{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T07:01:44Z","timestamp":1762671704050},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2004,10,1]],"date-time":"2004-10-01T00:00:00Z","timestamp":1096588800000},"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":[[2004,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Bisphosphonates induce major increases in strength of callus in distraction osteogenesis in the short term. Poor understanding of the underlying mechanism, however, raises concerns about long-term consequences. In this long-term study in 32 rabbits, zoledronic acid transiently increased trabeculae by delayed temporal progression of endochondral bone remodeling but did not prevent radiographic completion of bone repair.<\/jats:p>\n               <jats:p>Introduction: We hypothesized that bisphosphonate inhibition of osteoclast-mediated resorption would retain bone during repair, producing a larger callus in the short term. However, if remodeling was not restored, completion of the bone repair process in the long term could be jeopardized.<\/jats:p>\n               <jats:p>Materials and Methods: Juvenile rabbits underwent right tibial osteotomy and 2 weeks of distraction, followed by a period of consolidation. Animals received saline (controls) or zoledronic acid (ZA; 0.1 mg\/kg at surgery and again 2 weeks later), and distracted tibias were examined by radiograph, DXA, histology, and histomorphometry at 2, 4, 6, 18, and 44 weeks after surgery.<\/jats:p>\n               <jats:p>Results: Regenerated bone in ZA-treated animals was denser than controls on radiographs at 6 weeks and had more distinct radiodense trabeculae and retention of original cortices at 18 weeks. By 44 weeks, controls and ZA-treated animals were radiographically healed and indistinguishable. Regenerate BMD and BMC increased between 2 and 4 weeks in all animals, with a greater effect in ZA. At 6 weeks, BMD and BMC in ZA-treated animals were 1.6- and 2-fold greater, respectively, than controls (p &amp;lt; 0.01). From 6 to 44 weeks, the control values gradually increased and approached the ZA-treated values. Regenerate bone volume and trabecular number by histomorphometry were from 1.6- to 2-fold greater in ZA-treated animals at 6 and 18 weeks (p &amp;lt; 0.05). Endochondral cartilaginous matrix volume was up to 2.4-fold greater in ZA-treated animals at 2 and 4 weeks (p &amp;lt; 0.05). TRACP+ cells in ZA-treated animals were larger with more nuclei. Mineral apposition rate and osteoblast number and surface were lower in ZA-treated animals at 6 weeks (p &amp;lt; 0.01) but not at later times.<\/jats:p>\n               <jats:p>Conclusions: Disruption of TRACP+ cell function by ZA during bone regeneration seems to lead to an accretion of cancellous bone built on a larger endochondral cartilaginous matrix and increased bone mass, consistent with reported increases in short-term callus strength. This increase in bone mass, caused by a delay in remodeling, provided a transient advantage without preventing radiographic completion of the bone repair process in the long term. Noncontinuous treatment with nitrogen-containing bisphosphonates thus can have short-term beneficial effects without preventing long-term bone repair.<\/jats:p>","DOI":"10.1359\/jbmr.040709","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T06:03:46Z","timestamp":1146117826000},"page":"1698-1705","source":"Crossref","is-referenced-by-count":40,"title":["Transient Retention of Endochondral Cartilaginous Matrix With Bisphosphonate Treatment in a Long-Term Rabbit Model of Distraction Osteogenesis"],"prefix":"10.1093","volume":"19","author":[{"given":"Elisabeth J","family":"Smith","sequence":"first","affiliation":[{"name":"Bone and Mineral Research Program, Garvan Institute of Medical Research, Sydney, Australia"},{"name":"Orthopaedic Research Unit, Children's Hospital at Westmead, Sydney, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"McEvoy","sequence":"additional","affiliation":[{"name":"Orthopaedic Research Unit, Children's Hospital at Westmead, Sydney, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David G","family":"Little","sequence":"additional","affiliation":[{"name":"Orthopaedic Research Unit, Children's Hospital at Westmead, Sydney, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul A","family":"Baldock","sequence":"additional","affiliation":[{"name":"Bone and Mineral Research Program, Garvan Institute of Medical Research, Sydney, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A","family":"Eisman","sequence":"additional","affiliation":[{"name":"Bone and Mineral Research Program, Garvan Institute of Medical Research, Sydney, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edith M","family":"Gardiner","sequence":"additional","affiliation":[{"name":"Bone and Mineral Research Program, Garvan Institute of Medical Research, Sydney, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2009,12,2]]},"reference":[{"key":"2024013019184562200_bib1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S8756-3282(99)00116-7","article-title":"Bisphosphonates: From the laboratory to the clinic and back again","volume":"25","author":"Russel","year":"1999","journal-title":"Bone"},{"key":"2024013019184562200_bib2","doi-asserted-by":"crossref","first-page":"919","DOI":"10.2165\/00003495-199142060-00003","article-title":"Bisphosphonates. 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