Effects of tibolone on bone quality in ovariectomized monkeys.
OBJECTIVE
The purpose of this report is to examine the effects of two doses of tibolone on bone quality (bone biomarkers, bone density, and bone strength) in ovariectomized cynomolgus monkeys fed high-fat diets.


METHODS
Ovariectomized cynomolgus monkeys were randomized into one of five treatment groups: placebo-treated control, tibolone (0.2 mg/kg/day), tibolone (0.05 mg/kg/day), conjugated equine estrogens (Premarin, 0.042 mg/kg/day), and conjugated equine estrogens plus medroxyprogesterone acetate (0.042 and 0.167 mg/kg/day, respectively). Bone quality was assessed by determining bone strength and density in vertebrae and femora collected after 24 months of treatment.


RESULTS
Monkeys treated for 24 months with tibolone had increased bone mineral density in the distal femur and improved biomechanical properties in the midshaft femur compared with placebo-treated ovariectomized monkeys, as did monkeys treated with conjugated equine estrogens with or without medroxyprogesterone acetate. No treatment effects were seen in lumbar vertebra bone density or strength. There was no significant difference between tibolone and estrogen on biomechanical properties of the femur.


CONCLUSIONS
These data show that tibolone is comparable to conjugated equine estrogens with or without medroxyprogesterone acetate in decreasing bone turnover and increasing bone strength in ovariectomized monkeys.
Lees
Cynthia J
CJ
Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA. clees@wfubmc.edu
Ederveen
Antwan G H
AG
Spanjers
Cees P M
CP
Clarkson
Thomas B
TB
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects; D003271:Contraceptive Agents, Female / Q000494:pharmacology; D004041:Dietary Fats / Q000008:administration & dosage; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000502:physiology; D008252:Macaca fascicularis; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D009652:Norpregnenes / Q000494:pharmacology*; D010052:Ovariectomy; D011859:Radiography; D011897:Random Allocation
D003271:Contraceptive Agents, Female; D004041:Dietary Fats; D020847:Estrogen Receptor Modulators; D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D009652:Norpregnenes; D017258:Medroxyprogesterone Acetate; D000469:Alkaline Phosphatase; C027385:tibolone