Spatiotemporal Distribution of Linear Microcracks and Diffuse Microdamage Following Daily Bouts of Fatigue Loading of Rat Ulnae

Abstract

Microdamage accumulation contributes to impaired skeletal mechanical integrity. The bone can remove microdamage by initiating targeted bone remodeling. However, the spatiotemporal characteristics of microdamage initiation and propagation and their relationship with bone remodeling in response to fatigue loading, especially for more physiologically relevant daily bouts of compressive loading, remain poorly understood. The right forelimbs of 24 rats were cyclically loaded with a ramp waveform for 1,500 cycles/day, and contralateral ulnae were not loaded as the controls. The rats were divided into four equal groups and loaded for 1, 4, 7, and 10 days, respectively. We demonstrated that linear microcracking accumulation exhibited a non‐linear time‐varying process within 10 days of loading with peaked microcrack density at Day 7. Disrupted canaliculi surrounding linear microcracks showed high similarity with the temporal changes of linear microcracking accumulation. Observable intracortical resorption regions were found on Day 10. We found more linear microcracks accumulated in the tensile cortex, but longer cracks were observed in the compressive sides. Increased accumulation of diffuse microdamage was observed from Day 4, but no obvious peak was observed within the 10‐day loading period. Diffuse damage first initiated in the compressive cortices but extended to tension from Day 7. The diffuse damage exhibited no impacts on the surrounding osteocyte integrity. Together, our findings revealed a time‐dependent, bone remodeling‐mediated varying process of linear microcracking accumulation following daily bouts of fatigue loading (with observable peak at Day 7 under our loading regime). Our study also identified distinct spatial accumulation of linear and diffuse microdamage in rat ulnae with tensile and compressive strains. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2112–2121, 2019

Osteocyte apoptosis: the roles and key molecular mechanisms in resorption-related bone diseases

“…The fatigue may give rise to the microdamage in the skeleton mineralized matrix, and ensuing larger bone lesions, ultimately leading to obvious fracture 4,64 . Data analysis has shown that strains of 8000 microstrains enhanced a remarkably increased osteocyte apoptosis in ulnae of rodents 65 . Similarly, it has been indicated that osteocytes will undergo apoptosis once the fatigue induces bone structural microdamage upon overloading 4,64 .…”

Early protection against bone stress injuries by mobilization of endogenous targeted bone remodeling

“…Herein, we employed a daily ulnar uniaxial compression session model developed by our group, 27 , 28 which mimics the fatigue damage accumulation in soldiers and athletes during physical training. Another single compression session model was also used to compare the “self-repair” rate of post-fatigue damage in various interventions.…”

“…In this study, efficient approaches to early protection against bone stress injuries were explored by applying intervention before fatigue loading based on a rat ulnar axial compression model. 22 , 27 , 28 First, we investigated the effectiveness of anabolic PTH and anti-catabolic alendronate (ALN) (two common anti-osteoporotic agents), 29 as well as low-frequency electromagnetic fields (EMFs) and whole-body vibration (WBV), two biophysical modalities with reported osteogenic potential, 30 , 31 on the early prevention of bone stress injuries, and we also optimized the dosage and administration times. We further compared the effects of individual and combinational pharmaceutical/biophysical stimulation on early protection against microdamage accumulation to determine the optimal strategy.…”

Glucose- and glutamine-dependent bioenergetics sensitize bone mechanoresponse after unloading by modulating osteocyte calcium dynamics

“…To establish the hind-limb unloading (HU) model, mice were maintained in an approximately 30° head-down-tilt position by tail suspension using a custom-designed Plexiglas cage for 4 weeks. Then, the right tibiae of mice were subjected to daily uniaxial cyclic compressive loading for 2 weeks (5 d/wk) using a custom-designed mechanical loading system as described previously ( 29 , 51 ). The contralateral left tibiae were not loaded and were used as controls.…”