title: PTH(1-84) administration reverses abnormal bone-remodeling dynamics and structure in hypoparathyroidism.
abstract: Hypoparathyroidism is associated with abnormal structural and dynamic skeletal properties. We hypothesized that parathyroid hormone(1-84) [PTH(1-84)] treatment would restore skeletal properties toward normal in hypoparathyroidism. Sixty-four subjects with hypoparathyroidism were treated with PTH(1-84) for 2 years. All subjects underwent histomorphometric assessment with percutaneous iliac crest bone biopsies. Biopsies were performed at baseline and at 1 or 2 years. Another group of subjects had a single biopsy at 3 months, having received tetracycline before beginning PTH(1-84) and prior to the biopsy (quadruple-label protocol). Measurement of biochemical bone turnover markers was performed. Structural changes after PTH(1-84) included reduced trabecular width (144 ± 34 µm to 128 ± 34 µm, p = 0.03) and increases in trabecular number (1.74 ± 0.34/mm to 2.07 ± 0.50/mm, p = 0.02) at 2 years. Cortical porosity increased at 2 years (7.4% ± 3.2% to 9.2% ± 2.4%, p = 0.03). Histomorphometrically measured dynamic parameters, including mineralizing surface, increased significantly at 3 months, peaking at 1 year (0.7% ± 0.6% to 7.1% ± 6.0%, p = 0.001) and persisting at 2 years. Biochemical measurements of bone turnover increased significantly, peaking at 5 to 9 months of therapy and persisting for 24 months. It is concluded that PTH(1-84) treatment of hypoparathyroidism is associated with increases in histomorphometric and biochemical indices of skeletal dynamics. Structural changes are consistent with an increased remodeling rate in both trabecular and cortical compartments with tunneling resorption in the former. These changes suggest that PTH(1-84) improves abnormal skeletal properties in hypoparathyroidism and restores bone metabolism toward normal euparathyroid levels.
authors: Department of Medicine, Division of Endocrinology, Metabolic Bone Diseases Unit, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. mrr6@columbia.edu
authors: Mishaela R
authors: MR
authors: Rubin
authors: David W
authors: DW
authors: Dempster
authors: James
authors: J
authors: Sliney
authors: Hua
authors: H
authors: Zhou
authors: Thomas L
authors: TL
authors: Nickolas
authors: Emily M
authors: EM
authors: Stein
authors: Elzbieta
authors: E
authors: Dworakowski
authors: Maryann
authors: M
authors: Dellabadia
authors: Rebecca
authors: R
authors: Ives
authors: Donald J
authors: DJ
authors: McMahon
authors: Chiyuan
authors: C
authors: Zhang
authors: Shonni J
authors: SJ
authors: Silverberg
authors: Elizabeth
authors: E
authors: Shane
authors: Serge
authors: S
authors: Cremers
authors: John P
authors: JP
authors: Bilezikian
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology*; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007011:Hypoparathyroidism / Q000188:drug therapy* / Q000503:physiopathology*; D007085:Ilium / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D010281:Parathyroid Hormone