Clark Emma M, Durup Darshana
Academic Rheumatology, Musculoskeletal Research Unit, University of Bristol, Learning and Research Building, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, UK.
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Ther Adv Musculoskelet Dis. 2015 Feb;7(1):11-6. doi: 10.1177/1759720X14566424.
Inflammatory eye reactions (IERs) are rare but have been associated with medications to treat osteoporosis. The aim of this review is to summarize the current literature on the association between IERs and specific medications to treat osteoporosis (bisphosphonates, selective estrogen receptor modulators, strontium, denosumab and teriparatide). We cover the known epidemiology, potential pathogenic mechanisms and a resume of unanswered questions. Briefly, this review highlights that none of the existing randomized clinical trials were powered to identify these rare adverse events, and the majority of the information available is from spontaneous case reports and case series reporting associations between bisphosphonates and IERs. No case reports describe IERs after other anti-osteoporosis medications. Importantly, some case reports describe recurrence of the IER after affected patients were rechallenged with the same or another bisphosphonate, and that no reported cases resolved without discontinuation of the bisphosphonate. However, three large population-based cohort studies have shown conflicting results between osteoporosis treatments and IERs, but overall these studies suggest that IERs may actually be part of underlying inflammatory disease processes that also cause osteoporosis, rather than due to the medications used to treat osteoporosis themselves. There are no clear pathogenic mechanisms for how bisphosphonates could potentially cause IERs. However, the drug is secreted into the tears by the lacrimal gland and could cause irritation to the mucous membranes with subsequent release of inflammatory mediators, similar to the systemic response typically seen after infusion of bisphosphonates. However, in summary it is still not known whether there is a true causal association between bisphosphonates or other anti-osteoporosis medications and IERs, or whether it is confounding by indication and is actually due to underlying inflammatory diseases that cause both osteoporosis and IERs.
眼部炎症反应（IERs）较为罕见，但与治疗骨质疏松症的药物有关。本综述的目的是总结当前关于IERs与治疗骨质疏松症的特定药物（双膦酸盐、选择性雌激素受体调节剂、锶、地诺单抗和特立帕肽）之间关联的文献。我们涵盖了已知的流行病学、潜在的致病机制以及未解决问题的概述。简而言之，本综述强调现有的随机临床试验均未针对识别这些罕见不良事件进行足够的样本量设计，现有大部分信息来自自发的病例报告以及双膦酸盐与IERs之间关联的病例系列报告。没有病例报告描述其他抗骨质疏松药物后的IERs。重要的是，一些病例报告描述了受影响患者再次使用相同或另一种双膦酸盐后IERs复发，且没有报告的病例在未停用双膦酸盐的情况下得到缓解。然而，三项基于人群的大型队列研究在骨质疏松症治疗与IERs之间得出了相互矛盾的结果，但总体而言，这些研究表明IERs实际上可能是导致骨质疏松症的潜在炎症性疾病过程的一部分，而非归因于用于治疗骨质疏松症的药物本身。双膦酸盐如何潜在地导致IERs尚无明确的致病机制。然而，该药物由泪腺分泌到泪液中，可能会刺激黏膜，随后释放炎症介质，类似于输注双膦酸盐后典型的全身反应。然而，总体而言，双膦酸盐或其他抗骨质疏松药物与IERs之间是否存在真正的因果关联，或者是否是由适应证混淆，实际上是由于导致骨质疏松症和IERs的潜在炎症性疾病，目前仍不清楚。
