD. Methods and results: Anthropometric, laboratory, cardiovascular fitness, 24h blood pressure monitoring and Doppler echocardiography parameters were obtained in 50 untreated children (37 males; mean age 12.2+2.5) with biopsy-proven NAFLD.Abnormalities in both cardiac function and geometry could be identified in the whole study population: prevalence of about 35% in left ventricular hypertrophy, 14% of concentric remodelling and 16% of left atrial dilatation. Furthermore children with NAFLD (NAS score <5) showed lower cardiac alterations compared to NASH patients (NAS score >5). After adjusting for age, sex and BMI, a positive correlation was found only between LV mass and NAS score (p<0.001). Conclusion: Our results suggest that cardiac dysfunction can be detectable early in NAFLD children and this is not linked to cardiovascular and metabolic alteration, other than to liver damage. Although as a preliminary stage, we can speculate a possible direct relationship between liver and heart steatosis, already occurring during childhood. © 2013 Elsevier B.V.

Passeri E.,Endocrinology and Diabetology Unit | Benedini S.,University of Milan | Costa E.,Clinical Laboratory | Corbetta S.,University of Milan
International Journal of Endocrinology | Year: 2015

Background. The RANKL/RANK/OPG signaling pathway is crucial for the regulation of osteoclast activity and bone resorption being activated in osteoporosis. The pathway has been also suggested to influence glucose metabolism as observed in chronic low inflammation. Aim. To test whether systemic blockage of RANKL by the monoclonal antibody denosumab influences glucose metabolism in osteoporotic women. Study Design. This is a prospective study on the effect of a subcutaneously injected single 60 mg dose of denosumab in 14 postmenopausal severe osteoporotic nondiabetic women evaluated at baseline and 4 and 12 weeks after their first injection by an oral glucose tolerance test. Results. A single 60 mg dose of denosumab efficiently inhibited serum alkaline phosphatase while it did not exert any significant variation in fasting glucose, insulin, or HOMA-IR at both 4 and 12 weeks. No changes could be detected in glucose response to the glucose load, Matsuda Index, or insulinogenic index. Nonetheless, 60 mg denosumab induced a significant reduction in the hepatic insulin resistance index at 4 weeks and in HbA1c levels at 12 weeks. Conclusions. A single 60 mg dose of denosumab might positively affect hepatic insulin sensitivity though it does not induce clinical evident glucose metabolic disruption in nondiabetic patients. © 2015 Elena Passeri et al.

Giordano U.,Sport Medicine Unit | Della Corte C.,Liver Research Unit | Cafiero G.,Sport Medicine Unit | Liccardo D.,Liver Research Unit | And 7 more authors.
European Journal of Pediatrics | Year: 2014

The aim of this study was to analyse the relationship between insulin–glucose metabolism, nocturnal blood pressure dipping and nonalcoholic fatty liver disease (NAFLD) in obese adolescents without diabetes. One hundred one consecutive children, with biopsy-proven NAFLD, were included in this study. Blood samples were drawn for the analyses of liver function tests, insulin–glucose metabolism and lipid profile appraisal. An ambulatory blood pressure measurement (ABPM) was performed. Seventy-six children (75.3 %) were systolic nondippers, and 23 of them were diastolic nondippers (30.3 %). No differences were found in the anthropometric parameters between the two groups. When compared to the systolic dippers, the systolic nondippers had higher medians of mean nocturnal blood pressure, glucose at 0, 60 and 120 min in the oral glucose tolerance test (OGTT), OGTT insulin at all time points and insulin-resistance values. No correlation of histopathological features with dipping/nondipping statuses was found. Conclusions: We found an association between a nocturnal blood pressure fall and measures of insulin levels, independent of obesity, or daytime blood pressure levels, among the obese patients with NAFLD. Although no association between nondipping profiles and NAFLD was observed in our study, further studies with a longer term follow-up are needed, to better elucidate the complex link between these particular entities. © 2014, Springer-Verlag Berlin Heidelberg.

Filopanti M.,Endocrine and Diabetology Unit | Corbetta S.,University of Milan | Corbetta S.,Endocrinology and Diabetology Unit | Barbieri A.M.,University of Milan | And 2 more authors.
Clinical Cases in Mineral and Bone Metabolism | Year: 2013

Calcium sensing receptor (CASR) is a G-protein couple receptor which plays a key role in calcium homeostasis in vertebrates. Its extracellular domain is sensitive to divalent cations, aminoacids and polyamines. In parathyroid glands, CASR activation causes parathyroid hormone (PTH) reduction and subsequently a decrease in blood calcium concentration. In PTH-dependent disorders, e.g. primary and secondary hyperparathyroidism (HPT), the need for therapeutic options other than surgery led to the synthesis of various allosteric CASR agonists (calcimimetics), such as cinacalcet. Cinacalcet is the only calcimimetic approved for HPT secondary to chronic kidney disease (CDK), parathyroid carcinoma, and, in some countries, primary HPT. Clinical trials showed that cinacalcet reduced PTH and calcemia both in CDK and primary HPT, lowering the risk of bone fractures, surgery, and cardiovascular complications in the former patients. Long-term safety and pharmacoeconomics have to be fully tested yet. Few both in vitro and in vivo studies showed an association between Arg990Gly-CASR polymorphism and cinacalcet sensitivity, though in patients with severe CASR inactivating mutations the drug substantially retained its positive clinical effects. Recently, a new class of allosteric antagonists of CASR, i.e. calcilytics, has been synthesized. Calcilytics are structurally similar to calcimimetics, but exert their effects acting on a different allosteric site. Infusion of calcilytics was followed by transient rise in PTH and calcium. One of these compounds, ronacaleret, was able to increase femur BMD in post menopausal women, but with induction of mild hyperparathyroidism. In the future, calcilytics may contribute to the osteoporosis treatment choice.

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