USE OF BISPHOSPHONATES IN PREGNANCY

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(Date of issue: September 2017, Version: 3)

This is a UKTIS monograph for use by health care professionals. For case-specific advice please contact UKTIS on 0344 892 0909. To report an exposure please download and complete a pregnancy reporting form. Please encourage all women to complete an online reporting form.

A corresponding patient information leaflet on bisphosphonate use in pregnancy is available at www.medicinesinpregnancy.org.

Summary

Bisphosphonates inhibit both bone resorption by osteoclasts and hydroxyapatite crystal formulation and dissolution, thereby reducing bone remodelling and turnover. They are licensed for the treatment of osteoporosis (both idiopathic and glucocorticoid-induced), Paget’s disease of the bone, and skeletal pain associated with metastatic breast cancer, and are also used off-license in children in the management of osteogenesis imperfecta. Six bisphosphonates are currently available for clinical use in the UK: alendronic acid, ibandronic acid, pamidronate disodium, risedronate sodium, sodium clodronate and zoledronic acid.

As bisphosphonates are incorporated into bone, the terminal half-life is long (up to 10 years). Fetal exposure could therefore occur in pregnant women with a history of bisphosphonate use prior to conception as a consequence of bisphosphonates stored in maternal bone becoming mobilised.

Some animal studies have demonstrated increased embryofetal resorption/decreased implantation, impaired fetal bone ossification, urinary tract anomalies and orofacial clefting following antenatal exposure to bisphosphonates at doses lower than equivalent human therapeutic doses. Impaired uterine contractility which correlated with decreased maternal calcium concentrations and resulted in obstructed labour has also been described.

The available human exposure data are limited to a small number of uncontrolled case reports and two small cohort studies which collectively describe the outcomes of 61 pregnancies with bisphosphonate exposure either prior to conception or during pregnancy. Although these data do not currently signal a major teratogenic effect, they are insufficient to permit an accurate assessment of the risk. Controlled studies have demonstrated possible associations between preconceptual/gestational bisphosphonate exposure and increased risk of spontaneous abortion, decreased infant birth weight, and lower gestational age at delivery. However, these findings may reflect data limitations and/or uncontrolled confounding. Transient disturbances in neonatal calcium levels have also been reported in a small number of cases of maternal bisphosphonate use following exposure prior to or during pregnancy.

Exposure to bisphosphonates at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy. Where exposure to bisphosphonates has occurred, either prior to or during pregnancy, monitoring of fetal growth, skeletal development and neonatal calcium levels may be warranted. However, other risk factors may be present in individual cases. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.                      

This document is regularly reviewed and updated. Only use full UKTIS monographs downloaded directly from TOXBASE.org to be sure you are using the most up-to-date version. The summaries of these monographs are openly available on UKTIS.org.

This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to health care professionals at www.toxbase.org.

If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.

If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.

Disclaimer: Every effort has been made to ensure that this monograph was accurate and up-to-date at the time of writing, however it cannot cover every eventuality and the information providers cannot be held responsible for any adverse outcomes of the measures recommended. The final decision regarding which treatment is used for an individual patient remains the clinical responsibility of the prescriber. This material may be freely reproduced for education and not for profit purposes within the UK National Health Service, however no linking to this website or reproduction by or for commercial organisations is permitted without the express written permission of this service. This document is regularly reviewed and updated. Only use UKTIS monographs downloaded directly from TOXBASE.org or UKTIS.org to ensure you are using the most up-to-date version.