Low-magnitude mechanical loading becomes osteogenic when rest is inserted between each load cycle.

Strategies to counteract bone loss with exercise have had fairly limited success, particularly those regimens subjecting the skeleton to mild activity such as walking. In contrast, here we show that it is possible to induce substantial bone formation with low-magnitude loading. In two distinct in vivo models of bone adaptation, we found that insertion of a 10-s rest interval between each load cycle transformed a locomotion-like loading regime that minimally influenced osteoblast activity into a potent anabolic stimulus. In the avian ulna model, the minimal mean (+SE) periosteal labeled surface (Ps.LS) observed in the intact contralateral bones (1.6 +/- 1.5%) was doubled after 3 consecutive days of low-magnitude loading (3.8 +/- 1.5%; p = 0.03). However, modifying the regimen by inserting 10 s of rest between each load cycle significantly enhanced the periosteal response (21.9 +/- 4.5%; p = 0.03). In the murine tibia model, 5 consecutive days of 100 low-magnitude loading cycles did not significantly alter mean periosteal bone formation rate (BFR) compared with contralateral bones (0.011 +/- 0.005 microm3/microm2 per day vs. 0.021 +/- 0.013 microm3/microm2 per day). In contrast, separating each of 10 of the same loading cycles with 10 s of rest significantly elevated periosteal BFR (0.167 +/- 0.049 microm3/microm2 per day; p = 0.01). Endocortical bone formation parameters were not altered by any loading regimen in either model. We conclude that 10 s of rest between each load cycle of a low-magnitude loading protocol greatly enhances the osteogenic potential of the regimen.