title: Repetition of continuous PTH treatments followed by periodic withdrawals exerts anabolic effects on rat bone.
abstract: Various animal experiments and human studies have shown that intermittent injections of parathyroid hormone (PTH) exert anabolic effects on bone, whereas continuous PTH treatment decreases the bone mass and causes hypercalcemia in animals. However, limited data are available with regard to the effects of a repetitive regimen of continuous treatments of PTH followed by periodic withdrawals on the bone metabolism. We investigated the effects of this regimen by comparing the findings of intermittent and continuous PTH treatments in rats. Infusions of PTH for 24 h followed by 6-day withdrawal periods from PTH transiently increased the serum calcium levels on day 1, but these levels were within the normocalcemic range. The repetition of 4 cycles of continuous PTH infusions followed by PTH withdrawals as well as intermittent PTH treatment increased the trabecular bone thickness, osteoblast surface, and bone formation rate. Continuous PTH infusions followed by PTH withdrawals also increased the cortical thickness of the femoral diaphysis and the osteoid volume in trabecular bones, whereas the continuous treatment failed to induce these changes. These findings suggest that continuous PTH treatment followed by PTH withdrawal is a potential regimen that can induce the anabolic effects of PTH in bone metabolism without inducing hypercalcemia.
authors.affiliation: Section of Oral Pathology, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Etoh
authors.forename: Akira
authors.initials: A
authors.lastname: Yamaguchi
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism*; D002118:Calcium / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D005269:Femur / Q000187:drug effects / Q000502:physiology; D005272:Femur Neck / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019379:Teriparatide / Q000008:administration & dosage*; D013977:Tibia / Q000187:drug effects / Q000502:physiology
chemical_list: D019379:Teriparatide; D002118:Calcium
references.citation: Drug Dev Ind Pharm. 2010 Jan;36(1):31-44
references.pmid: 19640245
references.citation: Bone. 2003 Sep;33(3):372-9
references.pmid: 13678779
references.citation: Endocrinology. 2001 Sep;142(9):4047-54
references.pmid: 11517184
references.citation: J Bone Miner Res. 2005 Oct;20(10):1792-803
references.pmid: 16160737
references.citation: Z Ernahrungswiss. 1998 Jun;37(2):183-9
references.pmid: 9698646
references.citation: Osteoporos Int. 2006 Jan;17(1):85-90
references.pmid: 15981021
references.citation: Bone. 1995 Apr;16(4):477-84
references.pmid: 7605709
references.citation: J Bone Miner Res. 1993 Sep;8(9):1097-101
references.pmid: 8237479
references.citation: Expert Opin Drug Deliv. 2005 Nov;2(6):993-1002
references.pmid: 16296804
references.citation: J Bone Miner Res. 2004 Jul;19(7):1165-71
references.pmid: 15177000
references.citation: N Engl J Med. 2001 May 10;344(19):1434-41
references.pmid: 11346808
references.citation: Bone. 2007 Jan;40(1):169-74
references.pmid: 16876496
references.citation: Bone. 1998 Sep;23(3):249-55
references.pmid: 9737347
references.citation: J Bone Miner Res. 2001 Oct;16(10):1846-53
references.pmid: 11585349
references.citation: J Bone Miner Res. 2009 Sep;24(9):1586-97
references.pmid: 19419301
references.citation: Endocrinology. 1988 Jun;122(6):2899-904
references.pmid: 3371266
references.citation: J Clin Endocrinol Metab. 2008 Jun;93(6):2166-72
references.pmid: 18349061
references.citation: J Bone Miner Res. 1987 Dec;2(6):595-610
references.pmid: 3455637
references.citation: Bone. 2000 Feb;26(2):175-82
references.pmid: 10678413
references.citation: J Pharm Sci. 2002 Feb;91(2):350-61
references.pmid: 11835195
references.citation: J Endocrinol. 2005 Sep;186(3):549-57
references.pmid: 16135674
references.citation: J Biol Chem. 2007 Nov 9;282(45):33098-106
references.pmid: 17690108
references.citation: Endocrinology. 1997 Nov;138(11):4607-12
references.pmid: 9348185
references.citation: J Bone Miner Res. 1994 Jan;9(1):59-67
references.pmid: 8154310