Variation in bone biomechanical properties, microstructure, and density in BXH recombinant inbred mice

Turner, Charles H.; Hsieh, Yeou‐Fang; Müller, Ralph; Bouxsein, Mary L.; Rosen, Clifford J.; McCrann, Margaret E.; Donahue, Leah Rae; Beamer, Wesley G.

Affiliations

¹Biomechanics and Biomaterials Research Center, Indiana University, Indianapolis, Indiana, USA

²Orthopedic Biomechanics Laboratory, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA

³Maine Center for Osteoporosis Research and Education, Bangor, Maine, USA

⁴The Jackson Laboratory, Bar Harbor, Maine, USA

Abstract and keywords

To test the hypothesis that factors associated with bone strength (i.e., volumetric bone mineral density [vBMD], geometry, and microstructure) have heritable components, we exploited the 12 BXH recombinant inbred (RI) strains of mice derived from C57BL/6J (B6; low bone mass) and C3H/HeJ (C3H; high bone mass) progenitor strains. The femurs and lumbar vertebrae from each BXH RI strain were characterized for phenotypes of vBMD, microstructural, biomechanical, and geometrical properties. Methods included bending (femur) and compression (vertebra) testing, peripheral quantitative computed tomography (pQCT), and microcomputed tomography (μCT). Segregation patterns of femoral and vertebral biomechanical properties among the BXH RI strains suggested polygenic regulation. Femoral biomechanical properties were strongly associated with femoral width in the anteroposterior (AP) direction and cortical thickness‐geometric properties with complex genetic regulation. Vertebral vBMD and biomechanical properties measured in BXH RI strains showed a greater variability than either B6 or C3H progenitors, suggesting both progenitor strains have independent subsets of genes that yield similar vBMD and strength. The μCT and pQCT data suggested that the distribution of vertebral mineral into cortical and trabecular compartments is regulated genetically. Although the B6 and C3H progenitors had similar vertebral strength, their vertebral structures were markedly different: B6 had good trabecular bone structure and modest cortical bone mineral content (BMC), whereas C3H had high cortical BMC combined with a deficiency in trabecular structure. These structural traits segregated independently in the BXH RI strains. Finally, vertebral strength was not correlated consistently with femoral strength among the BXH RI strains, suggesting genetic regulation of bone strength is site specific.

Keywords: biomechanics; bone density; osteoporosis; genetics

Links

DOI: 10.1359/jbmr.2001.16.2.206

PubMed: 11204420

WoS: 000166494200003

History

Received: 2000-05-16

Revised: 2000-08-10

Accepted: 2000-09-05

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2001	Beamer WG, Shultz KL, Donahue LR, Churchill GA, Sen S, Wergedal JR, Baylink DJ, Rosen CJ. Quantitative trait loci for femoral and lumbar vertebral bone mineral density in C57BL/6J and C3H/HeJ inbred strains of mice. J Bone Miner Res. July 2001;16(7):1195-1206.
2005	Tommasini SM, Morgan TG, van der Meulen MCH, Jepsen KJ. Genetic variation in structure‐function relationships for the inbred mouse lumbar vertebral body. J Bone Miner Res. May 2005;20(5):817-827.
2019	Emami AJ, Toupadakis CA, Telek SM, Fyhrie DP, Yellowley CE, Christiansen BA. Age dependence of systemic bone loss and recovery following femur fracture in mice. J Bone Miner Res. January 2019;34(1):157-170.
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2019	Martig S. Compressive Fatigue Life and Micromorphology of Equine Metacarpal Subchondral Bone [PhD thesis]. University of Melbourne; June 2019.