{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T21:04:57Z","timestamp":1792184697804,"version":"4.4.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2005,6,1]],"date-time":"2005-06-01T00:00:00Z","timestamp":1117584000000},"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":[[2005,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Bisphosphonates have been widely administered to children with OI based on observational trials. A randomized controlled trial of q3m intravenous pamidronate in children with types III and IV OI yielded positive vertebral changes in DXA and geometry after 1 year of treatment, but no further significant improvement during extended treatment. The treated group did not experience significantly decreased pain or long bone fractures or have increased motor function or muscle strength.<\/jats:p>\n               <jats:p>Introduction: Bisphosphonates, antiresorptive drugs for osteoporosis, are widely administered to children with osteogenesis imperfecta (OI). Uncontrolled pamidronate trials in OI reported increased BMD, vertebral coronal area, and mobility, and decreased pain. We conducted a randomized controlled trial of pamidronate in children with types III and IV OI.<\/jats:p>\n               <jats:p>Materials and Methods: This randomized trial included 18 children (4-13 years of age) with types III and IV OI. The first study year was controlled; 9 children received pamidronate (10 mg\/m2\/day IV for 3 days every 3 months). Four children in each group also received recombinant growth hormone (rGH) injections (0.06 mg\/kg\/day for 6 days\/week). Seven children in the treatment group received pamidronate for an additional 6-21 months. All patients had L1-L4 DXA, spine QCT, spine radiographs, and musculoskeletal and functional testing.<\/jats:p>\n               <jats:p>Results: In the controlled phase, treated patients experienced a significant increase in L1-L4 DXA z score (p &amp;lt; 0.001) and increased L1-L4 midvertebral height (p = 0.014) and total vertebral area (p = 0.003) compared with controls. During extended treatment, DXA z scores and vertebral heights and areas did not increase significantly beyond the 12-month values. Fracture rate decreased significantly in the upper extremities (p = 0.04) but not the lower extremities (p = 0.09) during the first year of treatment. Gross motor function, muscle strength, and pain did not change significantly during the controlled or extended treatment phases.<\/jats:p>\n               <jats:p>Conclusions: A controlled trial confirmed the spine benefits of short-term pamidronate treatment in children with types III and IV OI. Pamidronate increased L1-L4 vertebral DXA and decreased vertebral compressions and upper extremity fractures. Vertebral measures did not improve during the extended treatment phase. The treatment group did not experience decreased lower extremity long bone fractures, significant improvement in growth, ambulation, muscle strength, or pain. There was substantial variability in individual response to treatment.<\/jats:p>","DOI":"10.1359\/jbmr.050109","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T08:40:51Z","timestamp":1146127251000},"page":"977-986","source":"Crossref","is-referenced-by-count":163,"title":["Controlled Trial of Pamidronate in Children With Types III and IV Osteogenesis Imperfecta Confirms Vertebral Gains but Not Short-Term Functional Improvement"],"prefix":"10.1093","volume":"20","author":[{"given":"Anne D","family":"Letocha","sequence":"first","affiliation":[{"name":"Section on Connective Tissue Disorders, BEMB, NICHD, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly L","family":"Cintas","sequence":"additional","affiliation":[{"name":"Rehabilitation Medicine Department, NIH Clinical Center, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James F","family":"Troendle","sequence":"additional","affiliation":[{"name":"Biometry and Mathematical Statistics Branch, NICHD, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Department, NIH Clinical Center, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher E","family":"Cann","sequence":"additional","affiliation":[{"name":"Mindways Software, Inc., San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith J","family":"Chernoff","sequence":"additional","affiliation":[{"name":"Section on Connective Tissue Disorders, BEMB, NICHD, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suvimol C","family":"Hill","sequence":"additional","affiliation":[{"name":"Radiology Department, NIH Clinical Center, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn H","family":"Gerber","sequence":"additional","affiliation":[{"name":"Rehabilitation Medicine Department, NIH Clinical Center, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan C","family":"Marini","sequence":"additional","affiliation":[{"name":"Section on Connective Tissue Disorders, BEMB, NICHD, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,4]]},"reference":[{"key":"2024013019240586500_bib1","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1002\/0471221929.ch8","volume-title":"Connective Tissue and Its Heritable Disorders","author":"Byers","year":"2002","edition":"2nd ed."},{"key":"2024013019240586500_bib2","first-page":"281","volume-title":"Management of Genetic Syndromes","author":"Marini","year":"2001"},{"key":"2024013019240586500_bib3","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1146\/annurev.bi.64.070195.002155","article-title":"Collagens: Molecular biology, diseases, and potentials for therapy","volume":"64","author":"Prockop","year":"1995","journal-title":"Annu Rev Biochem"},{"key":"2024013019240586500_bib4","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1136\/jmg.16.2.101","article-title":"Genetic heterogeneity in osteogenesis imperfecta","volume":"16","author":"Sillence","year":"1979","journal-title":"J Med Genet"},{"key":"2024013019240586500_bib5","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1359\/jbmr.2000.15.9.1650","article-title":"Type V osteogenesis imperfecta: A new form of brittle bone disease","volume":"15","author":"Glorieux","year":"2000","journal-title":"J Bone Miner Res"},{"key":"2024013019240586500_bib6","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1359\/jbmr.2002.17.1.30","article-title":"Osteogenesis imperfecta type VI: A form of brittle bone disease with a mineralization defect","volume":"17","author":"Glorieux","year":"2002","journal-title":"J Bone Miner Res"},{"key":"2024013019240586500_bib7","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/S8756-3282(02)00790-1","article-title":"Osteogenesis imperfecta type VII: An autosomal recessive form of bone disease","volume":"31","author":"Ward","year":"2002","journal-title":"Bone"},{"key":"2024013019240586500_bib8","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/S1471-4892(02)00218-7","article-title":"New uses of bisphosphonates: Osteogenesis imperfecta","volume":"2","author":"Devogelaer","year":"2002","journal-title":"Curr Opin Pharmacol"},{"key":"2024013019240586500_bib9","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1046\/j.1440-1754.2003.00083.x","article-title":"Use of bisphosphonate therapy for osteoporosis in childhood and adolescence (position paper)","volume":"39","author":"Batch","year":"2003","journal-title":"J Paediatr Child Health"},{"key":"2024013019240586500_bib10","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1172\/JCI0217051","article-title":"Modeling the benefits of pamidronate in children with osteogenesis imperfecta","volume":"110","author":"Lindsay","year":"2002","journal-title":"J Clin Invest"},{"key":"2024013019240586500_bib11","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1210\/jc.2003-030106","article-title":"Editorial: Improvement of bone in patients with osteogenesis imperfecta treated with pamidronate\u2014lessons from biochemistry","volume":"88","author":"Langman","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"2024013019240586500_bib12","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1056\/NEJMoa011807","article-title":"Intravenous zoledronic acid in postmenopausal women with low bone mineral density","volume":"346","author":"Reid","year":"2002","journal-title":"N Engl J Med"},{"key":"2024013019240586500_bib13","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1136\/adc.83.2.143","article-title":"Intravenous pamidronate in juvenile osteoporosis","volume":"83","author":"Shaw","year":"2000","journal-title":"Arch Dis Child"},{"key":"2024013019240586500_bib14","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S1297-319X(01)00336-0","article-title":"Bisphosphonates in bone diseases other than osteoporosis","volume":"69","author":"Orcel","year":"2002","journal-title":"Joint Bone Spine"},{"key":"2024013019240586500_bib15","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1097\/00002281-200307000-00014","article-title":"Bisphosphonates: New indications and methods of administration","volume":"15","author":"Reid","year":"2003","journal-title":"Curr Opin Rheumatol"},{"key":"2024013019240586500_bib16","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1067\/mpd.2000.107836","article-title":"Intravenous pamidronate treatment of polyostotic fibrous dysplasia associated with the McCune Albright syndrome","volume":"137","author":"Zacharin","year":"2000","journal-title":"J Pediatr"},{"key":"2024013019240586500_bib17","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/S0022-3476(97)70074-X","article-title":"Intravenous pamidronate treatment in osteogenesis imperfecta","volume":"131","author":"Bembi","year":"1997","journal-title":"J Pediatr"},{"key":"2024013019240586500_bib18","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1515\/JPEM.1999.12.4.555","article-title":"Bisphosphonates in children with osteogenesis imperfecta may improve bone mineralization but not bone strength. Report of two patients","volume":"12","author":"Roldan","year":"1999","journal-title":"J Pediatr Endocrinol Metab"},{"key":"2024013019240586500_bib19","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1111\/j.1651-2227.1998.tb01388.x","article-title":"Beneficial effect of bisphosphonate during five years of treatment of severe osteogenesis imperfecta","volume":"87","author":"Astr\u00f6m","year":"1998","journal-title":"Acta Paediatr"},{"key":"2024013019240586500_bib20","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1056\/NEJM199810013391402","article-title":"Cyclic administration of pamidronate in children with severe osteogenesis imperfecta","volume":"339","author":"Glorieux","year":"1998","journal-title":"N Engl J Med"},{"key":"2024013019240586500_bib21","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1515\/JPEM.2001.14.5.529","article-title":"Efficacy of low dose schedule pamidronate infusion in children with osteogenesis imperfecta","volume":"14","author":"Gonzalez","year":"2001","journal-title":"J Pediatr Endocrinol Metab"},{"key":"2024013019240586500_bib22","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1007\/s004310100844","article-title":"Cyclic pamidronate infusion improves bone mineralisation and reduces fracture incidence in osteogenesis imperfecta","volume":"160","author":"Lee","year":"2001","journal-title":"Eur J Pediatr"},{"key":"2024013019240586500_bib23","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1136\/adc.86.5.356","article-title":"Beneficial effect of long term intravenous bisphosphonate treatment of osteogenesis imperfecta","volume":"86","author":"Astr\u00f6m","year":"2002","journal-title":"Arch Dis Child"},{"key":"2024013019240586500_bib24","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1136\/adc.87.6.562-a","article-title":"Osteogenesis imperfecta and intravenous pamidronate","volume":"87","author":"Banerjee","year":"2002","journal-title":"Arch Dis Child"},{"key":"2024013019240586500_bib25","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1515\/JPEM.2002.15.2.163","article-title":"Pamidronate treatment of osteogenesis imperfecta-lack of correlation between clinical severity, age at onset of treatment, predicted collagen mutation and treatment response","volume":"15","author":"Zacharin","year":"2002","journal-title":"J Pediatr Endocrinol Metab"},{"key":"2024013019240586500_bib26","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1542\/peds.111.3.573","article-title":"Intravenous bisphosphonate therapy in children with osteogenesis imperfecta","volume":"111","author":"Falk","year":"2003","journal-title":"Pediatrics"},{"key":"2024013019240586500_bib27","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.bone.2003.11.019","article-title":"Intravenous pamidronate treatment in children with moderate to severe osteogenesis imperfecta: Assessment of indices of dual-energy X-ray absorptiometry and bone metabolic markers during the first year of therapy","volume":"34","author":"Arikoski","year":"2004","journal-title":"Bone"},{"key":"2024013019240586500_bib28","first-page":"1846","article-title":"Pamidronate treatment of severe osteogenesis imperfecta in children under 3 years of age","volume":"85","author":"Plotkin","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"2024013019240586500_bib29","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1172\/JCI0215952","article-title":"The effects of intravenous pamidronate on the bone tissue of children and adolescents with osteogenesis imperfecta","volume":"110","author":"Rauch","year":"2002","journal-title":"J Clin Invest"},{"key":"2024013019240586500_bib30","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1016\/S0140-6736(04)16101-1","article-title":"Skeletal effects and functional outcome with olpadronate in children with osteogenesis imperfecta: A 2-year randomised placebo-controlled study","volume":"363","author":"Sakkers","year":"2004","journal-title":"Lancet"},{"key":"2024013019240586500_bib31","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/S0022-3476(85)80351-6","article-title":"Serum osteocalcin concentrations in children with metabolic bone disease","volume":"106","author":"Cole","year":"1985","journal-title":"J Pediatr"},{"key":"2024013019240586500_bib32","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/8756-3282(88)90031-2","article-title":"Brisk walking does not stop bone loss in postmenopausal women","volume":"9","author":"Cavanaugh","year":"1988","journal-title":"Bone"},{"key":"2024013019240586500_bib33","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1148\/radiology.166.3.3340782","article-title":"Vertebral bone density in children: Effect of puberty","volume":"166","author":"Gilsanz","year":"1988","journal-title":"Radiology"},{"key":"2024013019240586500_bib34","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1097\/00002060-200301000-00006","article-title":"Brief assessment of motor function: Reliability and concurrent validity of the gross motor scale","volume":"82","author":"Cintas","year":"2003","journal-title":"Am J Phys Med Rehabil"},{"key":"2024013019240586500_bib35","volume-title":"Muscles: Testing and Function","author":"Kendall","year":"1993","edition":"4th ed."},{"key":"2024013019240586500_bib36","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/S1297-319X(02)00434-7","article-title":"Effect of cyclical intravenous pamidronate therapy in children with osteogenesis imperfecta","volume":"69","author":"Giraud","year":"2002","journal-title":"Open-label study in seven patients. Joint Bone Spine"},{"key":"2024013019240586500_bib37","doi-asserted-by":"crossref","DOI":"10.1056\/NEJMp038103","article-title":"Do bisphosphonates make children's bones better or brittle?","author":"Marini","year":"2003","journal-title":"N Engl J Med"},{"key":"2024013019240586500_bib38","first-page":"S2","article-title":"Alendronate treatment of Brtl mouse model for osteogenesis imperfecta increases bone strength by increasing bone volume but fails to improve femoral brittleness or mineralization","volume":"18","author":"Marini","year":"2003","journal-title":"J Bone Miner Res"},{"key":"2024013019240586500_bib39","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1542\/peds.111.5.1030","article-title":"Height and weight development during four years of therapy with cyclical intravenous pamidronate in children and adolescents with osteogenesis imperfecta types I, III, and IV","volume":"111","author":"Zeitlin","year":"2003","journal-title":"Pediatrics"},{"key":"2024013019240586500_bib40","doi-asserted-by":"crossref","first-page":"e601","DOI":"10.1542\/peds.111.5.e601","article-title":"Rapid increase in grip force after start of pamidronate therapy in children and adolescents with severe osteogenesis imperfecta","volume":"111","author":"Montpetit","year":"2003","journal-title":"Pediatrics"},{"key":"2024013019240586500_bib41","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1056\/NEJMoa023110","article-title":"Bisphosphonate-induced osteopetrosis","volume":"349","author":"Whyte","year":"2003","journal-title":"N Engl J Med"},{"key":"2024013019240586500_bib42","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1359\/JBMR.040814","article-title":"Delayed osteotomy but not fracture healing in pediatric osteogenesis imperfecta patients receiving pamidronate","volume":"19","author":"Munns","year":"2004","journal-title":"J Bone Miner Res"},{"key":"2024013019240586500_bib43","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1359\/JBMR.040303","article-title":"Sclerotic metaphyseal lines in a child treated with pamidronate: Histomorphometric analysis","volume":"19","author":"Rauch","year":"2004","journal-title":"J Bone Miner Res"},{"key":"2024013019240586500_bib44","author":"Uveges","year":"2004"}],"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.050109","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/20\/6\/977\/56476333\/5650200612.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/20\/6\/977\/56476333\/5650200612.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T15:08:53Z","timestamp":1710342533000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/20\/6\/977-986\/7592967"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,6,1]]},"references-count":44,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2009,12,4]]},"published-print":{"date-parts":[[2005,6,1]]}},"URL":"https:\/\/doi.org\/10.1359\/jbmr.050109","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2005,6,1]]},"published":{"date-parts":[[2005,6,1]]}}}