Validation of a technique for studying functional adaptation of the mouse ulna in response to mechanical loading

Abstract

Functional adaptation of the mouse ulna in response to artificial loading in vivo was assessed using a technique previously developed in the rat. Strain gauge recordings from the mouse ulnar midshaft during locomotion showed peak strains of 1680 muepsilon and maximum strain rates of 0.03 sec(-1). During falls from 20 cm these reached 2620 muepsilon and 0.10 sec(-1). Axial loads of 3.0 N and 4.3 N, applied through the olecranon and flexed carpus, engendered peak strains at the lateral ulnar midshaft of 2000 muepsilon and 3000 muepsilon, respectively. The left ulnae of 17, 17-week-old female CD1 mice were loaded for 10 min with a 4 Hz trapezoidal wave engendering a strain rate of 0.1 sec(-1) for 5 days/week for 2 weeks. The mice were killed 3 days later. The response of the cortical bone of the diaphysis was assessed histomorphometrically using double calcein labels administered on days 3 and 12 of the loading period. Loading to peak strains of 2000 muepsilon stimulated lamellar periosteal bone formation, but no response endosteally. The greatest increase in cortical bone area was 4 mm distal to the midshaft (5 +/- 0.4% compared with 0.1 +/- 0.1% in controls [p < 0.01]). Periosteal bone formation rate (BFR) at this site was 0.73 +/- 0.06 microm(2)/microm per day, compared with 0.03 +/- 0.02 microm(2)/microm per day in controls (p < 0.01). Loading to peak strains of 3000 muepsilon induced a mixed woven/lamellar periosteal response and lamellar endosteal bone formation. Both of these were greatest 3-4 mm distal to the ulnar midshaft. At this level, the loading-induced periosteal response increased cortical bone area by 21 +/- 4% compared with 0.03 +/- 0.02% in controls, and resulted in a BFR of 2.84 +/- 0.42 microm(2)/microm per day, compared with 0.01 +/- 0.01 microm(2)/microm per day in controls (p < 0.05). Endosteal new bone formation resulted in a 2 +/- 0.4% increase in cortical bone area, compared with 0.4 +/- 0.3% in controls, and a BFR of 1.05 +/- 0.23 microm(2)/microm per day, compared with 0.22 +/- 0.15 microm(2)/microm per day in controls (p < 0.05). These data show that the axial ulna loading technique developed in the rat can be used successfully in the mouse. As in the rat, a short daily period of loading results in an osteogenic response related to peak strain magnitude. One important advantage in using mice over rats involves the potential for assessing the effects of loading in transgenics.