Therapeutic potential of zoledronic acid in enhancing immune function in aged mice (106.3)

Abstract

Abstract Hematopoietic stem cells originate in the bone marrow and give rise to immune cells. Zoledronic acid (ZA) is a bisphosphonate shown to modulate skeletal and immune systems. Hip fracture patients treated with ZA had a significant increase in bone density and increased longevity over placebo. We hypothesize ZA treatment will promote bone density in aged mice which in turn will enhance immunity. Young/aged mice were treated with saline or ZA (IV 100ug/kg) and euthanized at 1, 3 and 6 months to determine the impact of ZA on immune homeostasis. Compared to control, ZA-treated young mice showed significant improvement in bone volume. ZA-treated aged mice showed a qualitative improvement in bone volume. Frequency of DN thymocytes and sjTREC were increased over control in ZA-treated aged mice, suggesting improved thymopoiesis. Potential of ZA for improving immunity was also explored. Mice were treated with ZA (3 mo), immunized with flu HA protein (IN, d0,7,14) and then challenged with PR8 influenza (d42). HA-specific Ab response and survival was assessed. No difference in response was observed with ZA treatment in young mice. ZA-treated aged mice however had a stronger HA-specific response over control, suggesting ZA enhanced host response to immunization. Survival of ZA-treated aged mice was also higher than control, suggesting a single infusion of ZA enhances immunity. Given these data, further investigation of ZA as a potential therapeutic for immune senescence is warranted.