Leder Benjamin Z, Tsai Joy N, Jiang Linda A, Lee Hang
Harvard Medical School, Endocrine Unit, Massachusetts General Hospital, United States.
Harvard Medical School, Endocrine Unit, Massachusetts General Hospital, United States.
Bone. 2017 May;98:54-58. doi: 10.1016/j.bone.2017.03.006. Epub 2017 Mar 9.
When teriparatide and denosumab are discontinued, bone mineral density (BMD) abruptly decreases. To compare rates of bone loss in postmenopausal women who discontinue denosumab or teriparatide and receive no additional prescription osteoporosis medications to women who discontinue these drugs followed by prompt antiresorptive therapy, we asked women concluding the Denosumab and Teriparatide Administration (DATA) study and its extension, DATA-Switch, to return for BMD measurements 1-2years after study completion. In these studies, women received 2-years of either teriparatide, denosumab or both medications followed by 2-years of the alternate therapy (women who received combination therapy initially received an additional 2-years of denosumab alone). Fifty of 69 women who completed DATA-Switch returned after a mean of 15.4±3.5months. Of the 28 women who received antiresorptive therapy (10 denosumab, 10 oral bisphosphonates, 8 intravenous zoledronic acid), the mean interval between ending DATA-Switch and beginning antiresorptive therapy was 3.8±3.1months. In the 22 women not receiving follow-up therapy, femoral neck, total hip, and spine BMD decreased by -4.2±4.3%, -4.5±3.6%, and -10.0±5.4%, respectively, while BMD was maintained in those who did receive follow-up antiresorptive drugs (femoral neck, total hip, and spine BMD changes of -0.6±2.7%, -0.8±3.1%, and -1.2±4.7%, respectively, P<0.001 for all between-group comparisons). Among untreated women, femoral neck BMD decreased more in those discontinuing denosumab (-5.8±4.0%) than in those discontinuing teriparatide (-0.8±2.6%, P=0.008). Total hip BMD, but not spine BMD, showed a similar pattern. Among treated women, denosumab increased femoral neck and total hip BMD more than bisphosphonates while BMD changes at the spine did not differ significantly. In summary, the large teriparatide and denosumab-induced gains in BMD achieved with 4years of intensive therapy in the DATA and DATA-Switch studies were maintained in patients who received prompt antiresorptive therapy but not in those left untreated. These results demonstrate the negative consequences of delaying consolidation therapy in women treated with these drugs and underscore the importance of timely medication transitions in such patients.
特立帕肽和地诺单抗停用后,骨密度(BMD)会突然下降。为了比较停用 地诺单抗或特立帕肽且未接受其他骨质疏松症处方药物治疗的绝经后女性与停用这些药物后立即接受抗吸收治疗的女性的骨质流失率,我们邀请完成地诺单抗和特立帕肽给药(DATA)研究及其扩展研究 DATA-Switch 的女性在研究完成后 1 - 2 年返回进行骨密度测量。在这些研究中,女性接受了 2 年的特立帕肽、地诺单抗或两种药物治疗,随后接受 2 年的替代治疗(最初接受联合治疗的女性单独额外接受 2 年的地诺单抗治疗)。69 名完成 DATA-Switch 的女性中有 50 名在平均 15.4±3.5 个月后返回。在 28 名接受抗吸收治疗的女性中(10 名接受地诺单抗,10 名接受口服双膦酸盐,8 名接受静脉注射唑来膦酸),结束 DATA-Switch 至开始抗吸收治疗的平均间隔时间为 3.8±3.1 个月。在 22 名未接受后续治疗的女性中,股骨颈、全髋和脊柱的骨密度分别下降了 -4.2±4.3%、-4.5±3.6% 和 -10.0±5.4%,而接受后续抗吸收药物治疗的女性骨密度得以维持(股骨颈、全髋和脊柱骨密度变化分别为 -0.6±2.7%、-0.8±3.1% 和 -1.2±4.7%,所有组间比较 P<0.001)。在未治疗的女性中,停用 地诺单抗的女性股骨颈骨密度下降幅度(-5.8±4.0%)大于停用特立帕肽的女性(-0.8±2.6%,P = 0.008)。全髋骨密度呈现类似模式,但脊柱骨密度并非如此。在接受治疗的女性中,地诺单抗使股骨颈和全髋骨密度的增加幅度大于双膦酸盐,而脊柱骨密度变化无显著差异。总之,在 DATA 和 DATA-Switch 研究中通过 4 年强化治疗使骨密度大幅增加的特立帕肽和地诺单抗,在接受立即抗吸收治疗的患者中得以维持,但未治疗的患者则不然。这些结果表明了在接受这些药物治疗的女性中延迟巩固治疗的负面后果,并强调了在此类患者中及时进行药物转换的重要性。