Karl J Jepsen, PhD
Associate Dean for Research
Professor of Orthopaedic Surgery
Professor of Biomedical Engineering
[email protected]

Available to mentor

Karl J Jepsen, PhD
  • About
  • Qualifications
  • Research Overview
  • Recent Publications
  • About

    The primary objective of my research program is to understand how complex adaptive systems like bone establish function during growth and maintain function during aging. Having a better understanding of how complex systems work will benefit efforts to reduce skeletal fracture risk by identifying the genetic and environmental factors that impair (or promote) specific components of the functional adaptation process and that compromise (or improve) fracture resistance.

    • Postdoctoral Fellow
      Case Western Reserve University, Cleveland, 1996
    • PhD
      University of Michigan, Ann Arbor, 1994
    • MS
      University Of Michigan, Ann Arbor, 1992
    • MS
      Wayne State University, Detroit, 1988
    • BS
      Wayne State University, Detroit, 1987
    Research Overview

    Using a genetic randomization approach, my laboratory identified a pattern in the way skeletal traits covary across a population of recombinant inbred mouse strains. This line of research established that variation in bone morphology is functionally related to tissue-mineralization (tissue-quality). These functional interactions, known in the broader literature as phenotypic integration, are part of the functional adaptation process wherein mutations affecting external bone size are compensated by coordinated changes in tissue-quality. I have placed a large emphasis on translating the biological concepts learned from the mouse directly to the human skeleton, which shows similar functional trait interactions as the mouse skeleton. Further, we demonstrated that individuals are at risk of developing an insufficiency fracture for different biomechanical reasons. Importantly, studies of the mouse and human skeletons have shown that functional interactions among adult traits are established by 2-4 weeks of age in the mouse and by 4 years in humans. This latter research effort is the reason why a major focus of my lab involves studying how and when these functional interactions arise during postnatal growth. I expect that genetic or environmental perturbations expressed during this critical window will impair the development of bone strength and lead to increased fracture risk later in life.
    Recently, my lab discovered a novel association between a measure of external bone size and the internal remodeling process that is central to establishing and maintaining bone strength. This observation motivated us to apply what we learned thus far in complex adaptive systems and to conduct an analysis of secondary data utilize existing longitudinally acquired human data to test whether individuals with narrow bones would show age-related changes in bone structure and strength that differed from individuals with wide bones. Examination of 14 year changes in BMC, bone area and BMC indeed revealed that women with narrow femoral necks showed small reductions in BMC (consistent with having a lower baseline level of intra-cortical remodeling) but large increases in bone area. In contrast, women with wide femoral necks showed large reductions in BMC (consistent with having a higher baseline level of intra-cortical remodeling) but only small increases in bone area. Our current research efforts are directed toward better understanding how external-size dependent changes in structure and mass affect bone strength and thus create different strength-decline trajectories during the menopausal transition. Better understanding this global-level regulation of intra-cortical remodeling may be critically important for developing prophylactic treatments for reducing stress (insufficiency) and fragility fractures that are personalized to the biological needs of the individual. Together, these studies have demonstrated how a simple measure like external bone size can help predict how bones grow and age.

    Recent Publications See All Publications
    • Journal Article
      Structural differences contributing to sex-specific associations between femoral neck bone mineral density and whole bone strength for adult white women and men
      Jepsen KJ, Bigelow EMR, Goulet RW, Nolan BT, Casden MA, Kennedy K, Hertz S, Kadur C, Clines GA, Leis AM, Karvonen-Gutierrez CA, Bredbenner TL. JBMR Plus, ziae013 DOI:10.1093/jbmrpl/ziae013
    • Journal Article
      Perspective: A multi-trait integrative approach to understanding the structural basis of bone fragility for pediatric conditions associated with abnormal bone development.
      Whitney DG, Caird MS, Raggio CL, Hurvitz EA, Clines GA, Jepsen KJ. Bone, 2023 Oct; 175: 116855 DOI:10.1016/j.bone.2023.116855
      PMID: 37481149
    • Journal Article
      Associations Among Hip Structure, Bone Mineral Density, and Strength Vary With External Bone Size in White Women.
      Jepsen KJ, Bigelow EM, Casden MA, Goulet RW, Kennedy K, Hertz S, Kadur C, Nolan BT, Richards-McCullough K, Merillat S, Karvonen-Gutierrez CA, Clines G, Bredbenner TL. JBMR Plus, 2023 Mar; 7 (3): e10715 DOI:10.1002/jbm4.10715
      PMID: 36936363
    • Journal Article
      Correction: Bringing Mechanical Context to Image-Based Measurements of Bone Integrity.
      Loundagin LL, Bredbenner TL, Jepsen KJ, Edwards WB. Curr Osteoporos Rep, 2023 Oct 14; DOI:10.1007/s11914-023-00829-z
      PMID: 37837513
    • Journal Article
      Divergent mechanical properties of older human male femora reveal unique combinations of morphological and compositional traits contributing to low strength.
      Bolger MW, Romanowicz GE, Bigelow EMR, Ward FS, Ciarelli A, Jepsen KJ, Kohn DH. Bone, 2022 Oct; 163: 116481 DOI:10.1016/j.bone.2022.116481
      PMID: 35817317
    • Journal Article
      Sex and External Size Specific Limitations in Assessing Bone Health From Adult Hand Radiographs.
      Bigelow EMR, Goulet RW, Ciarelli A, Schlecht SH, Kohn DH, Bredbenner TL, Harlow SD, Karvonen-Gutierrez CA, Jepsen KJ. JBMR Plus, 2022 Aug; 6 (8): e10653 DOI:10.1002/jbm4.10653
      PMID: 35991534
    • Journal Article
      A Word from OLAW and USDA.
      Brown P, Goldentyer B. Lab Anim (NY), 2022 Jun; 51 (6): 150 DOI:10.1038/s41684-022-00983-4
      PMID: 35641624
    • Journal Article
      Clinical bone health among adults with cerebral palsy: moving beyond assessing bone mineral density alone.
      Whitney DG, Caird MS, Clines GA, Hurvitz EA, Jepsen KJ. Dev Med Child Neurol, 2022 Apr; 64 (4): 469 - 475. DOI:10.1111/dmcn.15093
      PMID: 34658010