{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:28:34Z","timestamp":1787502514632,"version":"build-2736575974"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2009,4,1]],"date-time":"2009-04-01T00:00:00Z","timestamp":1238544000000},"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":[[2009,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Intravenous pamidronate is widely used to treat children with moderate to severe osteogenesis imperfecta (OI). Changes in the appearance of osteoclasts have previously been noted in children receiving pamidronate and have been interpreted as signs of toxicity. In this study, we analyzed osteoclast parameters in paired iliac bone specimens before and after 2\u20134 yr of cyclical intravenous pamidronate therapy in 44 pediatric OI patients (age range: 1.4\u201317.5 yr; 21 girls). During pamidronate treatment, average osteoclast diameter and the mean number of nuclei present per osteoclast increased by 18% (p = 0.02) and 43% (p &amp;lt; 0.001), respectively. The number of samples containing large osteoclasts (LOcs, diameter &amp;gt; 50 \u03bcm) increased from 6 (14%) before treatment to 23 (52%) after pamidronate therapy (p &amp;lt; 0.001 by \u03c72 test). Post-treatment samples containing LOcs had a greater core width (p = 0.04) and a higher cancellous bone volume per tissue volume (p &amp;lt; 0.001), because cancellous bone volume had increased more during pamidronate treatment (p &amp;lt; 0.001). Osteoclast number and surface were higher in samples with LOcs, but there was no difference in cancellous bone formation parameters. The presence of LOcs was independent of OI type, type of collagen type I mutation, lumbar spine BMD, and other clinical or biochemical measures. In conclusion, this study did not show any indication that LOcs during pamidronate treatment are indicative of toxicity. It seems more likely that the observed abnormalities in osteoclast morphology are part of the mechanism of action of this drug.<\/jats:p>","DOI":"10.1359\/jbmr.081225","type":"journal-article","created":{"date-parts":[[2008,12,8]],"date-time":"2008-12-08T16:57:36Z","timestamp":1228755456000},"page":"669-674","source":"Crossref","is-referenced-by-count":33,"title":["Large Osteoclasts in Pediatric Osteogenesis Imperfecta Patients Receiving Intravenous Pamidronate"],"prefix":"10.1093","volume":"24","author":[{"given":"Moira S","family":"Cheung","sequence":"first","affiliation":[{"name":"Genetics Unit, Shriners Hospital for Children and McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis H","family":"Glorieux","sequence":"additional","affiliation":[{"name":"Genetics Unit, Shriners Hospital for Children and McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Rauch","sequence":"additional","affiliation":[{"name":"Genetics Unit, Shriners Hospital for Children and McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,4]]},"reference":[{"key":"2024020320023450100_bib1","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1016\/S0140-6736(04)16051-0","article-title":"Osteogenesis imperfecta","volume":"363","author":"Rauch","year":"2004","journal-title":"Lancet"},{"key":"2024020320023450100_bib2","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":"2024020320023450100_bib3","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":"Astrom","year":"2002","journal-title":"Arch Dis Child"},{"issue":"Suppl 2","key":"2024020320023450100_bib4","doi-asserted-by":"crossref","first-page":"S150","DOI":"10.1542\/peds.2006-2023H","article-title":"Bisphosphonates: Mode of action and pharmacology","volume":"119","author":"Russell","year":"2007","journal-title":"Pediatrics"},{"key":"2024020320023450100_bib5","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/S8756-3282(01)00615-9","article-title":"Inhibition of bone resorption by alendronate and risedronate does not require osteoclast apoptosis","volume":"29","author":"Halasy-Nagy","year":"2001","journal-title":"Bone"},{"key":"2024020320023450100_bib6","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1007\/BF02547219","article-title":"Effect of ethane-1-hydroxy-1,1-diphosphonate (EHDP) and dichloromethylene diphosphonate (Cl 2 MDP) on the calcification and resorption of cartilage and bone in the tibial epiphysis and metaphysis of rats","volume":"11","author":"Schenk","year":"1973","journal-title":"Calcif Tissue Res"},{"key":"2024020320023450100_bib7","doi-asserted-by":"crossref","first-page":"4793","DOI":"10.1210\/endo.141.12.7921","article-title":"In vivo effects of bisphosphonates on the osteoclast mevalonate pathway","volume":"141","author":"Fisher","year":"2000","journal-title":"Endocrinology"},{"key":"2024020320023450100_bib8","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":"2024020320023450100_bib9","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":"2024020320023450100_bib10","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S8756-3282(99)00257-4","article-title":"Normative data for iliac bone histomorphometry in growing children","volume":"26","author":"Glorieux","year":"2000","journal-title":"Bone"},{"key":"2024020320023450100_bib11","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1002\/jbmr.5650020617","article-title":"Bone histomorphometry: Standardization of nomenclature, symbols, and units. 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