二膦酸盐应用于育龄期女性的生殖安全性

Reproductive safety of bisphosphonates in women of childbearing age

二膦酸盐是一种骨吸收抑制剂,在临床上越来越多地应用于育龄期女性骨代谢疾病的治疗。目前尚不清楚育龄期女性使用二膦酸盐是否会影响其后代健康。本文通过在Pubmed,Embase,Ovid,Medline等数据库上检索,回顾了过去近40年的相关文献,共检索到66例相关报道。通过检索发现,部分案例报道发现二膦酸盐可能是造成孕龄缩短、自然流产率升高以及新生儿出生体重下降的原因。有3例女性的后代在出生后被发现血钙异常。关于骨骼生殖畸形的案例包括2例马蹄双边足,1例Apert综合征以及1例佝偻病样的骨骼畸形。也有许多报道没有发现后代生殖畸形和异常血钙。偶有接受过二膦酸盐的女性乳汁喂养的孩子曾有一过性低钙血症。目前尚缺乏足够的证据证实二膦酸盐在妊娠或妊娠前期使用会产生明显的生殖畸形。但由于双膦酸盐长期存在于骨骼中的特性,有妊娠需求的育龄期女性,应该谨慎选择使用此类药物。

Bisphosphonates (BPs) are bone resorption inhibitors, which are increasingly used in the treatment of bone metabolic diseases in women of childbearing age. It is unclear whether the use of BPs in women of childbearing age will affect the health of their offspring. This article retrieved 66 reports in the past 40 years by searching on the databases of Pubmed, Embase, Ovid, Medline and so on. A number of reports found that BPs may be responsible for shortening gestational age, increasing spontaneous abortion, and decreasing neonatal birth weight. Three women′s offsprings were found to have abnormal blood calcium after birth. Cases of skeletal malformations include two bilateral talipes equinus, one Apert′s syndrome and one rickets. However, there have been many reports of no reproductive abnormalities or abnormal blood calcium level. Occasionally, children breast-fed by women who had received BPs have had a transient hypocalcemia. There is currently insufficient evidence to confirm that BPs can cause significant reproductive malformations during pregnancy or pre-pregnancy. However, due to the long-term presence of BPs in the bones, women of childbearing age who have a need for pregnancy should choose to use these drugs with caution.