{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T06:45:18Z","timestamp":1780382718009,"version":"3.54.1"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2018,10,8]],"date-time":"2018-10-08T00:00:00Z","timestamp":1538956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100008272","name":"Novartis Pharmaceuticals Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Zoledronic acid (ZA), a potent bisphosphonate used for treatment of bone metastasis, has high bone affinity. This post hoc analysis evaluated the effects of long-term treatment and reduction in dosing frequency of ZA on bone saturation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Materials and Methods<\/jats:title>\n                  <jats:p>Pharmacokinetic data from three independent studies, OPTIMIZE-2 (patients receiving \u22659 doses of bisphosphonates) and two phase I studies, CZOL4460503 and CZOL4460506 (patients who were bisphosphonate na\u00efve\/bisphosphonate free for \u22651 year after previous dosing), were pooled. Serial urine and plasma samples were used as surrogate markers to determine ZA plasma area under the curve (AUC) over 6 hours (AUC0\u20136h) and dose excreted in urine over 6 hours (urine0\u20136h). Potential relationships between the number of years for which patients had been treated previously at time of study entry and AUC0\u20136h or urine0\u20136h were analyzed graphically.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Creatinine clearances for patients were similar across the three studies and at all time points analyzed. The levels of AUC0\u20136h ZA in plasma at week 0 in every (q) 4 and q12 weekly arms of OPTIMIZE-2 were 0.366 h\u2009\u00d7\u2009mg\/L and 0.397 h \u00d7 mg\/L compared with 0.345 h\u2009\u00d7\u2009mg\/L and 0.356 h\u2009\u00d7\u2009mg\/L in CZOL4460503 and CZOL4460506, respectively. In OPTIMIZE-2, the AUC0\u20136h ZA plasma levels were the same (0.428 h\u2009\u00d7\u2009mg\/L) at week 36 in both q4 and q12 arms. The levels of ZA urine0\u20136h at week 36 in OPTIMIZE-2 (q4 and q12 week arms), CZOL4460503, and CZOL4460506 were 36.6%, 30.8%, 26.5%, and 27.3%, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Long-term ZA treatment may not impact bone saturation, and ZA dosing frequency does not seem to influence drug retention rates.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Implications for Practice<\/jats:title>\n                  <jats:p>Zoledronic acid (ZA), used along with standard antineoplastic therapy to treat bone metastases associated with solid tumors and multiple myeloma, requires frequent (every 3\u20134 or every 12 weeks) long-term administration. This may result in bone saturation and subsequently lead to a higher risk of adverse events such as osteonecrosis of the jaw and atypical fractures. This post hoc analysis used surrogate markers to demonstrate that prolonged ZA administration does not cause bone saturation. Furthermore, reduction in ZA dosing frequency does not affect its retention level in bones over time. These findings will help in addressing clinicians' concerns regarding prolonged ZA administration.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1634\/theoncologist.2018-0218","type":"journal-article","created":{"date-parts":[[2018,10,8]],"date-time":"2018-10-08T14:25:22Z","timestamp":1539008722000},"page":"178-184","source":"Crossref","is-referenced-by-count":5,"title":["Indirect Evaluation of Bone Saturation with Zoledronic Acid After Long-Term Dosing"],"prefix":"10.1093","volume":"24","author":[{"given":"Gabriel N.","family":"Hortobagyi","sequence":"first","affiliation":[{"name":"Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zheng","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, 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