Effect of 16 months of treatment with tibolone on bone mass, turnover, and biomechanical quality in mature ovariectomized rats.
Tibolone (Org OD14) is a tissue-specific steroid with estrogenic effects on the bone and vagina but not endometrium or breast and has been shown to prevent ovariectomy-induced bone loss in young and old rats. We evaluated the effect of long-term tibolone treatment on bone parameters in mature ovariectomized (OVX) rats. Six-month-old rats were allotted to one of six groups (n = 8). Sham-operated and control OVX groups received vehicle, whereas other groups (all OVX) received tibolone (125, 250, or 500 microg/day orally) or 17alpha-ethinylestradiol (EE; 24 microg/day orally) for 16 months. Treatment with tibolone prevented ovariectomy-induced bone loss in peripheral (femur and tibia) and axial (L1-L2 and L4) skeleton. In peripheral skeleton, tibolone and EE prevented loss of bone mass and quality to a similar extent. Tibolone dose-dependently inhibited trabecular bone volume loss in L1-L2 and tibia, and at 500 microg/day it inhibited 88% of L1-L2 and 55% of tibial volume loss (p < or = 0.05 in each case). Tibolone, 500 microg, resulted in 10% greater cortical strength of femur (p < or = 0.05) and 60% greater compressive strength of L4 (p < or = 0.05) compared with vehicle-treated OVX rats. Tibolone and EE inhibited bone resorption and turnover, assessed by urinary deoxypyridinoline/ creatinine and plasma osteocalcin, respectively. We conclude that 16 months of tibolone treatment prevents ovariectomy-induced deterioration of axial and peripheral skeleton and preserves cortical and trabecular bone strength by reducing bone resorption.
Ederveen
A G
AG
Department of Pharmacology, Research and Development, NV Organon, Oss, The Netherlands.
Spanjers
C P
CP
Quaijtaal
J H
JH
Kloosterboer
H J
HJ
D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000652:urine; D045930:Anabolic Agents / Q000627:therapeutic use*; D000818:Animals; D015415:Biomarkers; D015519:Bone Density; D003404:Creatinine / Q000652:urine; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000187:drug effects* / Q000503:physiopathology; D008099:Liver / Q000378:metabolism; D009652:Norpregnenes / Q000627:therapeutic use*; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000517:prevention & control*; D010052:Ovariectomy / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D013977:Tibia / Q000187:drug effects* / Q000503:physiopathology; D013997:Time Factors
D000596:Amino Acids; D045930:Anabolic Agents; D015415:Biomarkers; D009652:Norpregnenes; D015675:Osteocalcin; C015484:pyridinoline; D003404:Creatinine; D000469:Alkaline Phosphatase; C027385:tibolone