Androgen-deprivation therapy and the risk of newly developed fractures in patients with prostate cancer: a nationwide cohort study in Korea

Do Kyung Kim,Jong Won Kim,Jee Soo Ha,Hyun Kyu Ahn,Ju-Young Park,Hye Sun Lee,Kang Su Cho

doi:10.1038/s41598-021-89589-3

Abstract

We evaluated the risk of osteoporosis and fractures associated with androgen deprivation therapy (ADT) use and duration in men with prostate cancer. From the nationwide claims database in South Korea, a total of 218,203 men with prostate cancer were identified between 2008 and 2017. After applying the inclusion and exclusion criteria, a total of 144,670 patients were included in the analysis. To adjust for comorbidities between cohorts, 1:1 propensity score matching was used. Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of events associated with ADT, after controlling for potential confounding factors. In the matched cohort, there were differences in the incidence of newly developed osteoporosis (8.79% in the ADT group vs. 7.08% in the non-ADT group, p < 0.0001) and fractures (8.12% in the ADT group vs. 5.04% in the non-ADT group, p < 0.0001). Age-adjusted Cox regression analysis revealed that the ADT group had a significantly higher risk of osteoporosis (HR, 1.381; 95% CI, 1.305–1.461; p < 0.0001) and fractures (HR, 1.815; 95% CI, 1.703–1.935; p < 0.0001) compared to the non-ADT group. Furthermore, the risk of osteoporosis and fractures increased as the duration of ADT increased. The ADT was associated with an increased risk of osteoporosis and fractures in prostate cancer patients. Clinicians who administer ADT for patients with prostate cancer should always be mindful of the risk of osteoporosis and fracture, avoid unnecessary ADT, and perform regular bone health check-ups.

Highlights

We evaluated the risk of osteoporosis and fractures associated with androgen deprivation therapy (ADT) use and duration in men with prostate cancer
In this large population-based study, we found that the use of ADT in the treatment of prostate cancer was associated with an increased risk of osteoporosis and fracture
The risk of osteoporosis and fracture increased as the duration of ADT increased, concurrent use of antiandrogens did not increase the harmful effects of ADT

Summary

Introduction

We evaluated the risk of osteoporosis and fractures associated with androgen deprivation therapy (ADT) use and duration in men with prostate cancer. The ADT was associated with an increased risk of osteoporosis and fractures in prostate cancer patients. Meng et al identified that nearly 50% of patients with prostate cancer in their study cohort received ADT at some point after d iagnosis[6]. As the use of ADT increases, potentially serious side effects, including diabetes, cardiovascular disease, osteoporosis, and fractures, are increasing[7,8,9]. Of the many adverse effects, osteoporosis and bone fractures are important in relation to increased mortality in prostate cancer[12]. Alibhai et al reported that ADT for at least 6 months is associated with an increased risk of fracture, according to Canada’s population d atabase[20]

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Results

Conclusion