Department of Medicine, Endocrine Unit, Massachusetts General Hospital, Harvard University, Boston, MA, USA.
Biostatistics Center, Massachusetts General Hospital, Boston, MA, USA.
Osteoporos Int. 2024 Feb;35(2):255-263. doi: 10.1007/s00198-023-06932-2. Epub 2023 Oct 6.
Denosumab discontinuation results in accelerated bone remodeling, decreased bone mineral density (BMD), and an increased risk of multiple vertebral fractures. Bisphosphonates are at least partially effective at inhibiting these consequences but there have been no randomized clinical trials assessing the efficacy of alternative antiresorptives.
The aim of this study was to evaluate the comparative efficacy of alendronate and the SERM, raloxifene, in preventing the post-denosumab high-turnover bone loss.
We conducted an open-label randomized controlled trial in which 51 postmenopausal women at increased risk of fracture were randomized with equal probability to receive 12-months of denosumab 60-mg 6-monthly followed by 12-months of either alendronate 70-mg weekly or raloxifene 60-mg daily. Serum bone remodeling markers were measured at 0,6,12,15,18, and 24 and areal BMD of the distal radius, spine, and hip were measured at 0,12,18 and 24 months.
After denosumab discontinuation, serum markers of bone remodeling remained suppressed when followed by alendronate, but gradually increased to baseline when followed by raloxifene. In the denosumab-to-alendronate group, denosumab-induced BMD gains were maintained at all sites whereas in the denosumab-to-raloxifene group, BMD decreased at the spine by 2.0% (95% CI -3.2 to -0.8, P = 0.003) and at the total hip by 1.2% (-2.1 to -0.4%, P = 0.008), but remained stable at the femoral neck and distal radius and above the original baseline at all sites. The decreases in spine and total hip BMD in the denosumab-to-raloxifene group (but not the femoral neck or distal radius) were significant when compared to the denosumab-to-alendronate group.
These results suggest that after one year of denosumab, one year of alendronate is better able to maintain the inhibition of bone remodeling and BMD gains than raloxifene.
地舒单抗停药会导致骨重建加速、骨密度（BMD）下降，以及发生多处椎体骨折的风险增加。双膦酸盐至少能部分抑制这些后果，但目前还没有评估其他抗吸收药物疗效的随机临床试验。
本研究旨在评估阿仑膦酸钠和选择性雌激素受体调节剂雷洛昔芬预防地舒单抗治疗后高转换性骨丢失的疗效比较。
我们开展了一项开放标签、随机对照试验，将 51 名有骨折高风险的绝经后妇女等概率随机分为两组，分别接受地舒单抗 60mg 每 6 个月 1 次共 6 次，随后分别接受阿仑膦酸钠 70mg 每周 1 次或雷洛昔芬 60mg 每日 1 次，共 12 个月。在 0、6、12、15、18 和 24 时测量血清骨重塑标志物，在 0、12、18 和 24 时测量桡骨远端、脊柱和髋部的骨密度。
地舒单抗停药后，继续使用阿仑膦酸钠时，血清骨重塑标志物仍保持抑制状态，但当改用雷洛昔芬时则逐渐恢复到基线水平。在接受地舒单抗联合阿仑膦酸钠治疗的患者中，所有部位的地舒单抗诱导的骨密度增加均得以维持，而在接受地舒单抗联合雷洛昔芬治疗的患者中，脊柱骨密度下降 2.0%（95%CI -3.2 至 -0.8，P=0.003），全髋骨密度下降 1.2%（-2.1 至 -0.4%，P=0.008），但股骨颈和桡骨远端骨密度保持稳定，且所有部位均高于初始基线。与接受地舒单抗联合阿仑膦酸钠治疗的患者相比，接受地舒单抗联合雷洛昔芬治疗的患者脊柱和全髋骨密度下降（但股骨颈和桡骨远端除外）有显著差异。
这些结果表明，在接受地舒单抗治疗 1 年后，阿仑膦酸钠治疗 1 年在维持骨重塑抑制和骨密度增加方面优于雷洛昔芬。
