{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:29:25Z","timestamp":1791404965421,"version":"4.3.3"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2001,2,1]],"date-time":"2001-02-01T00:00:00Z","timestamp":980985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>To assess the influence of factors affecting fracture risk and bone density in adult hypopituitary patients with growth hormone deficiency (GHD), data from a large-scale pharmacoepidemiological survey (the Pharmacia &amp; Upjohn International Metabolic Database [KIMS]) were analyzed and compared with data from a control population (the European Vertebral Osteoporosis Study [EVOS]). The KIMS group consisted of 2084 patients (1112 men and 972 women) with various types of pituitary disease and EVOS consisted of 1176 individuals (581 men and 595 women). Fracture and bone mineral density (BMD) data were available from 2024 patients from the KIMS group and 392 patients from EVOS. The prevalence of fractures in patients with hypopituitarism was 2.66 times that in the non-GH-deficient EVOS population. Adult-onset hypopituitarism with GHD was associated with a higher fracture risk than childhood-onset disease, and patients with isolated GHD had a similar prevalence of fractures to those with multiple pituitary hormone deficiencies. Hormonal replacement therapy with L-thyroxine, glucocorticoids, and sex steroids did not affect the risk of fracture in KIMS patients. In addition, fracture rates in KIMS were independent of body mass index (BMI) and the country of origin. However, smoking was associated with a higher fracture rate in this group. In summary, this is the first large-scale analysis to support the hypothesis of an increased fracture risk in adult patients with hypopituitarism and GHD. This increased risk appears to be attributable to GHD alone, rather than to other pituitary hormone deficiencies or to their replacement therapy.<\/jats:p>","DOI":"10.1359\/jbmr.2001.16.2.398","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T04:50:23Z","timestamp":1146113423000},"page":"398-405","source":"Crossref","is-referenced-by-count":213,"title":["The Influence of Growth Hormone Deficiency, Growth Hormone Replacement Therapy, and Other Aspects of Hypopituitarism on Fracture Rate and Bone Mineral Density"],"prefix":"10.1093","volume":"16","author":[{"given":"Christian","family":"W\u00fcster","sequence":"first","affiliation":[{"name":"Department of Internal Medicine 1, Endocrinology and Metabolism, University Medical Clinic, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Abs","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, University Hospital, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bengt-\u00c5ke","family":"Bengtsson","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Sahlgrenska Hospital, G\u00f6teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helge","family":"Bennmarker","sequence":"additional","affiliation":[{"name":"KIMS Outcomes Research Department, Metabolic Diseases, Pharmacia & Upjohn, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulla","family":"Feldt-Rasmussen","sequence":"additional","affiliation":[{"name":"Clinic of Endocrinology, National University Hospital, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Hernberg-St\u00e5hl","sequence":"additional","affiliation":[{"name":"KIMS Outcomes Research Department, Metabolic Diseases, Pharmacia & Upjohn, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Monson","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, St Bartholomew's Hospital, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f8rn","family":"Westberg","sequence":"additional","affiliation":[{"name":"KIMS Outcomes Research Department, Metabolic Diseases, Pharmacia & Upjohn, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Wilton","sequence":"additional","affiliation":[{"name":"KIMS Outcomes Research Department, Metabolic Diseases, Pharmacia & Upjohn, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,2]]},"reference":[{"key":"2024020714112425700_bib1","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1111\/j.1365-2796.1992.tb00613.x","article-title":"The bone mineral density in acquired growth hormone deficiency correlates with circulating levels of insulin-like growth factor I","volume":"232","author":"Johansson","year":"1992","journal-title":"J Intern Med"},{"key":"2024020714112425700_bib2","first-page":"118","article-title":"Bone mineral status in growth hormone-deficient males with isolated and multiple pituitary deficiencies of childhood onset","volume":"74","author":"Kaufman","year":"1992","journal-title":"J Clin Endocrinol Metab"},{"key":"2024020714112425700_bib3","first-page":"326","article-title":"Low bone mineral density in adults with previous hypothalamic-pituitary tumors: Correlations with serum growth hormone responses to GH-releasing hormone, insulin-like growth factor I and IGF binding protein 3","volume":"32","author":"Bing-You","year":"1993","journal-title":"Calcif Tissue Int"},{"key":"2024020714112425700_bib4","first-page":"201","article-title":"Reduced bone mineral content in adult patients with growth hormone deficiency","volume":"129","author":"Ros\u00e9n","year":"1993","journal-title":"Acta Endocrinol (Copenh)"},{"key":"2024020714112425700_bib5","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1002\/jbmr.5650090822","article-title":"Consequences of childhood-onset growth hormone deficiency for adult bone mass","volume":"9","author":"de Boer","year":"1994","journal-title":"J Bone Miner Res"},{"key":"2024020714112425700_bib6","first-page":"669","article-title":"Reduced bone mineral density in patients with adult onset growth hormone deficiency","volume":"78","author":"Holmes","year":"1994","journal-title":"J Clin Endocrinol Metab"},{"key":"2024020714112425700_bib7","first-page":"3","article-title":"Growth hormone, insulin-like growth factors and bone metabolism","volume":"2","author":"W\u00fcster","year":"1995","journal-title":"Endocrinol Metab"},{"key":"2024020714112425700_bib8","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1002\/jbmr.5650081010","article-title":"Long-term fracture prediction by bone mineral assessed at different skeletal sites","volume":"8","author":"Melton","year":"1993","journal-title":"J Bone Miner Res"},{"key":"2024020714112425700_bib9","doi-asserted-by":"crossref","first-page":"6S","DOI":"10.1016\/0002-9343(93)90374-X","article-title":"Bone mass measurement: Prediction of risk","volume":"95","author":"Wasnich","year":"1993","journal-title":"Am J Med"},{"key":"2024020714112425700_bib10","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1007\/BF01797616","article-title":"Erh\u00f6hte pr\u00e4valenz von osteoporose und arteriosklerose bei konventionell substituierter hypophysenvorderlappeninsuffizienz: Bedarf einer zus\u00e4tzlichen wachtumshormonsubstitution?","volume":"69","author":"W\u00fcster","year":"1991","journal-title":"Klin Wochenschr"},{"key":"2024020714112425700_bib11","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1530\/eje.0.1370240","article-title":"Increased fracture frequency in adult patients with hypopituitarism and GH deficiency","volume":"137","author":"Ros\u00e9n","year":"1997","journal-title":"Eur J Endocrinol"},{"key":"2024020714112425700_bib12","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1046\/j.1365-2796.1998.00408.x","article-title":"A UK Consensus Group on management of glucocorticoid-induced osteoporosis: An update","volume":"244","author":"Eastell","year":"1998","journal-title":"J Intern Med"},{"key":"2024020714112425700_bib13","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1056\/NEJM198411153112002","article-title":"Relative contributions of aging and estrogen deficiency to post-menopausal bone loss","volume":"311","author":"Richelson","year":"1984","journal-title":"N Engl J Med"},{"key":"2024020714112425700_bib14","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1097\/00005792-199005000-00002","article-title":"Osteoporosis in men: Diagnosis, pathophysiology, and prevention","volume":"69","author":"Jackson","year":"1990","journal-title":"Medicine"},{"key":"2024020714112425700_bib15","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/S0889-8529(18)30046-X","article-title":"Drug-induced metabolic bone disease","volume":"24","author":"Wolinsky-Friedland","year":"1995","journal-title":"Endocrinol Metab Clin North Am"},{"issue":"Suppl 2","key":"2024020714112425700_bib16","first-page":"14","article-title":"Growth hormone and bone","volume":"128","author":"W\u00fcster","year":"1993","journal-title":"Acta Endocrinol"},{"key":"2024020714112425700_bib17","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/j.1365-2265.1993.tb02387.x","article-title":"Short and long-term effects of growth hormone treatment on bone turnover and bone mineral content in adult growth hormone-deficient males","volume":"39","author":"Vandeweghe","year":"1993","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2024020714112425700_bib18","doi-asserted-by":"crossref","first-page":"883","DOI":"10.7326\/0003-4819-125-11-199612010-00003","article-title":"Effects of physiologic growth hormone therapy on bone density and body composition in patients with adult-onset GH deficiency","volume":"125","author":"Baum","year":"1996","journal-title":"Ann Intern Med"},{"key":"2024020714112425700_bib19","first-page":"2865","article-title":"Two years of growth hormone (GH) treatment increases bone mineral content and density in hypopituitary patients with adult-onset GH deficiency","volume":"81","author":"Johannsson","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"2024020714112425700_bib20","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1210\/jcem.82.6.3982","article-title":"The effect of growth hormone (GH) on histomorphometric indices of bone structure and bone turnover in GH-deficient men","volume":"82","author":"Bravenboer","year":"1997","journal-title":"J Clin Endocrinol Metab"},{"issue":"Suppl A","key":"2024020714112425700_bib21","first-page":"8","article-title":"Long-term effects of growth hormone treatment on bone density","volume":"4","author":"Ter Maaten","year":"1997","journal-title":"Endocrinol Metab"},{"key":"2024020714112425700_bib22","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1046\/j.1365-2265.1998.00439.x","article-title":"Effect of long-term treatment with GH on bone metabolism, bone mineral density and bone elasticity in GH-deficient adults","volume":"48","author":"Kann","year":"1998","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2024020714112425700_bib23","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1046\/j.1365-2265.1998.00465.x","article-title":"Long-term change in the bone mineral density of adults with adult onset growth hormone (GH) deficiency in response to short or long-term GH replacement therapy","volume":"48","author":"Rahim","year":"1998","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2024020714112425700_bib24","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1007\/978-1-4612-0221-9","volume-title":"Osteoporosis","author":"Rosen","year":"1996"},{"issue":"Suppl A","key":"2024020714112425700_bib25","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S1096-6374(98)80016-6","article-title":"Benefits of growth hormone treatment on bone metabolism, bone density and bone strength in growth hormone deficiency and osteoporosis","volume":"8","author":"W\u00fcster","year":"1998","journal-title":"Growth Horm IGF Res"},{"key":"2024020714112425700_bib26","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1210\/jcem.83.2.4594","article-title":"Growth hormone deficiency in adulthood and the effects of growth hormone replacement: A review","volume":"83","author":"Carroll","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"2024020714112425700_bib27","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1046\/j.1365-2265.1999.00695.x","article-title":"GH replacement in 1034 growth hormone deficient adults: Demographic and clinical characteristics, dosing and safety","volume":"50","author":"Abs","year":"1999","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2024020714112425700_bib28","doi-asserted-by":"crossref","first-page":"3929","DOI":"10.1210\/jcem.84.11.6088","article-title":"The effects of treatment and the individual responsiveness to growth hormone (GH) replacement therapy in 665 GH-deficient adults","volume":"84","author":"Bengtsson","year":"1999","journal-title":"J Clin Endocrinol Metab"},{"key":"2024020714112425700_bib29","doi-asserted-by":"crossref","first-page":"4291","DOI":"10.1210\/jcem.84.11.6171-1","article-title":"Growth hormone replacement therapy is not associated with any increase in mortality","volume":"84","author":"Bengtsson","year":"1999","journal-title":"J Clin Endocrinol Metab"},{"issue":"Suppl 2","key":"2024020714112425700_bib30","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/BF03041992","article-title":"Epidemiologie der Osteoporose","volume":"93","author":"Scheidt-Nave","year":"1998","journal-title":"Med Klin"},{"key":"2024020714112425700_bib31","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1359\/jbmr.1998.13.3.415","article-title":"Bone mineral, histomorphometry, and body composition in adults with growth hormone receptor deficiency","volume":"13","author":"Bachrach","year":"1998","journal-title":"J Bone Miner Res"},{"key":"2024020714112425700_bib32","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1016\/S0140-6736(96)07088-2","article-title":"Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures","volume":"348","author":"Black","year":"1996","journal-title":"Lancet"},{"key":"2024020714112425700_bib33","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1111\/j.1532-5415.1989.tb05678.x","article-title":"Impaired vision and hip fracture","volume":"37","author":"Felson","year":"1989","journal-title":"J Am Geriatr Soc"},{"key":"2024020714112425700_bib34","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0140-6736(96)01440-7","article-title":"Fall-related factors and risk of hip fractures: The EPIDOS prospective study","volume":"348","author":"Dargent-Molina","year":"1996","journal-title":"Lancet"},{"key":"2024020714112425700_bib35","doi-asserted-by":"crossref","first-page":"43","DOI":"10.2165\/00002512-199812010-00005","article-title":"Epidemiology of medication-related falls and fractures in the elderly","volume":"12","author":"Cumming","year":"1998","journal-title":"Drugs Aging"},{"key":"2024020714112425700_bib36","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1210\/jcem-70-5-1330","article-title":"Measurement of bone mineral content of the lumbar spine by dual energy x-ray absorptiometry in normal children: correlations with growth parameters","volume":"70","author":"Glastre","year":"1990","journal-title":"J Clin Endocrinol Metab"},{"key":"2024020714112425700_bib37","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/0169-6009(91)90091-D","article-title":"The relationship of bone mineral density and anthropometric variables in healthy male and female children","volume":"14","author":"Miller","year":"1991","journal-title":"Bone Miner"},{"key":"2024020714112425700_bib38","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S8756-3282(98)00071-4","article-title":"Changes in the fracture toughness of bone may not be reflected in its mineral density, porosity, and tensile properties","volume":"23","author":"Wang","year":"1998","journal-title":"Bone"},{"issue":"Suppl 1","key":"2024020714112425700_bib39","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.1007\/BF01673397","article-title":"The epidemiology of fragility fractures: Is there a role for bone quality?","volume":"53","author":"Cooper","year":"1993","journal-title":"Calcif Tissue Int"},{"issue":"Suppl 1","key":"2024020714112425700_bib40","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.1007\/BF01673398","article-title":"Bone quality: A determinant for certain risk factors for bone fragility","volume":"53","author":"Schnitzler","year":"1993","journal-title":"Calcif Tissue Int"},{"key":"2024020714112425700_bib41","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1093\/ajcn\/64.4.603","article-title":"Influence of body composition on bone mineral content in children and adolescents","volume":"64","author":"Manzoni","year":"1996","journal-title":"Am J Clin Nutr"}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1359%2Fjbmr.2001.16.2.398","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/16\/2\/398\/56604874\/5650160223.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/16\/2\/398\/56604874\/5650160223.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T15:02:19Z","timestamp":1710342139000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/16\/2\/398-405\/7515101"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,2,1]]},"references-count":41,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2009,12,2]]},"published-print":{"date-parts":[[2001,2,1]]}},"URL":"https:\/\/doi.org\/10.1359\/jbmr.2001.16.2.398","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2001,2,1]]},"published":{"date-parts":[[2001,2,1]]}}}