title: Microdamage repair and remodeling requires mechanical loading.
abstract: Bone remodeling is necessary to avoid microdamage accumulation, which could lead to whole-bone failure. Previous studies have shown that this bone-repair mechanism is triggered by osteocyte apoptosis. Through the use of a rodent hindlimb suspension model and tibial four-point bending model, the effects of disuse on microdamage remodeling was examined. At day 0, male rats were assigned to one of three groups: weight bearing (WB), hindlimb suspension (HS), or hindlimb suspension with daily intermittent weight bearing following damage-inducing loading (HW). Within each group, the rats were further divided into subgroups corresponding to three sacrifice time points [day 14 (WB and HS only), day 18, or day 35]. At day 14, animals were anesthetized, and their left tibiae underwent cyclic four-point bending to produce fatigue-induced microdamage. At sacrifice, the tibiae were examined using 3D micro-computed tomography (microCT), flow cytometry, and histologic and immunohistochemical stains. The results indicate that only the WB and HW groups had a significant increase in intracortical TRAP-positive resorption pits following damage induction, which was paralleled by a significant decrease in microdamage over time in combination with a shift in the osteoclast lineage owing to a decrease in monocytes. These results demonstrate that osteocyte apoptosis may be insufficient for repair of microdamage without the stimulation provided through physiologic loading. In addition, this potentially could have clinical implications for the current therapeutic paradigm for treating stress fractures, where extended non-weight bearing is employed.
authors.affiliation: Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI 48109-2200, USA.
authors.forename: Erik I
authors.initials: EI
authors.lastname: Waldorff
authors.forename: Katya B
authors.initials: KB
authors.lastname: Christenson
authors.forename: Laura A
authors.initials: LA
authors.lastname: Cooney
authors.forename: Steven A
authors.initials: SA
authors.lastname: Goldstein
mesh_terms: D000818:Animals; D017209:Apoptosis; D016723:Bone Remodeling / Q000502:physiology*; D015775:Fractures, Stress / Q000628:therapy*; D019417:Hindlimb Suspension; D008297:Male; D009000:Monocytes; D010010:Osteoclasts / Q000502:physiology; D010011:Osteocytes / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000293:injuries* / Q000473:pathology / Q000502:physiology; D016474:Weight-Bearing