title: Effects of Parathyroid Hormone Administration on Bone Strength in Hypoparathyroidism.
abstract: The microstructural skeletal phenotype of hypoparathyroidism (HypoPT), a disorder of inadequate parathyroid hormone secretion, is altered trabecular microarchitecture with increased trabecular bone volume and thickness. Using 2-D histomorphometric analysis, we previously found that 2 years of PTH(1-84) in HypoPT is associated with reduced trabecular thickness (Tb.Th) and an increase in trabecular number (Tb.N). We have now utilized direct 3-D microstructural analysis to determine the extent to which these changes may be related to bone strength. Iliac crest bone biopsies from HypoPT subjects (n = 58) were analyzed by microcomputed tomography (μCT) and by microfinite element (μFE) analysis. Biopsies were performed at baseline and at 1 or 2 years of recombinant human PTH(1-84) [rhPTH(1-84)]. In a subset of subjects (n = 13) at 3 months, we demonstrated a reduction in trabecular separation (Tb.Sp, 0.64 ± 0.1 to 0.56 ± 0.1 mm; p = 0.005) and in the variance of trabecular separation (Tb.SD, 0.19 ± 0.1 to 0.17 ± 0.1 mm; p = 0.01), along with an increase in bone volume/total volume (BV/TV, 26.76 ± 10.1 to 32.83 ± 13.5%; p = 0.02), bone surface/total volume (BS/TV, 3.85 ± 0.7 to 4.49 ± 1.0 mm(2) /mm(3) ; p = 0.005), Tb.N (1.84 ± 0.5 versus 2.36 ± 1.3 mm(-1) ; p = 0.02) and Young's modulus (649.38 ± 460.7 to 1044.81 ± 1090.5 N/mm(2) ; p = 0.049). After 1 year of rhPTH(1-84), Force increased (144.08 ± 102.4 to 241.13 ± 189.1 N; p = 0.04) and Young's modulus tended to increase (662.15 ± 478.2 to 1050.80 ± 824.1 N/m(2) ; p = 0.06). The 1-year change in cancellous mineralizing surface (MS/BS) predicted 1-year changes in μCT variables. The biopsies obtained after 2 years of rhPTH(1-84) showed no change from baseline. These data suggest that administration of rhPTH(1-84) in HypoPT is associated with transient changes in key parameters associated with bone strength. The results indicate that rhPTH(1-84) improves skeletal quality in HypoPT early in treatment. © 2016 American Society for Bone and Mineral Research.
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Mishaela R
authors.initials: MR
authors.lastname: Rubin
authors.affiliation: Institute for Biomechanics, ETH Zurich, Zurich, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Zwahlen
authors.affiliation: Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.|Regional Bone Center, Helen Hayes Hospital, West Haverstraw, NY, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Dempster
authors.affiliation: Regional Bone Center, Helen Hayes Hospital, West Haverstraw, NY, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Natalie E
authors.initials: NE
authors.lastname: Cusano
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Chengchen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Institute for Biomechanics, ETH Zurich, Zurich, Switzerland.
authors.forename: Ralph
authors.initials: R
authors.lastname: Müller
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Bilezikian
mesh_terms: D000328:Adult; D015519:Bone Density / Q000187:drug effects*; D000071556:Cancellous Bone / Q000000981:diagnostic imaging / Q000378:metabolism; D055119:Elastic Modulus / Q000187:drug effects*; D005260:Female; D006801:Humans; D007011:Hypoparathyroidism / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000008:administration & dosage*; D055114:X-Ray Microtomography
chemical_list: D010281:Parathyroid Hormone
keywords: BONE MICROARCHITECTURE; FINITE ELEMENT ANALYSIS; HYPOPARATHYROIDISM; MICROCOMPUTED TOMOGRAPHY; PTH(1-84)