The safety of bisphosphonate use in pre-menopausal women on corticosteroids

Glucocorticoid therapy, the mainstay treatment of many chronic diseases, has many complications including osteoporosis. Pre-menopausal women requiring glucocorticoids are at a significant risk of developing glucocorticoid-induced osteoporosis. Bisphosphonate therapy is a vital option in the prevention and treatment of glucocorticoid-induced osteoporosis. Animal studies with bisphosphonates have displayed maternal toxicity, foetal underdevelopment, embryolethlity, hypocalcaemia and skeletal retardation during pregnancy. Bisphosphonates are therefore contra-indicated in pregnancy and have a FDA category C pregnancy risk. Their use in pre-menopausal women prior to conception may also pose a teratogenic risk because bisphosphonates remain in mineralised bone for several years. Consequently a clinical dilemma exists in treating and preventing glucocorticoid-induced osteoporosis in pre-menopausal women. This article aims to review the available evidence regarding the use of bisphosphonates in pre-menopausal woman. Bisphosphonate treatment of metastatic hypercalcaemia during pregnancy has not demonstrated adverse foetal events. Cases of pre-conception bisphosphonate exposure have failed to describe developmental or bone density abnormalities, however neonatal hypocalcaemia has occurred. Lower birth weight, lower gestational age at birth and higher rate of spontaneous abortion in mothers with pre-conception and first trimester bisphosphonate exposure have been described but notable confounding factors and lack of adequate sample size make extrapolation of this data difficult. Human pre-conception and first trimester bisphosphonate use has to date not been associated with the same adverse effects evident in animals however, larger well-controlled studies in premenopausal women with pre-conception and peri-natal bisphosphonate exposure are required to confirm the safe use throughout pregnancy to both mother and foetus.