Retrospective evaluation of serum CTX levels after denosumab discontinuation in patients with or without prior exposure to bisphosphonates
Retrospective evaluation of serum CTX levels after denosumab discontinuation in patients with or without prior exposure to bisphosphonates
复制标题
既往曾接触过或未接触过双膦酸盐的患者停用狄诺塞麦后血清 CTX 水平的回顾性评估
DOI：
10.1007/s00198-017-4080-6
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发表时间：
2017
影响因子：
4
通讯作者：
Serge Ferrari
中科院分区：
文献类型：
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作者：
Brigitte Florence Uebelhart;R. Rizzoli;Serge Ferrari
SummaryDenosumab（Dmab）治疗的中止与先前暴露于双膦酸盐的脊椎病患者的血清CTX水平较低相关，与那些没有暴露于双膦酸盐的患者相比。IntroductionDmab治疗的中止之后是骨转换标志物（BTM）的短暂增加高于治疗前的值，以及加速的骨丢失，并且可能增加多发性脊椎骨折的风险。由于停用Dmab的患者中有相当一部分以前曾暴露于双膦酸盐（BPs），我们假设，由于BPs对骨的生物学效应延长，因此以前的BP治疗可以减弱骨转换的增加。（33名女性和4名男性，年龄50至84岁）。CTX水平进行了分析，根据Dmab注射（1或多个）和以前的暴露BPS.ResultsIn 8例谁只接受了1 Dmab注射，7出8个以前的BPs，没有一个显示CTX值以上的绝经前范围Dmab停药后。在17例多次注射（4.1 ± 1.4，范围2-7）后停用Dmab但既往暴露于BP的患者中，14例患者的CTX也保持在绝经前范围内（平均暴露时间6.9 ± 5.8年，范围11个月-15年; BP暴露与Dmab开始治疗之间的平均时间间隔25 ± 10个月，范围0-48）。相比之下，在12例多次治疗后停用Dmab的患者中，（5，范围3-9）次注射，既往未暴露于BP，平均11.3个月测量的平均CTX水平末次Dmab注射后（范围6-23）高于绝经前范围的上限（平均+114%，28 - 320%，p = 0.003-0.005 vs既往BP）.结论接受多次注射Dmab的患者停用Dmab后出现的较高CTX水平可通过既往暴露于BP来预防。该观察结果可能与BP对骨的持续作用有关，当RANK配体不再拮抗时，BP可阻止新形成的破骨细胞的再吸收活性。
SummaryDiscontinuation of denosumab (Dmab) therapy is associated with lower serum CTX levels in osteoporotic patients previously exposed to bisphosphonates compared to those who were not.IntroductionDiscontinuation 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.MethodsIn 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.ResultsIn 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).ConclusionThe 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.