Estrogen Deficiency, Postmenopausal Osteoporosis, and Age-Related Bone Loss

Sundeep Khosla, Roberto Pacifici

Research output: Chapter in Book/Report/Conference proceedingChapter

14 Scopus citations


Estrogen deficiency is a pivotal cause of postmenopausal bone loss and contributes to age-related bone loss in both sexes. At the cellular level, estrogen acts on multiple cell types, including T cells. Estrogen deficiency is associated with increased production of tumor necrosis factor by bone marrow T cells, which augments receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis. Moreover, estrogen deficiency alters the regulatory cross-talk between T cells and stromal cells (SC), resulting in enhanced production of osteoclastogenic cytokines by SCs. Estrogen also has indirect positive effects on calcium metabolism and its deficiency reduces both intestinal and renal calcium absorption. In addition, estrogen is a major regulator of bone metabolism in men, and low estrogen levels are associated with increased fracture risk, even in the setting of normal testosterone levels. Thus, although the causes of osteoporotic fractures are multifactorial, estrogen deficiency plays a prominent role in the pathogenesis of osteoporosis in both sexes.

Original languageEnglish (US)
Title of host publicationOsteoporosis
Subtitle of host publicationFourth Edition
PublisherElsevier Inc.
Number of pages24
ISBN (Print)9780124158535
StatePublished - Jun 2013


  • Aging
  • CD40L gene
  • Estrogen deficiency
  • Follicle stimulating hormone (FSH)
  • IL-7 receptor knockout mice
  • OVX
  • SHBG
  • Sex steroids
  • VBMD

ASJC Scopus subject areas

  • General Dentistry
  • General Medicine


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