The Effects of Leptin and Estradiol Administration on Cancellous Bone Microarchitecture in Male Rats: 2710 Board #2 May 31 1:00 PM - 3:00 PM

Both leptin (Lep) and estradiol (E2) influence bone formation. However, the combinatory effects of Lep and E2 on bone microstructure require further elucidation. PURPOSE: To investigate whether central Lep gene expression and/or systemic E2 treatment alter cancellous bone microstructure in male rodents. METHODS: 3-month-old male Sprague-Dawley rats (n=28) were assigned to the following groups: 1) Vehicle-Lep (Veh-Lep) (n=7), 2) E2-Lep (n=9), 3) Veh-green florescence protein control (Veh-GFP) (n=5), or 4) E2-GFP (n=7). Lep or GFP (control) were delivered into the third ventricle of the brain at a dose of 1 mL of rAAV1 (2.3 x 1013 vg/mL). E2 (25 μg/kg diluted in 0.5 ml/kg sesame oil) or Veh (sesame oil, 0.5 ml/kg) were injected subcutaneously on a daily basis. At day 24, femurs were excised and analyzed via ex vivo micro-CT. The outcomes reported were: 1) cancellous bone volume/total volume (cBV/TV, %), 2) trabecular thickness (Tb.Th, mm), 3) trabecular number (Tb.N, #/mm), 4) trabecular separation (Tb.Sp, mm), and 5) trabecular pattern factor (Tb.Pf). Separate One-Way ANOVAs were performed and Tukey's post hoc tests were used when appropriate. RESULTS: Both E2 treated groups exhibited directionally higher cBV/TV when compared with Veh-GFP (controls), while Veh-Lep displayed directionally lower cBV/TV vs controls, although, these values did not reach the level of statistical significance. In comparison, the Veh-Lep group exhibited 40% lower cBV/TV vs E2-GFP, characterized by 35% lower Tb.N and 64% higher Tb.Sp (all p<0.05). Veh-Lep also exhibited higher Tb.Pf than E2-GFP (p<0.01), indicating a less connected trabecular network. Correspondingly, Veh-Lep displayed 36% lower cBV/TV and higher Tb.Pf values compared to E2-Lep (p<0.05). No significant differences were observed between the E2-GFP and E2-Lep groups for any cancellous outcome. CONCLUSION: Our data indicate that neither the combination nor individual administration of E2 and Lep produced higher cancellous bone outcomes than Veh-GFP controls. However, E2 treated groups exhibited higher cBV/TV than Lep treated groups. Further investigation is necessary to determine whether E2 stimulated bone accretion and/or whether Lep suppressed bone gain in our male rodent model.