title: Preservation of bone mass in hypogonadal female monkeys with recombinant human growth hormone administration.
abstract: 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)
authors.affiliation: Morehouse School of Medicine, Atlanta, Georgia.
authors.forename: D R
authors.initials: DR
authors.lastname: Mann
authors.forename: C G
authors.initials: CG
authors.lastname: Rudman
authors.forename: M A
authors.initials: MA
authors.lastname: Akinbami
authors.forename: K G
authors.initials: KG
authors.lastname: Gould
mesh_terms: 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
chemical_list: 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