title: Pathomechanism of loss of elasticity and hypertrophy of lumbar ligamentum flavum in elderly patients with lumbar spinal canal stenosis.
abstract: METHODS
  A histologic, biologic, and immunohistochemical assessment using human samples of lumbar ligamentum flavum.
  
  
  OBJECTIVE
  To clarify the pathomechanism of loss of elasticity and hypertrophy of the lumbar ligamentum flavum (LF) in the elderly population.
  
  
  BACKGROUND
  The most common spinal disorder in elderly patients is lumbar spinal canal stenosis, causing low back and leg pain, and paresis. Canal narrowing, in part, results from hypertrophy of the LF. Although histologic and biologic literature on this topic is available, the pathomechanism of loss of elasticity and hypertrophy of the LF is still unknown.
  
  
  METHODS
  One fetus, 5 young, and 5 elderly LF were obtained for histologic study. Hematoxylin and eosin, Alcian blue, Masson Trichrome, and Elastica Van Gieson stains were performed for each LF. Nine LF were collected and were used for biologic study of real time RT-PCR to quantitatively measure mRNA expression of Type I collagen and elastin in each LF.
  
  
  RESULTS
  In the LF of the fetus, elastic fibers accounted for about 75% of the entire area. In the dural aspect of the LF in the young and elderly group, the ratio was also around 75%; however, the ratio of the dorsal aspect decreased with age. Almost half of the area showing loss of elastic fibers was shown to be converted to cartilaginous tissue producing Type II collagen and proteoglycan by Alcian blue and Type II collagen immunohistochemistry. The area, which did not stain black with EV nor blue with AB stain, was positively stained blue with T stain, indicating scarring. The area of the normal dural layer was 18.0 +/- 2.3 and 33.8 +/- 4.3 (mm2), for young and elderly group, respectively. Accordingly, it was 3.2 +/- 0.8 and 18.0 +/- 10.2 (mm2), for the dorsal abnormal layer. Elastin mRNA showed a relatively strong correlation (r = 0.44) with age; however, the slope was very gentle. Type I collagen mRNA showed a very strong correlation (r = 0.80) with age. The slope was steeper, and the value reached at 1000% (10-fold) around 65 years old when compared with the LF from younger patient. Elastin mRNA showed a weak correlation (r = 0.36) with thickness, and the slope was gentle. Type I collagen mRNA showed relatively strong correlation (r = 0.52) with thickness. The slope was steeper, and the line reached at 1000% (10-fold) around 6.5 (mm) when compared with a thin LF.
  
  
  CONCLUSIONS
  Decreased elasticity of LF in the elderly is due to the loss of elastic fibers and a concomitant increase of collagenous fibers in the dorsal aspect. LF hypertrophy could be due to the thickening of the normal elastic layer as well as of the abnormal collagenous layer.
authors.affiliation: Department of Orthopedics, University of Tokushima, Tokushima, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kosaka
authors.forename: Koichi
authors.initials: K
authors.lastname: Sairyo
authors.forename: Ashok
authors.initials: A
authors.lastname: Biyani
authors.forename: Douglas
authors.initials: D
authors.lastname: Leaman
authors.forename: Richard
authors.initials: R
authors.lastname: Yeasting
authors.forename: Kosaku
authors.initials: K
authors.lastname: Higashino
authors.forename: Toshinori
authors.initials: T
authors.lastname: Sakai
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Katoh
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sano
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Goel
authors.forename: Natsuo
authors.initials: N
authors.lastname: Yasui
mesh_terms: D000328:Adult; D000367:Age Factors; D000375:Aging / Q000378:metabolism / Q000473:pathology*; D024042:Collagen Type I / Q000032:analysis / Q000235:genetics; D024043:Collagen Type II / Q000032:analysis; D004548:Elasticity; D004549:Elastin / Q000032:analysis / Q000235:genetics; D005333:Fetus / Q000737:chemistry; D006801:Humans; D006984:Hypertrophy; D017843:Ligamentum Flavum / Q000737:chemistry / Q000196:embryology / Q000473:pathology*; D008159:Lumbar Vertebrae / Q000737:chemistry / Q000196:embryology / Q000473:pathology*; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D013130:Spinal Stenosis / Q000378:metabolism / Q000473:pathology*
chemical_list: D024042:Collagen Type I; D024043:Collagen Type II; D012333:RNA, Messenger; D004549:Elastin