The effect of maximal strength training and peroxisome proliferator-activated receptor agonists on bone and muscle: Studies in humans and rats

Abstract

Estrogen deficiency after menopause is known to increase the risk of musculoskeletal diseases, such as sarcopenia and osteoporosis. The highest incidence of osteoporosis and osteoporotic fractures is found in Norway. Osteoporotic fractures may cause prolonged hospitalization, disability and increased mortality.

Current guidelines recommend weight-bearing activities, preferably strength training for improving skeletal health in patients with osteoporosis. What type of strength training that is most beneficial for these patients is not well established. Peroxisome proliferator activated receptors (PPARs) α, δ and γ are nuclear transcription factors that modulate the expression of a variety of genes involved in lipid metabolism and fat storage. The skeletal effects of PPARδ agonists are unknown, but PPARγ agonists induce deleterious skeletal effects, while PPARα agonists promote beneficial effects on bone and muscle. PPARδ agonists ameliorate the effects of exercise in muscle, but it is unknown whether PPAR agonists can also enhance the osteogenic effect of exercise in bone.

One aim of this thesis was to investigate the skeletal effects of a maximal strength training program (MST) in pre- and postmenopausal women. Another aim was to investigate the effects of a PPARδ-specific agonist on bone and skeletal muscle in estrogen-deficient rats. The final aim was to investigate whether administration of a PPARα activator during exercise may enhance skeletal properties during estrogen deficiency in rats. In summary, our results showed that MST improved skeletal properties in pre- and postmenopausal women. Furthermore, it was demonstrated that administration of a PPARδ agonist negatively affected bone properties in estrogen-deficient rats, while no effects were detected in muscle. Finally, administration of a PPARα agonist combined with exercise promoted beneficial skeletal effects that seemed to exceed the effect of each intervention alone, while preserving lean mass in estrogen deficient rats.

In conclusion, this thesis shows that maximal strength training alone, or combined with PPARα agonists may serve as an effective treatment strategy for postmenopausal osteoporosis and sarcopenia. This thesis also shows unfavorable skeletal effects of PPARδ agonist in estrogen-deficient rats, which may exclude PPARδ as a therapeutic target in postmenopausal osteoporosis.