Bones' adaptive response to mechanical loading is essentially linear between the low strains associated with disuse and the high strains associated with the lamellar/woven bone transition

There is a widely held view that the relationship between mechanical loading history and adult bone mass/strength includes an adapted state or "lazy zone" where the bone mass/strength remains constant over a wide range of strain magnitudes. Evidence to support this theory is circumstantial. We investigated the possibility that the "lazy zone" is an artifact and that, across the range of normal strain experience, features of bone architecture associated with strength are linearly related in size to their strain experience. Skeletally mature female C57BL/6 mice were right sciatic neurectomized to minimize natural loading in their right tibiae. From the fifth day, these tibiae were subjected to a single period of external axial loading (40, 10-second rest interrupted cycles) on alternate days for 2 weeks, with a peak dynamic load magnitude ranging from 0 to 14 N (peak strain magnitude: 0-5000 µε) and a constant loading rate of 500 N/s (maximum strain rate: 75,000 µε/s). The left tibiae were used as internal controls. Multilevel regression analyses suggest no evidence of any discontinuity in the progression of the relationships between peak dynamic load and three-dimensional measures of bone mass/strength in both cortical and cancellous regions. These are essentially linear between the low-peak locomotor strains associated with disuse (∼300 µε) and the high-peak strains derived from artificial loading and associated with the lamellar/woven bone transition (∼5000 µε). The strain:response relationship and minimum effective strain are site-specific, probably related to differences in the mismatch in strain distribution between normal and artificial loading at the locations investigated.