Division of Endocrinology/Department of Medicine, Columbia University, New York, NY, USA.
Amgen Inc., Thousand Oaks, CA, USA.
J Bone Miner Res. 2022 Nov;37(11):2112-2120. doi: 10.1002/jbmr.4705. Epub 2022 Oct 12.
It is uncertain whether the risk of vertebral fracture (VF) and multiple vertebral fractures (MVFs; ≥2 VFs) after denosumab (DMAb) discontinuation is related to treatment duration. A prior analysis of Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) and FREEDOM Extension trials did not find a relationship with DMAb duration and may have underreported MVF incidence because it included women who did not have radiographs. In this post hoc exploratory analysis, the crude incidence and annualized rates of VF and MVF were determined in patients with ≥7 months' follow-up and ≥1 spine radiograph after discontinuing placebo or DMAb. A multivariate analysis was performed to identify predictors of MVF. Clinical characteristics of patients with ≥4 VFs were explored. This analysis included women who discontinued after placebo (n = 327) or DMAb either from FREEDOM or FREEDOM Extension (n = 425). The DMAb discontinuation group was subsequently dichotomized by treatment duration: short-term (≤3 years; n = 262) and long-term (>3 years; n = 213) treatment. For any VF, exposure-adjusted annualized rates per 100 patient-years (95% confidence interval [CI]) were 9.4 (95% CI, 6.4-13.4) for placebo, 6.7 (95% CI, 4.2-10.1) for short-term DMAb, and 10.7 (95% CI, 7.4-15) for long-term DMAb. Annualized rates for MVF were 3.6 (95% CI, 1.9-6.3), 2.9 (95% CI, 1.4-5.4), and 7.5 (95% CI, 4.8-11.1), respectively. Annualized rates for ≥4 VFs were 0.59 (95% CI, 0.1-2.1), 0.57 (95% CI, 0.1-2.1), and 3.34 (95% CI, 1.7-6.0), respectively. In a multivariate regression model, DMAb duration was significantly associated with MVF risk (odds ratio 3.0; 95% CI, 1.4-6.5). Of 15 patients with ≥4 VFs, 13 had DMAb exposure (mean ± standard deviation [SD], 4.9 ± 2.2 years). The risk of MVF after DMAb discontinuation increases with increased duration of DMAb treatment. Patients transitioning off DMAb after 3 years may warrant more frequent administration of zoledronic acid or another bisphosphonate to maintain bone turnover and bone mineral density (BMD) and prevent MVF. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
目前尚不确定地舒单抗（DMAb）停药后椎体骨折（VF）和多发椎体骨折（MVF；≥2 个 VF）的风险是否与治疗持续时间有关。对骨质疏松症每 6 个月使用地舒单抗评估骨折减少（FREEDOM）和 FREEDOM 扩展试验的先前分析并未发现与 DMAb 持续时间有关，并且可能报告的 MVF 发生率较低，因为它包括未进行 X 光检查的女性。在本事后探索性分析中，在停药后至少有 7 个月随访和至少有 1 次脊柱 X 光片的患者中确定了 VF 和 MVF 的粗发生率和年化发生率。进行了多变量分析以确定 MVF 的预测因素。探讨了≥4 个 VF 患者的临床特征。该分析包括从 FREEDOM 或 FREEDOM 扩展试验停药的安慰剂（n=327）或 DMAb（n=425）患者。DMAb 停药组随后根据治疗持续时间分为两类：短期（≤3 年；n=262）和长期（>3 年；n=213）治疗。对于任何 VF，每 100 患者年（95%置信区间[CI]）的暴露调整年化发生率分别为安慰剂组 9.4（95%CI，6.4-13.4）、短期 DMAb 组 6.7（95%CI，4.2-10.1）和长期 DMAb 组 10.7（95%CI，7.4-15）。MVF 的年化发生率分别为 3.6（95%CI，1.9-6.3）、2.9（95%CI，1.4-5.4）和 7.5（95%CI，4.8-11.1）。≥4 个 VF 的年化发生率分别为 0.59（95%CI，0.1-2.1）、0.57（95%CI，0.1-2.1）和 3.34（95%CI，1.7-6.0）。在多变量回归模型中，DMAb 持续时间与 MVF 风险显著相关（比值比 3.0；95%CI，1.4-6.5）。在 15 名≥4 个 VF 的患者中，有 13 名有 DMAb 暴露（平均值±标准偏差[SD]，4.9±2.2 年）。DMAb 治疗持续时间的增加与 DMAb 停药后 MVF 风险的增加有关。停药后 3 年以上转为 DMAb 的患者可能需要更频繁地给予唑来膦酸或其他双膦酸盐，以维持骨转换和骨矿物质密度（BMD），并预防 MVF。© 2022 作者。《骨质与矿物研究杂志》由 Wiley 期刊出版公司代表美国骨与矿物研究协会（ASBMR）出版。
