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

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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.