Mechanism underlying post-menopausal osteoporosis: HIF1α is required for osteoclast activation by estrogen deficiency

Takeshi Miyamoto

Research output: Contribution to journalReview articlepeer-review

33 Citations (Scopus)


The aging of the population worldwide has sharply increased the number of post-menopausal osteoporosis patients. Bone fragility caused by osteoporosis often results in fractures; therefore, controlling osteoporosis is crucial to prevent such injuries. To date, various drugs to treat osteoporosis have been developed and launched; however, the molecular mechanisms underlying post-menopausal osteoporosis have not been fully elucidated, and additional factors that could be targeted to treat patients remain to be characterized. Recently, hypoxia inducible factor l alpha (HIFlα) was identified as essential for osteoclast activation, an activity that promotes bone loss following menopausal estrogen deficiency. Although osteoclasts, which are located in hypoxic regions of the bone surface, express HIFlα mRNA, in pre-menopausal conditions the presence of estrogen decreases HIFlα protein levels in these cells. In menopausal conditions, however, estrogen deficiency allows HIFlα protein to accumulate in osteoclasts, leading to osteoclast activation and bone loss. Osteoclast-specific conditional HIFlα inactivation protects mice from estrogen deficiency-induced osteoclast activation and bone loss, as does systemic administration of a HIFlα inhibitor. Therefore, HIFlα represents a potential therapeutic target to prevent osteoclast activation and bone loss in post-menopausal patients.

Original languageEnglish
Pages (from-to)44-47
Number of pages4
JournalKeio Journal of Medicine
Issue number3
Publication statusPublished - 2015 Sept 25


  • Estrogen
  • HIFlα
  • Hypoxia
  • Osteoclasts
  • Postmenopausal osteoporosis

ASJC Scopus subject areas

  • General Medicine


Dive into the research topics of 'Mechanism underlying post-menopausal osteoporosis: HIF1α is required for osteoclast activation by estrogen deficiency'. Together they form a unique fingerprint.

Cite this