Alendronate is known to increase bone density and decrease fracture incidence in women with osteoporosis (1) (Black, J Clin Endocrin Metab, 2000). Recently, bisphosphonates have been tried in clinical studies on children with osteogenesis imperfecta (OI), also known as “brittle bone disease,” with promising results, including decreased fracture incidence, increased bone density and improvement in ambulation (2) (Plotkin, J Clin Endicrinol Metab, 2000). Since many of the more severe forms of OI result in fractures in utero and in the process of childbirth, these severely affected infants may benefit from treatment initiated prior to birth. Several recent publications have affirmed that bisphosphonates do cross the placenta in rats and bind to fetal bone (3) (Patlas, Teratology, 1999) (4) (Graepel, Arzneimittelforschung, 1992). Furthermore, reproduction toxicity studies in rats and rabbits using the bisphosphonate pamidronate ruled out any teratogenic potential. The current study is a pilot study in wild-type mice to see if both the mothers and nursing pups can tolerate the treatment and to examine effects of in utero treatment on offspring. If we can prove that alendronate can be safely administered to wildtype mice before and during pregnancy, then a larger study will be performed to test the drug in mice affected with OI. The study design included three treatment groups: (1) control mother receiving saline via subcutaneous injection, (2) mothers receiving alendronate from 1 month prior to conception and throughout pregnancy, and (3) mothers receiving alendronate from 1 month prior to conception. Offspring were sacrificed randomly at three time points: 3 weeks of age, 6 weeks of age, and 14 weeks of age. After sacrifice, the bones were dissected and analyzed for bone density and geometrical properties. Histological analyses are ongoing. Safety measures analyzed included weight gain and femur length in both mothers and offspring. No materno-toxicity or embryo-lethality was noted at the dose administered, in contrast to prior rat studies in which rat dams failed to complete or survive a protracted parturition, secondary to hypocalcemia, resulting in a reduced number of viable pups. Analyses of geometrical properties revealed treatment of wildtype mice with alendronate both pre and post-conception appears to be safe to both the mothers and offspring. Analyses of bone density revealed in wildtype mice treated with alendronate both pre and post-conception femoral metaphyseal density increased in offspring by 14 weeks of age. In wildtype mice treated with alendronate pre-conception, cortical density in offspring increased by 6 weeks of age. Histological analyses of tibial and spinal bone will be performed to evaluate bone quality with alendronate treatment. Future studies will examine treatment of OI in utero with alendronate using a mouse model of osteogenesis imperfecta.