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Schematic model of postmenopausal osteoporosis. (A) Osteoclasts are localized in the endosteal zone, where oxygen levels are low. Even in hypoxic conditions, HIFα protein is continuously destabilized by estrogen in osteoclasts. (B) After menopause or Ovx, HIFα is stabilized in osteoclasts due to estrogen depletion. (C) HIFα stabilization in osteoclasts promotes osteoclast activation, which promotes reduced bone mass and osteoporosis.
