Time-course of vertebral and femoral bone loss in rats administered gonadotrophin-releasing hormone agonist.
This study was carried out (1) to compare the time-course of the change in bone metabolism in rats administered gonadotrophin-releasing hormone agonist (GnRHa) and bilaterally ovariectomized (OVX) rats and (2) to investigate the changes in bone metabolism after discontinuance of GnRHa. Seventy female Sprague-Dawley rats, aged 90 days, were divided into four groups. Group 1 underwent a sham operation, group 2 was surgically ovariectomized and group 3 was given a GnRHa (leuprorelin acetate for depot suspension) s.c. injection every 30 days. Group 3 was further divided into three subgroups: rats were administered GnRHa for 12 months (GnRHa 12M), 6 months (GnRHa 6M) or 3 months (GnRHa 3M). Group 4 served as a basal control. The bone mineral density (BMD) of lumbar vertebrae and femoral bone, measured by dual-energy X-ray absorptiometry, and the serum bone metabolic parameters were determined every 45-90 days. The bone histomorphometry of lumbar vertebra was measured on days 180 and 360 after surgery. GnRHa 12M rats showed significantly lower BMD of vertebrae and femoral bone, lower bone volume and higher bone turnover compared with sham-operated rats and those with secondary hyperparathyroidism on days 180 and 360. Their time-course for changes in bone metabolism was almost the same as that of OVX rats. GnRHa-discontinued rats showed a recovery of bone turnover. The recovery of BMD in GnRHa 6M rats was smaller than that of GnRHa 3M rats after GnRHa discontinuance. The bone volume for GnRHa 6M rats was significantly lower than that for GnRHa 3M on day 360.
Kurabayashi
T
T
Department of Obstetrics and Gynecology, Niigata University School of Medicine, Japan.
Fujimaki
T
T
Yasuda
M
M
Yamamoto
Y
Y
Tanaka
K
K
D015502:Absorptiometry, Photon; D000818:Animals; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood; D005260:Female; D005269:Femur / Q000378:metabolism* / Q000502:physiology; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006961:Hyperparathyroidism / Q000503:physiopathology; D016729:Leuprolide / Q000494:pharmacology*; D008159:Lumbar Vertebrae / Q000378:metabolism* / Q000502:physiology; D007986:Luteinizing Hormone / Q000097:blood; D010024:Osteoporosis / Q000378:metabolism* / Q000503:physiopathology; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone; D016729:Leuprolide; D002118:Calcium