Effects of follow-on therapy after denosumab discontinuation in patients with postmenopausal osteoporosis

To clarify the effects of follow-on therapy after denosumab (DMAb) discontinuation. In this retrospective, multicenter study, postmenopausal patients with osteoporosis who were previously treated by oral bisphosphonates (BP) (n = 26) or teriparatide (TPTD) (n = 27) were switched to DMAb (administered 2.6 times), and then discontinued. Patients (73.1 years, T-scores of the lumbar spine [LS] − 2.7 and femoral neck [FN] − 2.2) were switched to either (1) raloxifene (RAL) (n = 13) or BP [(2) weekly or monthly BP (wmBP) (n = 29) or (3) zoledronate (ZOL) (n = 11)], based on each physician’s decision (mean interval after final DMAb administration was 7.2 months). Bone mineral density (BMD) at final DMAb administration were set as baseline. Changes in LS BMD at 1.5 years after final DMAb administration were −2.7% in the RAL, 0.7% in the wmBP, and 1.9% in the ZOL (p = .31 between groups), and in FN BMD were −3.8%, −0.8%, and 1.8%, respectively (p = .02 between the RAL and ZOL; p = .048 between the RAL and BP). Clinical vertebral fracture incidence during 1.5 years after final DMAb administration was 23.1% in the RAL, 3.4% in the wmBP, and 0.0% in the ZOL (p = .048 between the RAL and ZOL; p = .015 between the RAL and BP). No significant differences were observed in these parameters between the wmBP and ZOL. These results may contribute to the selection of adequate follow-on therapy after DMAb discontinuation, although further investigations are required.

为明确地舒单抗（denosumab, DMAb）停药后后续治疗的临床效应，本研究为回顾性多中心研究。纳入曾接受口服双膦酸盐类药物（bisphosphonates, BP）治疗（n=26）或特立帕肽（teriparatide, TPTD）治疗（n=27）的绝经后骨质疏松症患者，将其转为地舒单抗治疗（给药次数为2.6次），随后停药。入组患者平均年龄73.1岁，腰椎（lumbar spine, LS）T值为-2.7，股骨颈（femoral neck, FN）T值为-2.2；根据每位医师的临床决策，患者后续转为以下任一治疗方案：(1) 雷洛昔芬（raloxifene, RAL）（n=13）；(2) 每周/每月口服双膦酸盐（weekly or monthly BP, wmBP）（n=29）；(3) 唑来膦酸（zoledronate, ZOL）（n=11）。地舒单抗末次给药至后续治疗开始的平均间隔时间为7.2个月。以患者在地舒单抗末次给药时的骨密度（bone mineral density, BMD）作为研究基线。地舒单抗末次给药后1.5年时，腰椎骨密度变化率分别为：雷洛昔芬组-2.7%、每周/每月双膦酸盐组0.7%、唑来膦酸组1.9%（组间比较p=0.31）；股骨颈骨密度变化率分别为-3.8%、-0.8%、1.8%（雷洛昔芬组与唑来膦酸组比较p=0.02；雷洛昔芬组与双膦酸盐组比较p=0.048）。地舒单抗末次给药后1.5年随访期间，临床椎体骨折发生率分别为：雷洛昔芬组23.1%、每周/每月双膦酸盐组3.4%、唑来膦酸组0.0%（雷洛昔芬组与唑来膦酸组比较p=0.048；雷洛昔芬组与双膦酸盐组比较p=0.015）。每周/每月双膦酸盐组与唑来膦酸组在上述各项指标中均未观察到显著差异。本研究结果可为地舒单抗停药后的合理后续治疗方案选择提供参考，尽管仍需开展更多的后续研究。