Androgens and Skeletal Biology: Basic Mechanisms

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The obvious impact of the menopause on skeletal health has focused much of the research describing the general action of gonadal steroids on the specific effects of estrogen in bone. However, androgens clearly have important beneficial effects, in both men and women, on skeletal development and on the maintenance of bone mass. Thus it has been demonstrated that androgens (a) influence growth plate maturation and closure helping to determine longitudinal bone growth during development, (b) mediate regulation of trabecular (cancellous) and cortical bone mass in a fashion distinct from estrogen, leading to a sexually dimorphic skeleton, (c) modulate peak bone mass acquisition, and (d) inhibit bone loss. In castrated animals, replacement with nonaromatizable androgens (e.g., 5α-dihydrotestosterone (DHT)) yields beneficial effects that are clearly distinct from those observed with estrogen replacement. In intact females, blockade of the androgen receptor (AR) with the specific AR antagonist hydroxyflutamide results in osteopenia. Furthermore, treatment with nonaromatizable androgen alone in females results in improvements in bone mineral density (BMD). Finally, combination therapy with estrogen and androgen in postmenopausal women is more beneficial than either steroid alone, indicating complementary but nonparallel and distinct pathways of action. Combined, these reports illustrate the distinct actions of androgens and estrogens on the skeleton. Thus, in both men and women it is probable that androgens and estrogens each have important yet distinct functions during bone development, and in the subsequent maintenance of skeletal homeostasis. As is clear from the osteopenia that develops after androgen deprivation therapy (ADT) used for the treatment of prostate cancer and with the loss of sex steroids in older men, androgen signaling is important for bone health in the adult and during aging. With the awareness of the importance of the effects of androgen on skeletal homeostasis, and the potential to make use of this information for the treatment of bone disorders, much remains to be learned.

Original languageEnglish (US)
Title of host publicationOsteoporosis
Subtitle of host publicationFourth Edition
PublisherElsevier Inc.
Pages345-371
Number of pages27
ISBN (Print)9780124158535
DOIs
StatePublished - Jun 2013

Keywords

  • Androgens
  • Aromatase
  • Epiphyseal closure
  • Osteoblasts
  • Osteoclast
  • Skeletal biology
  • Testosterone metabolism

ASJC Scopus subject areas

  • Dentistry(all)
  • Medicine(all)

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