Service of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
Service des Maladies Osseuses, Hôpitaux Universitaires et Faculté de Médecine de Genève, 1211, Geneva 14, Switzerland.
Osteoporos Int. 2017 Sep;28(9):2701-2705. doi: 10.1007/s00198-017-4080-6. Epub 2017 May 24.
Discontinuation of denosumab (Dmab) therapy is associated with lower serum CTX levels in osteoporotic patients previously exposed to bisphosphonates compared to those who were not.
Discontinuation of Dmab therapy is followed by a transient increase of bone turnover markers (BTMs) above pretreatment values, together with accelerated bone loss, and potentially an increased risk of multiple vertebral fractures. Since a substantial proportion of patients discontinuing Dmab have previously been exposed to bisphosphonates (BPs), we hypothesized that previous BP therapy could attenuate this increase in bone turnover because of the prolonged biological effects of BPs on bone.
In a retrospective observation, we assessed serum CTX levels between 7 and 24 months after the last Dmab injection in 37 patients (33 women and 4 men, aged 50 to 84 years). CTX levels were analyzed according to the number of Dmab injections (1 or multiple) and previous exposure to BPs.
In 8 patients who had received only 1 Dmab injection, 7 out of 8 were previously on BPs and none of them showed CTX values above the premenopausal range after Dmab discontinuation. CTX also remained in the premenopausal range in 14 out of 17 patients who discontinued Dmab after multiple (4.1 ± 1.4, range 2-7) injections but were previously exposed to BPs (mean exposure 6.9 ± 5.8 years, range 11 months-15 years; mean time interval between BP exposure and Dmab initiation 25 ± 10 months, range 0-48). In contrast, in 12 patients who discontinued Dmab after multiple (5, range 3-9) injections without prior exposure to BPs, mean CTX levels as measured on average 11.3 months (range 6-23) after the last Dmab injection were above the upper limit of premenopausal range (mean +114%, range 28-320%, p = 0.003-0.005 vs previous BPs).
The higher CTX levels occurring after Dmab discontinuation in patients who have received multiple injections may be prevented by prior exposure to BPs. This observation may be related to the persistent effects of BPs on bone that prevent the resorbing activity of newly formed osteoclasts when RANK Ligand is no more antagonized.
本研究旨在评估先前接受过双膦酸盐（BP）治疗的骨质疏松症患者与未接受过 BP 治疗的患者相比，在停止地舒单抗（Dmab）治疗后，其血清 CTX 水平是否会发生变化。
我们对 37 名（33 名女性和 4 名男性，年龄 50 至 84 岁）患者在停止 Dmab 治疗后 7 至 24 个月的血清 CTX 水平进行了回顾性观察。CTX 水平根据 Dmab 注射次数（1 次或多次）和先前接触 BP 进行分析。
在仅接受 1 次 Dmab 注射的 8 名患者中，有 7 名患者在 Dmab 停药后有 CTX 值高于绝经前范围，这 7 名患者此前均接受过 BP 治疗。在接受多次（4.1±1.4，范围 2-7）Dmab 注射且此前接受过 BP 治疗的 17 名患者中，有 14 名患者的 CTX 值仍在绝经前范围内（BP 暴露的平均时间为 6.9±5.8 年，范围为 11 个月至 15 年；BP 暴露和 Dmab 开始之间的平均时间间隔为 25±10 个月，范围为 0-48 个月）。相比之下，在 12 名在停止 Dmab 治疗后未接触过 BP 且接受多次（5，范围 3-9）Dmab 注射的患者中，在最后一次 Dmab 注射后平均 11.3 个月（范围 6-23 个月）测量的 CTX 水平高于绝经前范围上限（平均+114%，范围 28-320%，p=0.003-0.005 与先前的 BP 相比）。
在接受多次 Dmab 注射的患者中，停止 Dmab 治疗后出现的更高 CTX 水平可能是由于先前接触过 BP 所致。这一观察结果可能与 BP 对骨骼的持续作用有关，当 RANK 配体不再被拮抗时，它可以阻止新形成的破骨细胞的吸收活性。
