title: Early changes in biochemical markers of bone formation correlate with improvements in bone structure during teriparatide therapy.
abstract: BACKGROUND
  Biochemical markers of bone turnover may reflect bone structure during anabolic treatment.
  
  
  OBJECTIVE
  The objective was to evaluate associations between changes in biochemical markers and structural and dynamic bone parameters during teriparatide treatment.
  
  
  METHODS
  This study was a randomized, multicenter, double-blind, placebo-controlled fracture prevention trial, with 20-month median treatment duration for biopsy subset.
  
  
  METHODS
  The trial was conducted at 11 clinical study sites.
  
  
  METHODS
  Sixty-one postmenopausal women with osteoporosis who had paired transiliac biopsy specimens participated in the study.
  
  
  METHODS
  Once-daily sc injections of either placebo or teriparatide (20 or 40 microg) were administered.
  
  
  METHODS
  The study measured: 1) serum and urinary biochemical markers of bone formation [bone alkaline phosphatase and procollagen I C-terminal propeptide (PICP)] and resorption (N-telopeptide and deoxypyridinoline); and 2) structural and dynamic analyses of bone biopsies, including two-dimensional (2D) histomorphometry and three-dimensional (3D) micro-computed tomography evaluations measured at baseline (n = 57) and 12 (n = 21) or 22 (n = 36) months.
  
  
  RESULTS
  U-N-telopeptide/creatinine and serum-PICP correlated with bone structure and dynamic indices at baseline, respectively. Changes in bone alkaline phosphatase at 1 month correlated with changes at 22 months in 2D wall thickness (r = 0.73; P = 0.001), trabecular bone volume (trabecular bone volume per total volume, BV/TV) (r = 0.58; P < 0.05), marrow star volume (r = -0.51; P = 0.05); 3D trabecular thickness (r = 0.49; P < 0.05), and BV/TV (r = 0.54; P < 0.05). Changes in PICP at 1 month correlated with changes in wall thickness (r = 0.60; P = 0.01), and 2D BV/TV (r = 0.51; P < 0.05) at 22 months. Changes in markers at 6 or 12 months were not associated with changes in structural or dynamic parameters.
  
  
  CONCLUSIONS
  Early (1-month) changes in biochemical markers of bone formation, but not resorption, correlated with improvements in bone structure after 22 months of teriparatide therapy.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Medical University, Auenbruggerplatz 15, A-8036 Graz, Austria. harald.dobnig@meduni-graz.at
authors.forename: Harald
authors.initials: H
authors.lastname: Dobnig
authors.forename: Adrien
authors.initials: A
authors.lastname: Sipos
authors.forename: Yebin
authors.initials: Y
authors.lastname: Jiang
authors.forename: Astrid
authors.initials: A
authors.lastname: Fahrleitner-Pammer
authors.forename: Louis-Georges
authors.initials: LG
authors.lastname: Ste-Marie
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Gallagher
authors.forename: Imre
authors.initials: I
authors.lastname: Pavo
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Wang
authors.forename: Erik F
authors.initials: EF
authors.lastname: Eriksen
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000652:urine; D001842:Bone and Bones / Q000187:drug effects*; D003094:Collagen / Q000652:urine; D024042:Collagen Type I; D005260:Female; D006801:Humans; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects*; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000652:urine; D011347:Procollagen / Q000097:blood; D019379:Teriparatide / Q000627:therapeutic use*
chemical_list: D000596:Amino Acids; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C042813:procollagen type I carboxy terminal peptide; D019379:Teriparatide; C036020:deoxypyridinoline; D003094:Collagen; D000469:Alkaline Phosphatase