{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T21:09:41Z","timestamp":1774645781304,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,6,5]],"date-time":"2014-06-05T00:00:00Z","timestamp":1401926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Growth hormone deficiency (<jats:styled-content style=\"fixed-case\">GHD<\/jats:styled-content>) in adulthood may be associated with a decreased bone mineral density (<jats:styled-content style=\"fixed-case\">BMD<\/jats:styled-content>), a decreased bone mineral content (<jats:styled-content style=\"fixed-case\">BMC<\/jats:styled-content>) and an increased fracture risk. Recombinant human <jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content> (rh<jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content>) replacement induces a progressive increase in <jats:styled-content style=\"fixed-case\">BMD<\/jats:styled-content> for up to 5\u20137\u00a0years of treatment. Data on longer follow\u2010up are, however, scarce.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Two hundred and thirty\u2010adult <jats:styled-content style=\"fixed-case\">GHD<\/jats:styled-content> patients (mean age 47\u00b71\u00a0years, 52\u00b76% female), of whom 88% patients had adult\u2010onset (<jats:styled-content style=\"fixed-case\">AO<\/jats:styled-content>) <jats:styled-content style=\"fixed-case\">GHD<\/jats:styled-content>, receiving rh<jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content> replacement for \u22655\u00a0years were included in the study. Most patients had multiple pituitary hormone deficiencies. Bone turnover markers, <jats:styled-content style=\"fixed-case\">BMC<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">BMD<\/jats:styled-content> and <jats:italic>T<\/jats:italic>\u2010scores at the lumbar spine and femoral neck were evaluated at baseline, and after 5, 10 and 15\u00a0years of rh<jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content> replacement. In addition, clinical fracture incidence was assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mean lumbar spine <jats:styled-content style=\"fixed-case\">BMD<\/jats:styled-content>, lumbar spine <jats:styled-content style=\"fixed-case\">BMC<\/jats:styled-content> and <jats:italic>T<\/jats:italic>\u2010scores gradually increased during the first 10\u00a0years of rh<jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content> replacement and remained stable thereafter. Largest effects of rh<jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content> supplementation were found in men. In the small subset of patients using bisphosphonates, use of bisphosphonates did not impact additional beneficial effects in the long term. Low baseline <jats:styled-content style=\"fixed-case\">BMD<\/jats:styled-content> positively affected the change in <jats:styled-content style=\"fixed-case\">BMD<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">BMC<\/jats:styled-content> over time, but there was a negative effect of high <jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content> dose at 1\u00a0year on the change in <jats:styled-content style=\"fixed-case\">BMD<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">BMC<\/jats:styled-content> over time. Clinical fracture incidence during long\u2010term rh<jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content> replacement was 20.1\/1000\u00a0py.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Fifteen years of rh<jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content> replacement in <jats:styled-content style=\"fixed-case\">GHD<\/jats:styled-content> adults resulted in a sustained increase in <jats:styled-content style=\"fixed-case\">BMD<\/jats:styled-content> values at the lumbar spine, particularly in men, and stabilization of <jats:styled-content style=\"fixed-case\">BMD<\/jats:styled-content> values at the femoral neck. Clinical fracture incidence was suggested not to be increased during long\u2010term rh<jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content> replacement.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.12493","type":"journal-article","created":{"date-parts":[[2014,5,10]],"date-time":"2014-05-10T15:48:47Z","timestamp":1399736927000},"page":"727-735","source":"Crossref","is-referenced-by-count":42,"title":["Effects of up to 15 years of recombinant human <scp>GH<\/scp> (rh<scp>GH<\/scp>) replacement on bone metabolism in adults with Growth Hormone Deficiency (<scp>GHD<\/scp>): The Leiden Cohort Study"],"prefix":"10.1111","volume":"81","author":[{"given":"Natasha M.","family":"Appelman\u2010Dijkstra","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism Center for Endocrine Tumors Leiden and Leiden The Netherlands"},{"name":"Center for Bone Quality Leiden Leiden University Medical Center Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim M. 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