Increased Bone Formation From Isolated Eccentric Muscle Contraction In Old Mice

Skeletal muscle is a major contributor of mechanical signals for bone, where muscular contractions increase bone strains, resulting in mechanotransduction. Subsequently, bone remodeling occurs leading to increased bone accumulation and mineralization. However, the type of muscle contraction required to produce optimal bone formation has yet to be explored. This is especially true for the aged skeleton where bone formation rates are slower. PURPOSE: To determine if isometric, eccentric or a combination of both types of muscle contraction produce optimal bone gain. METHODS: C57Bl/6 male mice, aged 6 or 20-months, were stratified to 4 groups: 1) Isometric (Iso), 2) Eccentric (ECC), and Isometric+Eccentric (Iso + ECC) contractions, and 4) Non-Stimulated (NS) cage controls exposed to isoflurane inhalation. Mice were unilaterally stimulated using needle electrodes targeting the sciatic nerve, while the foot is secured to the foot pedal and the knee joint was clamped. Each stimulation was induced for 800 ms pulse duration with a frequency of 150 Hz and were repeated 4 times with 12 seconds rest in between each stimulation (1 set). Iso contraction was performed with a 90° foot angle (neutral position) throughout the stimulation, and ECC with 200 ms at 90°, 300 ms at 70° and 300 ms at 110° foot angle. Each training session consisted of 4 sets of 5 stimulations with 3 minutes rest between each set. Iso + ECC animals performed 2 sets of Iso and 2 sets of ECC contractions. Animals were trained for 3 sessions a week for 4 weeks, and peak torque was measured before and after training sessions. Hindlimb muscles and bones were harvested 10 days after the last session. RESULTS: The ECC group exhibited a 2-fold increase in normalized plantarflexor force in young mice, while old mice increased 30% in dorsiflexor strength from Iso contraction, when compared to age-matched NS mice. While there were significant (p < 0.05) increases in cortical bone thickness in all stimulated mice, significant (p < 0.01) increases in trabecular bone formation were found only in old mice, and only as a result of ECC contraction. CONCLUSION: This study suggests that eccentric muscle contraction produced a larger osteogenic effect in old mice when compared to isometric contraction. However, further assessments in the microstructure within the muscle and bone are required. NIH K00AG068438