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Author Notes:

Address correspondence to: Roberto Pacifici, Division of Endocrinology, Metabolism, and Lipids, Emory University School of Medicine, 101 Woodruff Circle, Room 1307, Atlanta, Georgia 30322, USA. Phone: (404) 712-8420; Fax: (404) 727-1300; E-mail: roberto.pacifici@emory.edu .

We are grateful to Francesco Grassi (Emory University, Atlanta, Georgia, USA) and Timothy Chambers (St. George’s Hospital Medical School, London, United Kingdom) for their helpful suggestions.

Nonstandard abbreviations used: CIITA, class II transactivator; ER, estrogen receptor; OB, osteoblast; OC, osteoclast; RANK, receptor activator of NF-κB; RANKL, RANK ligand; ovx, ovariectomy, ovariectomized; SC, stromal cell.

The authors have declared that no conflict of interest exists.


Research Funding:

M.N. Weitzmann is supported in part by grants from the National Osteoporosis Foundation and the National Institutes of Diabetes and Digestive and Kidney Diseases (DK067389).

R. Pacifici is supported in part by grants from the National Institutes of Health (AR 49659).

Estrogen deficiency and bone loss: an inflammatory tale


Journal Title:

Journal of Clinical Investigation


Volume 116, Number 5


, Pages 1186-1194

Type of Work:

Article | Final Publisher PDF


Estrogen plays a fundamental role in skeletal growth and bone homeostasis in both men and women. Although remarkable progress has been made in our understanding of how estrogen deficiency causes bone loss, the mechanisms involved have proven to be complex and multifaceted. Although estrogen is established to have direct effects on bone cells, recent animal studies have identified additional unexpected regulatory effects of estrogen centered at the level of the adaptive immune response. Furthermore, a potential role for reactive oxygen species has now been identified in both humans and animals. One major challenge is the integration of a multitude of redundant pathways and cytokines, each apparently capable of playing a relevant role, into a comprehensive model of postmenopausal osteoporosis. This Review presents our current understanding of the process of estrogen deficiency–mediated bone destruction and explores some recent findings and hypotheses to explain estrogen action in bone. Due to the inherent difficulties associated with human investigation, many of the lessons learned have been in animal models. Consequently, many of these principles await further validation in humans.

Copyright information:

© 2006, American Society for Clinical Investigation

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