Department of Medicine, Endocrine Unit, Massachusetts General Hospital, Harvard University, Boston, MA, USA.
Department of Medicine, Endocrine Unit, Austin Hospital, The University of Melbourne, Heidelberg, VIC, Australia.
J Bone Miner Res. 2021 May;36(5):921-930. doi: 10.1002/jbmr.4259. Epub 2021 Feb 16.
Combined teriparatide and denosumab rapidly and substantially increases bone mineral density (BMD) at all anatomic sites. Discontinuation of denosumab however, results in high-turnover bone loss and increased fracture risk. The optimal way to prevent this bone loss remains undefined. This study is a preplanned extension of the DATA-HD study, where postmenopausal women with osteoporosis were randomized to receive 9 months of either 20 μg or 40 μg of teriparatide daily overlapping with denosumab (60 mg administered at months 3 and 9). At the completion of this 15-month study, women were invited to enroll in the DATA-HD Extension where they received a single dose of zoledronic acid (5 mg) 24 to 35 weeks after the last denosumab dose. Areal BMD and bone turnover markers were measured at month 27 and 42 (12 and 27 months after zoledronic acid, respectively) and spine and hip volumetric bone density by quantitative CT was measured at month 42. Fifty-three women enrolled in the DATA-HD Extension. At the femoral neck and total hip, the mean 5.6% and 5.1% gains in BMD achieved from month 0 to 15 were maintained both 12 and 27 months after zoledronic acid administration. At the spine, the mean 13.6% gain in BMD achieved from month 0 to 15 was maintained for the first 12 months but modestly decreased thereafter, resulting in a 3.0% reduction (95% CI, -4.0% to -2.0%, p < .0001) 27 months after zoledronic acid. The pattern of BMD changes between months 15 and 42 were qualitatively similar in the 20-μg and 40-μg groups. A single dose of zoledronic acid effectively maintains the large and rapid total hip and femoral neck BMD increases achieved with combination teriparatide/denosumab therapy for at least 27 months following the transition. Spine BMD was also largely, though not fully, maintained during this period. These data suggest that the DATA-HD Extension regimen may be an effective strategy in the long-term management of patients at high risk of fragility fracture. © 2021 American Society for Bone and Mineral Research (ASBMR).
特立帕肽与地舒单抗联合使用可迅速且显著增加所有解剖部位的骨密度（BMD）。然而，停用地舒单抗会导致高转换性骨丢失和骨折风险增加。预防这种骨丢失的最佳方法尚未确定。本研究是 DATA-HD 研究的预计划扩展，该研究将绝经后骨质疏松症女性随机分为两组，分别接受每日 20 μg 或 40 μg 特立帕肽联合地舒单抗治疗（第 3 个月和第 9 个月给予 60 mg 地舒单抗）。在这项为期 15 个月的研究完成后，女性被邀请参加 DATA-HD 扩展研究，在该研究中，她们在最后一次地舒单抗给药后 24 至 35 周接受单次唑来膦酸（5 mg）治疗。在第 27 个月和第 42 个月（分别为唑来膦酸治疗后 12 个月和 27 个月）测量 BMD 面积和骨转换标志物，并在第 42 个月通过定量 CT 测量脊柱和髋部容积骨密度。53 名女性参加了 DATA-HD 扩展研究。在股骨颈和全髋关节，从 0 个月到 15 个月，BMD 平均增加 5.6%和 5.1%，在唑来膦酸给药后 12 个月和 27 个月均得到维持。在脊柱，从 0 个月到 15 个月，BMD 平均增加 13.6%，在前 12 个月保持不变，但此后略有下降，导致 27 个月后减少 3.0%（95%CI，-4.0%至-2.0%，p<.0001）。在 20 μg 和 40 μg 组中，从第 15 个月到第 42 个月的 BMD 变化模式在定性上是相似的。单次唑来膦酸治疗可有效维持特立帕肽/地舒单抗联合治疗后至少 27 个月的全髋关节和股骨颈 BMD 快速增加。在此期间，脊柱 BMD 也在很大程度上得到维持，尽管不是完全维持。这些数据表明，DATA-HD 扩展方案可能是治疗高脆性骨折风险患者的一种有效策略。
