Zoledronic acid does not affect insulin resistance in men receiving androgen deprivation therapy: a prespecified secondary analysis of a randomised controlled trial

Autor: Ada S. Cheung, Rudolf Hoermann, Jasmine Zhu, Daryl Lim Joon, Jeffrey D. Zajac, Mathis Grossmann
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Therapeutic Advances in Endocrinology and Metabolism, Vol 12 (2021)
Druh dokumentu: article
ISSN: 2042-0196
20420188
DOI: 10.1177/20420188211012118
Popis: Background: 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. Methods: 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. Results: 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
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