Preservation of bone mass in hypogonadal female monkeys with recombinant human growth hormone administration.
This study examined the effect of human recombinant GH supplementation on bone loss in female monkeys made hypogonadal with GnRH agonist (GnRH-Ag). Animals were randomly assigned to three treatment groups: vehicle, GnRH-Ag, and GnRH-Ag and GH. After an initial 5-month pretreatment period during which all animals were maintained on a normal monkey chow diet containing a high level of calcium (1%) animals were maintained on a normal monkey chow diet containing a high level of calcium (1%), animals were shifted to a lower calcium diet (0.1%) for 4 to 5 months before the beginning of treatment and were maintained on this diet throughout the remainder of the study. Monkeys were treated continuously for 10 months with 25 micrograms/day GnRH-Ag or vehicle. GH was administered by im injection three times per week at a dose of 100 micrograms/kg body wt/day. Animals treated with GnRH-Ag were amenorrheic throughout the treatment period, and serum estradiol and progesterone levels were below minimum levels of detection. Vehicle-treated animals continued to cycle throughout the study. Monkeys treated with GnRH-Ag alone showed a significant decline (12%) in bone mineral density (BMD) of the lumbar spine. BMD was reduced below pretreatment levels from 6 months of GnRH-Ag treatment through 3 months post treatment in this group. GH supplementation reduced the decline of BMD in GnRH-Ag-treated monkeys. BMD did not change significantly with time in the GH-supplemented group. BMD values in GH supplemented animals between 5 and 10 months of the treatment period exceeded levels in animals treated with GnRH-Ag alone, but BMD levels during this interval were lower than in the vehicle-treated group. In the vehicle-treated group, there was small, but significant, increase in BMD over the course of the study. Serum osteocalcin concentrations were elevated above pretreatment values after 6 and 9 months of GnRH-Ag treatment alone or with GH supplementation, but did not change in vehicle-treated animals. GH also increased serum insulin-like growth factor 1 levels. In response to the lower calcium diet, serum PTH levels increased approximately 200% in vehicle-treated monkeys and animals treated with GnRH-Ag alone. GH attenuated this increase in serum PTH. The data indicate that the level of calcium in the diet of adult monkeys can be reduced more than 10-fold without affecting lumbar BMD provided ovarian function is normal, but if animals are made hypogonadal with a GnRH-Ag, bone mass declines.(ABSTRACT TRUNCATED AT 400 WORDS)
Mann
D R
DR
Morehouse School of Medicine, Atlanta, Georgia.
Rudman
C G
CG
Akinbami
M A
MA
Gould
K G
KG
D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D004032:Diet; D004958:Estradiol / Q000097:blood; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives; D013006:Growth Hormone / Q000627:therapeutic use*; D007006:Hypogonadism / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008252:Macaca fascicularis; D015675:Osteocalcin / Q000097:blood; D010281:Parathyroid Hormone / Q000097:blood; D011374:Progesterone / Q000097:blood; D011994:Recombinant Proteins / Q000627:therapeutic use
D010281:Parathyroid Hormone; D011994:Recombinant Proteins; D015675:Osteocalcin; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C030741:lutrelin acetate; D002118:Calcium