Skeletal effects of plyometric exercise and metformin in ovariectomized rats

Stunes, A. K.; Erben, R. G.; Schüler, C.; Eriksen, E. F.; Tice, M.; Vashishth, D.; Syversen, U.; Mosti, M. P.

Affiliations

¹Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway

²St. Olavs University Hospital, Trondheim, Norway

³Department of Biomedical Sciences, University of Veterinary Medicine Vienna, Vienna, Austria

⁴Department of Endocrinology, Oslo University Hospital, Oslo, Norway

⁵Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA

⁶Department of Endocrinology, St Olavs University Hospital HF, Trondheim, Norway

Abstract and keywords

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.

Keywords: Bone mineral density; Bone microarchitecture; Skeletal muscle; Estrogen deficiency; AMPK

Links

DOI: 10.1016/j.bone.2019.115193

PubMed: 31857252

WoS: 000510529200009

History

Received: 2019-08-19

Revised: 2019-12-13

Accepted: 2019-12-16

Online: 2019-12-17

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Cited By (1)

Year	Entry
2022	Tice MJL. Loss and Modulation of Bone Matrix and Fragility During Diabetes Mellitus [PhD thesis]. Troy, NY: Rensselaer Polytechnic Institute; May 2022.