Anterior cruciate ligament (ACL) tears are activity-related knee injuries associated with an elevated risk of developing post-traumatic osteoarthritis 10-20 years post-injury. Immediately after the injury bone mass is lost. This is followed by a recovery period, though full recovery is not achieved even years later. Due to a lack of appropriate imaging modalities, no information is available on how the underlying bone microarchitecture is affected. In addition, the effects of concurrent soft-tissue injuries, such as meniscus tears or traumatic bone marrow lesions, on the underlying bone microarchitecture in human knees are not known.
In this thesis, a new method for in vivo assessment of bone microarchitecture of the human knee is introduced. Next, in two cross-sectional studies this technique is applied to populations that experienced unilateral ACL tears six to nine years earlier. Both studies revealed that bone is primarily affected in the femur of the injured knee. Trabecular bone mass is lower in the medial femur (-4.8% to -10.4%) while the subchondral bone plate is thicker in the lateral femur (9% to 29.6%) as compared to the contralateral knee. Further, the thicker subchondral bone plate is associated with surgical meniscus treatment (meniscectomy or repair) at the time of ligament reconstruction.
In a year-long longitudinal study, the new imaging technique is applied to a cohort with acute unilateral ACL tears to investigate how early injury-induced bone changes affect microstructure. Immediately following the injury, trabecular bone is lost throughout the injured knee (-4.9% to -15.8%), driven by a loss of trabecular elements and increased trabecular separation. Concurrently, the subchondral bone plate of the lateral femur thins (-9%). The trabecular bone changes are further accelerated in traumatic bone marrow lesions (-18.2% to -20.6%).
These findings show that while initial bone mass loss following the injury may recover six to nine years later (primarily in the tibia), the femur is affected long-term. The underlying structural changes are believed to be permanent, and while it is not known which individuals will develop osteoarthritis, limiting early injury-induced bone changes may reduce long-term risk of joint degradation.
|1996||Rüegsegger P, Koller B, Müller R. A microtomographic system for the nondestructive evaluation of bone architecture. Calcif Tiss Int. 1996;58(1):24-29.|
|1984||Parfitt AM. The cellular basis of bone remodeling: the quantum concept reexamined in light of recent advances in the cell biology of bone. Calcif Tiss Int. March 1984;36(suppl 1):S37-S45.|
|2001||Day JS, Ding M, van der Linden JC, Hvid I, Sumner DR, Weinans H. A decreased subchondral trabecular bone tissue elastic modulus is associated with pre‐arthritic cartilage damage. J Orthop Res. September 2001;19(5):914-918.|
|1999||Laib A, Rüegsegger P. Calibration of trabecular bone structure measurements of in vivo three-dimensional peripheral quantitative computed tomography with 28-μm-resolution microcomputed tomography. Bone. January 1999;24(1):35-39.|
|2003||Patel V, Issever AS, Burghardt A, Laib A, Ries M, Majumdar S. MicroCT evaluation of normal and osteoarthritic bone structure in human knee specimens. J Orthop Res. 2003;21(1):6-13.|
|2008||Clarke B. Normal bone anatomy and physiology. Clin J Am Soc Nephrol. November 2008;3(suppl 3):S131-S139.|
|1995||Glüer C-C, Blake G, Lu Y, Blunt BA, Jergas M, Genant HK. Accurate assessment of precision errors: how to measure the reproducibility of bone densitometry techniques. Osteoporos Int. 1995;5(4):262-270.|
|2000||Boyd SK, Matyas JR, Wohl GR, Kantzas A, Zernicke RF. Early regional adaptation of periarticular bone mineral density after anterior cruciate ligament injury. J Appl Physiol. December 2000;89(6):2359-2364.|
|2011||Macdonald HM, Nishiyama KK, Kang J, Hanley DA, Boyd SK. Age‐related patterns of trabecular and cortical bone loss differ between sexes and skeletal sites: a population‐based HT‐pQCT study. J Bone Miner Res. January 2011;26(1):50-62.|
|1986||Radin EL, Rose RM. Role of subchondral bone in the initiation and progression of cartilage damage. Clin Orthop Relat Res. December 1986;213:34-40.|
|1999||Laib A, Rüegsegger P. Comparison of structure extraction methods for in vivo trabecular bone measurements. Comput Vis Image Understand. March–April 1999;23(2):69-74.|
|1983||Parfitt AM, Mathews CH, Villanueva AR, Kleerekoper M, Frame B, Rao DS. Relationships between surface, volume, and thickness of iliac trabecular bone in aging and in osteoporosis: implications for the microanatomic and cellular mechanisms of bone loss. J Clin Invest. October 1983;72(4):1396-1409.|
|1999||Hawkins RD, Fuller CW. A prospective epidemiological study of injuries in four English professional football clubs. Br J Sports Med. June 1999;33(3):196-203.|
|2009||Meganck JA, Kozloff KM, Thornton MM, Broski SM, Goldstein SA. Beam hardening artifacts in micro-computed tomography scanning can be reduced by x-ray beam filtration and the resulting images can be used to accurately measure bmd. Bone. 2009;45(6):1104-1116.|
|2007||Lohmander LS, Englund PM, Dahl LL, Roos EM. The long-term consequence of anterior cruciate ligament and meniscus injuries: osteoarthritis. Am J Sports Med. October 2007;35(10):1756-1769.|
|2005||Agel J, Arendt EA, Bershadsky B. Anterior cruciate ligament injury in National Collegiate Athletic Association basketball and soccer: a 13-year review. Am J Sports Med. April 2005;33(4):524-530.|
|1997||Hildebrand T, Rüegsegger P. A new method for the model-independent assessment of thickness in three-dimensional images. J Microsc (Oxford). 1997;185(1):67-75.|
|1993||Fazzalari NL. Trabecular microfracture. Calcif Tiss Int. February 1993;53(suppl 1):S143-S147.|
|1995||Arendt E, Dick R. Knee injury patterns among men and women in collegiate basketball and soccer: NCAA data and review of literature. Am J Sports Med. December 1995;23(6):694-701.|
|1986||Wolff J. The Law of Bone Remodelling. Maquet P, Furlong R, trans. New York, NY: Springer; 1986.|
|2002||Burr DB. Targeted and nontargeted remodeling. Bone. January 2002;30(1):2-4.|
|2002||Parfitt AM. Targeted and nontargeted bone remodeling: relationship to basic multicellular unit origination and progression. Bone. January 2002;30(1):5-7.|
|1999||Hildebrand T, Laib A, Müller R, Dequeker J, Rüegsegger P. Direct three-dimensional morphometric analysis of human cancellous bone: microstructural data from spine, femur, iliac crest, and calcaneus. J Bone Miner Res. 1999;14(7):1167-1174.|
|2007||Buie HR, Campbell GM, Klinck RJ, MacNeil JA, Boyd SK. Automatic segmentation of cortical and trabecular compartments based on a dual threshold technique for in vivo micro-CT bone analysis. Bone. October 2007;41(4):505-515.|
|2002||Boyd SK, Müller R, Zernicke RF. Mechanical and architectural bone adaptation in early stage experimental osteoarthritis. J Bone Miner Res. April 2002;17(4):687-694.|
|2003||Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. May 15, 2003;423(6937):337-342.|
|2007||Burghardt AJ, Kazakia GJ, Majumdar S. A local adaptive threshold strategy for high resolution peripheral quantitative computed tomography of trabecular bone. Annals Biomed Eng. October 2007;235(10):1678-1686.|