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To examine the effects of a single dose of zoledronic acid on bone microarchitecture, we conducted a 2-year randomized placebo controlled trial in 76 men, mean age (interquartile range [IQR]) 67.8\u2009years (63.8 to 73.9) with non-metastatic prostate cancer commencing adjuvant ADT; 39 were randomized to zoledronic acid and 37 to matching placebo. Bone microarchitecture was measured using high-resolution peripheral quantitative computed tomography (HR-pQCT). Using a mixed model, mean adjusted differences (MAD; 95% confidence interval [95% CI]) between the groups are reported as the treatment effect at several time points. Over 24\u2009months, zoledronic acid showed no appreciable treatment effect on the primary outcomes for total volumetric bone mineral density (vBMD); radius (6.7\u2009mg HA\/cm3 [\u22122.0 to 15.4], p = 0.21) and tibia (1.9\u2009mg HA\/cm3 [\u22123.3 to 7.0], p = 0.87). Similarly, there were no between-group differences in other measures of microarchitecture, with the exception of a modest effect of zoledronic acid over placebo in total cortical vBMD at the radius over 12\u2009months (17.3 mgHA\/cm3 [5.1 to 29.5]). In contrast, zoledronic acid showed a treatment effect over 24\u2009months on areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) at all sites, including lumbar spine (0.10\u2009g\/cm2 [0.07 to 0.13]), p\u2009&amp;lt;\u20090.001), and total hip (0.04\u2009g\/cm2 [0.03 to 0.05], p\u2009&amp;lt;\u20090.001). Bone remodeling markers were initially suppressed in the treatment group then increased but remained lower relative to placebo (MADs at 24\u2009months CTX \u2212176\u2009ng\/L [\u2212275 to \u201376], p\u2009&amp;lt;\u20090.001; P1NP \u201318\u2009mg\/L [\u221232 to \u20135], p\u2009&amp;lt;\u20090.001). These findings suggest that a single dose of zoledronic acid over 2\u2009years is ineffective in preventing the unbalanced bone remodeling and severe microstructural deterioration associated with ADT therapy. \u00a9 2020 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.4106","type":"journal-article","created":{"date-parts":[[2020,6,16]],"date-time":"2020-06-16T08:46:24Z","timestamp":1592297184000},"page":"1871-1880","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Differing Effects of Zoledronic Acid on Bone Microarchitecture and Bone Mineral Density in Men Receiving Androgen Deprivation Therapy: A Randomized Controlled Trial"],"prefix":"10.1093","volume":"35","author":[{"given":"Ada S","family":"Cheung","sequence":"first","affiliation":[{"name":"Department of Endocrinology Austin Health Heidelberg Australia"},{"name":"Department of Medicine (Austin Health) The University of Melbourne Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Hoermann","sequence":"additional","affiliation":[{"name":"Department of Medicine (Austin Health) The University of Melbourne Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5284-9239","authenticated-orcid":false,"given":"Ali","family":"Ghasem-Zadeh","sequence":"additional","affiliation":[{"name":"Department of Medicine (Austin Health) The University of Melbourne Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alistair J","family":"Tinson","sequence":"additional","affiliation":[{"name":"Department of Medicine (Austin Health) The University of Melbourne Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian","family":"Ly","sequence":"additional","affiliation":[{"name":"Department of Medicine (Austin Health) The University of Melbourne Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan V","family":"Milevski","sequence":"additional","affiliation":[{"name":"Department of Medicine (Austin Health) The University of Melbourne Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daryl Lim","family":"Joon","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Austin Health Heidelberg Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D","family":"Zajac","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Austin Health Heidelberg Australia"},{"name":"Department of Medicine (Austin Health) The University of Melbourne Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ego","family":"Seeman","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Austin Health Heidelberg Australia"},{"name":"Department of Medicine (Austin Health) 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