title: A Longitudinal Study of Skeletal Histomorphometry at 6 and 24 Months Across Four Bone Envelopes in Postmenopausal Women With Osteoporosis Receiving Teriparatide or Zoledronic Acid in the SHOTZ Trial.
abstract: Previously, we reported the effects of teriparatide (TPTD) and zoledronic acid (ZOL) on bone formation based on biochemical markers and bone histomorphometry of the cancellous envelope at month 6 in postmenopausal women with osteoporosis who participated in the 12-month primary Skeletal Histomorphometry in Subjects on Teriparatide or Zoledronic Acid Therapy (SHOTZ) study. Patients were eligible to enter a 12-month extension on their original treatment regimen: TPTD 20 μg/day (s.c. injection) or ZOL 5 mg/year (i.v. infusion). A second biopsy was performed at month 24. Here we report longitudinal changes between and within each treatment group in the cancellous, endocortical, intracortical, and periosteal bone envelopes in patients with evaluable biopsies at months 6 and 24 (paired data set: TPTD, n = 10; ZOL, n = 9). Between-group differences are also reported in the larger set of patients with evaluable biopsies at month 6 (TPTD, n = 28; ZOL, n = 30). Data from the cancellous envelope at month 6 or month 24 provided a reference to compare differences across envelopes within each treatment group. The 24-month results extend our earlier report that TPTD and ZOL possess different tissue-level mechanisms of action. Moreover, these differences persisted for at least 2 years in all four bone envelopes. Few longitudinal differences were observed within or across bone envelopes in ZOL-treated patients, suggesting that the low bone formation indices at month 6 persisted to month 24. Conversely, the magnitude of the effect of TPTD on bone formation varied across individual envelopes: median values for mineralizing surface (MS/BS) and bone formation rate (BFR/BS) at month 6 were approximately 3-fold to 5-fold higher in the endocortical and intracortical envelopes compared to the cancellous envelope. Although MS/BS and BFR/BS declined in these envelopes at month 24, median values continued to exceed, or were not significantly different from, those in the cancellous envelope. This study demonstrates for the first time that bone formation indices are higher with TPTD treatment than with ZOL in all four bone envelopes and the difference persists for at least 2 years. Moreover, the magnitude of the effect of TPTD in cortical bone remains robust at 24 months. © 2016 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).
authors: Regional Bone Center, Helen Hayes Hospital, West Haverstraw, NY, USA.
authors: David W
authors: DW
authors: Dempster
authors: Regional Bone Center, Helen Hayes Hospital, West Haverstraw, NY, USA.
authors: Hua
authors: H
authors: Zhou
authors: School of Medicine, Creighton University, Omaha, NE, USA.
authors: Robert R
authors: RR
authors: Recker
authors: CHU de Québec (CHUL) Research Centre, Laval University, Quebec City, Canada.
authors: Jacques P
authors: JP
authors: Brown
authors: Bethesda Health Research, Bethesda, MD, USA.
authors: Michael A
authors: MA
authors: Bolognese
authors: United Osteoporosis Centers, Gainesville, GA, USA.
authors: Christopher P
authors: CP
authors: Recknor
authors: Prohealth Clinical Research, Vancouver, British Columbia, Canada.
authors: David L
authors: DL
authors: Kendler
authors: New Mexico Clinical Research & Osteoporosis Center, Albuquerque, NM, USA.
authors: E Michael
authors: EM
authors: Lewiecki
authors: Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors: David A
authors: DA
authors: Hanley
authors: Bone & Mineral Research Laboratory, Detroit, MI, USA.
authors: Sudhaker D
authors: SD
authors: Rao
authors: Colorado Center for Bone Research, Lakewood, CO, USA.
authors: Paul D
authors: PD
authors: Miller
authors: Atlanta Research Center, Atlanta, GA, USA.
authors: Grattan C
authors: GC
authors: Woodson
authors: Regional Bone Center, Helen Hayes Hospital, West Haverstraw, NY, USA.
authors: Robert
authors: R
authors: Lindsay
authors: University of Wisconsin, Madison, WI, USA.
authors: Neil
authors: N
authors: Binkley
authors: Lilly USA, LLC, Indianapolis, IN, USA.
authors: Jahangir
authors: J
authors: Alam
authors: Lilly USA, LLC, Indianapolis, IN, USA.
authors: Valerie A
authors: VA
authors: Ruff
authors: inVentiv Health Clinical, Princeton, NJ, USA.
authors: Eileen R
authors: ER
authors: Gallagher
authors: Lilly USA, LLC, Indianapolis, IN, USA.
authors: Kathleen A
authors: KA
authors: Taylor
mesh_terms: D000368:Aged; D015519:Bone Density / Q000187:drug effects; D000071556:Cancellous Bone / Q000378:metabolism / Q000473:pathology; D004164:Diphosphonates / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D008137:Longitudinal Studies; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010521:Periosteum / Q000378:metabolism / Q000473:pathology; D017698:Postmenopause / Q000378:metabolism*; D019379:Teriparatide / Q000008:administration & dosage*; D013997:Time Factors; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D019379:Teriparatide; D000077211:Zoledronic Acid
keywords: ANABOLIC; ANTIRESORPTIVE; OSTEOPOROSIS; TERIPARATIDE; ZOLEDRONIC ACID