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Horm Metab Res 2014; 46(01): 27-35
DOI: 10.1055/s-0033-1355356
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Effects of the Selective Estrogen Receptor Modulator Ospemifene on Bone in Rats

L. Kangas
1   Hormos Medical Ltd., Turku, Finland
,
P. Härkönen
2   Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland
,
K. Väänänen
2   Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland
,
Z. Peng
3   Pharmatest Ltd., Turku, Finland
› Author Affiliations
Further Information

Publication History

received 24 April 2013

accepted 19 August 2013

Publication Date:
09 October 2013 (online)

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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
 

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