Low mechanical signals strengthen long bones

Rubin, Clinton<sup>1</sup>; Turner, A. Simon<sup>2</sup>; Bain, Steven<sup>3</sup>; Mallinckrodt, Craig<sup>2</sup>; McLeod, Kenneth<sup>1</sup>

Year	Entry
2003	Cardinale M, Pope MH. The effects of whole body vibration on humans: dangerous or advantageous? Acta Physiol Hung. 2003;90(3):195-206.
2002	Currey JD. Bones: Structure and Mechanics. Princeton, NJ: Princeton University Press; 2002.
2021	Saers JPP, DeMars LJ, Stephens NB, Jashashvili T, Carlson KJ, Gordon AD, Shaw CN, Ryan TM, Stock JT. Combinations of trabecular and cortical bone properties distinguish various loading modalities between athletes and controls. Am J Phys Anthropol. March 2021;174(3):434-450.
2003	Judex S, Boyd S, Qin Y-X, Turner S, Ye K, Müller R, Rubin C. Adaptations of trabecular bone to low magnitude vibrations result in more uniform stress and strain under load. Ann Biomed Eng. January 2003;31(1):12-20.
2006	Robling AG, Castillo AB, Turner CH. Biomechanical and molecular regulation of bone remodeling. Annu Rev Biomed Eng. 2006;8:455-498.
2002	Rubin C, Turner AS, Mallinckrodt C, Jerome C, Mcleod K, Bain S. Mechanical strain, induced noninvasively in the high-frequency domain, is anabolic to cancellous bone, but not cortical bone. Bone. March 2002;30(3):445-452.
2004	Warden SJ, Turner CH. Mechanotransduction in the cortical bone is most efficient at loading frequencies of 5–10 hz. Bone. February 2004;34(2):261-270.
2010	Sugiyama T, Price JS, Lanyon LE. Functional adaptation to mechanical loading in both cortical and cancellous bone is controlled locally and is confined to the loaded bones. Bone. February 2010;46(2):314-321.
2021	Pagnotti GM, Thompson WR, Guise TA, Rubin CT. Suppression of cancer-associated bone loss through dynamic mechanical loading. Bone. September 2021;150:115998.
2021	Birks S, Uzer G. At the nuclear envelope of bone mechanobiology. Bone. October 2021;151:116023.
2003	Turner CH, Robling AG. Designing exercise regimens to increase bone strength. Exerc Sport Sci Rev. January 2003;31(1):45-50.
2001	Rubin C, Xu G, Judex S. The anabolic activity of bone tissue, suppressed by disuse, is normalized by brief exposure to extremely low‐magnitude mechanical stimuli. FASEB J. October 2001;15(12):2225-2229.
2002	Judex S, Donahue L, Rubin C. Genetic predisposition to low bone mass is paralleled by an enhanced sensitivity to signals anabolic to the skeleton. FASEB J. August 2002;16(10):1280-1282.
2006	Rubin J, Rubin C, Jacobs CR. Molecular pathways mediating mechanical signaling in bone. Gene. February 15, 2006;367:1-16.
2012	Thompson WR, Rubin CT, Rubin J. Mechanical regulation of signaling pathways in bone. Gene. July 25, 2012;503(2):179-193.
2019	Georgiou L, Kivell TL, Pahr DH, Buck LT, Skinner MM. Trabecular architecture of the great ape and human femoral head. J Anat. May 2019;234(5):679-693.
2007	Judex S, Lei X, Han D, Rubin C. Low-magnitude mechanical signals that stimulate bone formation in the ovariectomized rat are dependent on the applied frequency but not on the strain magnitude. J Biomech. 2007;40(6):1333-1339.
2011	Sen B, Xie Z, Case N, Styner M, Rubin CT, Rubin J. Mechanical signal influence on mesenchymal stem cell fate is enhanced by incorporation of refractory periods into the loading regimen. J Biomech. February 24, 2011;44(4):593-599.
2002	Rubin C, Turner AS, Müller R, Mittra E, McLeod K, Lin W, Qin Y. Quantity and quality of trabecular bone in the femur are enhanced by a strongly anabolic, noninvasive mechanical intervention. J Bone Miner Res. February 2002;17(2):349-357.
2002	Srinivasan S, Weimer DA, Agans SC, Bain SD, Gross TS. Low‐magnitude mechanical loading becomes osteogenic when rest is inserted between each load cycle. J Bone Miner Res. September 2002;17(9):1613-1620.
2004	Rubin C, Recker R, Cullen D, Ryaby J, McCabe J, McLeod K. Prevention of postmenopausal bone loss by a low‐magnitude, high‐frequency mechanical stimuli: a clinical trial assessing compliance, efficacy, and safety. J Bone Miner Res. March 2004;19(3):343-351.
2004	Ward K, Alsop C, Caulton J, Rubin C, Adams J, Mughal Z. Low magnitude mechanical loading is osteogenic in children with disabling conditions. J Bone Miner Res. March 2004;19(3):360-369.
2006	Gilsanz V, Wren TAL, Sanchez M, Dorey F, Judex S, Rubin C. Low‐level, high‐frequency mechanical signals enhance musculoskeletal development of young women with low bmd. J Bone Miner Res. September 2006;21(9):1464-1474.
2008	Kiiski J, Heinonen A, Järvinen TL, Kannus P, Sievänen H. Transmission of vertical whole body vibration to the human body. J Bone Miner Res. August 2008;23(8):1318-1325.
2012	Lu XL, Huo B, Chiang V, Guo XE. Osteocytic network is more responsive in calcium signaling than osteoblastic network under fluid flow. J Bone Miner Res. March 2012;27(3):563-574.
2021	Rajapakse CS, Johncola AJ, Batzdorf AS, Jones BC, Al Mukaddam M, Sexton K, Shults J, Leonard MB, Snyder PJ, Wehrli FW. Effect of low‐intensity vibration on bone strength, microstructure, and adiposity in pre‐osteoporotic postmenopausal women: a randomized placebo‐controlled trial. J Bone Miner Res. April 2021;36(4):673-684.
2007	Garman R, Gaudette G, Donahue L-R, Rubin C, Judex S. Low-level accelerations applied in the absence of weight bearing can enhance trabecular bone formation. J Orthop Res. June 2007;25(6):732-740.
2022	Munford MJ, Xiao D, Jeffers JRT. Lattice implants that generate homeostatic and remodeling strains in bone. J Orthop Res. April 2022;40(4):871-877.
2007	Skedros JG, Baucomb SL. Mathematical analysis of trabecular "trajectories" in apparent trajectorial structures: the unfortunate historical emphasis on the human proximal femur. J Theo Biol. January 7, 2007;244(1):15-45.
2010	Ozcivici E, Luu YK, Adler B, Qin Y-X, Rubin J, Judex S, Rubin CT. Mechanical signals as anabolic agents in bone. Nat Rev Rheumatol. January 2010;6(1):50-59.
2002	Ehrlich PJ, Lanyon LE. Mechanical strain and bone cell function: a review. Osteoporos Int. September 2002;13(9):688-700.
2007	Wang Y, McNamara LM, Schaffler MB, Weinbaum S. A model for the role of integrins in flow induced mechanotransduction in osteocytes. Proc Natl Acad Sci USA. October 2, 2007;104(40):15941-15946.
2007	Fratzl P, Weinkamer R. Nature’s hierarchical materials. Prog Mater Sci. November 2007;52(8):1263-1334.
2003	Rubin CP, Pope M, Fritton C, Magnusson M, Hansson T, McLeod K. Transmissibility of 15-Hertz to 35-Hertz vibrations to the human hip and lumbar spine: determining the physiologic feasibility of delivering low-level anabolic mechanical stimuli to skeletal regions at greatest risk of fracture because of osteoporosis. Spine. December 1, 2003;28(23):2621-2627.
2004	Pearson OM, Lieberman DE. The aging of Wolff's "law": ontogeny and responses to mechanical loading in cortical bone. Yearb Phys Anthropol. 2004;47:63-99.
2006	Poole KES. The Effects of Stroke on the Skeleton [PhD thesis]. Cambridge, UK: University of Cambridge; 2006.
2017	Saers JPP. Ontogeny and Functional Adaptation of Trabecular Bone in the Human Foot [PhD thesis]. Cambridge, UK: University of Cambridge; July 2017.
2004	Samuel SP. Fluid/solid Interactions in Cancellous Bone [PhD thesis]. Cleveland State University; August 2004.
2002	Wang L. Investigating the Role of Interstitial Fluid Flow in Bone Adaptation and Metabolism [PhD thesis]. New York, NY: The City University of New York; 2002.
2009	Wang Y. Roles of Integrins in Flow Induced Mechanotransduction in Osteocytes [PhD thesis]. New York, NY: The City University of New York; 2009.
2005	Day JS. Bone Quality: The Mechanical Effects of Microarchitecture and Matrix Properties [PhD thesis]. Erasmus University Rotterdam; 2005.
2008	Webster DJ. A Combined Experimental and Computational Model for Genetic Control of Micro Structural Bone Adaptation [PhD thesis]. Swiss Federal Institute of Technology Zürich; 2008.
2019	Ruehle MA. Cell-Based Vascular Therapeutics for Bone Regeneration [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; August 2019.
2008	Weeks BK. Improving Bone Health With Physical Activity: The Power PE Study and Development of the Bone-Specific Physical Activity Questionnaire (BPAQ) [PhD thesis]. Brisbane, Australia: Griffith University; January 2008.
2010	Chennimalai Kumar N. Numerical Modeling of Cortical Bone Adaptation Due to Mechanical Loading Using the Finite Element Method [PhD thesis]. University of Illinois at Urbana-Champaign; 2010.
2020	Fox MC. The Biomechanical Consequences of Body Size Differences in Humans [PhD thesis]. University of Illinois at Urbana-Champaign; 2020.
2014	Ferro Pereira A. Cortical Bone Adaptation: A Finite-Element Study of the Mouse Tibia [PhD thesis]. Imperial College London; January 2014.
2013	Khayat G. Low Frequency Stimulation of Stem Cells in Dynamic Culture Modulates Differentiation Pathways [PhD thesis]. McGill University; July 2013.
2017	Draghici AE. Rescuing Osteoporotic Bone in Individuals With Spinal Cord Injury [PhD thesis]. Northeastern University; April 2017.
2015	Coughlin TR. Mechanobiological Signals in Trabecular Bone and Marrow [PhD thesis]. University of Notre Dame; July 2015.
2017	Kreipke TC. Structural, Mechanical, and Biological Relationships of Trabecular Bone in Osteoporosis [PhD thesis]. Notre Dame, IN: University of Notre Dame; April 2017.
2015	Noble GJ. Evaluation of a Press Fit, Percutaneous, Skeletally Anchored Endoprosthesis for Prosthetic Limb Attachment: Bone Response and the Effect of Low Intensity Vibration [PhD thesis]. The Ohio State University; 2015.
2006	Hannay G. Mechanical and Electrical Environments to Stimulate Bone Cell Development [PhD thesis]. Queensland University of Technology; August 2006.
2006	Garman RA. Low-Level Accelerations Applied in the Absence of Weight Bearing Can Alter Cellular Activity and Tissue Morphology in the Skeleton [PhD thesis]. Stony Brook, NY: Stony Brook University; May 2006.
2006	Xie L. Low Level Mechanical Vibrations Enhance Musculoskeletal Accretion in Growing Mice [PhD thesis]. Stony Brook, NY: Stony Brook University; December 2006.
2008	Luu YK. Biomechanical Promotion of Mesenchymal Stem Cell Proliferation as a Countermeasure to the Development of Obesity and Osteoporosis [PhD thesis]. Stony Brook, NY: Stony Brook University; May 2008.
2009	Ferreri SL. Anti-Catabolic Role of Ultrasonic Mechanical Perturbation in Prevention of Bone Loss and Turnover in OVX Rat Model: A Combined Empirical, Nanomechanical and Micro-Numerical Simulation Approach [PhD thesis]. Stony Brook, NY: Stony Brook University; August 2009.
2009	Ozcivici E. Recovery of Trabecular Bone from Disuse Induced Deterioration in Cellular, Morphological and Biomechanical Properties [PhD thesis]. Stony Brook, NY: Stony Brook University; May 2009.
2011	Appiah-Nkansah K. Integration of Refractory Periods in the Administration of Low-Magnitude Mechanical Signals Increases Mesenchymal Stem Cell Numbers in the Bone Marrow [Master's thesis]. Stony Brook, NY: Stony Brook University; May 2011.
2011	Patri N. Low Intensity Vibrations Applied Locally Can be Transmitted to the Alveolar Bone Thereby Enhancing the Quality of the Bone in Adults Rats [Master's thesis]. Stony Brook, NY: Stony Brook University; May 2011.
2012	Hu M. Mitigation of Bone Loss and Augment of Anabolic Adaptation by Physiological Dynamic Fluid Flow Stimulation [PhD thesis]. Stony Brook, NY: Stony Brook University; December 2012.
2012	Uzer G. Role of Fluid Shear Modulation on Bone Cell Metabolism During High-Frequency Oscillatory Vibrations [PhD thesis]. Stony Brook, NY: Stony Brook University; December 2012.
2014	Pagnotti GM. Low Intensity Vibrations Mitigate Cancer-Induced Bone Loss With Indications of Reduced Tumor Progression [PhD thesis]. Stony Brook, NY: Stony Brook University; August 2014.
2018	Patel VS. Harnessing Cell Mechanosensitivity to Combat Obesity-Induced Systemic Metabolic Disruptions and to Promote Protein Production for Bioprocessing [PhD thesis]. Stony Brook, NY: Stony Brook University; December 2018.
2005	Ashe MC. Upper Limb Bone Health: Cadaveric, Imaging and Clinical Studies With Special Emphasis on Peripheral Quantitative Computed Tomography [PhD thesis]. Vancouver, BC: University of British Columbia; April 2005.
2004	LaMothe JM. Functional Adaptation of Bone [PhD thesis]. Calgary, AB: University of Calgary; September 2004.
2010	Manske SL. Muscle Disuse and Vibration Effects on Bone Morphology [PhD thesis]. Calgary, AB: University of Calgary; December 2010.
2013	Friesenbichler BM. The Influence of Externally Applied Vibration and Compression on Muscular Performance and Recovery [PhD thesis]. Calgary, AB: University of Calgary; November 2013.
2004	Taboas JM. Mechanobiologic Regulation of Skeletal Progenitor Cell Differentiation [PhD thesis]. University of Michigan; 2004.
2007	Wallace JM III. Investigating the Inbred Strain-Specific Response to Biglycan-Deficiency and Exercise: A Study in Genetically-Mediated Skeletal Adaptation [PhD thesis]. University of Michigan; 2007.
2023	Cosman MN. Trabecular and Cortical Skeletal Correlates of Locomotor Ontogeny in Pan With Comparisonsto Skeletal Variation and Adaptation in Gorilla and Pongo [PhD thesis]. University of Michigan; 2023.
2003	Rüberg T. Computer Simulation of Adaptive Bone Remodeling [Master's thesis]. Universidad de Zaragoza; 2003.
2010	Beckstrom AB. Histologic and Geometric Data Challenge the Assumption of Habitual Superior-Inferior (tension-Compression) Bending Across the Chimpanzee Proximal Femur [Master's thesis]. University of Utah; August 2010.
2014	Hu Z. The Development of a Digital X-Ray Imaging System for the Characterization of Transmission of Whole-Body Vibration in Mice [Master's thesis]. London, ON: Western University; 2014.
2007	Christiansen BA. Vibrational Stimulation of Bone Formation in Mice [PhD thesis]. St. Louis, MO: Washington University in St. Louis; December 2007.

Year	Entry
1995	Rubin CT, Gross TS, McLeod KJ, Bain SD. Morphologie stages in lamellar bone formation stimulated by a potent mechanical stimulus. J Bone Miner Res. March 1995;10(3):488-495.
1990	Schaffler MB, Radin EL, Burr DB. Long-term fatigue behavior of compact bone at low strain magnitude and rate. Bone. 1990;11(5):321-326.
2000	Fritton SP, McLeod KJ, Rubin CT. Quantifying the strain history of bone: spatial uniformity and self-similarity of low-magnitude strains. J Biomech. March 2000;33(3):317-325.
1986	Wolff J. The Law of Bone Remodelling. Maquet P, Furlong R, trans. New York, NY: Springer; 1986.
1985	Burr DB, Martin RB, Schaffler MB, Radin EL. Bone remodeling in response to in vivo fatigue microdamage. J Biomech. 1985;18(3):189-200.
1997	Fritton JC, Rubin CT, Qin Y-X, McLeod KJ. Whole-body vibration in the skeleton: development of a resonance-based testing device. Ann Biomed Eng. September–October 1997;25(5):831-839.