title: Improvement of cancellous bone microstructure in patients on teriparatide following alendronate pretreatment.
abstract: An increase in procollagen type I amino-terminal propeptide (PINP) early after teriparatide initiation was shown to correlate with increased lumbar spine areal BMD and is a good predictor of the anabolic response to teriparatide. Few data exist correlating PINP and bone microstructure, and no data exist in patients on teriparatide following prior potent antiresorptive treatment. This exploratory analysis aimed to investigate the effects of teriparatide on cancellous bone microstructure and correlations of bone markers with microstructure in alendronate-pretreated patients. This was a post hoc analysis of changes in bone markers and three-dimensional indices of bone microstructure in paired iliac crest biopsies from a prospective teriparatide treatment study in postmenopausal women with osteoporosis who were either treatment-naïve (TN, n=16) or alendronate-pretreated (ALN, n=29) at teriparatide initiation. Teriparatide (20μg/day) was given for 24months; biopsies were taken at baseline and endpoint, and serum concentrations of PINP and type 1 collagen cross-linked C-telopeptide (βCTX) were measured at intervals up to 24months. In the TN and ALN groups, respectively, mean (SD) increases in three-dimensional bone volume/tissue volume were 105 (356)% (P=0.039) and 55 (139)% (P<0.005) and trabecular thickness 30.4 (30)% (P<0.001) and 30.8 (53)% (P<0.001). No significant changes were observed in trabecular number or separation. In the ALN patients, 3-month change of neither PINP nor βCTX correlated with indices of cancellous bone microstructure. However, 12-month changes in biochemical bone markers correlated significantly with improvements in bone volume/tissue volume, r=0.502 (P<0.01) and r=0.378 (P<0.05), trabecular number, r=0.559 (P<0.01) and r=0.515 (P<0.01), and reduction of trabecular separation, r=-0.432 (P<0.05) and r=-0.530 (P<0.01), for PINP and βCTX, respectively. We conclude that cancellous bone microstructure improved with teriparatide therapy irrespective of prior antiresorptive use.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria. Electronic address: astrid.fahrleitner@medunigraz.at.
authors.forename: Astrid
authors.initials: A
authors.lastname: Fahrleitner-Pammer
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: David
authors.initials: D
authors.lastname: Burr
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Dobnig
authors.affiliation: Institute of Rheumatology and Faculty of Medicine 1, Charles University, Prague, Czech Republic.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Stepan
authors.affiliation: Lilly Research Centre, Vienna, Austria.
authors.forename: Helmut
authors.initials: H
authors.lastname: Petto
authors.affiliation: Department of Biology, Indiana University Purdue University, Indianapolis, IN, USA.
authors.forename: Jiliang
authors.initials: J
authors.lastname: Li
authors.affiliation: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Krege
authors.affiliation: Lilly Research Centre, Vienna, Austria.
authors.forename: Imre
authors.initials: I
authors.lastname: Pavo
mesh_terms: D000368:Aged; D019386:Alendronate / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects; D000071556:Cancellous Bone / Q000187:drug effects*; D024042:Collagen Type I / Q000097:blood; D005260:Female; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood; D019379:Teriparatide / Q000627:therapeutic use*
chemical_list: D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D019379:Teriparatide; D019386:Alendronate
keywords: Alendronate pretreatment; Cancellous bone microstructure; PINP; Teriparatide; Turnover markers