Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain

Kim C. Westerlind, Thomas J. Wronski, Erik L. Ritman, Zong Ping Luo, Kai Nan An, Norman H. Bell, Russell T. Turner

Research output: Contribution to journalArticle

157 Citations (Scopus)

Abstract

Estrogen deficiency induced bone loss is associated with increased bone turnover in rats and humans. The respective rules of increased bone turnover and altered balance between bone formation and bone resorption in mediating estrogen deficiency-induced cancellous bone loss was investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in the distal femur. However, cancellous bone was preferentially lost in the metaphysis, a site that normally experiences low strain energy. No bone loss was observed in the epiphysis, a site experiencing higher strain energy. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased and decreased in long bones of ovariectomized rats by treadmill exercise and functional unloading, respectively. Functional unloading was achieved during orbital spaceflight and following unilateral sciatic neurotomy. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing loading accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in the unloaded and prevented loss in the loaded limb following unilateral sciatic neurotomy in part by reducing indices of bone turnover. These results suggest that estrogen regulates the rate of bone turnover, but the overall balance between bone formation and bone resorption is influenced by prevailing levels of mechanical strain.

Original languageEnglish (US)
Pages (from-to)4199-4204
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number8
DOIs
StatePublished - Apr 15 1997

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Bone Remodeling
Estrogens
Bone and Bones
Epiphyses
Bone Resorption
Osteogenesis
Space Flight
Ovariectomy
Femur
Extremities
History

ASJC Scopus subject areas

  • Genetics
  • General

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Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain. / Westerlind, Kim C.; Wronski, Thomas J.; Ritman, Erik L.; Luo, Zong Ping; An, Kai Nan; Bell, Norman H.; Turner, Russell T.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 94, No. 8, 15.04.1997, p. 4199-4204.

Research output: Contribution to journalArticle

Westerlind, Kim C. ; Wronski, Thomas J. ; Ritman, Erik L. ; Luo, Zong Ping ; An, Kai Nan ; Bell, Norman H. ; Turner, Russell T. / Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain. In: Proceedings of the National Academy of Sciences of the United States of America. 1997 ; Vol. 94, No. 8. pp. 4199-4204.
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