title: Advantages of concurrent use of anabolic and antiresorptive agents over single use of these agents in increasing trabecular bone volume, connectivity, and biomechanical competence of rat vertebrae.
abstract: The purpose of this study was to evaluate the usefulness of a combination regimen of anabolic and antiresorptive agents in increasing skeletal quantity and quality in comparison to a single-drug regimen with these agents. We examined histomorphometrically and biomechanically the effects of separate and combined administration of intermittent parathyroid hormone (PTH) and estrogen or bisphosphonate on both axial and appendicular skeletons of male Wistar rats, which were 4 months old and weighed approximately 300 g at the beginning of the treatment. The animals were untreated or injected with vehicle, recombinant human PTH(1-84) (PTH; 100 microg/kg daily), 17beta-estradiol (E2, 500 microg/kg every other day), incadronate disodium (YM175, 80 microg/kg every other day), combined PTH and E2 (PTH + E2), or a combination of PTH and YM175 (PTH + YM175). After 1 month of treatment, the three groups in which PTH was administered (PTH, PTH + E2, and PTH + YM175) had significantly higher trabecular bone volume and connectivity in the proximal tibial metaphyses (PTMs) compared with the untreated and vehicle-treated groups, whereas only combination groups (PTH + E2 and PTH + YM175) showed significant increases in these indices in the lumbar vertebrae. This site-related discrepancy was attributed to the fact that PTH significantly elevated bone resorption not in the PTMs but in the vertebrae. This increased bone resorption in the vertebrae was suppressed by the addition of an antiresorptive agent. As a result, trabecular bone mass, connectivity, and mechanical strength of the vertebrae were significantly increased from control levels only in the concurrent treatment groups (PTH + E2 and PTH + YM175). The superior skeletal effects of PTH cotherapy over PTH monotherapy were not seen with regard to bone mass, but with increased connectivity and mechanical strength. The concurrent use of PTH and an antiresorptive agent has been shown to be superior to the single use of PTH for enhancing these properties of rat vertebrae, which encourages future research, especially in larger animals.
authors.affiliation: Department of Orthopaedic Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Shimizu
authors.forename: R
authors.initials: R
authors.lastname: Mehdi
authors.forename: M
authors.initials: M
authors.lastname: Nawata
authors.forename: S
authors.initials: S
authors.lastname: Kojima
authors.forename: T
authors.initials: T
authors.lastname: Tsutsumimoto
authors.forename: R
authors.initials: R
authors.lastname: Iorio
authors.forename: K
authors.initials: K
authors.lastname: Takaoka
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects*; D001862:Bone Resorption / Q000188:drug therapy*; D004164:Diphosphonates / Q000494:pharmacology*; D004357:Drug Synergism; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D008159:Lumbar Vertebrae / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D004164:Diphosphonates; D010281:Parathyroid Hormone; D011994:Recombinant Proteins; C071542:cimadronate; D004958:Estradiol