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Research Papers

Trabecular Bone Loss at a Distant Skeletal Site Following Noninvasive Knee Injury in Mice

[+] Author and Article Information
Blaine A. Christiansen

Department of Orthopaedic Surgery,
University of California-Davis Medical Center,
4635 2nd Avenue, Suite 2000,
Sacramento, CA 95817;
Biomedical Engineering Graduate Group,
University of California-Davis,
Davis, CA 95616
e-mail: bchristiansen@ucdavis.edu

Armaun J. Emami, Michael R. Hardisty

Department of Orthopaedic Surgery,
University of California-Davis Medical Center,
4635 2nd Avenue, Suite 2000,
Sacramento, CA 95817;
Biomedical Engineering Graduate Group,
University of California-Davis,
Davis, CA 95616

David P. Fyhrie

Department of Orthopaedic Surgery,
University of California-Davis Medical Center,
4635 2nd Avenue, Suite 2000,
Sacramento, CA 95817;
Biomedical Engineering Graduate Group,
University of California-Davis,
Davis, CA 95616

Patrick B. Satkunananthan

Department of Orthopaedic Surgery,
University of California-Davis Medical Center,
4635 2nd Avenue, Suite 2000,
Sacramento, CA 95817;
Biomedical Engineering Graduate Group,
University of California-Davis,
Davis, CA 95616

1Corresponding author.

Manuscript received June 17, 2014; final manuscript received September 9, 2014; accepted manuscript posted October 16, 2014; published online December 10, 2014. Assoc. Editor: Ara Nazarian.

J Biomech Eng 137(1), 011005 (Jan 01, 2015) Paper No: BIO-14-1271; doi: 10.1115/1.4028824 History: Received June 17, 2014; Revised September 09, 2014; Accepted October 16, 2014; Online December 10, 2014

Traumatic injuries can have systemic consequences, as the early inflammatory response after trauma can lead to tissue destruction at sites not affected by the initial injury. This systemic catabolism may occur in the skeleton following traumatic injuries such as anterior cruciate ligament (ACL) rupture. However, bone loss following injury at distant, unrelated skeletal sites has not yet been established. In the current study, we utilized a mouse knee injury model to determine whether acute knee injury causes a mechanically significant trabecular bone loss at a distant, unrelated skeletal site (L5 vertebral body). Knee injury was noninvasively induced using either high-speed (HS; 500 mm/s) or low-speed (LS; 1 mm/s) tibial compression overload. HS injury creates an ACL rupture by midsubstance tear, while LS injury creates an ACL rupture with an associated avulsion bone fracture. At 10 days post-injury, vertebral trabecular bone structure was quantified using high-resolution microcomputed tomography (μCT), and differences in mechanical properties were determined using finite element modeling (FEM) and compressive mechanical testing. We hypothesized that knee injury would initiate a loss of trabecular bone structure and strength at the L5 vertebral body. Consistent with our hypothesis, we found significant decreases in trabecular bone volume fraction (BV/TV) and trabecular number at the L5 vertebral body in LS injured mice compared to sham (−8.8% and −5.0%, respectively), while HS injured mice exhibited a similar, but lower magnitude response (−5.1% and −2.5%, respectively). Contrary to our hypothesis, this decrease in trabecular bone structure did not translate to a significant deficit in compressive stiffness or ultimate load of the full trabecular body assessed by mechanical testing or FEM. However, we were able to detect significant decreases in compressive stiffness in both HS and LS injured specimens when FE models were loaded directly through the trabecular bone region (−9.9% and −8.1%, and 3, respectively). This finding may be particularly important for osteoporotic fracture risk, as damage within vertebral bodies has been shown to initiate within the trabecular bone compartment. Altogether, these data point to a systemic trabecular bone loss as a consequence of fracture or traumatic musculoskeletal injury, which may be an underlying mechanism contributing to increased risk of refracture following an initial injury. This finding may have consequences for treatment of acute musculoskeletal injuries and the prevention of future bone fragility.

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References

Lenz, A., Franklin, G. A., and Cheadle, W. G., 2007, “Systemic Inflammation After Trauma,” Injury, 38(12), pp. 1336–1345. [CrossRef] [PubMed]
Pfeifer, R., Darwiche, S., Kohut, L., Billiar, T. R., and Pape, H. C., 2013, “Cumulative Effects of Bone and Soft Tissue Injury on Systemic Inflammation: A Pilot Study,” Clin. Orthop. Relat. Res., 471(9), pp. 2815–2821. [CrossRef] [PubMed]
Irie, K., Uchiyama, E., and Iwaso, H., 2003, “Intraarticular Inflammatory Cytokines in Acute Anterior Cruciate Ligament Injured Knee,” Knee, 10(1), pp. 93–96. [CrossRef] [PubMed]
Brophy, R. H., Rai, M. F., Zhang, Z., Torgomyan, A., and Sandell, L. J., 2012, “Molecular Analysis of Age and Sex-Related Gene Expression in Meniscal Tears With and Without a Concomitant Anterior Cruciate Ligament Tear,” J. Bone Jt. Surg. Am., 94(5), pp. 385–393. [CrossRef]
Lohmander, L. S., Atley, L. M., Pietka, T. A., and Eyre, D. R., 2003, “The Release of Crosslinked Peptides From Type II Collagen Into Human Synovial Fluid is Increased Soon After Joint Injury and in Osteoarthritis,” Arthritis Rheum., 48(11), pp. 3130–3139. [CrossRef] [PubMed]
Lohmander, L. S., Dahlberg, L., Ryd, L., and Heinegard, D., 1989, “Increased Levels of Proteoglycan Fragments in Knee Joint Fluid After Injury,” Arthritis Rheum., 32(11), pp. 1434–1442. [CrossRef] [PubMed]
Lohmander, L. S., Saxne, T., and Heinegard, D. K., 1994, “Release of Cartilage Oligomeric Matrix Protein (COMP) Into Joint Fluid After Knee Injury and in Osteoarthritis,” Ann. Rheum. Dis., 53(1), pp. 8–13. [CrossRef] [PubMed]
Lohmander, L. S., Roos, H., Dahlberg, L., Hoerrner, L. A., and Lark, M. W., 1994, “Temporal Patterns of Stromelysin-1, Tissue Inhibitor, and Proteoglycan Fragments in Human Knee Joint Fluid After Injury to the Cruciate Ligament or Meniscus,” J. Orthop. Res., 12(1), pp. 21–28. [CrossRef] [PubMed]
Dahlberg, L., Roos, H., Saxne, T., Heinegard, D., Lark, M. W., Hoerrner, L. A., and Lohmander, L. S., 1994, “Cartilage Metabolism in the Injured and Uninjured Knee of the Same Patient,” Ann. Rheum. Dis., 53(12), pp. 823–827. [CrossRef] [PubMed]
Mueller, M., Schilling, T., Minne, H. W., and Ziegler, R., 1991, “A Systemic Acceleratory Phenomenon (SAP) Accompanies the Regional Acceleratory Phenomenon (RAP) During Healing of a Bone Defect in the Rat,” J. Bone Miner. Res., 6(4), pp. 401–410. [CrossRef] [PubMed]
Christiansen, B. A., Anderson, M. J., Lee, C. A., Williams, J. C., Yik, J. H., and Haudenschild, D. R., 2012, “Musculoskeletal Changes Following Non-Invasive Knee Injury Using a Novel Mouse Model of Post-Traumatic Osteoarthritis,” Osteoarthritis Cartilage, 20(7), pp. 773–782. [CrossRef] [PubMed]
Lockwood, K. A., Chu, B. T., Anderson, M. J., Haudenschild, D. R., and Christiansen, B. A., 2013, “Comparison of Loading Rate-Dependent Injury Modes in a Murine Model of Post-Traumatic Osteoarthritis,” J. Orthop. Res., 32(1), pp. 79–88. [CrossRef] [PubMed]
Fyhrie, D. P., Lang, S. M., Hoshaw, S. J., Schaffler, M. B., and Kuo, R. F., 1995, “Human Vertebral Cancellous Bone Surface Distribution,” Bone, 17(3), pp. 287–291. [CrossRef] [PubMed]
Hou, F. J., Lang, S. M., Hoshaw, S. J., Reimann, D. A., and Fyhrie, D. P., 1998, “Human Vertebral Body Apparent and Hard Tissue Stiffness,” J. Biomech., 31(11), pp. 1009–1015. [CrossRef] [PubMed]
Fyhrie, D. P., Hoshaw, S. J., Hamid, M. S., and Hou, F. J., 2000, “Shear Stress Distribution in the Trabeculae of Human Vertebral Bone,” Ann. Biomed. Eng., 28(10), pp. 1194–1199. [CrossRef] [PubMed]
Turner, C. H., Hsieh, Y. F., Muller, R., Bouxsein, M. L., Rosen, C. J., McCrann, M. E., Donahue, L. R., and Beamer, W. G., 2001, “Variation in Bone Biomechanical Properties, Microstructure, and Density in BXH Recombinant Inbred Mice,” J. Bone Miner. Res., 16(2), pp. 206–213. [CrossRef] [PubMed]
Tommasini, S. M., Morgan, T. G., van der Meulen, M., and Jepsen, K. J., 2005, “Genetic Variation in Structure-Function Relationships for the Inbred Mouse Lumbar Vertebral Body,” J. Bone Miner. Res., 20(5), pp. 817–827. [CrossRef] [PubMed]
Reeves, G. M., McCreadie, B. R., Chen, S., Galecki, A. T., Burke, D. T., Miller, R. A., and Goldstein, S. A., 2007, “Quantitative Trait Loci Modulate Vertebral Morphology and Mechanical Properties in a Population of 18-Month-Old Genetically Heterogeneous Mice,” Bone, 40(2), pp. 433–443. [CrossRef] [PubMed]
Klotzbuecher, C. M., Ross, P. D., Landsman, P. B., Abbott, T. A., 3rd, and Berger, M., 2000, “Patients With Prior Fractures Have an Increased Risk of Future Fractures: A Summary of the Literature and Statistical Synthesis,” J. Bone Miner. Res., 15(4), pp. 721–739. [CrossRef] [PubMed]
Haentjens, P., Autier, P., Collins, J., Velkeniers, B., Vanderschueren, D., and Boonen, S., 2003, “Colles Fracture, Spine Fracture, and Subsequent Risk of Hip Fracture in Men and Women. A Meta-Analysis,” J. Bone Jt. Surg. Am., 85-A(10), pp. 1936–1943.
Robinson, C. M., Royds, M., Abraham, A., McQueen, M. M., Court-Brown, C. M., and Christie, J., 2002, “Refractures in Patients at Least Forty-Five Years Old. A Prospective Analysis of Twenty-Two Thousand and Sixty Patients,” J. Bone Jt. Surg. Am., 84-A(9), pp. 1528–1533.
Lauritzen, J. B., Schwarz, P., McNair, P., Lund, B., and Transbol, I., 1993, “Radial and Humeral Fractures as Predictors of Subsequent Hip, Radial or Humeral Fractures in Women, and Their Seasonal Variation,” Osteoporosis Int., 3(3), pp. 133–137. [CrossRef]
Black, D. M., Arden, N. K., Palermo, L., Pearson, J., and Cummings, S. R., 1999, “Prevalent Vertebral Deformities Predict Hip Fractures and New Vertebral Deformities But Not Wrist Fractures. Study of Osteoporotic Fractures Research Group,” J. Bone Miner. Res., 14(5), pp. 821–828. [CrossRef] [PubMed]
Wu, F., Mason, B., Horne, A., Ames, R., Clearwater, J., Liu, M., Evans, M. C., Gamble, G. D., and Reid, I. R., 2002, “Fractures Between the Ages of 20 and 50 Years Increase Women's Risk of Subsequent Fractures,” Arch. Intern. Med., 162(1), pp. 33–36. [CrossRef] [PubMed]
Melton, L. J.III, Ilstrup, D. M., Beckenbaugh, R. D., and Riggs, B. L., 1982, “Hip Fracture Recurrence. A Population-Based Study,” Clin. Orthop. Relat. Res., 167(7), pp. 131–138. [PubMed]
Silman, A. J., 1995, “The Patient With Fracture: The Risk of Subsequent Fractures,” Am. J. Med., 98(2A), pp. 12S–16S. [CrossRef] [PubMed]
Goulding, A., Cannan, R., Williams, S. M., Gold, E. J., Taylor, R. W., and Lewis-Barned, N. J., 1998, “Bone Mineral Density in Girls With Forearm Fractures,” J. Bone Miner. Res., 13(1), pp. 143–148. [CrossRef] [PubMed]
Johnell, O., Kanis, J. A., Oden, A., Sernbo, I., Redlund-Johnell, I., Petterson, C., De Laet, C., and Jonsson, B., 2004, “Fracture Risk Following an Osteoporotic Fracture,” Osteoporosis Int., 15(3), pp. 175–179. [CrossRef]
Clinton, J., Franta, A., Polissar, N. L., Neradilek, B., Mounce, D., Fink, H. A., Schousboe, J. T., and Matsen, F. A.III, 2009, “Proximal Humeral Fracture as a Risk Factor for Subsequent Hip Fractures,” J. Bone Jt. Surg. Am., 91(3), pp. 503–511. [CrossRef]
Lindsay, R., Silverman, S. L., Cooper, C., Hanley, D. A., Barton, I., Broy, S. B., Licata, A., Benhamou, L., Geusens, P., Flowers, K., Stracke, H., and Seeman, E., 2001, “Risk of New Vertebral Fracture in the Year Following a Fracture,” JAMA, 285(3), pp. 320–323. [CrossRef] [PubMed]
Cao, K. D., Grimm, M. J., and Yang, K. H., 2001, “Load Sharing Within a Human Lumbar Vertebral Body Using the Finite Element Method,” Spine (Phila Pa 1976), 26(12), pp. E253–E260. [CrossRef] [PubMed]
Eswaran, S. K., Gupta, A., Adams, M. F., and Keaveny, T. M., 2006, “Cortical and Trabecular Load Sharing in the Human Vertebral Body,” J. Bone Miner. Res., 21(2), pp. 307–314. [CrossRef] [PubMed]
Roux, J. P., Wegrzyn, J., Arlot, M. E., Guyen, O., Delmas, P. D., Chapurlat, R., and Bouxsein, M. L., 2010, “Contribution of Trabecular and Cortical Components to Biomechanical Behavior of Human Vertebrae: An Ex Vivo Study,” J. Bone Miner. Res., 25(2), pp. 356–361. [CrossRef] [PubMed]
Eswaran, S. K., Gupta, A., and Keaveny, T. M., 2007, “Locations of Bone Tissue at High Risk of Initial Failure During Compressive Loading of the Human Vertebral Body,” Bone, 41(4), pp. 733–739. [CrossRef] [PubMed]
Hosseini, H. S., Clouthier, A. L., and Zysset, P. K., 2014, “Experimental Validation of Finite Element Analysis of Human Vertebral Collapse Under Large Compressive Strains,” ASME J. Biomech. Eng., 136(4), p. 041006. [CrossRef]
Kazakia, G. J., Tjong, W., Nirody, J. A., Burghardt, A. J., Carballido-Gamio, J., Patsch, J. M., Link, T., Feeley, B. T., and Ma, C. B., 2014, “The Influence of Disuse on Bone Microstructure and Mechanics Assessed by HR-PQCT,” Bone, 63(6), pp. 132–140. [CrossRef] [PubMed]
Christen, P., van Rietbergen, B., Lambers, F. M., Muller, R., and Ito, K., 2012, “Bone Morphology Allows Estimation of Loading History in a Murine Model of Bone Adaptation,” Biomech. Model. Mechanobiol., 11(3–4), pp. 483–492. [CrossRef] [PubMed]

Figures

Grahic Jump Location
Fig. 1

Mouse L5 vertebra orthogonal view (left). Trabecular bone structure of the L5 vertebral body was analyzed with microcomputed tomography in a volume excluding the endplates and posterior elements (right).

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Fig. 2

Representative L5 vertebral body (reconstructed from μCT scan) used for finite element analysis with parallel-cut ends and posterior elements trimmed at the pedicle (left). FE models were compressed with two different boundary conditions (center/right). Full specimen compression was simulated by loading to the entire cross section at the top and bottom, including both trabecular bone and the cortical shell. Trabecular bone compression was simulated by loading 1.002 mm (167 pixel) diameter circular areas axially aligned on the top and bottom of the models.

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Fig. 3

L5 vertebral body trabecular bone structural parameters. BV/TV was 8.8% lower in LS injured mice than sham mice. Similarly, trabecular number was decreased 2.5% and 5.0% for HS and LS injured mice, respectively, while trabecular separation was increased 3.4% and 5.3% in HS and LS injured mice, respectively, compared to sham mice. No significant differences were observed for trabecular thickness. * p < 0.05

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Fig. 4

Representative stress distribution in the direction of the principal loading axis at the top boundary of the model (top row) and midfrontal section (middle row). Full specimen compression (left column) did not predict any significant differences between HS injured, LS injured, or sham specimens (bottom left). However, trabecular bone loading (right column) predicted significantly lower compressive stiffness for HS injured (−9.9%) and LS injured (−8.1%) specimens compared to sham (bottom right). * p < 0.05

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Fig. 5

Results for compressive mechanical testing of isolated mouse L5 vertebral bodies. No significant differences were observed between HS injured, LS injured, or sham specimens for stiffness or ultimate load.

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