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Title: Intermittent Fugu parathyroid hormone 1 (1-34) is an anabolic bone agent in young male rats and osteopenic ovariectomized rats.
Austin Authors: McManus, Julie F;Davey, Rachel A;Maclean, Helen E;Doust, Elizabeth A;Chiu, W S Maria;Sims, Natalie A;Bouxsein, Mary L;Glatt, Vaida;Zajac, Jeffrey D ;Danks, Janine A
Affiliation: Department of Medicine, University of Melbourne, Austin Health, Studley Road, Heidelberg, VIC, Australia
Issue Date: 13-Feb-2008
Publication information: Bone 2008; 42(6): 1164-74
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.
Gov't Doc #: 18387351
DOI: 10.1016/j.bone.2008.01.015
Journal: Bone
Type: Journal Article
Subjects: Anabolic Agents.pharmacology.therapeutic use
Biological Markers.metabolism
Bone Diseases, Metabolic.drug therapy.metabolism
Bone and Bones.anatomy & histology.drug effects.physiology
Osteogenesis.drug effects
Osteoporosis.drug therapy
Parathyroid Hormone.pharmacology.therapeutic use
Peptide Fragments.pharmacology.therapeutic use
Random Allocation
Rats, Sprague-Dawley
Stress, Mechanical
Appears in Collections:Journal articles

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