Long-term growth hormone-releasing factor administration on growth hormone, insulin-like growth factor-I concentrations, and bone healing in the Beagle.

Twelve 11 month old male Beagles were assigned to two treatment groups: a control group (saline) and a group receiving human growth hormone (GH)-releasing factor (hGRF) [1-29]NH2 (25 micrograms/kg, SC, TID). Treatment was started 6 days prior to surgery (day 1) and continued until necropsy (3 dogs per group/day) on d 29 or 58. Two porous polyethylene rods were surgically implanted on the lateral diaphysis of the femoral shaft and a 3 mm hole was drilled through the cortex between the two implants of each dog on day 1. Blood and urine were collected on d -6, 27 and 56. Human GRF injections produced a significant (P < 0.05) increase in GH release following each injection. An increase in GH response was also observed (P < 0.05) over time. The concentration of insulin-like growth factor-1 (IGF-1) increased for 5 weeks and then reached a plateau. None of the hematologic or urine measured parameters was affected by the treatment (P > 0.05). Albumin, calcium, and protein concentrations were higher (P < 0.05) on d 27 and 56 in GRF-treated animals. Histological sections of the onlay sites showed that bony ingrowth tended to be greater into the porous polyethylene material in GRF-treated animals than the controls at d 28 and 57, while no difference was observed in the degree of periosteal bone formation around the implants at either time period (P > 0.05). Bone formation into the cortical defect was greater in the GRF-treated dogs when compared to controls at day 57 only. In conclusion, chronic hGRF [1-29]NH2 treatment in Beagle dogs produced an increased GH response over time and increased IGF-1 concentrations. It also appeared to promote bony ingrowth into a porous polyethylene onlay and into a bony deficit.