Abstract
Ospemifene is a non-estrogen agent that exerts tissue-specific estrogen agonistic
and weak antagonistic effects (i. e., is a selective estrogen receptor modulator [SERM]).
The effects of various once-daily oral doses of ospemifene on bone are examined across
3 studies for 4 or 52 weeks after surgery in the ovariectomized (OVX) rat model of
postmenopausal bone loss. Ospemifene treatment reduced the loss of bone mineral content
and density observed in untreated OVX rats, significantly increased distal femur bone
mineral content at 51 weeks at 25 mg/kg dose compared with untreated OVX rats (p<0.01),
and significantly increased trabecular bone mineral density of the distal femur and
proximal tibia with 1, 5, or 25 mg/kg doses after 52 weeks. Ospemifene 5 and 25 mg/kg
preserved distal femur trabecular structure; trabecular number was significantly increased,
whereas trabecular separation and eroded surface values were significantly decreased
(all p<0.01). Structural changes associated with ospemifene were accompanied by increased
mechanical strength of femurs and 4th lumbar vertebra compared with untreated OVX rats. Ospemifene 10 mg/kg prevented OVX-induced
bone loss; trabecular bone volume of distal femurs was increased after 4 weeks. Further,
histomorphometric measures revealed decreased bone resorption after 4 weeks of ospemifene
treatment, with effects similar to other SERMs (raloxifene and droloxifene). Ospemifene
3 and 10 mg/kg significantly inhibited OVX-induced increases in osteoclast number,
and doses ≥0.3 mg/kg dose-dependently reversed the OVX-induced increase in the double-labeled
volume:bone volume ratio. These results demonstrate antiresorptive, selective agonist
effects of ospemifene on bone that appear similar to raloxifene in this in vivo animal
model of estrogen deficiency.
Key words
tissue-selective estrogen agonist - ovariectomized rat - bone mineral content - bone
mineral density - osteoporosis - estrogen deficiency
