Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/26729
Title: Zoledronic acid does not affect insulin resistance in men receiving androgen deprivation therapy: a prespecified secondary analysis of a randomised controlled trial.
Austin Authors: Cheung, Ada S ;Hoermann, Rudolf;Zhu, Jasmine J ;Lim Joon, Daryl ;Zajac, Jeffrey D ;Grossmann, Mathis 
Affiliation: Radiation Oncology
Medicine (University of Melbourne)
Endocrinology
Issue Date: 5-May-2021
Date: 2021-05-05
Publication information: Therapeutic Advances in Endocrinology and Metabolism 2021; online first: 5 May
Abstract: Animal studies suggest that undercarboxylated osteocalcin may improve insulin sensitivity via its effect on testicular testosterone production. Human studies have been conflicting. Men undergoing androgen deprivation therapy (ADT) for prostate cancer experience profound hypogonadism resulting in increased insulin resistance. In a randomised controlled trial (RCT) of zoledronic acid versus placebo in men commencing extended-duration ADT, we aimed to examine the effects on fat mass and glucose metabolism. We hypothesised that zoledronic acid, which reduces osteocalcin concentrations, would worsen ADT-induced insulin resistance. This was a prespecified secondary analysis of an RCT designed to evaluate the effects of zoledronic acid on bone microarchitecture in 76 men with non-metastatic prostate cancer undergoing curative radiotherapy combined with adjuvant ADT (n = 39 randomised to a single dose of zoledronic acid 5 mg, n = 37 randomised to matching placebo). Oral glucose tolerance tests to determine Matsuda Index were performed at 0, 3, 12 and 24 months. Using a mixed model, mean adjusted differences [MAD (95% confidence interval)] between the groups over time are reported. Over 24 months of ADT, fat mass increased and lean mass decreased for both groups, with no significant between group difference [MAD 401 g (-1307; 2103), p = 0.23 and -184 g (-1325; 955), p = 0.36 respectively]. Bone remodelling markers C-telopeptide [MAD -176 ng/l (-275; -76), p < 0.001 and P1NP -18 mg/l (-32; -5), p < 0.001] as a surrogate for osteocalcin, remained significantly lower in the zoledronic acid group, compared with placebo. There was no mean adjusted between-group difference for homeostatic model assessment 2 insulin resistance (HOMA2-IR) [-0.2 (-0.6; 0.2), p = 0.45], HbA1c [-0.1% (-0.3; 0.1), p = 0.64] or Matsuda Index [0.8 (-1.1; 2.7), p = 0.38]. The Matsuda Index decreased in both groups consistent with worsening insulin resistance with ADT. A single dose of zoledronic acid does not appear to influence glucose metabolism in men newly commencing ADT. Further study to evaluate the endocrine relationship between bisphosphonates, bone and glucose metabolism is required. [ClinicalTrials.gov identifier: NCT01006395].
URI: https://ahro.austin.org.au/austinjspui/handle/1/26729
DOI: 10.1177/20420188211012118
ORCID: 0000-0002-7158-8804
0000-0002-1326-4270
Journal: Therapeutic Advances in Endocrinology and Metabolism
PubMed URL: 34104395
ISSN: 2042-0188
Type: Journal Article
Subjects: androgen deprivation
bisphosphonates
diabetes
insulin resistance
Prostate cancer
Appears in Collections:Journal articles

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