Alpha-1 antitrypsin reduces ovariectomy-induced bone loss in mice

Proinflammatory cytokines are primary mediators of bone loss in estrogen deficiency. This study determined whether alpha-1 antitrypsin (AAT), a multifunctional protein with proteinase inhibitor and anti-inflammatory activities, mitigates bone loss induced by estrogen deficiency. Mice were either sham-operated or ovariectomized and injected with either AAT or phosphate buffered saline (PBS). Ovariectomy resulted in decreased wet uterus weight, significant bone loss, increased serum leptin concentrations, and higher body weight compared to sham. AAT injection increased tibial trabecular bone volume/total volume and trabecular thickness compared to PBS injection in ovariectomized mice. Ovariectomized mice with AAT treatment had higher uterus weight, lower serum osteocalcin levels, fewer bone marrow tartrate-resistant acid phosphatase-positive osteoclasts, and less expression of calcitonin receptor in bone than that in PBS-injected mice. These data demonstrate that AAT mitigates ovariectomy-induced bone loss in mice possibly through inhibiting osteoclast activity and bone resorption.