Pharmacoepidemiology and Pharmacovigilance Department, Spanish Agency of Medicines and Medical Devices (AEMPS), Calle Campezo n° 1, Edificio 8, 28022 Madrid, Spain.
Global CoE of Data Intelligence, Fujitsu, Camino Cerro de los Gamos, 1, 28224, Pozuelo de Alarcón, Madrid, Spain.
Bone. 2025 Jan;190:117325. doi: 10.1016/j.bone.2024.117325. Epub 2024 Nov 7.
Discontinuation of anti-osteoporotic medications (AOM), except for bisphosphonates (BP), is not favorable for the bone, being especially negative for Prolia® (60 mg denosumab-DMAb). DMAb withdrawal leads to a rapid and significant increase in bone turnover markers, and to an important loss in bone mineral density, which has been associated with an increased risk of multiple vertebral fractures (MVF).
To assess the risk of MVF (≥2 VF) recorded at the same time) after discontinuation of different AOM.
A case-control analysis nested in a cohort of new users of DMAb, BP, Teriparatide (TPTD), Strontium Ranelate (SrRan), or selective estrogen receptor modulators (SERM), aged ≥18 years from 2011 to 2018 with ≥1 year of prior available data, was performed using the Pharmacoepidemiological Research Database for the Public Health System (BIFAP) in Spain. Cases were first MVF recorded after AOM initiation (index date). Up to 4 controls per case, matched on index date, age, sex, and location, were randomly selected among non-cases from the cohort. Adjusted conditional OR (AOR) and 95 % CI: between discontinuation of a given AOM (supply of the last prescription ended >90 days before the index date) and occurrence of MVF was assessed compared with their current use and alternatively, with discontinuation of BP, among individuals who did not switch therapy in the study.
A total of 532 incident cases of MVF were identified and matched to 2121 controls (86 % women; median age 73 years). AOR of MVF after DMAb discontinuation was 2.82 (1.73-4.60) compared with DMAb current use. No risk was seen for the other AOM. The AOR was highest between 3 and 9 months after discontinuation of denosumab (8.58; 3.98-18.48) and after >1 year of cumulative use (5- and 11-times increased risk when discontinuing after 1-2 years and 2-5 years of use, respectively). Compared with BP discontinuers, discontinuation of DMAb (2.73, 1.66-4.50), TPTD (2.06, 1.09-3.88) and SrRan (1.93, 1.23-3.05) showed an increased risk of MVF; current use of DMAb showed no protective effect (1.44; 0.95-2.17).
Discontinuation of DMAb was associated with an immediate increased risk of MVF, especially after longest treatments compared with patients who continued therapy or discontinued BP. Although there were increased risks after discontinuation of other AOM in comparison with first- line therapy (BP), these were not found when the reference was current users. Confounding by indication cannot be discarded. Larger studies should investigate reasons for discontinuation and preventive retreatment options.
除双膦酸盐（BP）外，抗骨质疏松药物（AOM）的停药不利于骨骼健康，特别是对于普罗力（60mg 地舒单抗-DMAb）而言。地舒单抗停药会导致骨转换标志物的快速显著增加，并导致骨密度显著下降，这与多发椎体骨折（MVF）风险增加相关。
评估不同 AOM 停药后 MVF（≥2 个椎体骨折）的发生风险。
该研究使用西班牙公共卫生系统药物流行病学研究数据库（BIFAP），对 2011 年至 2018 年间新使用地舒单抗、BP、特立帕肽（TPTD）、雷奈酸锶（SrRan）或选择性雌激素受体调节剂（SERM）的新用户队列中的病例-对照分析进行嵌套，患者年龄≥18 岁，且在 AOM 起始前有≥1 年的可用数据。病例为 AOM 起始后首次记录的 MVF（索引日期）。在队列中，按照索引日期、年龄、性别和地点，为每个病例随机匹配至多 4 名对照。在研究中未进行治疗转换的个体中，评估特定 AOM 停药（最后一次处方供应结束>90 天前的索引日期）与 MVF 发生之间的调整后条件比值比（AOR）和 95%置信区间（CI）：与当前使用相比，或与 BP 停药相比。
共确定了 532 例 MVF 新发病例，并与 2121 例对照相匹配（86%为女性；中位年龄 73 岁）。与当前使用地舒单抗相比，地舒单抗停药后的 MVF AOR 为 2.82（1.73-4.60）。其他 AOM 未观察到风险。停药后 3-9 个月（8.58；3.98-18.48）和累积使用>1 年（停药后 1-2 年和 2-5 年时风险分别增加 5 倍和 11 倍）时，地舒单抗的 AOR 最高。与 BP 停药者相比，地舒单抗（2.73，1.66-4.50）、TPTD（2.06，1.09-3.88）和 SrRan（1.93，1.23-3.05）停药与 MVF 风险增加相关；当前使用地舒单抗无保护作用（1.44；0.95-2.17）。
与继续治疗或停药 BP 的患者相比，地舒单抗停药与 MVF 的即刻风险增加相关，尤其是在接受最长治疗的患者中。尽管与一线治疗（BP）相比，其他 AOM 停药后的风险增加，但与当前使用者相比，这些风险并未出现。不能排除指示性混杂。应进行更大规模的研究以调查停药原因和预防性再治疗选择。
