title: Enabling bone formation in the aged skeleton via rest-inserted mechanical loading.
abstract: The mild and moderate physical activity most successfully implemented in the elderly has proven ineffective in augmenting bone mass. We have recently reported that inserting 10 s of unloaded rest between load cycles transformed low-magnitude loading into a potent osteogenic regimen for both adolescent and adult animals. Here, we extended our observations and hypothesized that inserting rest between load cycles will initiate and enhance bone formation in the aged skeleton. Aged female C57BL/6 mice (21.5 months) were subject to 2-week mechanical loading protocols utilizing the noninvasive murine tibia loading device. We tested our hypothesis by examining whether (a) inserting 10 s of rest between low-magnitude load cycles can initiate bone formation in aged mice and (b) whether bone formation response in aged animals can be further enhanced by doubling strain magnitudes, inserting rest between these load cycles, and increasing the number of high-magnitude rest-inserted load cycles. We found that 50 cycles/day of low-magnitude cyclic loading (1200 microepsilon peak strain) did not influence bone formation rates in aged animals. In contrast, inserting 10 s of rest between each of these low-magnitude load cycles was sufficient to initiate and significantly increase periosteal bone formation (fivefold versus intact controls and twofold versus low-magnitude loading). However, otherwise potent strategies of doubling induced strain magnitude (to 2400 microepsilon) and inserting rest (10 s, 20 s) and, lastly, utilizing fivefold the number of high-magnitude rest-inserted load cycles (2400 microepsilon, 250 cycles/day) were not effective in enhancing bone formation beyond that initiated via low-magnitude rest-inserted loading. We conclude that while rest-inserted loading was significantly more osteogenic in aged animals than the corresponding low-magnitude cyclic loading regimen, age-related osteoblastic deficits most likely diminished the ability to optimize this stimulus.
authors.affiliation: Orthopaedic Science Laboratories, Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, WA 98104, USA. sundars@u.washington.edu
authors.forename: Sundar
authors.initials: S
authors.lastname: Srinivasan
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Agans
authors.forename: Katy A
authors.initials: KA
authors.lastname: King
authors.forename: Nicholas Y
authors.initials: NY
authors.lastname: Moy
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Poliachik
authors.forename: Ted S
authors.initials: TS
authors.lastname: Gross
mesh_terms: D000367:Age Factors; D000818:Animals; D001696:Biomechanical Phenomena; D001842:Bone and Bones / Q000033:anatomy & histology / Q000378:metabolism / Q000502:physiology*; D002113:Calcification, Physiologic / Q000502:physiology; D005260:Female; D020342:Finite Element Analysis; D021621:Imaging, Three-Dimensional; D051379:Mice; D008810:Mice, Inbred C57BL; D010012:Osteogenesis / Q000502:physiology*; D010521:Periosteum / Q000254:growth & development; D013314:Stress, Mechanical; D013977:Tibia / Q000033:anatomy & histology / Q000254:growth & development; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016474:Weight-Bearing / Q000502:physiology