Skeletal effects of plyometric exercise and metformin in ovariectomized rats.

Estrogen deficiency causes bone loss and skeletal muscle dysfunction, and attenuates the musculoskeletal effects of exercise. The anti-diabetic drug metformin has been suggested to promote beneficial skeletal effects. To explore whether metformin can improve musculoskeletal training response during estrogen deficiency, we investigated the skeletal effects of plyometric exercise and metformin, in an ovarectomized (OVX) rat model of osteoporosis. Female Sprague Dawley rats, 12 weeks of age, rats were allocated to a sham-operated group (Sham), and four OVX groups; metformin (OVX-Met), exercise (OVX-Ex), combined metformin and exercise (OVX-MetEx) and a control group (OVX-Ctr), n = 12/group. Dual X-ray absorptiometry, micro computed tomography, fracture toughness testing, histomorphometry and plasma analyses were performed to explore skeletal effects. All intervention groups exhibited a higher gain in femoral bone mineral density (BMD) than OVX-Ctr (p < .01). The combined intervention also resulted in a higher gain in femoral and spine BMD compared to OVX-Met (p < .01). Both exercise groups displayed improved microarchitecture, including both cortical and trabecular parameters (p < .05). This was most evident in the OVX-MetEx group where several indices were at sham level or superior to OVX-Ctr (p < .05). The OVX-MetEx group also exhibited an enhanced toughening effect compared to the other OVX groups (p < .05). The beneficial skeletal effects seemed to be mediated by inhibition of bone resorption and stimulation of bone formation. The training response (i.e. jumping height) was also greater in the metformin treated rats compared to OVX-Ex (p < .01), indicating a performance-enhancing effect of metformin. Both exercise groups displayed higher lean mass than OVX-Ctr (p < .05). In conclusion, the combination of plyometric exercise and metformin improved trabecular microarchitecture and bone material properties relative to OVX controls. However, no additive effect of the combined intervention was observed compared to exercise alone.