NDLI: Effects of the selective estrogen receptor modulator ospemifene on bone in rats.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kangas, L. Härkönen, P. Väänänen, K. Peng, Z.
Description	Country affiliation: Finland Author Affiliation: Kangas L ( Hormos Medical Ltd., Turku, Finland.); Härkönen P ( Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland.); Väänänen K ( Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland.); Peng Z ( Pharmatest Ltd., Turku, Finland.)
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.
File Format	HTM / HTML
ISSN	00185043
e-ISSN	14394286
Journal	Hormone and Metabolic Research
Issue Number	1
Volume Number	46
Language	English
Publisher	Thieme
Publisher Date	2014-01-01
Publisher Place	Germany
Access Restriction	Open
Subject Keyword	Discipline Metabolism Discipline Endocrinology Bone And Bones Drug Effects Physiology Selective Estrogen Receptor Modulators Pharmacology Tamoxifen Analogs & Derivatives Animals Biomechanical Phenomena Body Weight Bone Density Bone Remodeling Anatomy & Histology Cell Count Compressive Strength Femur Lumbar Vertebrae Luteinizing Hormone Blood Organ Size Osteoclasts Cytology Ovariectomy Rats, Sprague-dawley Tibia Uterus Metabolism Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Biochemistry (medical) Endocrinology, Diabetes and Metabolism Biochemistry Clinical Biochemistry Endocrinology

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