The response of rat tibiae to incremental bouts of mechanical loading: a quantum concept for bone formation.

To investigate the minimum number of loading bouts necessary to produce new lamellar or woven bone formation, and the time required for its initiation, bone formation was measured in 32 retired breeder female Sprague-Dawley rats following one, two, three, or five bouts of applied loading. Bending forces of 54 N were applied to right tibiae using a four-point loading apparatus, and left tibiae served as contralateral controls. Loading was applied as a sine wave with a frequency of 2 Hz for 18 s (36 cycles) per loading bout. Rats were injected with alizarin on day 1 and calcein on days 5 and 12, and were killed on day 19. One bout of loading was sufficient to increase the periosteal woven bone surface (Wb.Pm/B.Pm) from 0% to 40% (p < 0.01), and to 80% after five bouts of loading (p < 0.01), with a dose-response relationship for increases in Wb.Pm/B.Pm (p < 0.0001), mineral apposition rate (Wb.AR; p = 0.002), and bone formation rate (Wb.BFR/BS; p = 0.0001). In the first labeling period (days 1-5), the endocortical lamellar bone forming surface (BSf/BS) was increased slightly (p < 0.05), but no significant differences were shown for BFR/BS or MAR. From days 5 to 19, right tibiae showed a dose-response increase in BFR/BS (p = 0.002) and BSf/BS (p = 0.008), but not MAR. These results are consistent with a "quantum" model of bone formation such that a "quantum" of bone cells is activated in response to the loading bout and the strain magnitude dictate the size or microstructural organization of a given packet of new bone. Conversely, the distributed nature of loading may define the recruitment, rather than size, of new packets of bone.