protocolSection identificationModule nctId: NCT06324084, orgStudyIdInfo id: 05M201, briefTitle: PATHophysiology of OSteoporosis: Role of Hidden Cortisol Excess and Its Predictors in Bone Fragility, acronym: PATHOS, statusModule overallStatus: RECRUITING, startDateStruct date: 2023-04-24, primaryCompletionDateStruct date: 2024-10-24, completionDateStruct date: 2025-04-24, studyFirstPostDateStruct date: 2024-03-21, lastUpdatePostDateStruct date: 2024-03-21, sponsorCollaboratorsModule leadSponsor name: Istituto Auxologico Italiano, class: OTHER, descriptionModule briefSummary: Osteoporosis is a chronic skeletal disease which leads to a decrease in bone strength which increases the risk of fractures.Clinically overt hypercortisolism leads to hypertension, central obesity, diabetes and osteoporosis. More recently, even the condition of mild and asymptomatic hypercortisolism has been associated with increased prevalence of chronic complications of cortisol excess and mortality. In patients with osteoporosis this form of hypercortisolism may remain occult (hidden hypercortisolism, HidHyCo).Although asymptomatic, however, this subtle cortisol excess is associated with an increased risk of osteoporosis and fragility fractures.Moreover, HidHyCo prevalence seems to be increased in osteoporotic patients. The HidHyCo case finding is of utmost importance. However, given the high prevalence of bone fragility and the relatively low diagnostic accuracy of the currently available tests for the HidHyCo detection, a mass screening for HidHyCo is considered unthinkable. As now, no guidelines are available for addressing the HidHyCo screening in osteoporosis.Therefore, the aims of the present study are the following: i) to assess the HidHyCo prevalence in a sample of osteoporotic patients; ii) to compare the clinical characteristics between osteoporotic/osteopenic patients with HidHyCo and those without HidHyCo in order to determine the clinical characteristics more frequently associated with the HidHyCo presence and to identify those osteoporotic patients worthy of HidHyCo screening; iii) to further investigate bone quality and turnover in HidHyCo patients, to characterize HidHyco patients from a molecular and genetic point of view and to evaluate the pathogenetic mechanisms explaining the negative effects of endogenous cortisol excess on bone health in these patients and the potential role of the genetic background and of the gut microbiome.The HidHyCo could be present in a not negligible percentage of osteopenic/osteoporotic patients. In these patients, osteoporosis and, if present, other comorbidities can improve by the surgical resection of the adrenal or pituitary adenoma if feasible, or by the use of drugs able to modulate cortisol secretion or glucocorticoid sensitivity. Moreover, the case-finding could be reserved in those patients at higher risk of having HidHyCo, therefore, reducing the costs of a scarcely specific mass screening., conditionsModule conditions: Osteoporosis, conditions: Bone Fracture, conditions: Cortisol Excess, designModule studyType: OBSERVATIONAL, designInfo observationalModel: CASE_CONTROL, timePerspective: CROSS_SECTIONAL, enrollmentInfo count: 1500, type: ESTIMATED, outcomesModule primaryOutcomes measure: Prevalence of hidden hypercortisolism in osteoporosis, primaryOutcomes measure: Statistical comparison of the clinical and biochemical characteristics of osteoporotic/osteopenic patients with HidHyCo and those without HidHyCo to identify the characteristics predictive of the presence of HidHyCo in osteoporosis, secondaryOutcomes measure: Further investigation of bone turnover in HidHyCo patients, as assessed by serum osteocalcin, CrossLaps, bone alkaline phosphatase and amino-terminal propeptide of type 1 procollagen (P1NP) and additional new potential serum markers of bone status., secondaryOutcomes measure: Further investigation of bone quality as assessed by Radiofrequency Echographic Multi Spectrometry (REMS), secondaryOutcomes measure: Characterization of HidHyco patients from a molecular and genetic point of view by the determination of circulating microRNAs, peripheral glucocorticoid activity and the polymorphic variants of the 11ßHSD1, GR and B2AR gene., secondaryOutcomes measure: Assessment of gut microbiome composition by the analysis of fecal samples, eligibilityModule sex: ALL, minimumAge: 18 Years, maximumAge: 75 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: Azienda Ospedaliera Universitaria Policlinico "G. Rodolico-San Marco", status: NOT_YET_RECRUITING, city: Catania, country: Italy, contacts name: Agostino Gaudio, Professor, role: CONTACT, geoPoint lat: 37.49223, lon: 15.07041, locations facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, status: RECRUITING, city: Milan, country: Italy, contacts name: Cristina Eller-Vainicher, MD, role: CONTACT, contacts name: Giorgia Grassi, MD, role: SUB_INVESTIGATOR, geoPoint lat: 45.46427, lon: 9.18951, locations facility: Istituto Auxologico Italiano IRCCS, status: RECRUITING, city: Milan, country: Italy, contacts name: Elisa Cairoli, MD, role: CONTACT, contacts name: Carmen Aresta, MD, role: SUB_INVESTIGATOR, geoPoint lat: 45.46427, lon: 9.18951, locations facility: Ospedale "Casa Sollievo della Sofferenza" IRCCS, status: RECRUITING, city: San Giovanni Rotondo, country: Italy, contacts name: Alfredo Scillitani, MD, role: CONTACT, contacts name: Flavia Pugliese, MD, role: SUB_INVESTIGATOR, geoPoint lat: 41.70643, lon: 15.7277, locations facility: Azienda Ospedaliera Universitaria Senese, status: NOT_YET_RECRUITING, city: Siena, country: Italy, contacts name: Luigi Gennari, Professor, role: CONTACT, geoPoint lat: 43.31822, lon: 11.33064, hasResults: False