TRANSLATIONAL RESEARCH IN THE JEPSEN LABORATORY
Much of the research conducted using inbred mouse strains, and many of the concepts learned from the mouse, have been successfully translated to the human skeleton. One important question that we addressed and answered is 'how effective is this adaptive process at establishing function across a population?' We identified an intrinsic "flaw" in the functional adaptation process of human bone that contributes to increased fracture susceptibility in a healthy, young adult population. Using a collection of pQCT images from over 1000 men and women from three countries (US, UK, Israel), we found that the skeletal system was inherently limited in its ability to fully compensate the natural variation in bone size (robustness), leaving a predictable segment of the population at a functional deficit. This functional inequivalence was not problematic for daily load conditions, but increased fracture risk under extreme loading conditions. We propose to apply these methods to the aging population because it is expected that starting the aging process with a functional deficit will increase fracture risk earlier in life.
Human diaphyseal bone shows a pattern of interactions among morphological and tissue-quality traits that is similar to what was observed in the mouse femur. Identifying patterns in the way traits covary across a population has tremendous clinical value for predicting an individuals skeletal strength and fracture risk, for predicting an individuals adaptive response to age-related bone loss, for investigating the biological basis of functionality, for identifying genetic and environmental factors that promote or impair the development and maintenance of function.
The ATLAS project is looking at remodeling using bone from adult human cadavers. These bones are scanned using a nanoCT system and then tested mechanically for stiffness, using an Instron materials testing system. The bones from the other side of the body are prepared for histology.
PROTOCOLS(Clicking on links below will open the protocol .pdf file in a new window)
General bone preparation protocols
NanoCT protocols. The nanoCT system allows us to scan both cadaver and dry bone at high resolution.
pQCT protocols. We have scanned a wide range of bones including live individuals, cadavers, anatomical collections, and archeological collections.
- Protocol for scanning cadaver bones
- Protocol for scanning dry bones(Will be uploaded soon, please check back)
- Protocol for analyzing pQCT images of cadaver bones
Mechanical testing protocols. These protocols are designed for use with custom fixtures on an Instron testing frame.
- Four point bending for human long bones, excluding metacarpals
- Four point bending for human metacarpals (Will be uploaded soon, please check back)
- Tommasini SM, Nasser P, Schaffler MB, Jepsen KJ. The relationship between bone morphology and bone quality in male tibiae: Implications for stress fracture risk. Journal of Bone and Mineral Research, 20(8):1372-1380, 2005.
- Tommasini SM, Nasser P, Jepsen KJ. Sexual dimorphism affects tibial size and shape but not tissue-level mechanical properties. Bone, Bone, 40, 498-505, 2007.
- Tommasini SM, Nasser P, Hu B, Jepsen KJ. Biological co-adaptation of morphological and compositional traits contributes to mechanical functionality and skeletal fragility. Journal of Bone and Mineral Research, 23(2):236-246, 2008. PMC2665697
- Jepsen KJ. Systems analysis of bone. Invited review, Wiley Interdisciplinary Reviews: Systems Biology and Medicine 1(1):73-88, 2009. PMC2790199
- Pandey N, Bhola S, Goldstone A, Chen F, Chrzanowski J, Terranova CJ, Ghillani R, Jepsen KJ. Inter-individual variation in functionally adapted trait sets is established during post-natal growth and predictable based on bone robusticity. J Bone Miner Res, 24(12):1969-1980, 2009. PMC2791514
- Jepsen KJ, Centi A, Duarte GF, Galloway K, Goldman H, Hampson N, Lappe JM, Cullen DM, Greeves J, Izard R, Nindl BC, Kraemer WJ, Negus CH, Evans RK. Biological constraints that limit compensation of a common skeletal trait variant lead to inequivalence of tibial function among healthy young adults. Journal of Bone and Mineral Research, 26:2872-2885, 2011. PMID 21898595 (PMC Journal - In Process).
- Andarawis-Puri N, Sereysky JB, Jepsen KJ, Flatow EL. The relationships between cyclic fatigue loading, changes In initial mechanical properties, and the in vivo temporal mechanical response of the rat patellar tendon. Journal of Biomechanics, 45(1):59-65, 2012. PMID 22055428
- Epelboym Y, Gendron RN, Mayer J, Fusco J, Nasser P, Gross G, Ghillani R, Jepsen KJ. The inter-individual variation in femoral neck width is associated with the acquisition of predictable sets of morphological and tissue-quality traits and differential bone loss patterns. Journal of Bone and Mineral Research, 27(7):1501-1510, 2012. PMID 22461103 (PMC Journal - In Process)
- Jepsen KJ, Evans R, Negus CH, Gagnier JJ, Centi A, Erlich T, Hadid A, Yanovich R, Moran DS. Variation in tibial functionality and fracture susceptibility among healthy, young adults arises from the acquisition of biologically distinct sets of traits. Journal of Bone and Mineral Research, in press, 2013.
- Schlecht SH, Jepsen KJ. Functional integration of skeletal traits: an intraskeletal assessment of bone size, mineralization and volume covariance. Bone 56:127–138, 2013
- Schlecht SH, Bigelow EMR, Jepsen KJ. Mapping the natural variation in whole bone stiffness across skeletal sites. Bone; 2014; 67:15-22.
- Khoury BM, Bigelow EMR, Smith LM, Schlecht SH, Scheller EL, Andarawis-Puri N, Jepsen KJ. The use of nano-computed tomography to enhance musculoskeletal research. Conn Tissue Res; 2014; early view, doi:10.3109/03008207.2015.1005211.
- Jepsen KJ, Bigelow EMR, Schlecht SH. Women build long bones with less cortical mass relative to body size and bone size compared with men. Clin Orthop Rel Res; 2015; early view, doi:10.1007/s11999-015-4184-2.
- Schlecht SH, Bigelow EMR, Jepsen KJ. How does bone strength compare across sex, site, and ethnicity?. Clin Orthop Rel Res; 2015; early view, doi:10.1007/s11999-015-4229-6.
Porosity in a section of human bone. Created by looking at an inverse image of the bone nanoCT image.