Guidelines for the diagnosis, prevention and management of osteoporosis

Osteoporosis poses a significant public health issue. National Societies have developed Guidelines for the diagnosis and treatment of this disorder with an effort of adapting specific tools for risk assessment on the peculiar characteristics of a given population. The Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS) has recently revised the previously published Guidelines on the diagnosis, riskassessment, prevention and management of primary and secondary osteoporosis. The guidelines were first drafted by a working group and then approved by the board of SIOMMMS. Subsequently they received also the endorsement of other major Scientific Societies that deal with bone metabolic disease. These recommendations are based on systematic reviews of the best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on leading experts' experience and opinion, and on good clinical practice. The osteoporosis prevention should be based on the elimination of specific risk factors. The use of drugs registered for the treatment of osteoporosis are recommended when the benefits overcome the risk, and this is the case only when the risk of fracture is rather high as measured with variables susceptible to pharmacological effect. DeFRA (FRAX® derived fracture risk assessment) is recognized as a useful tool for easily estimate the long-term fracture risk. Several secondary forms of osteoporosis require a specific diagnostic and therapeutic management

Simple Detection of Unstained Live Senescent Cells with Imaging Flow Cytometry

Cellular senescence is a hallmark of aging and a promising target for therapeutic approaches. The identification of senescent cells requires multiple biomarkers and complex experimental procedures, resulting in increased variability and reduced sensitivity. Here, we propose a simple and broadly applicable imaging flow cytometry (IFC) method. This method is based on measuring autofluorescence and morphological parameters and on applying recent artificial intelligence (AI) and machine learning (ML) tools. We show that the results of this method are superior to those obtained measuring the classical senescence marker, senescence-associated beta-galactosidase (SA-β-Gal). We provide evidence that this method has the potential for diagnostic or prognostic applications as it was able to detect senescence in cardiac pericytes isolated from the hearts of patients affected by end-stage heart failure. We additionally demonstrate that it can be used to quantify senescence “in vivo” and can be used to evaluate the effects of senolytic compounds. We conclude that this method can be used as a simple and fast senescence assay independently of the origin of the cells and the procedure to induce senescence

Social cognition in people with schizophrenia: A cluster-analytic approach

Background The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses. Method A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer-Salovey-Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters. Results We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI <10), but not in simple sarcasm. Moreover, functioning, neurocognition, disorganization and SC had a linear relationship across the three clusters, while positive symptoms were significantly lower in patients with unimpaired SC as compared with patients with impaired and very impaired SC. On the other hand, negative symptoms were highest in patients with impaired levels of SC. Conclusions If replicated, the identification of such subtypes in clinical practice may help in tailoring rehabilitation efforts to the person's strengths to gain more benefit to the person

Il superamento degli Ospedali Psichiatrici Giudiziari: A new deal per la salute mentale?

Il 31 marzo 2015 \ue8 entrata in vigore la Legge 81/2014 che ha decretato la definitiva e storica chiusura dei sei Ospedali Psichiatrici Giudiziari in Italia. Con tale legge viene tracciato un nuovo assetto assistenziale che prevede la messa in funzione di strutture alternative ai vecchi ospedali, quali le Residenze per Emissione delle Misure di Sicurezza (REMS), ma soprattutto viene promosso un nuovo approccio curativo-riabilitativo nei confronti della persona affetta da disturbo mentale autrice di reato, pericolosa socialmente, approccio finalizzato al recupero sociale con tempi misurati sui bisogni assistenziali personalizzati. Dopo aver descritto sinteticamente quanto accade all\u2019estero, il lavoro evidenzia gli aspetti positivi della legge che, nel suo complesso, \ue8 da considerare innovativa e ineludibile. Vengono passate in rassegna le principali criticit\ue0, quali: la mancata riforma del codice penale; l\u2019equazione ritenuta non corretta tra infermit\ue0 mentale e malattia mentale e pericolosit\ue0 sociale; l\u2019accertamento della pericolosit\ue0 sociale, in base alle sole qualit\ue0 soggettive della persona; la creazione delle REMS, ritenute costose e impostate principalmente su criteri di sicurezza e meno su quelli della cura e della riabilitazione, il ritardo nella loro costruzione e il ricorso a strutture residenziali alternative; i confini incerti della responsabilit\ue0 professionale. Vengono poi proposte diverse azioni che possono sostenere l\u2019applicazione della Legge 81: azioni informative rivolte alla popolazione; azioni formative per gli operatori; potenziamento dell\u2019attenzione sulla popolazione forense; attuazione di protocolli d\u2019intesa e collaborazione con la magistratura. Viene sollecitato un impegno fattivo delle societ\ue0 scientifiche nell\u2019affrontare tale tematica, con particolare riferimento alle societ\ue0 che si occupano di riabilitazione, coinvolte nelle problematiche relative all\u2019identificazione dei percorsi di cura e riabilitazione che seguono al superamento degli OPG

Acute Effects of Glucocorticoid Treatment, TNF\u3b1 or IL-6R Blockade on Bone Turnover Markers and Wnt Inhibitors in Early Rheumatoid Arthritis: A Pilot Study

Tumor Necrosis Factor (TNF)-alpha and Interleukin (IL)-6 play a fundamental role in bone loss in rheumatoid arthritis (RA), partly due to the inhibition of the Wnt canonical pathway. The aim of our study was to investigate the short-term effects of three different treatments on Wnt inhibitors (Dkk-1 and sclerostin) and on bone turnover markers (BTMs): N-propeptide of type I collagen (PINP) and C-terminal telopeptide of type I collagen (beta-CTX-I). We performed a retrospective analysis of prospectively collected data. We enrolled women affected by early RA (&lt; 12 months) with active disease (DAS28 &gt;= 2.6) despite a 6-month treatment with methotrexate (10-15 mg/week), who then started certolizumab pegol, tocilizumab, or methyl-prednisolone (8 mg/daily). Patients were divided into three groups according to the treatment. Blood samples were collected at baseline, week 1, and week 4. We selected 14 patients treated with certolizumab pegol, 14 patients with tocilizumab, and 20 patients with methyl-prednisolone. No difference between any of the tested parameters was found at baseline. beta-CTX-I, Dkk-1, and sclerostin decreased after 1 week of treatment with certolizumab pegol (- 27% +/- 21.5, - 50% +/- 13.2, and - 30% +/- 30.4, respectively, p &lt; 0.05). Methyl-prednisolone induced similar changes, albeit less marked, on beta-CTX-I and Wnt inhibitors, with a decrease in PINP (- 16.1% +/- 16.5, p &lt; 0.05). Tocilizumab did not significantly affect BTMs or Wnt inhibitors. No significant changes were found for PTH and 25OHD. In the first four weeks of treatment, TNF alpha inhibition showed strong effects on BTMs and Wnt inhibitors, differently from IL-6 blockade. Glucocorticoids induced similar changes; nonetheless, they showed undesired effects on bone formation

How the knowledge of fracture risk might influence adherence to oral therapy of osteoporosis in Italy: the ADEOST study

11nononeSummary: The patients’ adherence to osteoporosis treatments is low. In our study population a history of osteoporotic fractures was associated to better compliance and persistence; however, a 12-month randomized study carried out on 816 osteoporotic women showed that providing the patients with their individual fracture risk information did not prove effective. Purpose: Several drugs are currently available for the treatment of osteoporosis, but the patients’ compliance and persistence with these treatments are low. This study aimed to both analyze the adherence to oral osteoporosis medications among Italian osteoporotic patients (cross-sectional study) and evaluate if providing patients with their individual fracture risk information may improve compliance and persistence (prospective study). Methods: A total of 3379 osteoporotic patients referred as outpatients for a visit 1 year after receiving a prescription of oral osteoporosis medications for the first time, were enrolled for the retrospective study. Moreover, 816 postmenopausal women receiving an oral prescription for osteoporosis for the first time, were randomized into two groups: group 1 (managed according to standard clinical practice) and group 2 (managed with greater patient involvement and information on the individual risk of major osteoporotic fractures calculated by DeFRA algorithm). Results: In the retrospective study, a history of osteoporotic fractures, the frequency of drug administration and a condition of being overweight/obese had a significant influence on both compliance and persistence. Of the 816 patients enrolled in the longitudinal study, 731 (374 of group 1 and 357 of group 2) attended the 1 year follow-up visit. The percentage of women with high compliance or persistence was greater in group 2 (64.2 vs. 58.1 % and 66.8 vs. 62.6 %, respectively), but without reaching any statistical significance. Conclusions: Although providing the patients with their individual fracture risk information was not statistically effective, further studies on additional interventions able to improve the patients’ perceived risk of fracture are warranted.mixedGonnelli, Stefano; Caffarelli, Carla; Rossi, Stefania; Di Munno, Ombretta; Malavolta, Nazzarena; Isaia, Giancarlo; Muratore, Maurizio; D’Avola, Giovanni; Gatto, Salvatore; Minisola, Giovanni; Nuti, RanuccioGonnelli, Stefano; Caffarelli, Carla; Rossi, Stefania; Di Munno, Ombretta; Malavolta, Nazzarena; Isaia, Giancarlo; Muratore, Maurizio; D’Avola, Giovanni; Gatto, Salvatore; Minisola, Giovanni; Nuti, Ranucci

Inducers of Senescence, Toxic Compounds, and Senolytics: The Multiple Faces of Nrf2-Activating Phytochemicals in Cancer Adjuvant Therapy

The reactivation of senescence in cancer and the subsequent clearance of senescent cells are suggested as therapeutic intervention in the eradication of cancer. Several natural compounds that activate Nrf2 (nuclear factor erythroid-derived 2-related factor 2) pathway, which is involved in complex cytoprotective responses, have been paradoxically shown to induce cell death or senescence in cancer. Promoting the cytoprotective Nrf2 pathway may be desirable for chemoprevention, but it might be detrimental in later stages and advanced cancers. However, senolytic activity shown by some Nrf2-activating compounds could be used to target senescent cancer cells (particularly in aged immune-depressed organisms) that escape immunosurveillance. We herein describe in vitro and in vivo effects of fifteen Nrf2-interacting natural compounds (tocotrienols, curcumin, epigallocatechin gallate, quercetin, genistein, resveratrol, silybin, phenethyl isothiocyanate, sulforaphane, triptolide, allicin, berberine, piperlongumine, fisetin, and phloretin) on cellular senescence and discuss their use in adjuvant cancer therapy. In light of available literature, it can be concluded that the meaning and the potential of adjuvant therapy with natural compounds in humans remain unclear, also taking into account the existence of few clinical trials mostly characterized by uncertain results. Further studies are needed to investigate the therapeutic potential of those compounds that display senolytic activity