Young and healthy C57BL/6 J mice performing sprint interval training reveal gender- and site-specific changes to the cortical bone

Abstract

Physical exercise is considered to impede the bone loss associated with physiological ageing however, a training program that efficiently leads to bone accrual in the healthy does not yet exist. We turned to the C57BL/6 J mouse and designed a sprint interval training for treadmill that was tailored to the individual performance limits. It consisted of four weeks with five training sessions each, followed by another four weeks with three. After completion of the training period, mice were sacrificed and the hind legs were analyzed via µCT and MRI for changes in bone parameters and muscle volume, respectively. Increased performance limits in both sexes confirmed an effect of the treadmill training. However, while male tibiae after eight weeks revealed a significant reduction of cortical bone mass at the distal metaphysis, the cross sectional analysis of female tibiae showed a transient decrease of cortical bone mass after four weeks that was reversed into a significant accrual after eight weeks of training and occurred over the entire length of the tibia. The observed net reduction of female bone mass after four weeks of training is suggestive of a remodelling process which may be delayed in the males.

Interval Training Is Not Superior to Endurance Training With Respect to Bone Accrual of Ovariectomized Mice

“…Our μCT data further suggested that even though OVX decreased the trabecular bone mass, treadmill training had no additional impact, neither positive nor negative. These observations are in line with previous publications, showing a lack of exercise-associated changes at the proximal tibia and the vertebral bodies alike (Iwamoto et al, 1999;Bennell et al, 2002;Hollinski et al, 2008). This distinctive feature of the trabecular bone is difficult to explain and has in the past been interpreted as a consequence from females accumulating trabecular bone mass in excess of the optimal bone mass, in order to provide a buffer against the bone loss during lactation (Bennell et al, 2002).…”

“…We and others have evidence that longer training periods may be required before a true remodeling and bone accrual can be detected (Hollinski et al, 2008;Hsu et al, 2018). We have previously shown that while 4 weeks of high intensity interval training in young and healthy mice led to a reduction of the tibial cortical thickness, another 4 weeks of training reversed this finding (Hollinski et al, 2008). Likewise, Hsu et al (2018) showed the upregulation of osteogenesis-related genes in osteoblasts of OVX C57BL/6 mice after 8 weeks of training.…”

“…The ART served to determine the individual V max of mice in groups III-V (Hollinski et al, 2008). The treadmill started with a speed of 0.17 m/s for 3 min.…”

“…Apart from that, the literature on the effect of treadmill training on murine bone shows mixed findings. For example, short term and moderate training periods of 3 weeks led to significantly increased tibial cortical area and periosteal perimeter in male C57BL/6 mice while 8 weeks of a strenuous sprint interval training in the same strain and sex resulted in the significant reduction of cortical bone mass (Wallace et al, 2007;Hollinski et al, 2008). These findings are difficult to reconcile with the hypothesis that bone accrual can be achieved by increasing the frequency and intensity of the impact (Robling and Turner, 2009).…”

“…These findings are difficult to reconcile with the hypothesis that bone accrual can be achieved by increasing the frequency and intensity of the impact (Robling and Turner, 2009). Furthermore, recent evidence suggested that male mice may benefit from moderate training regimen while females may require more strain for efficient bone accrual (Wallace et al, 2007;Hollinski et al, 2008;Koenen et al, 2017). All of these studies used different mouse strains, different sexes, and different training regimens, suggesting that firm comparisons can only be drawn from identical experimental set-ups.…”