Djokanovic Nada, Klieger-Grossmann Chagit, Koren Gideon
The Motherisk Program, Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, University of Toronto, Toronto ON.
J Obstet Gynaecol Can. 2008 Dec;30(12):1146-1148. doi: 10.1016/S1701-2163(16)34026-9.
Bisphosphonates are clinically used in the treatment of various bone diseases including corticosteroid-induced osteoporosis, hypercalcemia associated with malignancy, and osteogenesis imperfecta. They are therefore often used in women of childbearing age, but little is known about their possible effects on the human embryo and fetus. Animal studies have revealed unfavourable effects of bisphosphonate treatment on the fetus, mainly in the skeleton. Since bisphosphonates are retained for a long time in the human skeleton, concerns have been raised that even pre-pregnancy administration of bisphosphonates may result in embryofetal exposure and alter fetal bone modelling. To obtain current information on the risks and safety of bisphosphonate use in pregnancy, we performed a systematic search of the Medline and Embase databases, from 1950 and 1974, respectively, to September 2008. Fifty-one cases of exposure to bisphosphonates before or during pregnancy were identified; none of them described any skeletal abnormalities or other congenital malformations in the infants. The bisphosphonates used were alendronate (32 cases), pamidronate (11), etidronate (5), risedronate (2), and zoledronic acid (1). Although in theory bisphosphonates may affect bone modelling and development in the fetus, the 51 cases reported to date did not detect such pathology.
双膦酸盐类药物在临床上用于治疗多种骨病,包括皮质类固醇诱导的骨质疏松症、与恶性肿瘤相关的高钙血症和成骨不全症。因此,它们常用于育龄女性,但人们对其对人类胚胎和胎儿可能产生的影响知之甚少。动物研究显示,双膦酸盐治疗对胎儿有不良影响,主要是对骨骼的影响。由于双膦酸盐类药物会在人体骨骼中长时间留存,因此有人担心,即使在怀孕前使用双膦酸盐类药物也可能导致胚胎-胎儿暴露,并改变胎儿骨骼的形成。为了获取有关孕期使用双膦酸盐类药物的风险和安全性的最新信息,我们分别对1950年和1974年至2008年9月期间的Medline和Embase数据库进行了系统检索。共识别出51例孕期或孕前接触双膦酸盐类药物的病例;其中无一例描述婴儿有任何骨骼异常或其他先天性畸形。所使用的双膦酸盐类药物为阿仑膦酸钠(32例)、帕米膦酸钠(11例)、依替膦酸钠(5例)、利塞膦酸钠(2例)和唑来膦酸(1例)。虽然理论上双膦酸盐类药物可能会影响胎儿骨骼的形成和发育,但迄今为止报告的51例病例中均未发现此类病变。