This Article Full Text Full Text (PDF) All Versions of this Article: 148/6/2778    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Samadfam, R. Articles by Goltzman, D. Search for Related Content PubMed PubMed Citation Articles by Samadfam, R. Articles by Goltzman, D.

Pretreatment with Anticatabolic Agents Blunts But Does Not Eliminate the Skeletal Anabolic Response to Parathyroid Hormone in Oophorectomized Mice

The Calcium Research Laboratory and the Department of Medicine, McGill University Health Centre and McGill University, Montréal, Québec, Canada H3A 1A1

Address all correspondence and requests for reprints to: David Goltzman, M.D., Royal Victoria Hospital, Room H467, 687 Pine Avenue, Montréal, Québec, Canada H3A 1A1. E-mail: david.goltzman{at}mcgill.ca.

Previous studies have indicated that bisphosphonate pretreatment can inhibit the anabolic actions of PTH. We examined the capacity of two anticatabolic agents with different mechanisms of action, alendronate and osteoprotegerin (OPG), to influence the anabolic activity of PTH. Oophorectomized mice were pretreated for 30 d with alendronate or OPG and then treated for 30 d with the respective anticatabolic alone or the respective anticatabolic plus PTH(1–34). Bones were analyzed by bone mineral density (BMD), microcomputed tomography, histology and histomorphometry, and biochemical bone markers. OPG pretreatment produced a greater inhibition of bone turnover and a greater increase in bone than alendronate. Increases in bone were sustained during subsequent treatment with vehicle or continued administration of the anticatabolic. Pretreatment with each anticatabolic blunted the capacity of PTH to increase BMD and bone volume and continued treatment with each anticatabolic agent also reduced the effectiveness of PTH. Although both anticatabolics decreased the maximal PTH effect, BMD and bone volume increased more when PTH was added than when only anticatabolics were used. These results demonstrate that mechanistically distinct anticatabolics may reduce PTH efficacy, that the characteristics of this inhibition may reflect the different modes of action of the anticatabolics, but that the addition of PTH still provides a skeletal benefit even if the anabolic effect is submaximal.

This article has been cited by other articles:

				S. Ferrari Are Osteoclasts Necessary for PTH Anabolism? A Reappraisal from Osteoprotegerin Studies IBMS BoneKEy, October 1, 2007; 4(10): 278 - 281. [Full Text] [PDF]

				S. Johnston, S. Andrews, V. Shen, F. Cosman, R. Lindsay, D. W. Dempster, and A. Iida-Klein The Effects of Combination of Alendronate and Human Parathyroid Hormone(1 34) on Bone Strength Are Synergistic in the Lumbar Vertebra and Additive in the Femur of C57BL/6J Mice Endocrinology, September 1, 2007; 148(9): 4466 - 4474. [Abstract] [Full Text] [PDF]