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Effect of androgen deprivation therapy on serum levels of sclerostin, Dickkopf-1, and osteoprotegerin: a cross-sectional and longitudinal analysis.

ABSTRACT: Androgen deprivation therapy (ADT) for men with prostate cancer (PCa) results in accelerated bone loss and increased risk of bone fracture. The aim of the present study was to evaluate serum bone markers-sclerostin, Dickkopf-1 (DKK-1) and osteoprotegerin (OPG), in a cohort of 88 PCa patients without known bone metastases, managed with and without ADT, and to analyse their relationship with bone mineral density (BMD) and sex steroids. The cross-sectional analysis between acute-, chronic- and former-ADT groups and PCa controls showed that sclerostin and OPG levels significantly differed between them (p = 0.029 and p = 0.032). Groups contributing to these significant changes were recorded. There were no significant differences in serum DKK-1 levels across the four groups (p = 0.683). In the longitudinal analysis, significant % decreases within groups were seen for DKK-1 [chronic-ADT (- 10.06%, p = 0.0057), former-ADT (- 12.77%, p = 0.0239), and in PCa controls group (- 16.73, p = 0.0022); and OPG levels in chronic ADT (- 8.28%, p = 0.003) and PCa controls group (- 12.82%, p = 0.017)]. However, % changes in sclerostin, DKK-1, and OPG did not differ significantly over 6-months across the evaluated groups. Sclerostin levels showed significant positive correlations with BMD at baseline in the ADT group, while in PCa controls this correlation existed at both baseline and 6-month time points. Sclerostin correlated negatively with testosterone in former ADT users and in PCa controls. Possible prognostic features denoted by parallel increases in sclerostin and BMD are discussed.

SUBMITTER: Wang A

PROVIDER: S-EPMC8295319 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:OBJECTIVES:Although estrogenic modulation of serum urate levels is well-known, the androgenic effect on urate homeostasis remains controversial. We investigated the effect of androgen deprivation therapy (ADT) on serum urate levels. METHODS:We retrospectively enrolled a total of 489 prostate cancer patients with available serum urate levels at baseline and 3 and 6 months after ADT (n = 150) or prostate surgery (n = 339). We extracted the demographic, clinical, and laboratory data from a data warehouse and compared the changes in urate levels between the two treatment groups and between the different ADT regimens (with versus without luteinizing hormone-releasing hormone (LHRH) agonists) using generalized estimating equation (GEE). RESULTS:The baseline urate levels and the proportion of hyperuricemic subjects were comparable between the two groups. After 6 months, the urate levels were significantly decreased (by -0.66 mg/dL, 95% confidence interval (CI) [-0.81 to -0.51]) in the ADT group, whereas they did not significantly change in the surgery group in the univariate GEE analysis. The ADT group (4.7% from 18.0% at baseline) had a significantly lower proportion of hyperuricemic patients than surgery group (16.5% from 15.9% at baseline) at 6-month (p < 0.001). Regardless of whether LHRH agonists were used, the serial urate levels were lowered by the ADT. Temporal changes in the urate levels were significantly associated with the treatment group, baseline hyperuricemia, and poor functional or advanced cancer status. The ADT-related serum urate level reduction also remained significant in the multivariate GEE analysis (regression coefficient = -0.43 [-0.67 to -0.19] after 3 months and -0.37 [-0.64 to -0.10] after 6 months). Moreover, propensity-score-matched analyses yielded the same results. CONCLUSIONS:Our results showed that longitudinal serum urate levels were significantly reduced in men receiving ADT. This finding suggests that androgen could have an independent role in urate homeostasis.

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Effect of androgen deprivation therapy on serum levels of sclerostin, Dickkopf-1, and osteoprotegerin: a cross-sectional and longitudinal analysis.

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