Strain rate as a controlling influence on adaptive modeling in response to dynamic loading of the ulna in growing male rats

Abstract

To test the hypothesis that the rate of change of strain to which a bone is subjected is an important determinant to the subsequent functionally adaptive modeling response, the ulnae of growing male rats were subjected to dynamic axial loading in vivo for a short period each day over 2 weeks. Due to the longitudinal curvature of the ulna, such axial loading leads to both compression and bending. The left ulna in three groups of rats was loaded cyclically between 1 and 20 N in a trapezoidal pattern to produce dynamic, longitudinal compressive strains of −0.004 (−4000 microstrain) at the medial midshaft with one of three strain rates: low (±0.018 sec⁻¹; n = 7); moderate (±0.030 sec⁻¹; n = 7); and high (±0.100 sec⁻¹; n = 8). These strain rates span the range recorded from strain gauges bonded to the bone at this site during a variety of normal activities. At the end of the experiment, the loaded ulnae were slightly, but significantly, shorter than their contralateral controls (2.7% to 5.6% mean change in length; p < 0.0001). This effect was most marked at lower strain rates, associated with an increased load-bearing time. The pattern of adaptive modeling along the bone shaft was similar for all groups, each showing a reduced rate of periosteal expansion proximally, and increased periosteal new bone production distally. This distal increase was achieved through enhanced periosteal bone formation on the lateral (tension) cortex, and arrest of resorption, with conversion to formation on the medial (compression) surface. The modeling response to axial loading therefore involves complex location-dependent increases and decreases in both formation and resorption. The high-strain-rate group demonstrated a 54% greater osteogenic response than the moderate-strain-rate group, which in turn showed a 13% larger response than the low-strain-rate group. Rate of strain change is therefore a major determinant of the adaptive osteogenic/antiresorptive response to mechanical load. Across the physiological range, a high rate of strain change provides a greater osteogenic stimulus than the same peak strain achieved more slowly.

Introduction

Normal daily activity loads the skeleton in a complex manner, involving many different loading configurations, peak loads, loading rates, and a range of primary and component frequencies. Interspersed between the loads associated with normal coordinated activity are less frequent “loading accidents,” which produce less usual strain patterns. Because many strain variables are interrelated, it has been difficult to investigate the contribution made by different components of the strain environment, because, in experimental loading systems, adjusting one variable simultaneously affects the others. There are currently only two in vivo studies in the literature that directly address the role of strain rate.15, 26

Nevertheless, there is much indirect evidence from exercise intervention studies in humans, and from controlled exercise studies in other mammals, which suggests that high strain magnitudes and high strain rates are associated with greater osteogenic responses than are low ones.2, 6, 17, 18, 21, 22 The aim of the current study was to test the hypothesis that for any given set of loading conditions (frequency, peak strain magnitude, and distribution of strain), the osteogenic potential of the adaptive modeling response is positively related to the rate of strain change. This was achieved by varying the rate of strain engendered during a short, daily period of noninvasive axial loading applied to the ulna of growing male rats, and assessment of the subsequent adaptive modeling and remodeling response.