Endocrine Unit, Massachusetts General Hospital, Boston, MA, USA.
Division of Endocrinology, Department of Medicine, Columbia University, New York, NY, USA.
J Bone Miner Res. 2017 Oct;32(10):2001-2009. doi: 10.1002/jbmr.3198. Epub 2017 Aug 10.
In postmenopausal osteoporosis, switching from teriparatide to denosumab results in continued bone mineral density (BMD) gains whereas switching from denosumab to teriparatide results in BMD loss. To assess the effects of these transitions on bone microarchitecture and strength, we performed high-resolution peripheral QCT (HR-pQCT) at the distal tibia and radius in postmenopausal osteoporotic women who received 24 months of teriparatide 20 μg daily followed by 24 months of denosumab 60 mg every 6 months, 24 months of denosumab followed by 24 months of teriparatide, or 24 months of both medications followed by 24 months of denosumab. The 77 women who completed at least one post-switch visit are included in this analysis. Tibial cortical volumetric BMD (vBMD) increased between months 24 and 48 in the teriparatide-to-denosumab (net 48-month change -0.8% ± 2.4%) and combination-to-denosumab groups (net 48-month changes +2.4% ± 4.1%) but decreased in the denosumab-to-teriparatide group (net 48-month change -3.4% ± 3.2%, p < 0.001 for all between-group comparisons). Changes in total vBMD, cortical thickness, and estimated stiffness (by micro-finite element analysis [µFEA]) followed a similar pattern, as did changes at the radius. Conversely, tibial cortical porosity remained stable between months 24 and 48 in the teriparatide-to-denosumab and combination-to-denosumab groups (net 48-month changes +7.2% ± 14.8% and -3.4% ± 12.1%, respectively) but increased in the denosumab-to-teriparatide group (net 48-month change +16.2% ± 11.5%, p < 0.05 versus other groups). Trabecular vBMD changes did not differ among groups. Together, these findings demonstrate that in women treated with denosumab, switching to teriparatide is associated with a reduction in total and cortical vBMD, cortical thickness, and estimated strength, whereas switching to denosumab from teriparatide or combination therapy results in improvements in these parameters with the greatest improvements observed in women treated with combined therapy followed by denosumab. These findings strongly suggest that the use of teriparatide after denosumab should be avoided and that the use of combined teriparatide/denosumab followed by denosumab alone may be a useful treatment strategy in those with severe osteoporosis. © 2017 American Society for Bone and Mineral Research.
在绝经后骨质疏松症中，从特立帕肽转换为地舒单抗可导致骨密度（BMD）持续增加，而从地舒单抗转换为特立帕肽则会导致 BMD 丢失。为了评估这些转换对骨微结构和强度的影响，我们对接受了 24 个月每日 20μg 特立帕肽治疗后，再接受 24 个月每 6 个月 60mg 地舒单抗、24 个月地舒单抗后再接受 24 个月特立帕肽、或 24 个月两种药物治疗后再接受 24 个月地舒单抗治疗的绝经后骨质疏松女性进行了高分辨率外周定量计算机断层扫描（HR-pQCT）检测，这些女性的桡骨和胫骨远端均接受了检测。本分析纳入了至少完成一次转换后访视的 77 名女性。特立帕肽至地舒单抗（48 个月净变化-0.8%±2.4%）和联合治疗至地舒单抗（48 个月净变化+2.4%±4.1%）组的胫骨皮质体积 BMD（vBMD）在 24 个月至 48 个月之间增加，但地舒单抗至特立帕肽组（48 个月净变化-3.4%±3.2%，所有组间比较均 p<0.001）则减少。总 vBMD、皮质厚度和估计刚度（通过微有限元分析[µFEA]）的变化呈现出类似的模式，桡骨也呈现出类似的变化。相反，特立帕肽至地舒单抗和联合治疗至地舒单抗组的胫骨皮质骨孔隙度在 24 个月至 48 个月之间保持稳定（48 个月净变化分别为+7.2%±14.8%和-3.4%±12.1%），但地舒单抗至特立帕肽组的骨孔隙度增加（48 个月净变化+16.2%±11.5%，与其他组相比 p<0.05）。各组之间的小梁 vBMD 变化没有差异。综上所述，这些发现表明，在接受地舒单抗治疗的女性中，从特立帕肽转换为地舒单抗会导致总和皮质 vBMD、皮质厚度和估计强度降低，而从特立帕肽或联合治疗转换为地舒单抗会改善这些参数，且在接受联合治疗后再接受地舒单抗治疗的女性中观察到最大的改善。这些发现强烈表明，应避免在使用地舒单抗后使用特立帕肽，而在严重骨质疏松症患者中，使用特立帕肽/地舒单抗联合治疗后再单独使用地舒单抗可能是一种有用的治疗策略。
