Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/23557
Title: Differing effects of zoledronic acid on bone microarchitecture and bone mineral density in men receiving androgen deprivation therapy: a randomised controlled trial.
Authors: Cheung, Ada S;Hoermann, Rudolf;Ghasem-Zadeh, Ali;Tinson, Alistair J;Ly, Vivian;Milevski, Stefan V;Lim Joon, Daryl;Zajac, Jeffrey D;Seeman, Ego;Grossmann, Mathis
Affiliation: Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia
Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Department of Radiation Oncology, Austin Health, Heidelberg, Victoria, Australia
Issue Date: 16-Jun-2020
EDate: 2020
Citation: Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 2020; online first: 16 June
Abstract: Androgen deprivation therapy (ADT) given to men with prostate cancer causes rapid and severe sex steroid deficiency leading to increased bone remodeling and accelerated bone loss. To examine the effects of a single dose of zoledronic acid on bone microarchitecture we conducted a two year randomised placebo controlled trial in 76 men, mean age [IQR] 67.8 years [63.8;73.9] with non-metastatic prostate cancer commencing adjuvant ADT; 39 were randomised 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% CI]) between the groups are reported as the treatment effect at several time points. Over 24 months, zoledronic acid showed no appreciable treatment effect on the primary outcomes for total volumetric bone mineral density (vBMD); radius (6.7 mg HA/cm3 [-2.0;15.4], p=0.21) and tibia (1.9 mg HA/cm3 [-3.3;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 months (17.3 mgHA/cm3 [5.1;29.5]). In contrast, zoledronic acid showed a treatment effect over 24 months on aBMD by DXA at all sites, including lumbar spine (0.10 g/cm2 [0.07;0.13]), p<0.001), and total hip (0.04 g/cm2 [0.03;0.05], p<0.001). Bone remodeling markers were initially suppressed in the treatment group then increased but remained lower relative to placebo (MADs at 24 months CTX -176 ng/l [-275;-76], p<0.001, P1NP -18 mg/L [-32;-5], p<0.001). These findings suggest that a single dose of zoledronic acid over 2 years is ineffective in preventing the unbalanced bone remodeling and severe microstructural deterioration associated with ADT therapy. This article is protected by copyright. All rights reserved.
URI: http://ahro.austin.org.au/austinjspui/handle/1/23557
DOI: 10.1002/jbmr.4106
ORCID: 0000-0002-9692-048X
0000-0001-8261-3457
0000-0001-5257-5525
0000-0002-1326-4270
0000-0002-1947-9694
0000-0003-3933-5708
0000-0001-8261-3457
PubMed URL: 32542695
Type: Journal Article
Subjects: Androgen deprivation
bisphosphonates
bone
microarchitecture
prostate cancer
Appears in Collections:Journal articles

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