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不同月经状态的中国乳腺癌女性中化疗及不同化疗方案对骨骼健康的影响:一项自身对照研究。

Effect of chemotherapy and different chemotherapy regimens on bone health among Chinese breast cancer women in different menstrual status: a self-control study.

机构信息

Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

出版信息

Support Care Cancer. 2023 Aug 29;31(9):540. doi: 10.1007/s00520-023-07960-8.

Abstract

PURPOSE

Although the therapy-related bone loss attracts increasing attention nowadays, the differences in chemotherapy-induced bone loss and bone metabolism indexes change among breast cancer (BC) women with different menstrual statuses or chemotherapy regimens are unknown. The aim of the study is to explore the effects of different regimens of chemotherapy on bone health.

METHOD

The self-control study enrolled 118 initially diagnosed BC women without distant metastasis who underwent dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) screening and (or) bone metabolism index monitoring during chemotherapy at Chongqing Breast Cancer Center. Mann-Whitney U test, Cochran's Q test, and Wilcoxon sign rank test were performed.

RESULTS

After chemotherapy, the BMD in the lumbar 1-4 and whole lumbar statistically decreased (- 1.8%/per 6 months), leading to a significantly increased proportion of osteoporosis (27.1% vs. 20.5%, P < 0.05), which were mainly seen in the premenopausal group (- 7.0%/per 6 months). Of the chemotherapeutic regimens of EC (epirubicin + cyclophosphamide), TC (docetaxel + cyclophosphamide), TEC (docetaxel + epirubicin + cyclophosphamide), and EC-T(H) [epirubicin + cyclophosphamide-docetaxel and/or trastuzumab], EC regimen had the least adverse impact on BMD, while the EC-TH regimen reduced BMD most (P < 0.05) inspite of the non-statistical difference between EC-T regimen, which was mainly seen in the postmenopausal group. Chemotherapy-induced amenorrhea (estradiol 94 pg/ml vs, 22 pg/ml; FSH 9.33 mIU/ml vs. 61.27 mIU/ml) was proved in premenopausal subgroup (P < 0.001). Except the postmenopausal population with calcium/VitD supplement, the albumin-adjusted calcium increased significantly (2.21 mmol/l vs. 2.33 mmol/l, P < 0.05) after chemotherapy. In postmenopausal group with calcium/VitD supplement, β-CTX decreased significantly (0.56 ng/ml vs. 0.39 ng/ml, P < 0.05) and BMD were not affected by chemotherapy (P > 0. 05). In premenopausal group with calcium/VitD supplement, PTH decreased significantly (52.90 pg/ml vs. 28.80 pg/ml, P = 0. 008) and hip BMD increased after chemotherapy (0.845 g/m vs. 0.952 g/m, P = 0. 006). As for both postmenopausal and premenopausal group without calcium/VitD supplement, there was a significant decrease in bone mass in hip and lumbar vertebrae after chemotherapy (0.831 g/m vs. 0.776 g/m; 0.895 g/m vs. 0.870 g/m, P < 0.05).

CONCLUSION

Chemotherapy might induce lumbar vertebrae BMD loss and spine osteoporosis with regimen differences among Chinese BC patients. Calcium/VitD supplementation could improve bone turnover markers, bone metabolism indicators, and bone mineral density. Early interventions on bone health are needed for BC patients during chemotherapy.

摘要

目的

尽管治疗相关的骨丢失越来越受到关注,但不同月经状态或化疗方案的乳腺癌(BC)女性中化疗引起的骨丢失和骨代谢指标变化的差异尚不清楚。本研究旨在探讨不同化疗方案对骨健康的影响。

方法

采用自身对照研究,纳入 118 例初诊无远处转移的 BC 女性患者,这些患者在重庆乳腺癌中心接受化疗时进行了双能 X 线吸收法(DXA)骨密度(BMD)筛查和(或)骨代谢指标监测。采用 Mann-Whitney U 检验、Cochran's Q 检验和 Wilcoxon 符号秩检验进行分析。

结果

化疗后,腰椎 1-4 和全腰椎的 BMD 统计学上分别下降了(-1.8%/每 6 个月),导致骨质疏松的比例显著增加(27.1%比 20.5%,P<0.05),这主要见于绝经前组(-7.0%/每 6 个月)。在 EC(表柔比星+环磷酰胺)、TC(多西他赛+环磷酰胺)、TEC(多西他赛+表柔比星+环磷酰胺)和 EC-T(H)[表柔比星+环磷酰胺-多西他赛和/或曲妥珠单抗]化疗方案中,EC 方案对 BMD 的不良影响最小,而 EC-TH 方案对 BMD 的影响最大(P<0.05),尽管 EC-T 方案之间没有统计学差异,这主要见于绝经后组。在绝经前亚组中,证实了化疗引起的闭经(雌二醇 94 pg/ml 比 22 pg/ml;FSH 9.33 mIU/ml 比 61.27 mIU/ml;P<0.001)。除了补充钙/VitD 的绝经后人群外,白蛋白校正钙显著增加(2.21 mmol/L 比 2.33 mmol/L,P<0.05)。在补充钙/VitD 的绝经后人群中,β-CTX 显著下降(0.56 ng/ml 比 0.39 ng/ml,P<0.05),BMD 不受化疗影响(P>0.05)。在补充钙/VitD 的绝经前人群中,甲状旁腺激素(PTH)显著下降(52.90 pg/ml 比 28.80 pg/ml,P=0.008),化疗后髋关节 BMD 增加(0.845 g/m 比 0.952 g/m,P=0.006)。对于没有补充钙/VitD 的绝经前和绝经后组,化疗后髋关节和腰椎的骨量均有显著下降(0.831 g/m 比 0.776 g/m;0.895 g/m 比 0.870 g/m,P<0.05)。

结论

化疗可能导致中国 BC 患者的腰椎 BMD 丢失和脊柱骨质疏松症,且不同化疗方案之间存在差异。钙/VitD 补充可以改善骨转换标志物、骨代谢指标和骨矿物质密度。化疗期间需要对 BC 患者的骨骼健康进行早期干预。

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