title: Growth hormone receptor isoforms and fracture risk in adult-onset growth hormone-deficient patients.
abstract: BACKGROUND
  Growth hormone deficiency is considered the most important factor determining skeletal fragility in hypopituitary patients. Osteoblasts and chondrocytes express growth hormone (GH) receptor. Two GH receptor isoforms (GHRi) have been identified: they differ for the presence/absence of a protein fragment encoded by exon 3 of GHR gene. Consequently, three genotypes were identified: carriers of both the full-length proteins (flfl-GHR), carriers of one full-length protein and one deleted protein (fld3-GHR) and carriers of both deleted proteins (d3d3-GHR). This polymorphism confers a higher sensitivity to endogenous GH and to recombinant human GH (rhGH); its effect on bone metabolism and skeletal fragility is unknown. The aim of this article was to investigate the role of GHRi in predicting skeletal fragility in adult-onset GHD (AO-GHD) patients.
  
  
  METHODS
  A cross-sectional study was conducted to investigate the association between the d3-GHR isoform and the prevalence of morphometric vertebral fractures (VFs) in AO-GHD. Ninety-three AO-GHD were enrolled. Forty-nine patients carried flfl-GHRi (52·7%), and 44 patients (47·3%) carried at least one allele of the d3-GHR isoform. Thirty-two VFs were documented. Fifty-seven patients underwent rhGH replacement therapy.
  
  
  RESULTS
  Median age was significantly higher in fractured patients as compared to nonfractured ones; d3-carrier patients showed a lower VF risk as compared to flfl-GHRi (OR: 0·37, 95% IC: 0·24-0·55, P < 0·0001). This finding was also confirmed in AO-GHD undergoing rhGH replacement therapy.
  
  
  CONCLUSIONS
  This study suggests that d3-GHR may protect AO-GHD particularly when treated with rhGH from the risk of VFs.
authors.affiliation: Pituitary Unit, Section of Endocrinology, Department of Internal Medicine, Catholic University, School of Medicine, 'A. Gemelli' University Hospital, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Mormando
authors.affiliation: Pituitary Unit, Section of Endocrinology, Department of Internal Medicine, Catholic University, School of Medicine, 'A. Gemelli' University Hospital, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Chiloiro
authors.affiliation: Pituitary Unit, Section of Endocrinology, Department of Internal Medicine, Catholic University, School of Medicine, 'A. Gemelli' University Hospital, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bianchi
authors.affiliation: Pituitary Unit, Section of Endocrinology, Department of Internal Medicine, Catholic University, School of Medicine, 'A. Gemelli' University Hospital, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Giampietro
authors.affiliation: Laboratory of Vascular Biology and Genetics, Department of Medicine, Catholic University School of Medicine, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Angelini
authors.affiliation: Pituitary Unit, Section of Endocrinology, Department of Internal Medicine, Catholic University, School of Medicine, 'A. Gemelli' University Hospital, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Tartaglione
authors.affiliation: Division of Spine Surgery, Department of Orthopaedics and Traumatology, Catholic University, School of Medicine, 'A. Gemelli' University Hospital, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Nasto
authors.affiliation: Pituitary Unit, Section of Endocrinology, Department of Internal Medicine, Catholic University, School of Medicine, 'A. Gemelli' University Hospital, Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Milardi
authors.affiliation: Chair of Endocrinology, Spedali Civili, University of Brescia, Brescia, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Formenti
authors.affiliation: Chair of Endocrinology, Spedali Civili, University of Brescia, Brescia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Giustina
authors.affiliation: Pituitary Unit, Section of Endocrinology, Department of Internal Medicine, Catholic University, School of Medicine, 'A. Gemelli' University Hospital, Rome, Italy. laurademarinis@yahoo.it.
authors.forename: L
authors.initials: L
authors.lastname: De Marinis
mesh_terms: D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D005260:Female; D050723:Fractures, Bone / Q000209:etiology / Q000235:genetics*; D017353:Gene Deletion; D005838:Genotype; D020249:Hormone Replacement Therapy / Q000379:methods; D019382:Human Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020033:Protein Isoforms / Q000235:genetics; D011986:Receptors, Somatotropin / Q000235:genetics*; D011994:Recombinant Proteins / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D020033:Protein Isoforms; D011986:Receptors, Somatotropin; D011994:Recombinant Proteins; D019382:Human Growth Hormone