title: Extending Rest between Unloading Cycles Does Not Enhance Bone's Long-Term Recovery.
abstract: OBJECTIVE
  Multiple exposures to unloading are overall more deleterious to the skeleton than is single exposure, although the rate of bone loss may diminish during multiple exposures. Here, we determined whether extending the reambulation (RA) period from 3 wk to 9 wk will mitigate bone loss during three distinct 3-wk hindlimb unloading (HLU) periods and enhance long-term recovery in skeletally mature, genetically heterogeneous mice.
  
  
  METHODS
  Female adult mice (4 months old) were subjected to three cycles of 3-wk unloading with 3-wk or 9-wk RA periods in between. Mice were terminated 46 wk after initiation of the study. Outcome measures for the distal femur were determined from multiple in vivo micro-computed tomography scans and finite-element modeling.
  
  
  RESULTS
  Tripling RA duration enhanced trabecular bone recovery in between HLU periods but also increased the rate of loss of bone volume fraction (bone volume/tissue volume) and metaphyseal stiffness during subsequent HLU periods. With shorter RA periods, the magnitude of bone loss decreased by the second HLU period, whereas this decrease was delayed with longer RA periods. RA duration did not affect long-term recovery 46 wk after the start of the experimental protocol, as both HLU groups had similar levels of bone volume/tissue volume, cortical area, and stiffness. Individual cage activity levels were unrelated to the magnitude of bone loss during HLU or bone recovery during RA.
  
  
  CONCLUSIONS
  These data suggest that extending recovery duration between periods of unloading may provide temporary benefits but is an ineffective long-term strategy for combating the devastation of trabecular morphology and mechanics, as temporarily enhanced recovery is largely cancelled out by greater susceptibility to unloading. They also emphasize that cortical bone is more amenable to long-term recovery than is trabecular bone.
authors: 1Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY; and 2Department of Preventive Medicine, Stony Brook University, Stony Brook, NY.
authors: Sarah L
authors: SL
authors: Manske
authors: Surabhi
authors: S
authors: Vijayaraghavan
authors: Alyssa
authors: A
authors: Tuthill
authors: Olivier
authors: O
authors: Brutus
authors: Jie
authors: J
authors: Yang
authors: Shikha
authors: S
authors: Gupta
authors: Stefan
authors: S
authors: Judex
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015992:Body Mass Index; D001842:Bone and Bones / Q000473:pathology / Q000502:physiology*; D005260:Female; D019417:Hindlimb Suspension; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D012146:Rest; D013997:Time Factors; D016474:Weight-Bearing