title: Abnormal bone microarchitecture and evidence of osteoblast dysfunction in premenopausal women with idiopathic osteoporosis.
abstract: BACKGROUND
  Idiopathic osteoporosis (IOP) in premenopausal women is an uncommon disorder of uncertain pathogenesis in which fragility fractures occur in otherwise healthy women with intact gonadal function. It is unclear whether women with idiopathic low bone mineral density and no history of fragility fractures have osteoporosis.
  
  
  OBJECTIVE
  The objective of the study was to elucidate the microarchitectural and remodeling features of premenopausal women with IOP.
  
  
  METHODS
  We performed transiliac biopsies after tetracycline labeling in 104 women: 45 with fragility fractures (IOP), 19 with idiopathic low bone mineral density (Z score ≤-2.0) and 40 controls. Biopsies were analyzed by two-dimensional quantitative histomorphometry and three-dimensional microcomputed tomography. Bone stiffness was estimated using finite element analysis.
  
  
  RESULTS
  Compared with controls, affected women had thinner cortices; fewer, thinner, more widely separated, and heterogeneously distributed trabeculae; reduced stiffness; and lower osteoid width and mean wall width. All parameters were indistinguishable between women with IOP and idiopathic low bone mineral density. Although there were no group differences in dynamic histomorphometric remodeling parameters, serum calciotropic hormones, bone turnover markers, or IGF-I, subjects in the lowest tertile of bone formation rate had significantly lower osteoid and wall width, more severely disrupted microarchitecture, lower stiffness, and higher serum IGF-I than those in the upper two tertiles, suggesting that women with low turnover IOP have osteoblast dysfunction with resistance to IGF-I. Subjects with high bone turnover had significantly higher serum 1,25 dihydroxyvitamin D levels and a nonsignificant trend toward higher serum PTH and urinary calcium excretion.
  
  
  CONCLUSIONS
  These results suggest that the diagnosis of IOP should not require a history of fracture. Women with IOP may have high, normal or low bone turnover; those with low bone turnover have the most marked deficits in microarchitecture and stiffness. These results also suggest that the pathogenesis of idiopathic osteoporosis is heterogeneous and may differ according to remodeling activity.
authors.affiliation: Department of Radiology, Columbia University, New York, New York 10032, USA. ac1044@columbia.edu
authors.forename: Adi
authors.initials: A
authors.lastname: Cohen
authors.forename: David W
authors.initials: DW
authors.lastname: Dempster
authors.forename: Robert R
authors.initials: RR
authors.lastname: Recker
authors.forename: Emily M
authors.initials: EM
authors.lastname: Stein
authors.forename: Joan M
authors.initials: JM
authors.lastname: Lappe
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Wirth
authors.forename: G Harry
authors.initials: GH
authors.lastname: van Lenthe
authors.forename: Thomas
authors.initials: T
authors.lastname: Kohler
authors.forename: Alexander
authors.initials: A
authors.lastname: Zwahlen
authors.forename: Ralph
authors.initials: R
authors.lastname: Müller
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Rosen
authors.forename: Serge
authors.initials: S
authors.lastname: Cremers
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Nickolas
authors.forename: Donald J
authors.initials: DJ
authors.lastname: McMahon
authors.forename: Halley
authors.initials: H
authors.lastname: Rogers
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Staron
authors.forename: Jeanette
authors.initials: J
authors.lastname: LeMaster
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Shane
mesh_terms: D015502:Absorptiometry, Photon; D000293:Adolescent; D000328:Adult; D001696:Biomechanical Phenomena; D015519:Bone Density; D001846:Bone Development / Q000502:physiology; D016723:Bone Remodeling / Q000502:physiology; D001842:Bone and Bones / Q000473:pathology* / Q000648:ultrastructure; D002118:Calcium / Q000378:metabolism; D005260:Female; D006728:Hormones / Q000097:blood; D006801:Humans; D007085:Ilium / Q000473:pathology / Q000648:ultrastructure; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism; D008875:Middle Aged; D010006:Osteoblasts / Q000502:physiology*; D010024:Osteoporosis / Q000473:pathology*; D017697:Premenopause / Q000502:physiology*; D014057:Tomography, X-Ray Computed; D055815:Young Adult
chemical_list: D006728:Hormones; D007334:Insulin-Like Growth Factor I; D002118:Calcium