长期口服双膦酸盐停药后骨转换和骨密度的早期变化：一项事后分析。

Early changes in bone turnover and bone mineral density after discontinuation of long-term oral bisphosphonates: a post hoc analysis.

机构信息

University of Alabama, Birmingham, AL, USA.

Department of Medicine, Columbia University, New York, NY, USA.

出版信息

Osteoporos Int. 2021 Sep;32(9):1879-1888. doi: 10.1007/s00198-020-05785-3. Epub 2021 Feb 19.

DOI:10.1007/s00198-020-05785-3

PMID:33606045

Abstract

UNLABELLED

This post hoc analysis of a randomized, double-blind study of postmenopausal women with osteoporosis found that there were early increases in bone turnover markers and decreases in bone mineral density after discontinuation of long-term alendronate. These findings might help guide treatment decisions, including monitoring after alendronate withdrawal.

INTRODUCTION

The short-term effects of discontinuing long-term bisphosphonates are poorly characterized. This post hoc analysis investigated 1-12-month changes in bone mineral density (BMD) and bone turnover markers (BTM) after alendronate (ALN) discontinuation.

METHODS

Data were from a randomized, double-blind trial of MK-5442 (calcium-sensing receptor antagonist) following oral bisphosphonates, with placebo and continued ALN controls ( ClinicalTrials.gov NCT00996801). Postmenopausal women with osteoporosis had received oral bisphosphonate (≥ 3-4 preceding years; ALN for the 12 months pre-screening), continuing on ALN 70 mg/week (n = 87) or placebo (n = 88).

RESULTS

At 12 months, least-squares mean percent changes from baseline BMD (placebo vs. ALN) were lumbar spine (LS): - 0.36 vs. 1.29, total hip: - 1.44 vs. 0.46, and femoral neck (FN): - 1.26 vs. - 0.08 (all P < 0.05). BTM levels increased by 1-3 months, to 12 months, with placebo vs. ALN (P < 0.001). FN BMD decline was greater in the placebo subgroup with higher urinary N-terminal cross-linked telopeptides of type I collagen/creatinine [uNTx/Cr] (P < 0.01), and higher serum N-terminal pro-peptide of type 1 collagen [P1NP] levels (P < 0.05), at baseline. There was a trend toward greater FN BMD loss with higher BTM levels at 3 and/or 6 months. Younger age and higher LS BMD at baseline were associated with greater LS BMD loss at 12 months (P = 0.04 and < 0.01, respectively); higher baseline FN BMD predicted greater FN BMD loss (P = 0.04).

CONCLUSION

Early changes in BTM levels and BMD were observed after discontinuation of long-term ALN. Further characterization of factors associated with patients' risk of bone loss upon bisphosphonate discontinuation is warranted.

摘要

目的

本研究对绝经后骨质疏松症妇女进行的一项随机、双盲、安慰剂对照研究的事后分析发现，长期使用阿伦膦酸钠停药后，骨转换标志物早期增加，骨密度降低。这些发现可能有助于指导治疗决策，包括阿伦膦酸钠停药后的监测。

简介

长期双膦酸盐停药的短期影响特征较差。本事后分析研究了阿伦膦酸钠（ALN）停药后 1-12 个月骨密度（BMD）和骨转换标志物（BTM）的变化。

方法

数据来自 MK-5442（钙敏感受体拮抗剂）口服双膦酸盐治疗后与安慰剂和继续使用阿伦膦酸钠对照的随机、双盲试验（ClinicalTrials.gov NCT00996801）。绝经后骨质疏松症患者接受口服双膦酸盐治疗（≥3-4 年；筛选前 12 个月使用阿伦膦酸钠），继续服用阿伦膦酸钠 70mg/周（n=87）或安慰剂（n=88）。

结果

12 个月时，与安慰剂相比，最小二乘均值百分比变化基线 BMD（安慰剂 vs.ALN）为腰椎（LS）：-0.36 vs.1.29，全髋：-1.44 vs.0.46，股骨颈（FN）：-1.26 vs.-0.08（均 P<0.05）。BTM 水平在 1-3 个月内升高，至 12 个月时，安慰剂与 ALN 相比（P<0.001）。FN BMD 下降在基线时尿 1 型胶原 N 端交联肽/肌酐[uNTx/Cr]较高（P<0.01）和血清 1 型原胶原 N 端前肽[P1NP]水平较高（P<0.05）的安慰剂亚组中更大。3 个月和/或 6 个月时 BTM 水平较高，与 FN BMD 损失增加呈趋势相关。年龄较小和基线 LS BMD 较高与 12 个月时 LS BMD 丢失增加相关（P=0.04 和<0.01）；基线 FN BMD 较高预测 FN BMD 丢失（P=0.04）。