This Article Full Text Full Text (PDF) All Versions of this Article: 144/12/5521    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 VanHouten, J. N. Articles by Wysolmerski, J. J. Search for Related Content PubMed PubMed Citation Articles by VanHouten, J. N. Articles by Wysolmerski, J. J.

Low Estrogen and High Parathyroid Hormone-Related Peptide Levels Contribute to Accelerated Bone Resorption and Bone Loss in Lactating Mice

Section of Endocrinology and Metabolism, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520

Address all correspondence and requests for reprints to: John J. Wysolmerski, Section of Endocrinology and Metabolism, Department of Internal Medicine, FMP 102, 333 Cedar Street, New Haven, Connecticut 06520-8020. E-mail: john.wysolmerski{at}yale.edu.

Providing enough calcium for milk production stresses calcium homeostasis in lactating mammals. A universal response to these demands for calcium appears to be the mobilization of maternal skeletal reserves, and bone loss during lactation has been well documented. However, the regulation of calcium and skeletal metabolism during lactation remains enigmatic. Our study was designed to examine mineral and bone metabolism in lactating mice. We found that mice lose bone rapidly at all sites during lactation. Bone mineral density as determined by dual-energy x-ray absorptiometry was 20 to 30% lower at the spine, femur, and total body in lactating compared with either age-matched virgin or pregnant mice. The decrease in bone mineral density was accompanied by dramatic reductions in bone volume and changes in trabecular architecture. Bone loss was also accompanied by increases in bone turnover as determined by biochemical markers and histomorphometry. PTHrP levels were elevated during lactation and correlated positively with markers of bone resorption and negatively with bone mass at all sites. Estrogen levels were low during lactation and correlated negatively with bone resorption markers. Finally, estrogen and pamidronate treatment lowered rates of bone resorption to baseline virgin levels and mitigated, but did not prevent, bone loss. These data suggest that the combination of estrogen deficiency and elevations in circulating PTHrP during lactation act to stimulate bone resorption and promote bone loss.

This article has been cited by other articles:

				S. Khosla Estrogen and the Death of Osteoclasts: A Fascinating Story IBMS BoneKEy, October 1, 2007; 4(10): 267 - 272. [Full Text] [PDF]

				J. J. Wysolmerski Conversations Between Breast and Bone: Physiological Bone Loss During Lactation as Evolutionary Template for Osteolysis in Breast Cancer and Pathological Bone Loss After Menopause IBMS BoneKEy, August 1, 2007; 4(8): 209 - 225. [Abstract] [Full Text] [PDF]

				L. Ardeshirpour, P. Dann, D. J. Adams, T. Nelson, J. VanHouten, M. C. Horowitz, and J. J. Wysolmerski Weaning Triggers a Decrease in Receptor Activator of Nuclear Factor-{kappa}B Ligand Expression, Widespread Osteoclast Apoptosis, and Rapid Recovery of Bone Mass after Lactation in Mice Endocrinology, August 1, 2007; 148(8): 3875 - 3886. [Abstract] [Full Text] [PDF]

				J. P. Woodrow, C. J. Sharpe, N. J. Fudge, A. O. Hoff, R. F. Gagel, and C. S. Kovacs Calcitonin Plays a Critical Role in Regulating Skeletal Mineral Metabolism during Lactation Endocrinology, September 1, 2006; 147(9): 4010 - 4021. [Abstract] [Full Text] [PDF]

				S. C. Miller, B. L. Anderson, and B. M. Bowman Weaning Initiates a Rapid and Powerful Anabolic Phase in the Rat Maternal Skeleton Biol Reprod, July 1, 2005; 73(1): 156 - 162. [Abstract] [Full Text] [PDF]