接受雄激素剥夺疗法（ADT）治疗的前列腺癌（PCa）患者骨折风险增加。探索早期骨质流失检测的生物标志物引起了人们的极大兴趣。ARNEO 试验的预先计划子研究 (NCT03080116)：一项双盲、随机、安慰剂对照 2 期试验，在 2019 年 3 月期间在无骨转移的高危 PCa 患者中进行2021 年 4 月。在前列腺切除术前 12 周，患者以 1:1 的比例随机接受促性腺激素释放激素拮抗剂（地加瑞克）雄激素受体信号抑制剂（ARSI；阿帕鲁胺）与地加瑞克匹配安慰剂治疗。 ADT 之前和之后，收集血清和 24 小时尿液样本。主要终点是磷酸钙稳态和骨生物标志物的变化。在 89 名随机患者中，本亚组研究包括地加瑞克阿帕他胺组中的 43 名患者和地加瑞克安慰剂组中的 44 名患者。两个治疗组的血清校正钙水平均增加（平均差 0.04 mmol/L，95% 置信区间，0.02；0.06），甲状旁腺激素和 1,25-二羟基维生素 D3 水平下降。两组患者的血清和尿液中骨吸收标志物均有所增加，反映净骨矿物质平衡的稳定钙同位素比率也有相似的下降。这项探索性子研究表明，非转移性 PCa 患者接受 12 周的 ADT 会导致早期骨质流失。 ARSI 的额外治疗似乎不会对早期骨质流失产生更大的负面影响。未来的研究应该解决这些早期生物标志物是否能够预测骨折风险，并且可以在临床实践中实施，以跟踪接受 ADT 的前列腺癌患者的骨骼健康状况。弗兰德斯研究基金会；鲁汶大学；鲁汶大学医院。版权所有 © 2023 作者。由 Elsevier B.V. 出版。保留所有权利。

Prostate cancer (PCa) patients treated with androgen deprivation therapy (ADT) have an increased fracture risk. Exploring biomarkers for early bone loss detection is of great interest.Pre-planned substudy of the ARNEO-trial (NCT03080116): a double blind, randomised, placebo-controlled phase 2 trial performed in high-risk PCa patients without bone metastases between March 2019 and April 2021. Patients were 1:1 randomised to treatment with gonadotropin-releasing hormone antagonist (degarelix) + androgen receptor signalling inhibitor (ARSI; apalutamide) versus degarelix + matching placebo for 12 weeks prior to prostatectomy. Before and following ADT, serum and 24-h urinary samples were collected. Primary endpoints were changes in calcium-phosphate homeostasis and bone biomarkers.Of the 89 randomised patients, 43 in the degarelix + apalutamide and 44 patients in the degarelix + placebo group were included in this substudy. Serum corrected calcium levels increased similarly in both treatment arms (mean difference +0.04 mmol/L, 95% confidence interval, 0.02; 0.06), and parathyroid hormone and 1,25-dihydroxyvitamin D3 levels decreased. Bone resorption markers increased, and stable calcium isotope ratios reflecting net bone mineral balance decreased in serum and urine similarly in both groups.This exploratory substudy suggests that 12 weeks of ADT in non-metastatic PCa patients results in early bone loss. Additional treatment with ARSI does not seem to more negatively influence bone loss in the early phase. Future studies should address if these early biomarkers are able to predict fracture risk, and can be implemented in clinical practice for follow-up of bone health in PCa patients under ADT.Research Foundation Flanders; KU Leuven; University-Hospitals-Leuven.Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.