ECTS Abstracts (2015) 1 P278

Diabetes Mellitus Aggravates Cortical Bone Status in Ageing Mice

Sergio Portal-Núñez1, Juan A Ardura1, Daniel Lozano1, Alexander M Proctor2, Bram C J van der Eerden3, Marijke Schreuders-Koedam3, Johannes P T M van Leeuwen3, Francisca Mulero4 & Pedro Esbrit1

1Bone and Mineral Metabolism Laboratory IIS-FJD-UAM, Madrid, Spain; 2ActiveLife Scientific, Santa Bárbara, CA, USA; 3Internal Medicine, Erasmus MC, Rotterdam, The Netherlands; 4Molecular Imaging Unit, CNIO, Madrid, Spain.

The aim of this study was to explore the consequences of diabetes mellitus (DM) on cortical bone status at older age in mice. DM was induced in male CD1 mice (18 months-old) at 3 weeks after streptozotocin injection (45 μg/g BW) (Old-DM). Mice of the same age (Old) or aged 3 months (Young) were included as controls (n=7 each group). Femora were scanned using a GE eXplore Locus μCT scanner (93-μm resolution). Cortical bone analysis was performed at 25% of distal femur height from the growth plate. Blood vessels were identified by lectin staining in paraffin-embedded femoral sections. Mouse tibiae were exposed to 3-point bending evaluation. Tibia microindentation was performed with a BioDent Reference Point Indenter (ActiveLife Science) at the tibia-fibula junction (2N, 10 cycles). Both Old groups showed lower Ct.Th but higher outer and inner perimeter and Bone Marrow Area (BMA), compared with Young (p<0.05). Moreover, inner perimeter (mm) and BMA (mm2) were increased in Old-DM vs Old (mean±SD): 4.61±0.21 vs 4.22±0.42 and 1.40±0.05 vs 1.25±0.04, respectively (p<0.05). Old mice displayed reduced work to failure, which further decreased together with reduced strain in Old-DM vs Young (p<0.05). Old mice exhibited a trend to lower Total Indentation Distance (TID,μm), 34.08±3.55; Indentation Distance Increase (IDI,μm), 4.71±0.37; and Energy Dissipation (ED,μJ), 3.59±0.45 than Young (35.05±1.56, 4.86±0.43 and 3.92±0.42, respectively); but these parameters in the Old-DM group (TID 34.69±5.52; IDI 5.43±2.44; and ED 4.04±1.67) had larger SD, indicating a more heterogeneous bone behaviour. Loading and unloading slopes was unchanged by age in these mice, but have a trend to decrease or increase, respectively, in Old-DM mice vs Old mice: 0.18±0.03 vs 0.19±0.01 and 0.28±0.05 vs 0.27±0.02 (N/μm). Blood vessel number (#/mm2) was 17±8 and 10±4 in Old and Old-DM mice (p<0.01), respectively, vs Young (29±13). Our results indicate that DM aggravates the compromised cortical bone quality in Old mice, which might increase fracture risk in age-related osteopenia.

Disclosure: The authors declared no competing interests. This work has been founded by grants of Instituto de Salud Carlos III (PI11/00449) and RETICEF (RD12/0043/0008).