{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T12:53:46Z","timestamp":1765976026705},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Acromegaly is associated with an increased prevalence of vertebral fractures (VFs) in close relationship with GH hypersecretion. Two isoforms of the GH receptor (GHR) have been identified; the two isoforms differ or not by the expression of the protein fragment encoded by exon 3 of the <jats:italic>GHR<\/jats:italic> gene. Deletion of the exon 3 may influence the functional properties of the GHR and affect fracture risk in acromegalic patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>A cross-sectional study was designed to investigate the association between the d3-GHR isoform and the prevalence of VFs in patients with acromegaly.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, 109 acromegalic patients were included (M\/F, 48\/61): 73 with controlled\/cured acromegaly and 36 with active disease. <jats:italic>GHR<\/jats:italic> genotype was assessed in each patient. All patients were evaluated for VFs and bone mineral density at lumbar spine and hip. Serum IGF1 levels and bone metabolism markers were measured. A multivariate analysis was performed to establish risk factors for VFs in our population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>d3-GHR<\/jats:italic> carriers showed an increased prevalence of VFs when compared with patients expressing full-length <jats:italic>GHR<\/jats:italic> (35\/55 vs 12\/54; <jats:italic>P<\/jats:italic>&lt;0.001). The association between <jats:italic>GHR<\/jats:italic> deletion and VFs was demonstrated both in patients with active disease and in those with controlled\/cured disease. Out of 35 patients who were prospectively evaluated, 13 (37.1%) developed incident VFs. The incidence of VFs was significantly higher in patients for whom the <jats:italic>GHR<\/jats:italic> gene has been deleted when compared with those harboring the <jats:italic>fl<\/jats:italic> gene (<jats:italic>P<\/jats:italic>=0.04). In multivariate analysis, male sex (odds ratio (OR), 3.250; <jats:italic>P<\/jats:italic>=0.041), IGF1 levels (OR, 1.183; <jats:italic>P<\/jats:italic>=0.031), length of active diseases (OR, 1.038; <jats:italic>P<\/jats:italic>=0.001), and <jats:italic>d3-GHR<\/jats:italic> genotype (OR, 3.060; <jats:italic>P<\/jats:italic>=0.015) were all confirmed as risk factors of VFs in our population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study suggests for the first time that exon 3 deletion of <jats:italic>GHR<\/jats:italic> may predispose patients with active and controlled acromegaly to a higher risk of VFs.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-14-0205","type":"journal-article","created":{"date-parts":[[2014,5,28]],"date-time":"2014-05-28T05:50:46Z","timestamp":1401256246000},"page":"237-245","update-policy":"http:\/\/dx.doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":29,"title":["GH receptor isoforms and skeletal fragility in acromegaly"],"prefix":"10.1093","volume":"171","author":[{"given":"Marilda","family":"Mormando","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi A","family":"Nasto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Bianchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gherardo","family":"Mazziotti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Giampietro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrico","family":"Pola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfredo","family":"Pontecorvi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Giustina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"De Marinis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","reference":[{"issue":"5","key":"1_39932074","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1210\/er.2007-0036","volume":"29","year":"2008","journal-title":"Endocrine Reviews","ISSN":"http:\/\/id.crossref.org\/issn\/0163-769X","issn-type":"print"},{"issue":"20","key":"2_5438837","doi-asserted-by":"publisher","first-page":"8083","DOI":"10.1073\/pnas.86.20.8083","volume":"86","author":"Godowski","year":"1989","journal-title":"PNAS","ISSN":"http:\/\/id.crossref.org\/issn\/0027-8424","issn-type":"print"},{"issue":"2","key":"3_9807090","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1210\/me.6.2.279","volume":"6","author":"Urbanek","year":"1992","journal-title":"Molecular Endocrinology","ISSN":"http:\/\/id.crossref.org\/issn\/0888-8809","issn-type":"print"},{"issue":"1-2","key":"4_10175579","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/0014-5793(93)80028-S","volume":"319","author":"Sobrier","year":"1993","journal-title":"FEBS Letters","ISSN":"http:\/\/id.crossref.org\/issn\/1873-3468","issn-type":"print"},{"issue":"7","key":"5_18243759","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1038\/ng1379","volume":"36","author":"Dos Santos","year":"2004","journal-title":"Nature genetics","ISSN":"http:\/\/id.crossref.org\/issn\/1061-4036","issn-type":"print"},{"issue":"2","key":"6_21102964","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1210\/jc.2005-1581","volume":"91","year":"2006","journal-title":"Journal of Clinical Endocrinology &amp; 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