Review Bisphosphonates in patients with autoimmune rheumatic diseases: Can they be used in women of childbearing age? Inès Losada a , Leonardo Sartori b , Elena Di Gianantonio c , Margherita Zen d , Maurizio Clementi c , Andrea Doria d, ⁎ a Servicio de Medicina Interna, Hospital Son Llatzer, Mallorca Spain b Clinica Medica I, Department of Medical and Surgical Sciences, University of Padova Italy c Clinical and Epidemiological Genetics, Department of Pediatrics, University of Padova Italy d Division of Rheumatology, Department of Clinical and Experimental Medicine, University of Padova Italy abstract article info Article history: Received 1 March 2010 Accepted 15 March 2010 Available online 20 March 2010 Keywords: Autoimmunity Bisphosphonates Corticosteroids Foetus Osteoporosis Pregnancy Autoimmune rheumatic diseases (ARD) are prevalent in women during their childbearing age. For their treatment, high doses of corticosteroid (CS) for long-term periods are often required, increasing the risk of bone loss. According to recent guidelines, bisphosphonates (BP) should be used as first line treatment to prevent CS induced osteoporosis. However, due to their long-term release from bone and their ability to cross the placenta, it has been suggested to avoid BP in women during their fertile years. BP seem to decrease foetus bone length in pregnant animals, but not in humans, at least, when they are administered at therapeutic dosage. BP are embryo toxic in animals when used at high dosage. In a systematic literature review, we found 58 women treated with BP close before or during pregnancy, showing no related congenital malformations. However, the Unit of Clinical and Epidemiological Genetics in University of Padova collected ten cases of women treated with BP during pregnancy, reporting 20% of congenital malformations. Thus, we suggest to avoid BP during pregnancy and caution with their use in fertile women. When they have to be given before pregnancy, specific affinities of the BP have to be considered to plan the washout period beforehand. © 2010 Elsevier B.V. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 548 2. Use of BP in patients with ARD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 548 2.1. CS induced osteoporosis (OP) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 548 2.2. Avascular necrosis (AVN) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 548 2.3. Calcinosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 548 2.4. Other potential indications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 548 3. Adverse effects of BP IN patients with ARD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 549 4. BP pharmacokinetics, pharmacodistribution, and transplacental passage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 549 5. Potential effects of BP on pregnancy and lactation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 549 5.1. Effects on embryogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 549 5.2. Effects on bone growth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 551 5.3. Effects on breastfeeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 551 6. The timing of stopping BP before pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 551 7. The experience of the unit of clinical and epidemiological genetics of the University of Padova (CEPIG) . . . . . . . . . . . . . . . . . . . 551 8. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 551 . Take-home messages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 551 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 551 Autoimmunity Reviews 9 (2010) 547–552 ⁎ Corresponding author. Division of Rheumatology, University of Padova, Via Giustiniani, 2, 35128 Padova, Italy. Tel.: + 39 049 8212190, fax: + 39 049 8212191. E-mail address: adoria@unipd.it (A. Doria). 1568-9972/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.autrev.2010.03.002 Contents lists available at ScienceDirect Autoimmunity Reviews journal homepage: www.elsevier.com/locate/autrev