title: Differential Effects of Teriparatide and Zoledronic Acid on Bone Mineralization Density Distribution at 6 and 24 Months in the SHOTZ Study.
abstract: The Skeletal Histomorphometry in Patients on Teriparatide or Zoledronic Acid Therapy (SHOTZ) study assessed the progressive effects of teriparatide (TPTD) and zoledronic acid (ZOL) on bone remodeling and material properties in postmenopausal women with osteoporosis. Previously, we reported that biochemical and histomorphometric bone formation indices were significantly higher in patients receiving TPTD versus ZOL. Here we report bone mineralization density distribution (BMDD) results based on quantitative backscattered electron imaging (qBEI). The 12-month primary study was randomized and double blind until the month 6 biopsy, then open label. Patients (TPTD, n = 28; ZOL, n = 31) were then eligible to enter a 12-month open-label extension with their original treatment: TPTD 20 μg/d (subcutaneous injection) or ZOL 5 mg/yr (intravenous infusion). A second biopsy was collected from the contralateral side at month 24 (TPTD, n = 10; ZOL, n = 10). In cancellous bone, ZOL treatment was associated at 6 and 24 months with significantly higher average degree of mineralization (CaMEAN, +2.2%, p = 0.018; +3.9%, p = 0.009, respectively) and with lower percentage of low mineralized areas (CaLOW , -34.6%, p = 0.029; -33.7%, p = 0.025, respectively) and heterogeneity of mineralization CaWIDTH (-12.3%, p = 0.003; -9.9%, p = 0.012, respectively), indicating higher mineralization density and more homogeneous mineral content versus TPTD. Within the ZOL group, significant changes were found in all parameters from month 6 to 24, indicating a progressive increase in mineralization density. In sharp contrast, mineralization density did not increase over time with TPTD, reflecting ongoing deposition of new bone. Similar results were observed in cortical bone. In this study, TPTD stimulated new bone formation, producing a mineralized bone matrix that remained relatively heterogeneous with a stable mean mineral content. ZOL slowed bone turnover and prolonged secondary mineralization, producing a progressively more homogeneous and highly mineralized bone matrix. Although both TPTD and ZOL increase clinical measures of bone mineral density (BMD), this study shows that the underlying mechanisms of the BMD increases are fundamentally different. © 2016 American Society for Bone and Mineral Research.
authors.affiliation: Regional Bone Center, Helen Hayes Hospital, West Haverstraw, NY, USA.|Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Dempster
authors.affiliation: Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of WGKK and AUVA Trauma Center Meidling, 1st Med. Dept. Hanusch Hospital, Vienna, Austria.
authors.forename: Paul
authors.initials: P
authors.lastname: Roschger
authors.affiliation: Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of WGKK and AUVA Trauma Center Meidling, 1st Med. Dept. Hanusch Hospital, Vienna, Austria.
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Misof
authors.affiliation: Regional Bone Center, Helen Hayes Hospital, West Haverstraw, NY, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of WGKK and AUVA Trauma Center Meidling, 1st Med. Dept. Hanusch Hospital, Vienna, Austria.
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Paschalis
authors.affiliation: Lilly USA, LLC, Indianapolis, IN, USA.
authors.forename: Jahangir
authors.initials: J
authors.lastname: Alam
authors.affiliation: Lilly USA, LLC, Indianapolis, IN, USA.
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Ruff
authors.affiliation: Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of WGKK and AUVA Trauma Center Meidling, 1st Med. Dept. Hanusch Hospital, Vienna, Austria.
authors.forename: Klaus
authors.initials: K
authors.lastname: Klaushofer
authors.affiliation: Lilly USA, LLC, Indianapolis, IN, USA.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Taylor
mesh_terms: D000368:Aged; D001706:Biopsy; D015519:Bone Density / Q000187:drug effects*; D002113:Calcification, Physiologic / Q000187:drug effects*; D000071556:Cancellous Bone / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D000071538:Cortical Bone / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D004164:Diphosphonates / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008875:Middle Aged; D019379:Teriparatide / Q000494:pharmacology*; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D019379:Teriparatide; D000077211:Zoledronic Acid
keywords: ANABOLICS; ANTIRESPORPTIVES; CLINICAL TRIALS; MATRIX MINERALIZATION; OSTEOPOROSIS