BIFAP, Division of Pharmacoepidemiology and Pharmacovigilance, Spanish Agency of Medicines and Medical Devices (AEMPS), Calle Campezo 1, Edif. 8, 28022, Madrid, Spain.
Department of Primary Care and Population Health, University College London, Rowland Hill Street, London, NW3 2PF, UK.
Osteoporos Int. 2018 Feb;29(2):467-478. doi: 10.1007/s00198-017-4308-5. Epub 2017 Dec 3.
The venous thromboembolism risk among anti-osteoporotics is unknown. In this primary care study, the risk with other bisphosphonates [1.05 (0.94-1.18) and 0.96 (0.78-1.18)], strontium [0.90 (0.61-1.34) and 1.19 (0.82-1.74)], in the UK and Spain respectively, and denosumab [1.77 (0.25-12.66)] and teriparatide [1.27 (0.59-2.71)] in Spain, did not differ versus alendronate.
Most of the known adverse drug reactions described for anti-osteoporosis medication (AOM) have been described in studies comparing AOM users to non-users. We aimed to compare the risk of venous thromboembolism (VTE) among incident users of different AOM compared to alendronate (first line therapy).
Two cohort studies were performed using data from the UK (CPRD) and Spain (BIFAP) primary care records separately. All patients aged ≥ 50 years with at least 1 year of data available and a new prescription or dispensation of AOM (date for therapy initiation) during 2000-2014 (CPRD) or 2001-2013 (BIFAP) were included. Users of raloxifene/bazedoxifene were excluded from both databases. Five exposure cohorts were identified according to first treatment: (1) alendronate, (2) other bisphosphonates, (3) strontium ranelate, (4) denosumab, and (5) teriparatide. Participants were followed from the day after therapy initiation to the earliest of a treated VTE (cases), end of AOM treatment (defined by a refill gap of 180 days), switching to an alternative AOM, drop-out, death, or end of study period. Incidence rates of VTE were estimated by cohort. Adjusted hazard ratios (HR 95%CI) were estimated according to drug used.
Overall, 2035/159,209 (1.28%) in CPRD and 401/83,334 (0.48%) in BIFAP had VTE. Compared to alendronate, adjusted HR of VTE were 1.05 (0.94-1.18) and 0.96 (0.78-1.18) for other bisphosphonates, and 0.90 (0.61-1.34) and 1.19 (0.82-1.74) for strontium in CPRD and BIFAP, respectively; 1.77 (0.25-12.66) for denosumab and 1.27 (0.59-2.71) for teriparatide in BIFAP.
VTE risk during AO therapy did not differ by AOM drug use. Our data does not support an increased risk of VTE associated with strontium ranelate use in the community.
本研究旨在比较不同抗骨质疏松药物（AOM）使用者与阿仑膦酸钠使用者相比，静脉血栓栓塞（VTE）的风险。
使用英国（CPRD）和西班牙（BIFAP）初级保健记录中的数据分别进行了两项队列研究。所有年龄≥50 岁的患者，在 2000-2014 年（CPRD）或 2001-2013 年（BIFAP）期间至少有 1 年的数据，并接受了 AOM 的新处方或配药（治疗开始日期），被纳入研究。这两个数据库都排除了雷洛昔芬/巴多昔芬的使用者。根据首次治疗，确定了 5 个暴露队列：（1）阿仑膦酸钠；（2）其他双膦酸盐；（3）雷洛昔芬/巴多昔芬；（4）唑来膦酸；（5）特立帕肽。参与者从治疗开始后的第二天开始随访，直至发生治疗性 VTE（病例），或 AOM 治疗结束（定义为 180 天的配药间隔），或改用其他 AOM，或脱落，或死亡，或研究期结束。通过队列估计 VTE 的发生率。根据药物使用情况，估计调整后的危险比（HR 95%CI）。
在 CPRD 中，共有 2035/159209（1.28%）例和在 BIFAP 中，有 401/83334（0.48%）例发生 VTE。与阿仑膦酸钠相比，CPRD 和 BIFAP 中其他双膦酸盐的 VTE 调整后 HR 分别为 1.05（0.94-1.18）和 0.96（0.78-1.18），雷洛昔芬/巴多昔芬的 HR 分别为 0.90（0.61-1.34）和 1.19（0.82-1.74）；BIFAP 中唑来膦酸的 HR 为 1.77（0.25-12.66），特立帕肽的 HR 为 1.27（0.59-2.71）。
在 AO 治疗期间，VTE 风险不因 AOM 药物使用而不同。我们的数据不支持社区中使用雷洛昔芬/巴多昔芬与 VTE 风险增加相关。
