{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:08:24Z","timestamp":1791277704696,"version":"4.1.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2008,4,1]],"date-time":"2008-04-01T00:00:00Z","timestamp":1207008000000},"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":[[2008,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Current bisphosphonate therapies effectively prevent bone loss in postmenopausal women. We studied the effect of a single intravenous dose of ZOL in ovariectomized rats. Protection from bone loss was dose dependent, lasting for up to 32 weeks, supporting the rationale for an annual intravenous dosing regimen of ZOL for treatment of postmenopausal osteoporosis.<\/jats:p>\n                  <jats:p>Introduction: Once-yearly dosing with zoledronic acid (ZOL) 5 mg can increase BMD and reduce fracture rate in postmenopausal women with low BMD. The primary objective of this study was to determine the duration of bone protective effects of a single dose of ZOL in ovariectomized rats, an animal model of postmenopausal osteopenia. Secondary objectives were to determine the effects on bone turnover and mechanical properties.<\/jats:p>\n                  <jats:p>Materials and Methods: Female Wistar rats (10 per group) received single intravenous doses of ZOL 0.8, 4, 20, 100, or 500 \u03bcg\/kg, alendronate 200 \u03bcg\/kg, or isotonic saline 4 days before bilateral ovariectomy. Sham-operated controls were pretreated with saline. Mass and density of cancellous and cortical bone (pQCT) were measured at 4-wk intervals for 32 wk. Bone architecture (\u03bcCT), bone formation dynamics (fluorochrome label-based histomorphometry), and biomechanical strength in compression testing were also assessed at 32 wk.<\/jats:p>\n                  <jats:p>Results: Ovariectomy-associated BMD loss was significantly attenuated for 32 wk by ZOL \u22654 \u03bcg\/kg for total BMD, ZOL \u226520 \u03bcg\/kg for cortical BMD, and ZOL \u22654 \u03bcg\/kg for cancellous BMD (p &amp;lt; 0.01 versus ovariectomized controls). Alendronate 200 \u03bcg\/kg was of equivalent potency to ZOL 20 \u03bcg\/kg. Ovariectomy-associated decreases in trabecular architectural parameters were dose-dependently attenuated by ZOL. Alendronate 200 \u03bcg\/kg was equivalent to ZOL 20 \u03bcg\/kg. The bone resorption marker TRACP5b indicated transient suppression of elevated osteoclast activity by ZOL relative to OVX-rats even at the lowest dose of 0.8 \u03bcg\/kg, whereas at 100\u2013500 \u03bcg\/kg, the effect was significant relative to the OVX control for the entire duration of the study of 32 wk. Bone formation parameters were not significantly affected by ZOL 20 \u03bcg\/kg but were significantly reduced by ZOL 100\u2013500 \u03bcg\/kg. Alendronate 200 \u03bcg\/kg was equivalent to ZOL 100 \u03bcg\/kg. ZOL produced dose-related improvements in bone strength parameters after ovariectomy. Alendronate 200 \u03bcg\/kg was of similar potency to ZOL 20 \u03bcg\/kg.<\/jats:p>\n                  <jats:p>Conclusions: The duration and magnitude of the bone-protecting effect of a single intravenous dose of ZOL in ovariectomized rats is dose dependent and lasts for up to 32 wk. Compared with alendronate, ZOL shows 10-fold higher potency in preventing bone loss. These data support the use of an annual intravenous ZOL dosing regimen for the treatment of osteoporosis.<\/jats:p>","DOI":"10.1359\/jbmr.071207","type":"journal-article","created":{"date-parts":[[2007,12,11]],"date-time":"2007-12-11T13:13:13Z","timestamp":1197378793000},"page":"544-551","source":"Crossref","is-referenced-by-count":93,"title":["Long-Term Protective Effects of Zoledronic Acid on Cancellous and Cortical Bone in the Ovariectomized Rat"],"prefix":"10.1093","volume":"23","author":[{"given":"J\u00fcrg A","family":"Gasser","sequence":"first","affiliation":[{"name":"Novartis Institutes for Biomedical Research, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Ingold","sequence":"additional","affiliation":[{"name":"Novartis Institutes for Biomedical Research, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Venturiere","sequence":"additional","affiliation":[{"name":"Novartis Institutes for Biomedical Research, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Shen","sequence":"additional","affiliation":[{"name":"SkeleTech, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan R","family":"Green","sequence":"additional","affiliation":[{"name":"Novartis Institutes for Biomedical Research, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,4]]},"reference":[{"key":"2024020319551443900_bib1","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1002\/jbmr.5650090521","article-title":"Preclinical pharmacology of CGP 42\u2032446, a new, potent, heterocyclic bisphosphonate compound","volume":"9","author":"Green","year":"1994","journal-title":"J Bone Miner Res"},{"key":"2024020319551443900_bib2","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1007\/s00198-004-1588-3","article-title":"Loss of vertebral bone and mechanical strength in estrogen-deficient rats is prevented by long-term administration of zoledronic acid","volume":"15","author":"Glatt","year":"2004","journal-title":"Osteoporos Int"},{"key":"2024020319551443900_bib3","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/s00223-002-2015-4","article-title":"Long-term zoledronic acid treatment increases bone structure and mechanical strength of long bones of ovariectomized adult rats","volume":"72","author":"Hornby","year":"2003","journal-title":"Calcif Tissue Int"},{"key":"2024020319551443900_bib4","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1359\/jbmr.1998.13.11.1775","article-title":"Zoledronate prevents the development of absolute osteopenia following ovariectomy in adult rhesus monkeys","volume":"13","author":"Binkley","year":"1998","journal-title":"J Bone Miner Res"},{"key":"2024020319551443900_bib5","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1359\/jbmr.061001","article-title":"Long term control of bone turnover in Paget's disease with zoledronic acid and risedronate","volume":"22","author":"Hosking","year":"2007","journal-title":"J Bone Miner Res"},{"key":"2024020319551443900_bib6","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1056\/NEJMoa067312","article-title":"Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis","volume":"356","author":"Black","year":"2007","journal-title":"N Engl J Med"},{"key":"2024020319551443900_bib7","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s00223-004-0024-1","article-title":"From molds and macrophages to mevalonate: A decade of progress in understanding the molecular mode of action of bisphosphonates","volume":"75","author":"Rogers","year":"2004","journal-title":"Calcif Tissue Int"},{"key":"2024020319551443900_bib8","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1172\/JCI114100","article-title":"Inhibition of osteoclast-like cell formation by bisphosphonates in long-term cultures of human bone marrow","volume":"83","author":"Hughes","year":"1989","journal-title":"J Clin Invest"},{"key":"2024020319551443900_bib9","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/jbmr.5650030210","article-title":"Migration and phenotypic transformation of osteoclast precursors into mature osteoclasts: The effect of a bisphosphonate","volume":"3","author":"L\u00f6wik","year":"1988","journal-title":"J Bone Miner Res"},{"key":"2024020319551443900_bib10","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1172\/JCI115539","article-title":"Bisphosphonate action. 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