Bone adaptation in adult women is related to loading dose:​ a 12‐month randomized controlled trial

Troy, Karen L.; Mancuso, Megan E.; Johnson, Joshua E.; Wu, Zheyang; Schnitzer, Thomas J.; Butler, Tiffiny A.

Affiliations

¹Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, USA

²Orthopaedic Biomechanics Research Laboratory, University of Iowa, Iowa City, IA, USA

³Department of Mathematical Sciences, Worcester Polytechnic Institute, Worcester, MA, USA

⁴Department of Physical Medicine and Rehabilitation, Northwestern University, Chicago, IL, USA

Abstract and keywords

Although strong evidence exists that certain activities can increase bone density and structure in people, it is unclear what specific mechanical factors govern the response. This is important because understanding the effect of mechanical signals on bone could contribute to more effective osteoporosis prevention methods and efficient clinical trial design. The degree to which strain rate and magnitude govern bone adaptation in humans has never been prospectively tested. Here, we studied the effects of a voluntary upper extremity compressive loading task in healthy adult women during a 12‐month prospective period. A total of 102 women age 21 to 40 years participated in one of two experiments: (i) low (n = 21) and high (n = 24) strain magnitude; or (ii) low (n = 21) and high (n = 20) strain rate. Control (n = 16) no intervention. Strains were assigned using subject‐specific finite element models. Load cycles were recorded digitally. The primary outcome was change in ultradistal radius integral bone mineral content (iBMC), assessed with QCT. Interim time points and secondary outcomes were assessed with high resolution pQCT (HRpQCT) at the distal radius. Sixty‐six participants completed the intervention, and interim data were analyzed for 77 participants. Likely related to improved compliance and higher received loading dose, both the low‐strain rate and high‐strain rate groups had significant 12‐month increases to ultradistal iBMC (change in control: −1.3 ± 2.7%, low strain rate: 2.7 ± 2.1%, high strain rate: 3.4 ± 2.2%), total iBMC, and other measures. “Loading dose” was positively related to 12‐month change in ultradistal iBMC, and interim changes to total BMD, cortical thickness, and inner trabecular BMD. Participants who gained the most bone completed, on average, 128 loading bouts of (mean strain) 575 με at 1878 με/s. We conclude that signals related to strain magnitude, rate, and number of loading bouts contribute to bone adaptation in healthy adult women, but only explain a small amount of variance in bone changes.

Keywords: BIOMECHANICS; BONE MODELING AND REMODELING; BONE QCT/μCT; CLINICAL TRIALS; EXERCISE

Links

DOI: 10.1002/jbmr.3999

PubMed: 32154945

WoS: 000522297800001

History

Received: 2019-07-22

Revised: 2020-02-7

Accepted: 2020-02-27

Online: 2020-03-30

Cited Works (23)

Year	Entry
1997	Umemura Y, Ishiko T, Yamauchi T, Kurono M, Mashiko S. Five jumps per day increase bone mass and breaking force in rats. J Bone Miner Res. September 1997;12(10):1480-1485.
2007	Taddei F, Schileo E, Helgason B, Cristofolini L, Viceconti M. The material mapping strategy influences the accuracy of ct-based finite element models of bones: an evaluation against experimental measurements. Med Eng Phys. 2007;29(9):973-979.
2008	Weeks BK, Beck BR. The BPAQ: a bone-specific physical activity assessment instrument. Osteoporos Int. November 2008;19(11):1567-1577.
2003	Turner CH, Robling AG. Designing exercise regimens to increase bone strength. Exerc Sport Sci Rev. January 2003;31(1):45-50.
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.
1998	Turner CH. Three rules for bone adaptation to mechanical stimuli. Bone. November 1998;23(5):399-407.
2010	Burghardt AJ, Buie HR, Laib A, Majumdar S, Boyd SK. Reproducibility of direct quantitative measures of cortical bone microarchitecture of the distal radius and tibia by HR-pQCT. Bone. September 2010;47(3):519-528.
2000	Robling AG, Burr DB, Turner CH. Partitioning a daily mechanical stimulus into discrete loading bouts improves the osteogenic response to loading. J Bone Miner Res. August 2000;15(8):1596-1602.
2008	Gray HA, Taddei F, Zavatsky AB, Cristofolini L, Gill HS. Experimental validation of a finite element model of a human cadaveric tibia. J Biomech Eng. June 2008;130(3):031016.
2007	Milgrom C, Radeva-Petrova DR, Finestone A, Nyska M, Mendelson S, Benjuya N, Simkin A, Burr D. The effect of muscle fatigue on in vivo tibial strains. J Biomech. 2007;40(4):845-850.
2003	Donahue SW, Donahue HJ, Jacobs CR. Osteoblastic cells have refractory periods for fluid-flow-induced intracellular calcium oscillations for short bouts of flow and display multiple low-magnitude oscillations during long-term flow. J Biomech. January 2003;36(1):35-43.
1985	Rubin CT, Lanyon LE. Regulation of bone mass by mechanical strain magnitude. Calcif Tiss Int. 1985;37(4):411-417.
2001	Robling AG, Burr DB, Turner CH. Recovery periods restore mechanosensitivity to dynamically loaded bone. J Exp Biol. 2001;204(19):3389-3399.
2011	Howe TE, Shea B, Dawson LJ, Downie F, Murray A, Ross C, Harbour RT, Caldwell LM, Creed G. Exercise for preventing and treating osteoporosis in postmenopausal women. Cochrane Database Sys Rev. July 6, 2011;7:CD000333.
2007	Buie HR, Campbell GM, Klinck RJ, MacNeil JA, Boyd SK. Automatic segmentation of cortical and trabecular compartments based on a dual threshold technique for in vivo micro-CT bone analysis. Bone. October 2007;41(4):505-515.
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.
2012	Edwards WB, Troy KL. Finite element prediction of surface strain and fracture strength at the distal radius. Med Eng Phys. April 2012;34(3):290-298.
2001	Hsieh Y, Turner CH. Effects of loading frequency on mechanically induced bone formation. J Bone Miner Res. May 2001;16(5):918-924.
2010	Sode M, Burghardt AJ, Kazakia GJ, Link TM, Majumdar S. Regional variations of gender-specific and age-related differences in trabecular bone structure of the distal radius and tibia. Bone. June 2010;46(6):1652-1660.
1982	O'Connor JA, Lanyon LE, MacFie H. The influence of strain rate on adaptive bone remodelling. J Biomech. 1982;15(10):767-781.
2005	Schriefer JL, Warden SJ, Saxon LK, Robling AG, Turner CH. Cellular accommodation and the response of bone to mechanical loading. J Biomech. September 2005;38(9):1838-1845.
1997	Mosley JR, March BM, Lynch J, Lanyon LE. Strain magnitude related changes in whole bone architecture in growing rats. Bone. March 1997;20(3):191-198.
1998	Mosley JR, Lanyon LE. Strain rate as a controlling influence on adaptive modeling in response to dynamic loading of the ulna in growing male rats. Bone. October 1998;23(4):313-318.

Cited By (8)

Year	Entry
2023	Walle M, Whittier DE, Schenk D, Atkins PR, Blauth M, Zysset P, Lippuner K, Müller R, Collins CJ. Precision of bone mechanoregulation assessment in humans using longitudinal high-resolution peripheral quantitative computed tomography in vivo. Bone. July 2023;172:116780.
2020	Mancuso ME, Troy KL. Relating bone strain to local changes in radius microstructure following 12 months of axial forearm loading in women. J Biomech Eng. November 2020;142(11):111014.
2022	Chlebek C, Moore JA, Ross FP, van der Meulen MCH. Molecular identification of spatially distinct anabolic responses to mechanical loading in murine cortical bone. J Bone Miner Res. November 2022;37(11):2277-2287.
2021	Fang Y, Morse LR, Nguyen N, Battaglino RA, Goldstein RF, Troy KL. Functional electrical stimulation (FES)–assisted rowing combined with zoledronic acid, but not alone, preserves distal femur strength and stiffness in people with chronic spinal cord injury. Osteoporos Int. March 2021;32(3):549-558.
2020	Rooney A. Interactions Among Estrogen Receptor-Alpha, Parathyroid Hormone, and Mechanical Loading in Skeletal Health [PhD thesis]. Ithaca, NY: Cornell University; December 2020.
2022	Chlebek C. Identification of Novel Cellular Pathways Involved in Bone Mechanotransduction Using Transcriptomics [PhD thesis]. Ithaca, NY: Cornell University; May 2022.
2020	Mancuso ME. Defining the Multiscale Relationship Between Subject-Specific Bone Strain and Structural Adaptation in the Distal Radius of Women [PhD thesis]. Worcester, MA: Worcester Polytechnic Institute; July 2020.
2021	Mattson NE. Effects of Exoskeleton Walking Therapy in the Distal Femur and Proximal Tibia in Individuals With Chronic Spinal Cord Injury [Master's thesis]. Worcester, MA: Worcester Polytechnic Institute; May 2021.