Endocrinology, Vol 134, 2126-2134, Copyright © 1994 by Endocrine Society

ARTICLES

The effect on vertebral bone mass and strength of long term treatment with antiresorptive agents (estrogen and calcitonin), human parathyroid hormone-(1-38), and combination therapy, assessed in aged ovariectomized rats

L Mosekilde, CC Danielsen and J Gasser
Department of Connective Tissue Biology, University of Aarhus, Denmark.

The aim of the study was to assess the long term effect of the antiresorptive agents estrogen and salmon calcitonin, the anabolic drug PTH, and combination therapy on vertebral bone mass and bone biomechanical competence in aged osteopenic ovariectomized (OVX) rats. Seventy-nine 1-yr-old retired breeder Wistar rats were randomized into seven groups: 1) sham-operated, 2) OVX, 3) OVX plus estrogen, 4) OVX plus salmon calcitonin, 5) OVX plus human (h) PTH-(1-38), 6) OVX plus hPTH-(1-38) and estrogen, and finally, 7) OVX plus hPTH-(1-38) and calcitonin. Treatment regimens were initiated 8 weeks after ovariectomy and continued for 24 weeks. Whole body bone mass was measured by dual photon absorptiometry at intervals of 4 weeks and at death. Changes in spinal bone mass (BMC), biomechanical competence, and structure were assessed from the lumbar vertebral bodies. The results revealed a protective effect of both estrogen and calcitonin on ovariectomy- induced loss of whole body bone mass, but only estrogen had a significant effect on spinal BMC. hPTH-(1-38) monotherapy increased vertebral bone mass (BMC and ash content), size, and biomechanical parameters 20-80% over OVX levels. A more rapid effect on vertebral bone mass was seen when hPTH-(1-38) was combined with estrogen or salmon calcitonin. The study has shown that in aged OVX osteopenic rats, hPTH-(1-38) therapy increases vertebral bone mass and bone quality and also maintains trabecular connectivity. Both estrogen and calcitonin reduce the ovariectomy-induced bone loss, but cannot restore bone mass to sham-operated levels. On the basis of this study, it is concluded that PTH therapy seems to hold promise in the management of postmenopausal and age-related osteoporosis.

This article has been cited by other articles:

				C. Yamada, Y. Yamada, K. Tsukiyama, K. Yamada, N. Udagawa, N. Takahashi, K. Tanaka, D. J. Drucker, Y. Seino, and N. Inagaki The Murine Glucagon-Like Peptide-1 Receptor Is Essential for Control of Bone Resorption Endocrinology, February 1, 2008; 149(2): 574 - 579. [Abstract] [Full Text] [PDF]

				J. N. Miner, W. Chang, M. S. Chapman, P. D. Finn, M. H. Hong, F. J. Lopez, K. B. Marschke, J. Rosen, W. Schrader, R. Turner, et al. An Orally Active Selective Androgen Receptor Modulator Is Efficacious on Bone, Muscle, and Sex Function with Reduced Impact on Prostate Endocrinology, January 1, 2007; 148(1): 363 - 373. [Abstract] [Full Text] [PDF]

				A. B. Hodsman, D. C. Bauer, D. W. Dempster, L. Dian, D. A. Hanley, S. T. Harris, D. L. Kendler, M. R. McClung, P. D. Miller, W. P. Olszynski, et al. Parathyroid Hormone and Teriparatide for the Treatment of Osteoporosis: A Review of the Evidence and Suggested Guidelines for Its Use Endocr. Rev., August 1, 2005; 26(5): 688 - 703. [Abstract] [Full Text] [PDF]

				K. Kitahara, M. Ishijima, S. R. Rittling, K. Tsuji, H. Kurosawa, A. Nifuji, D. T. Denhardt, and M. Noda Osteopontin Deficiency Induces Parathyroid Hormone Enhancement of Cortical Bone Formation Endocrinology, May 1, 2003; 144(5): 2132 - 2140. [Abstract] [Full Text] [PDF]

				M. Sato, Y. L. Ma, J. M. Hock, M. S. Westmore, J. Vahle, A. Villanueva, and C. H. Turner Skeletal Efficacy with Parathyroid Hormone in Rats Was Not Entirely Beneficial with Long-Term Treatment J. Pharmacol. Exp. Ther., July 1, 2002; 302(1): 304 - 313. [Abstract] [Full Text] [PDF]

				P. J. Kostenuik, C. Capparelli, S. Morony, S. Adamu, G. Shimamoto, V. Shen, D. L. Lacey, and C. R. Dunstan OPG and PTH-(1-34) Have Additive Effects on Bone Density and Mechanical Strength in Osteopenic Ovariectomized Rats Endocrinology, October 1, 2001; 142(10): 4295 - 4304. [Abstract] [Full Text] [PDF]

				H. Z. Ke, H. Qi, D. T. Crawford, K. L. Chidsey-Frink, H. A. Simmons, and D. D. Thompson Lasofoxifene (CP-336,156), a Selective Estrogen Receptor Modulator, Prevents Bone Loss Induced by Aging and Orchidectomy in the Adult Rat Endocrinology, April 1, 2000; 141(4): 1338 - 1344. [Abstract] [Full Text] [PDF]

				H. A. Simmons, C. M. Pirie, D. D. Thompson, and H. Z. Ke Parathyroid Hormone (1-34) Increased Total Body Bone Mass in Aged Female Rats J. Pharmacol. Exp. Ther., July 1, 1998; 286(1): 341 - 344. [Abstract] [Full Text]

				A. Toromanoff, P. Ammann, L. Mosekilde, J. S. Thomsen, and J.-L. Riond Parathyroid Hormone Increases Bone Formation and Improves Mineral Balance in Vitamin D-Deficient Female Rats Endocrinology, June 1, 1997; 138(6): 2449 - 2457. [Abstract] [Full Text] [PDF]