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An immunohistochemical study of the tissue bridging adult spondylolytic defects—the presence and significance of fibrocartilaginous entheses

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Abstract

Introduction Spondylolytic spondylolisthesis is an osseous discontinuity of the vertebral arch that predominantly affects the fifth lumbar vertebra. Biomechanical factors are closely related to the condition. An immunohistochemical investigation of lysis-zone tissue obtained from patients with isthmic spondylolisthesis was performed to determine the molecular composition of the lysis-zone tissue and enable interpretation of the mechanical demands to which the tissue is subject. Methods: During surgery, the tissue filling the spondylytic defects was removed from 13 patients. Twelve spondylolistheses were at the L5/S1 level with slippage being less than Meyerding grade II. Samples were methanol fixed, decalcified and cryosectioned. Sections were labelled with a panel of monoclonal antibodies directed against collagens, glycosaminoglycans and proteoglycans. Results: The lysis-zone tissue had an ordered collagenous structure with distinct fibrocartilaginous entheses at both ends. Typically, these had zones of calcified and uncalcified fibrocartilage labelling strongly for type II collagen and aggrecan. Labelling was also detected around bony spurs that extended from the enthesis into the lysis-zone. The entheses also labelled for types I, III and VI collagens, chondroitin four and six sulfate, keratan and dermatan sulfate, link protein, versican and tenascin. Conclusions: Although the gap filled by the lysis tissue is a pathological feature, the tissue itself has hallmarks of a normal ligament—i.e. fibrocartilaginous entheses at either end of an ordered collagenous fibre structure. The fibrocartilage is believed to dissipate stress concentration at the hard/soft tissue boundary. The widespread occurrence of molecules typical of cartilage in the attachment of the lysis tissue, suggests that compressive and shear forces are present to which the enthesis is adapted, in addition to the expected tensile forces across the spondylolysis. Such a combination of tensile, shear and compressive forces must operate whenever there is any opening or closing of the spondylolytic gap.

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References

  1. Bareggi R, Grill V, Zweyer M, Narducci P, Forabosco A (1994) A quantitative study on the spatial and temporal ossification patterns of vertebral centra and neural arches and their relationship to the fetal age. Ann Anat 176:311–317

    PubMed  Google Scholar 

  2. Benjamin M, McGonagle D (2001) The anatomical basis for disease localisation in seronegative spondyloarthropathy at entheses and related sites. J Anat 199:503–526

    Article  PubMed  Google Scholar 

  3. Benjamin M, Kumai T, Milz S, Boszczyk BM, Boszczyk AA, Ralphs JR (2002) The skeletal attachment of tendons—tendon entheses. Comp Biochem Phys A Mol Integr Physiol 133:931–945

    Article  Google Scholar 

  4. Bono CM (2004) Low-back pain in athletes. J Bone Joint Surg Am 86A:382–396

    PubMed  Google Scholar 

  5. Boszczyk BM, Boszczyk AA, Putz R, Büttner A, Benjamin M, Milz S (2001) An immunohistochemical study of the dorsal capsule of the lumbar and thoracic facet joints. Spine 26:E338–E343

    Article  PubMed  Google Scholar 

  6. Boszczyk AA, Boszczyk BM, Putz R, Benjamin M, Milz S (2003) Expression of a wide range of fibrocartilage molecules at the enthesis of the alar ligaments—possible antigenic targets of rheumatoid arthritis. J Rheumatol 30:1420–1425

    PubMed  Google Scholar 

  7. Burr DB, Schaffler MB, Yang KH, Lukoschek M, Sivaneri N, Blaha JD, Radin EL (1989) Skeletal change in response to altered strain environments: is woven bone a response to elevated strain? Bone 10:223–233

    Article  PubMed  Google Scholar 

  8. Calabro A, Hascall VC, Caterson B (1992) Monoclonal antibodies directed against epitopes within the core protein structure of the large aggregating proetoglycan (aggrecan) from the swarm rat chondrosarcoma. Arch Biochem Biophys 298:349–360

    Article  PubMed  Google Scholar 

  9. Caterson B, Christner JE, Baker JR (1983) Identification of a monoclonal antibody that specifically recognizes corneal and skeletal keratan sulphate. Monoclonal antibodies to cartilage proteoglycan. J Biol Chem 258:8848–8854

    Google Scholar 

  10. Caterson B, Christner JE, Baker JR, Couchman JR (1985) Production and characterization of monoclonal antibodies directed against connective tissue proteoglycans. Fed Proc 44:386–393

    PubMed  Google Scholar 

  11. Chen CH, Chen WJ, Shih CH, Yang CY, Liu SJ, Lin PY (2003) Enveloping the tendon graft with periosteum to enhance tendon-bone healing in a bone tunnel: a biomechanical and histologic study in rabbits. Arthroscopy 19:290–296

    PubMed  Google Scholar 

  12. Chiari H (1892) Die Ätiologie und Genese der sogenannten spondylolisthesis lumbo-sacralis. Z Heilk 13:199–262

    Google Scholar 

  13. Cullinane DM, Salisbury KT, Alkhiary Y, Eisenberg S, Gerstenfeld L, Einhorn TA (2003) Effects of the local mechanical environment on vertebrate tissue differentiation during repair: does repair recapitulate development? J Exp Biol 206:2459–2471

    Article  PubMed  Google Scholar 

  14. Einhorn TA (1998) The cell and molecular biology of fracture healing. Clin Orthop 355(Suppl):S7–S21

    Article  PubMed  Google Scholar 

  15. Farfan HF, Osteria V, Lamy C (1975) The mechanical etiology of spondylolysis and spondylolisthesis. Clin Orthop 117:40–55

    Google Scholar 

  16. Fujioka H, Thakur R, Wang GJ, Mizuno K, Balian G, Hurwitz SR (1998) Comparison of surgically attached and non-attached repair of the rat achilles tendon-bone interface. Cellular organization and type X collagen expression. Connect Tissue Res 37:205–218

    Google Scholar 

  17. Gao J, Messner K, Ralphs JR, Benjamin M (1996) An immunohistochemical study of enthesis development in the medial collateral ligament of the rat knee joint. Anat Embryol 194:399–406

    Article  PubMed  Google Scholar 

  18. Haukipuro K, Keränen N, Koivisto E, Lindholm R, Norio R, Punto L (1978) Familial occurrence of lumbar spondylolysis and spondylolisthesis. Clin Genet 13:471–476

    PubMed  Google Scholar 

  19. Heggeness MH, Esses SI, Mody DR (1993) A histologic study of lumbar pseudarthrosis. Spine 18:1016–1020

    PubMed  Google Scholar 

  20. Hessle H, Engvall E (1984) Type VI collagen. Studies on its localization, structure, and biosynthetic form with monoclonal antibodies. J Biol Chem 259:3955–3961

    Google Scholar 

  21. Holmdahl R, Rubin K, Klareskog L, Larsson E, Wigzell H (1986) Characterization of the antibody response in mice with type II collagen-induced arthritis using monoclonal anti-type II collagen antibodies. Arth Rheum 29:400–410

    Google Scholar 

  22. Hutton WC, Stott JR, Cyron BM (1977) Is spondylolysis a fatigue fracture? Spine 2:202–209

    Google Scholar 

  23. Ikata T, Miyake R, Katoh S, Morita T, Murase M (1996) Pathogenesis of sports related spondylolisthesis in adolescents radiographic and magnetic resonance imaging study. Am J Sports Med 24:94–98

    PubMed  Google Scholar 

  24. Inoue H, Ohmori K, Ishida Y, Suzuki K, Tanaka K, Murakami S (1998) Finite element analysis of the lower lumbar neural arch under facet loading. J Spinal Disord 11:241–247

    PubMed  Google Scholar 

  25. Jackson RP, Phipps T, Hales C, Surber J (2003) Pelvic lordosis and alignment in spondylolisthesis. Spine 28:151–160

    Article  PubMed  Google Scholar 

  26. Kajiura K, Katoh S, Sairyo K, Ikata T, Goel VK, Murakami R (2001) Slippage mechanism of paediatric spondylolysis—biomechanical study using immature calf spines. Spine 26:2208–2213

    Article  PubMed  Google Scholar 

  27. Kilian HF (1853) De spondylolisthesi, gravissimae pelvangustiae causa nuper detecta. Commentatio anatomico-obstetricia. Bonn

    Google Scholar 

  28. Konz RJ, Goel VK, Grobler LJ, Grosland NM, Spratt KF, Scifert JL, Sairo K (2001) The pathomechanism of spondylolytic spondylolisthesis in immature primate lumbar spines—in vitro and finite element assessments. Spine 26:E38–E49

    Article  PubMed  Google Scholar 

  29. Lazennec JY, Laudet CG, Guerin-Surville H, Roy-Camille R, Saillant G (1997) Dynamic anatomy of the acetabulum: an experimental approach and surgical implications. Surg Radiol Anat 19:23–30

    PubMed  Google Scholar 

  30. Loboa EG, Beaupre GS, Carter DR (2001) Mechanobiology of initial pseudarthrosis formation with oblique fractures. J Orthop Res 19:1067–1072

    Article  PubMed  Google Scholar 

  31. Lonstein JE (1999) Spondylolisthesis in children—cause, natural history and management. Spine 24:2640–2648

    Article  PubMed  Google Scholar 

  32. Löhe F, Eckstein F, Sauer T, Putz R (1996) Structure, strain and function of the transverse acetabular ligament. Acta Anat (Basel) 157:315–323

    Google Scholar 

  33. Major NM, Helms CA, Richardson WJ (1999) MR imaging of fibrocartilaginous masses arising on the margins of spondylolysis defects. Am J Roentgenol 173:673–676

    Google Scholar 

  34. Marty C, Boisaubert B, Descamps H, Montigny JP, Hecquet J, Legaye J, Duval-Beaupère (2002) The sagittal anatomy of the sacrum among young adults, infants, and spondylolisthesis patients. Eur Spine J 11:119–125

    Article  PubMed  Google Scholar 

  35. McTimoney CA, Micheli LJ (2003) Current evaluation and management of spondylolysis and spondylolisthesis. Curr Sports Med Rep 2:41–46

    PubMed  Google Scholar 

  36. Milz S, Valassis G, Büttner A, Maier M, Putz R, Ralphs JR, Benjamin M (2001) Fibrocartilage in the transverse ligament of the human acetabulum. J Anat 198:223–228

    Article  PubMed  Google Scholar 

  37. Milz S, Schlüter T, Putz R, Moriggl B, Ralphs JR, Benjamin M (2001) Fibrocartilage in the transverse ligament of the human atlas. Spine 26:1765–1771

    Article  PubMed  Google Scholar 

  38. Moriggl B, Jax P, Milz S, Büttner A, Benjamin M (2001) Fibrocartilage at the entheses of the suprascapular (superior transverse scapular) ligament of man—a ligament spanning two regions of a single bone. J Anat 199:539–545

    Article  PubMed  Google Scholar 

  39. Mosimann P (1961) Die histologie der spondylolyse. Arch Orthop Unfallchir 53:264–285

    Article  PubMed  Google Scholar 

  40. Newell RL (1995) Spondylolysis—an historical review. Spine 20:1950–1956

    PubMed  Google Scholar 

  41. Oguma H, Murakami G, Takahashi-Iwanaga H, Aoki M, Ishii S (2001) Early anchoring collagen fibers at the bone-tendon interface are conducted by woven bone formation: light microscope and scanning electron microscope observation using a canine model. J Orthop Res 19:873–880

    Article  PubMed  Google Scholar 

  42. Reichmann S (1971) The postnatal development of form and orientation of the lumbar intervertebral joint surfaces. Z Anat Entwicklungsgesch 133:102–123

    Article  PubMed  Google Scholar 

  43. Robert (1855) Eine eigenthümliche angeborene lordose, wahrscheinlich bedingt durch eine verschiebung des körpers des letzten lendenwirbels auf die vordere fläche des ersten kreuzbeinwirbels (Spondylolisthesis Kilian), nebst bemerkungen über die mechanik dieser beckenformation. Monatsschr f Geburtsk 5:81–94

    Google Scholar 

  44. Rosenberg NJ, Bargar WL, Friedman B (1981) The incidence of spondylolysis and spondylolisthesis in nonambulatory patients. Spine 6:35–38

    PubMed  Google Scholar 

  45. Rufai A, Benjamin M, Ralphs JR (1992) Development and ageing of phenotypically distinct fibrocartilages associated with the rat achilles tendon. Anat Embryol 186:611–618

    Article  PubMed  Google Scholar 

  46. Sairo K, Katoh S, Sakamaki T, Inoue M, Komatsubara S, Ogawa T, Sano T, Goel VK, Yasui N (2004) Vertebral forward slippage in immature lumbar spine occurs following epiphyseal separation and its occurrence is unrelated to disc degeneration. Spine 29:524–527

    Article  PubMed  Google Scholar 

  47. Sakamaki T, Katoh S, Sairyo K (2002) Normal and spondylolytic pediatric spine movements with reference to instantaneous axis of rotation. Spine 27:141–145

    Article  PubMed  Google Scholar 

  48. Schneider H (1956) Zur struktur der sehnenansatzzonen. Z Anat 119:431–456

    Article  Google Scholar 

  49. Schreiber A, Willert HG (1970) Zur pathogenese der spondylolyse. Verhdl Dtsch Orthop Traumat Ges 56:333

    Google Scholar 

  50. Stewart T (1953) The age incidence of neural arch defects in alaskan natives, considered from the standpoint of etiology. J Bone Joint Surg 35-A:937–950

    PubMed  Google Scholar 

  51. Sys J, Michielsen J, Bracke P, Martens M, Verstreken J (2001) Nonoperative treatment of active spondylolysis in elite athletes with normal X-ray findings: literature review and results of conservative treatment. Eur Spine J 10:498–504

    Google Scholar 

  52. Taillard WF (1976) Etiology of spondylolisthesis. Clin Orthop 117:30–39

    PubMed  Google Scholar 

  53. Töndury G (1958) Entwicklungsgeschichte und fehlbildungen der wirbelsäule. In: Junghans H (ed) Die Wirbelsäule in Forschung und Praxis. Stuttgart: Hippokrates 39–46

    Google Scholar 

  54. Uhthoff HK, Seki M, Backman DS, Trudel G, Himori K, Sano H (2002) Tensile strength of the supraspinatus after reimplantation into a bony trough: an experimental study in rabbits. J Shoulder Elbow Surg 11:504–509

    Article  PubMed  Google Scholar 

  55. Valhmu WB, Stazzone EJ, Bachrach NM, Saed-Nejad F, Fischer SG, Mow VC, Ratcliffe A (1998) Load-controlled compression of articular cartilage induces a transient stimulation of aggrecan gene expression. Arch Biochem Biophys 353:29–36

    Article  PubMed  Google Scholar 

  56. Verstraeten AA, Mackie EJ, Hageman PC, Hilgers J, Schol DJ, De Jongh GJ, Schalkwijk J (1992) Tenascin expression in basal cell carcinoma. Br J Dermatol 127:571–574

    PubMed  Google Scholar 

  57. Wertzenberger KL, Peterson HA (1980) Acquired spondylolysis and spondylolisthesis in the young child. Spine 5:437–442

    PubMed  Google Scholar 

  58. Wiltse LL (1962) The etiology of spondylolisthesis. J Bone Joint Surg 44-A:539–560

    Google Scholar 

  59. Wiltse LL, Widell EH, Jackson DW (1975) Fatigue fracture: the basic lesion in isthmic spondylolisthesis. J Bone Joint Surg 57-A:17–22

    PubMed  Google Scholar 

  60. Wong MW, Qin L, Lee KM, Tai KO, Chong WS, Leung KS, Chan KM (2003) Healing of bone-tendon junction in a bone trough: a goat partial patellectomy model. Clin Orthop 413:291–302

    PubMed  Google Scholar 

  61. Wright IP (2003) Who was Meyerding? Spine 28:733–735

    Article  PubMed  Google Scholar 

  62. Wynne-Davies R, Scott JH (1979) Inheritance and spondylolisthesis. J Bone Joint Surg 61-B:301–305

    Google Scholar 

  63. Zippel H, Abesser EW (1965) Zur wirbelbogendysplasie und spondylolisthesis im ersten lebensdezennium. Arch Orthop Unfallchir 58:242–259

    Article  PubMed  Google Scholar 

  64. Zippel H, Runge H (1976) Pathologische anatomie und pathogenese von spondylolyse und spondylolisthesis im kindesalter. Z Orthop 114:189–201

    PubMed  Google Scholar 

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Acknowledgements

Antibodies CIICI, 5C6, 1C6, 8A4 and 12C5 were obtained from the Developmental Studies Hybridoma Bank (DSHB) maintained by the Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD., and the Department of Biology, University of Iowa, Iowa City, Iowa, under contract NO-HD-6-2915 from the NICHD.

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Authors and Affiliations

  1. Neurosurgery, Berufsgenossenschaftliche Unfallklinik Murnau, Murnau, Germany

    Bronek M. Boszczyk & Wolfdietrich Boos

  2. Orthopaedic Surgery, Inselspital, University of Berne, Bern, Switzerland

    Bronek M. Boszczyk & Bronek M. Boszczyk

  3. Anatomische Anstalt, Ludwig-Maximilians-Universität, München, Germany

    Alexandra A. Boszczyk, Reinhard Putz & Stefan Milz

  4. Spine Center, Orthopädische Klinik München Harlaching, München, Germany

    Andreas Korge & H. Michael Mayer

  5. School of Biosciences, University of Wales, Cardiff, UK

    Michael Benjamin

  6. AO-Research Institute, Davos, Switzerland

    Stefan Milz

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Boszczyk, B.M., Boszczyk, A.A., Boos, W. et al. An immunohistochemical study of the tissue bridging adult spondylolytic defects—the presence and significance of fibrocartilaginous entheses. Eur Spine J 15, 965–971 (2006). https://doi.org/10.1007/s00586-005-0986-3

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