{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:16:38Z","timestamp":1784556998538,"version":"3.55.0"},"reference-count":35,"publisher":"Bioscientifica","issue":"7","license":[{"start":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T00:00:00Z","timestamp":1680566400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,4,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This Italian survey aims to evaluate real-life long-term efficacy and safety of recombinant human growth hormone (rhGH) therapy in children with short stature homeobox-containing gene deficiency disorders (SHOX-D) and to identify potential predictive factors influencing response to rhGH therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design and methods<\/jats:title>\n                    <jats:p>This is a national retrospective observational study collecting anamnestic, anthropometric, clinical, instrumental and therapeutic data in children and adolescents with a genetic confirmation of SHOX-D treated on rhGH. Data were collected at the beginning of rhGH therapy (T0), yearly during the first 4 years of rhGH therapy (T1, T2, T3 and T4) and at near-final height (nFH) (T5), when available.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      One hundred and seventeen SHOX-D children started rhGH therapy (initial dose 0.23 \u00b1 0.04 mg\/kg\/week) at a mean age of 8.67 \u00b1 3.33 years (74% prepubertal), 99 completed the first year of treatment and 46 reached nFH. During rhGH therapy, growth velocity (GV), standard deviation score (SDS) and height (H) SDS improved significantly. Mean H SDS gain from T0 was +1.14 \u00b1 0.58 at T4 and +0.80 \u00b1 0.98 at T5. Both patients carrying mutations involving intragenic SHOX region (group A) and ones with regulatory region defects (group B) experienced a similar beneficial therapeutic effect. The multiple regression analysis identified the age at the start of rhGH treatment (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u2009\u22120.31,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.030) and the GV during the first year of rhGH treatment (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u20090.45,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.008) as main independent predictor factors of height gain. During rhGH therapy, no adverse event of concern was reported.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data confirm the efficacy and safety of rhGH therapy in SHOX-D children, regardless the wide variety of genotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>Among children with idiopathic short stature, the prevalence of SHOX-D is near to 1\/1000\u20132000 (1.1\u201315%) with a wide phenotypic spectrum. Current guidelines support rhGH therapy in SHOX-D children, but long-term data are still few. Our real-life data confirm the efficacy and safety of rhGH therapy in SHOX-D children, regardless of the wide variety of genotypes. Moreover, rhGH therapy seems to blunt the SHOX-D phenotype. The response to rhGH in the first year of treatment and the age when rhGH was started significantly impact the height gain.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/ec-22-0402","type":"journal-article","created":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T10:45:44Z","timestamp":1680605144000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":4,"title":["Real-life long-term efficacy and safety of recombinant human growth hormone therapy in children with short stature homeobox-containing deficiency"],"prefix":"10.1530","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3850-551X","authenticated-orcid":true,"given":"Patrizia","family":"Bruzzi","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences of Mothers, Children and Adults, University of Modena & Reggio Emilia, Paediatric Unit, Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Vannelli","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinologic Unit, Regina Margherita Children\u2019s Hospital, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Scarano","sequence":"additional","affiliation":[{"name":"Unit of Pediatrics, Department of Medical and Surgical Sciences, Policlinico St. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natascia","family":"Di Iorgi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, IRCCS Istituto Giannina Gaslini, University of Genova, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Parpagnoli","sequence":"additional","affiliation":[{"name":"Anna Meyer Children's University Hospital, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MariaCarolina","family":"Salerno","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University Federico II, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Pitea","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Ospedale San Raffaele, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Elisabeth Street","sequence":"additional","affiliation":[{"name":"Division of Paediatric Endocrinology and Diabetology, Paediatrics, Department of Mother and Child-AUSL of Reggio Emilia-IRCCS, Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Secco","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Azienda ospedaliero Nazionale SS Antonio e Biagio e Cesare Arrigo, Alessandria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adolfo","family":"Andrea Trettene","sequence":"additional","affiliation":[{"name":"Pediatric Unit, ASST Sette Laghi, Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Wasniewska","sequence":"additional","affiliation":[{"name":"Department of Human Pathology in Adulthood and Childhood, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Corciulo","sequence":"additional","affiliation":[{"name":"Pediatric Unit, P.O. 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