Skip to main content
Top
Published in: Clinical Rheumatology 5/2008

01-05-2008 | Original Article

Calcium pyrophosphate crystal deposition in the ligamentum flavum of degenerated lumbar spine: histopathological and immunohistological findings

Authors: Takafumi Yayama, Shigeru Kobayashi, Ryuichiro Sato, Kenzo Uchida, Yasuo Kokubo, Hideaki Nakajima, Takaharu Takamura, Erisa Mwaka, Norbert Orwotho, Hisatoshi Baba

Published in: Clinical Rheumatology | Issue 5/2008

Login to get access

Abstract

We investigated the histological and immunohistochemical features of degenerative changes in the ligamentum flavum of the lumbar spine with calcium crystal deposition. We investigated degenerative changes in 270 ligamentum flavum specimens harvested from 198 patients who underwent decompressive surgeries for lumbar spinal canal stenosis. En bloc sections of the ligamentum flavum were examined histologically. We also examined immunoreactivity for transforming growth factor (TGF)-β, vascular endothelial growth factor (VEGF), CD34, and CD68; immunoblot analysis for VEGF; and terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick end-labeling (TUNEL) method. The ligamentum flavum showed fragmented and disorganized elastic fiber bundles with increased collagen fibrils in the matrix. Calcium deposition, which was identified as calcium pyrophosphate dihydrate crystals, was evident in 72 of 198 patients and in 99 of 270 samples, and was associated with appearance of hypertrophic chondrocytes and new blood vessel formation. Areas of calcium deposits were surrounded by abundant hypertrophic chondrocytes (with marked immunoreactivity to TGF-β and VEGF) and a significant number of TUNEL-positive chondrocytes. Calcium crystal deposition in the lumbar ligamentum flavum progresses with reduction in elastic fibers and accumulation of collagen fibrils in the matrix as well as expansion of chondrometaplastic areas.
Literature
1.
go back to reference McCarty DJ, Kohn NN, Faires JS (1962) The significance of calcium pyrophosphate crystals in the synovial fluid of arthritis patients. The pseudogout syndrome. Ann Intern Med 56:711–737 McCarty DJ, Kohn NN, Faires JS (1962) The significance of calcium pyrophosphate crystals in the synovial fluid of arthritis patients. The pseudogout syndrome. Ann Intern Med 56:711–737
2.
go back to reference McCarty DJ (1976) Calcium pyrophosphate dihydrate crystal deposition disease. Arthritis Rheum 19:275–285PubMedCrossRef McCarty DJ (1976) Calcium pyrophosphate dihydrate crystal deposition disease. Arthritis Rheum 19:275–285PubMedCrossRef
3.
4.
go back to reference Ogata M (1985) A clinical study of calcium pyrophosphate dihydrate crystal deposition disease. J Jpn Orthop Assoc 59:819–834 (abstract in English) Ogata M (1985) A clinical study of calcium pyrophosphate dihydrate crystal deposition disease. J Jpn Orthop Assoc 59:819–834 (abstract in English)
5.
go back to reference Zitnan D, Sit’aj S (1963) Chondrocalcinosis articularis. Section 1. Clinical and radiological study. Ann Rheum Dis 22:142–152PubMedCrossRef Zitnan D, Sit’aj S (1963) Chondrocalcinosis articularis. Section 1. Clinical and radiological study. Ann Rheum Dis 22:142–152PubMedCrossRef
6.
go back to reference Baba H, Maezawa Y, Furusawa N et al (1995) The role of calcium deposition in the ligamentum flavum causing a cauda equina syndrome and lumbar radiculopathy. Paraplegia 33:219–223PubMed Baba H, Maezawa Y, Furusawa N et al (1995) The role of calcium deposition in the ligamentum flavum causing a cauda equina syndrome and lumbar radiculopathy. Paraplegia 33:219–223PubMed
7.
go back to reference Bywaters EG, Hamilton EB, Williams R (1971) The spine in idiopathic haemochromatosis. Ann Rheum Dis 30:453–465PubMed Bywaters EG, Hamilton EB, Williams R (1971) The spine in idiopathic haemochromatosis. Ann Rheum Dis 30:453–465PubMed
8.
go back to reference Ramos-Remus C, Russell AS, Gomez-Vargas A et al (1998) Ossification of the posterior longitudinal ligament in three geographically and genetically different populations of ankylosing spondylitis and other spondyloarthropathies. Ann Rheum Dis 57:429–433PubMed Ramos-Remus C, Russell AS, Gomez-Vargas A et al (1998) Ossification of the posterior longitudinal ligament in three geographically and genetically different populations of ankylosing spondylitis and other spondyloarthropathies. Ann Rheum Dis 57:429–433PubMed
9.
go back to reference Reginato AJ, Schumacher HR, Martinez VA (1974) The articular cartilage in familial chondrocalcinosis. Light and electron microscopic study. Arthritis Rheum 17:977–992PubMedCrossRef Reginato AJ, Schumacher HR, Martinez VA (1974) The articular cartilage in familial chondrocalcinosis. Light and electron microscopic study. Arthritis Rheum 17:977–992PubMedCrossRef
10.
go back to reference Gerster JC, Lagier R, Boivin G (1982) Olecranon bursitis related to calcium pyrophosphate dihydrate crystal deposition disease. Arthritis Rheum 25:989–996PubMedCrossRef Gerster JC, Lagier R, Boivin G (1982) Olecranon bursitis related to calcium pyrophosphate dihydrate crystal deposition disease. Arthritis Rheum 25:989–996PubMedCrossRef
11.
go back to reference Ishikawa K, Masuda I, Ohira T et al (1989) A histological study of calcium pyrophosphate dihydrate crystal deposition disease. J Bone Joint Surg 71A:875–886 Ishikawa K, Masuda I, Ohira T et al (1989) A histological study of calcium pyrophosphate dihydrate crystal deposition disease. J Bone Joint Surg 71A:875–886
12.
go back to reference Misra RP (2000) Calcium and disease: molecular determinants of calcium crystal deposition diseases. Cell Mol Life Sci 57:421–428PubMedCrossRef Misra RP (2000) Calcium and disease: molecular determinants of calcium crystal deposition diseases. Cell Mol Life Sci 57:421–428PubMedCrossRef
13.
go back to reference Rosenthal AK (2000) Formation of calcium pyrophosphate crystals: biologic implications. Curr Opin Rheumatol 12:219–222PubMedCrossRef Rosenthal AK (2000) Formation of calcium pyrophosphate crystals: biologic implications. Curr Opin Rheumatol 12:219–222PubMedCrossRef
14.
go back to reference Fam AG (2000) What is new about crystals other than monosodium urate? Curr Opin Rheumatol 12:228–234PubMedCrossRef Fam AG (2000) What is new about crystals other than monosodium urate? Curr Opin Rheumatol 12:228–234PubMedCrossRef
15.
go back to reference Halverson PB, Derfus BA (2001) Calcium crystal-induced inflammation. Curr Opin Rheumatol 13:221–224PubMedCrossRef Halverson PB, Derfus BA (2001) Calcium crystal-induced inflammation. Curr Opin Rheumatol 13:221–224PubMedCrossRef
16.
go back to reference Ryan LM, Kurup IV, Cheung HS (1999) Transduction mechanisms of porcine chondrocyte inorganic pyrophosphate elaboration. Arthritis Rheum 42:555–560PubMedCrossRef Ryan LM, Kurup IV, Cheung HS (1999) Transduction mechanisms of porcine chondrocyte inorganic pyrophosphate elaboration. Arthritis Rheum 42:555–560PubMedCrossRef
17.
go back to reference Yahia H, Drouin G, Maurais G et al (1989) Degeneration of the human lumbar spine ligaments: An ultrastructural study. Pathol Res Pract 184:369–375PubMed Yahia H, Drouin G, Maurais G et al (1989) Degeneration of the human lumbar spine ligaments: An ultrastructural study. Pathol Res Pract 184:369–375PubMed
18.
go back to reference Yoshida M, Shima K, Taniguchi Y et al (1992) Hypertrophied ligamentum flavum in lumbar spinal canal stenosis. Pathogenesis and morphologic and immunohistochemical observation. Spine 17:1353–1360PubMed Yoshida M, Shima K, Taniguchi Y et al (1992) Hypertrophied ligamentum flavum in lumbar spinal canal stenosis. Pathogenesis and morphologic and immunohistochemical observation. Spine 17:1353–1360PubMed
19.
go back to reference Schrader PK, Grob D, Rahn BA et al (1999) Histology of the ligamentum flavum in patients with degenerative lumbar spinal stenosis. Eur Spine J 8:323–328PubMedCrossRef Schrader PK, Grob D, Rahn BA et al (1999) Histology of the ligamentum flavum in patients with degenerative lumbar spinal stenosis. Eur Spine J 8:323–328PubMedCrossRef
20.
go back to reference Baba H, Maezawa Y, Kawaraha N et al (1993) Calcium crystal deposition in the ligamentum flavum of the cervical spine. Spine 18:2174–2181PubMedCrossRef Baba H, Maezawa Y, Kawaraha N et al (1993) Calcium crystal deposition in the ligamentum flavum of the cervical spine. Spine 18:2174–2181PubMedCrossRef
21.
go back to reference Furusawa N, Baba H, Maezawa Y et al (1997) Calcium crystal deposition in the ligamentum flavum of the lumbar spine. Clin Exp Rheumatol 15:641–647PubMed Furusawa N, Baba H, Maezawa Y et al (1997) Calcium crystal deposition in the ligamentum flavum of the lumbar spine. Clin Exp Rheumatol 15:641–647PubMed
22.
go back to reference Yayama T, Baba H, Furusawa N et al (2005) Pathogenesis of calcium crystal deposition in the ligamentum flavum correlates with lumbar spinal canal stenosis. Clin Exp Rheumatol 23:637–643PubMed Yayama T, Baba H, Furusawa N et al (2005) Pathogenesis of calcium crystal deposition in the ligamentum flavum correlates with lumbar spinal canal stenosis. Clin Exp Rheumatol 23:637–643PubMed
23.
go back to reference Yayama T, Furusawa N, Baba H et al (2003) Calcium crystal deposition in the ligamentum flavum of the lumbar spine: role of sex hormones and transforming factor-β. Acta Histochem Cytochem 36:83–91CrossRef Yayama T, Furusawa N, Baba H et al (2003) Calcium crystal deposition in the ligamentum flavum of the lumbar spine: role of sex hormones and transforming factor-β. Acta Histochem Cytochem 36:83–91CrossRef
24.
go back to reference Kokubo Y, Kobayashi S, Uchida K et al (2004) Herniated and spondylotic intervertebral discs of the human cervical spine: histological and immunohistological observations. Acta Histochem Cytochem 37:109–117CrossRef Kokubo Y, Kobayashi S, Uchida K et al (2004) Herniated and spondylotic intervertebral discs of the human cervical spine: histological and immunohistological observations. Acta Histochem Cytochem 37:109–117CrossRef
25.
go back to reference Blacher J, Dabire H, Pomies JP et al (2000) Long term cardiovascular effects of high “osteoprotective” dose levels of 17 beta-estradiol in spontaneously hypertensive rats. Cardiovasc Drugs Ther 14:303–307PubMedCrossRef Blacher J, Dabire H, Pomies JP et al (2000) Long term cardiovascular effects of high “osteoprotective” dose levels of 17 beta-estradiol in spontaneously hypertensive rats. Cardiovasc Drugs Ther 14:303–307PubMedCrossRef
26.
go back to reference Iwamoto Y, Tsukamoto N, Maeda T et al (2006) Effects of repetitive distraction stress on rat spinal ligaments: in vivo cell biological study. In: K Nakamura (ed) Annual report of researches on ossification of the spinal ligament. The University of Tokyo, pp 65–70 Iwamoto Y, Tsukamoto N, Maeda T et al (2006) Effects of repetitive distraction stress on rat spinal ligaments: in vivo cell biological study. In: K Nakamura (ed) Annual report of researches on ossification of the spinal ligament. The University of Tokyo, pp 65–70
27.
go back to reference Denhart BC, Guidi AJ, Tongazzi K et al (1997) Vascular permeability factor/vascular endothelial growth factor and its receptors in oral and laryngeal squamous cell carcinoma and dysplasia. Lab Invest 77:659–664PubMed Denhart BC, Guidi AJ, Tongazzi K et al (1997) Vascular permeability factor/vascular endothelial growth factor and its receptors in oral and laryngeal squamous cell carcinoma and dysplasia. Lab Invest 77:659–664PubMed
28.
go back to reference Takahashi K, Isobe T, Ohtsuki Y et al (1984) Immunohistochemical study on the distribution of alfa and beta subunits of S-100 protein in human neoplasm and normal tissues. Virchows Arch B Cell Pathol Incl Mol Pathol 45:385–389PubMedCrossRef Takahashi K, Isobe T, Ohtsuki Y et al (1984) Immunohistochemical study on the distribution of alfa and beta subunits of S-100 protein in human neoplasm and normal tissues. Virchows Arch B Cell Pathol Incl Mol Pathol 45:385–389PubMedCrossRef
29.
go back to reference Tanno M, Furukawa KI, Ueyama K et al (2003) Uniaxial cyclic stretch induces osteogenic differentiation and synthesis of bone morphogenetic proteins of spinal ligament cells derived from patients with ossification of the posterior longitudinal ligaments. Bone 33:475–484PubMedCrossRef Tanno M, Furukawa KI, Ueyama K et al (2003) Uniaxial cyclic stretch induces osteogenic differentiation and synthesis of bone morphogenetic proteins of spinal ligament cells derived from patients with ossification of the posterior longitudinal ligaments. Bone 33:475–484PubMedCrossRef
30.
go back to reference Kubota T, Kawano H, Yamashima T et al (1987) Ultrastructural study of calcification process in the ligamentum flavum of the cervical spine. Spine 12:317–323PubMedCrossRef Kubota T, Kawano H, Yamashima T et al (1987) Ultrastructural study of calcification process in the ligamentum flavum of the cervical spine. Spine 12:317–323PubMedCrossRef
Metadata
Title
Calcium pyrophosphate crystal deposition in the ligamentum flavum of degenerated lumbar spine: histopathological and immunohistological findings
Authors
Takafumi Yayama
Shigeru Kobayashi
Ryuichiro Sato
Kenzo Uchida
Yasuo Kokubo
Hideaki Nakajima
Takaharu Takamura
Erisa Mwaka
Norbert Orwotho
Hisatoshi Baba
Publication date
01-05-2008
Publisher
Springer-Verlag
Published in
Clinical Rheumatology / Issue 5/2008
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-007-0754-3

Other articles of this Issue 5/2008

Clinical Rheumatology 5/2008 Go to the issue