Aerobic training improves bone fragility by reducing the inflammatory microenvironment in bone tissue in type 2 diabetes

Aerobic training (AT) is indicated in type 2 diabetes mellitus (T2DM) to control hyperglycaemia and inflam-mation. AT improves bone microarchitecture and resistance to fracture. The intensity of AT and the mechanisms that lead to the improvement in bone quality are still unknown. Using a mouse model of T2DM, we evaluated the effects of two intensities of forced AT. We divided mice into: sedentary (SED), T2DM-SED, low runners (LOW), T2DM-LOW, high runners (HIGH) and T2DM-HIGH. The AT for low was 8 m/minute (m/min); 5 degrees slope or high 18 m/min; 15 degrees slope for 2 months. We measured metabolic parameters, the serum cytokines concentration, lipocalin-2 (LCN-2) and adiponectin; and the tibial concentrations of LCN-2, tumour necrosis factor alpha (TNF-alpha) and protein carbonylation (CO). We evaluated femur morphometry and biomechanical properties. We per-formed multiple correlation analysis. The T2DM-LOW versus T2DM-SED group, shown an increase of interleukin (IL)-10 (417 +/- 90 vs 102 +/- 25 pg/mL) and improved trabecular bone (BV/TV: 31.8 +/- 2.3 vs 19.25 +/- 1.4%; Tb. Sp.: 1.62 +/- 0.02 vs 2.0 +/- 0.07 mm), by a decrease bone CO (3.4 +/- 0.1 vs 6.0 +/- 0.5 nmol/mg), bone TNF-alpha (84 +/- 4 vs 239 +/- 13 pg/mL) and LCN-2 (2887 +/- 23 vs 3418 +/- 105 pg/mL). The T2DM-HIGH versus T2DM-SED group showed a greater hypoglycaemic effect (228 +/- 10 vs 408 +/- 5 mg/dL), with improved cortical bone density (0.26 +/- 0.012 vs 0.21 +/- 0.007 mm) and fracture resistance (102 +/- 8 vs 78 +/- 5 MPa), by a reduction of bone TNF-alpha (77 +/- 34 vs 239 +/- 13 pg/mL); LCN-2 (2768 +/- 20 vs 3418 +/- 105 pg/mL) and CO (4.8 +/- 0.5 vs 6.0 +/- 0.5 nmol/mg). In conclusion, AT improves bone morphometry and biomechanical properties by reducing the bone inflammatory microenvironment.