Intermittent Fugu parathyroid hormone 1 (1-34) is an anabolic bone agent in young male rats and osteopenic ovariectomized rats

Bone. 2008 Jun;42(6):1164-74. doi: 10.1016/j.bone.2008.01.015. Epub 2008 Feb 13.

Abstract

Human parathyroid hormone (hPTH) is currently the only treatment for osteoporosis that forms new bone. Previously we described a fish equivalent, Fugu parathyroid hormone 1 (fPth1) which has hPTH-like biological activity in vitro despite fPth1(1-34) sharing only 53% identity with hPTH(1-34). Here we demonstrate the in vivo actions of fPth1(1-34) on bone. In study 1, young male rats were injected intermittently for 30 days with fPth1 [30 microg-1,000 microg/kg body weight (b.w.), (30fPth1-1,000fPth1)] or hPTH [30 microg-100 microg/kg b.w. (30hPTH-100hPTH)]. In proximal tibiae at low doses, the fPth1 was positively correlated with trabecular bone volume/total volume (TbBV/TV) while hPTH increased TbBV/TV, trabecular thickness (TbTh) and trabecular number (TbN). 500fPth1 and 1000fPth1 increased TbBV/TV, TbTh, TbN, mineral apposition rate (MAR) and bone formation rate/bone surface (BFR/BS) with a concomitant decrease in osteoclast surface and number. In study 2 ovariectomized (OVX), osteopenic rats and sham operated (SHAM) rats were injected intermittently with 500 microg/kg b.w. of fPth1 (500fPth1) for 11 weeks. 500fPth1 treatment resulted in increased TbBV/TV (151%) and TbTh (96%) in the proximal tibiae due to increased bone formation as assessed by BFR/BS (490%) and MAR (131%). The effect was restoration of TbBV/TV to SHAM levels without any effect on bone resorption. 500fPth1 also increased TbBV/TV and TbTh in the vertebrae (L6) and cortical thickness in the mid-femora increasing bone strength at these sites. fPth1 was similarly effective in SHAM rats. Notwithstanding the low amino acid sequence homology with hPTH (1-34), we have clearly established the efficacy of fPth1 (1-34) as an anabolic bone agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anabolic Agents / pharmacology*
  • Anabolic Agents / therapeutic use
  • Animals
  • Biomarkers / metabolism
  • Bone Diseases, Metabolic / drug therapy
  • Bone Diseases, Metabolic / metabolism*
  • Bone and Bones / anatomy & histology
  • Bone and Bones / drug effects*
  • Bone and Bones / physiology
  • Female
  • Humans
  • Male
  • Osteogenesis / drug effects
  • Osteoporosis / drug therapy
  • Ovariectomy*
  • Parathyroid Hormone / pharmacology*
  • Parathyroid Hormone / therapeutic use
  • Peptide Fragments / pharmacology*
  • Peptide Fragments / therapeutic use
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Stress, Mechanical
  • Takifugu*

Substances

  • Anabolic Agents
  • Biomarkers
  • Parathyroid Hormone
  • Peptide Fragments