Transplacental effects of bisphosphonates on fetal skeletal ossification and mineralization in rats

Bisphosphonates are clinically used mainly to reduce bone resorption. We st udied the transplacental effects of two bisphosphonates on the fetal skelet on in rats. Pregnant rats were treated during days 11-20 of pregnancy with daily subcutaneous injections of 0.1 mg/kg of alendronate or a newly synthe sized bisphosphonate, VS-b6. This period of pregnancy was chosen because th e active development of bones from mesenchyme through cartilaginous models occurs during that time. Histological examination of midlongitudinal sectio ns of the 21-day-old fetuses showed an increase in the amount of diaphyseal bone trabeculae with slight shortening of the diaphysis in the experimenta l fetuses, in comparison to controls. Computerized histomorphometric studie s similarly showed an increase in the amount of diaphyseal bone trabeculae with a concomitant decrease in bone marrow volume, but no change in cartila ge volume. In addition, chemical analysis of the fetal bones showed an incr ease in calcium content in the treated fetuses. C-14-alendronate was shown to pass through the rat placenta and accumulate in the fetuses, most probab ly in their bones. This is presumed because bisphosphonates are known to ac cumulate in bone, being stored there for long periods of time. It is import ant, in light of our results, to give careful consideration to the treatmen t of women with bisphosphonates at childbearing age, whenever this is neede d. (C) 1999 Wiley-Liss, Inc.