IADR Abstract Archives
Administration of anti-RANKL antibody to pregnant mice results in impaired development of mammary gland and death of newborns
Objectives: Denosumab, a fully human monoclonal antibody (Ab) that neutralizes receptor activator of nuclear factor- B ligand (RANKL) and blocks bone resorption by osteoclasts, is currently administered to patients with osteoporosis and bone metastasis. However it is unclear how blocking RANKL activity affects pregnant mothers and their newborns.
Methods: We injected an anti-mouse-RANKL antibody （5 mg/kg） into mother mice On gestation day 7, and analyzed the mothers and newborns, including bones and mammary glands.
Results: Mothers injected with the anti-RANKL antibody had increased bone mass compared with the control mothers, although osteoclast number and serum level of tartrate-resistant acid phosphatase (TRAP) were increased at the end of pregnancy. Newborn mice exposed to the antibody in utero were normally born with increased bone mass, but they died within 48 hours after birth. All newborns were found to have no milk in their stomachs, suggesting that they died due to a maternal defect in lactation. Consistent with this, anti-RANKL antibody-injected mothers displayed impaired mammary gland development. However, fostering by healthy surrogate mothers rescued only 33% of antibody-exposed newborns, suggesting that neonatal lethality was due, at least in part, to an intrinsic defect in the newborns.
Conclusions: Anti-RANKL Ab administration during pregnancy results in not only an undesirable increase in bone mass, but also has harmful effects on newborn survival.
Methods: We injected an anti-mouse-RANKL antibody （5 mg/kg） into mother mice On gestation day 7, and analyzed the mothers and newborns, including bones and mammary glands.
Results: Mothers injected with the anti-RANKL antibody had increased bone mass compared with the control mothers, although osteoclast number and serum level of tartrate-resistant acid phosphatase (TRAP) were increased at the end of pregnancy. Newborn mice exposed to the antibody in utero were normally born with increased bone mass, but they died within 48 hours after birth. All newborns were found to have no milk in their stomachs, suggesting that they died due to a maternal defect in lactation. Consistent with this, anti-RANKL antibody-injected mothers displayed impaired mammary gland development. However, fostering by healthy surrogate mothers rescued only 33% of antibody-exposed newborns, suggesting that neonatal lethality was due, at least in part, to an intrinsic defect in the newborns.
Conclusions: Anti-RANKL Ab administration during pregnancy results in not only an undesirable increase in bone mass, but also has harmful effects on newborn survival.