Anabolic effect of parathyroid hormone is not modified by supplementation with insulinlike growth factor I (IGF-I) or growth hormone in aged female rats fed an energy-restricted or ad libitum diet.
PTH increases bone mass by stimulating bone formation in vivo, and IGF-I partially mediates the stimulatory effect of PTH on collagen synthesis in vitro. The objectives of this study were to determine if the anabolic effect of PTH in aged rats was diminished by an energy-restricted (ER) diet in which IGF-I levels have been shown to be decreased, and if GH or IGF-I modified the bone response to PTH. Two strains of aged female rats, 18-24 months, fed either ad libitum (AL) or 60% ER diets since weaning, were treated subcutaneously (SC) with 8 micrograms/100 g body weight hPTH 1-34 alone or in combination with GH given SC as 0.1 mg/100 g body weight twice daily for 24 or 32 days. Additional ER-fed rats were supplemented SC with 60 micrograms/100 g body weight rhIGF-I twice daily and treated with PTH and/or GH for 12 days. Histomorphometric indices of bone volume (BV/TV), mineral apposition rate (MAR) and bone formation rate (BFR/BS) in lumbar vertebrae and bone mineral content (BMC) of tibia increased in all PTH-treated rats. BV significantly increased after 32 (p < 0.01) or 24 (p < 0.05) days, but not 12 days (NS). Significant increases in mineralizing surfaces (MS/BS) and MAR resulted in 2.9-3.6-fold increases in BFR associated with PTH treatment alone or with GH (p < 0.01). These increases occurred regardless of an ER diet, and were not modified by IGF-I or GH. Although ER rats weighed less, femur length was not affected and serum chemistry values were within the physiologic range for rats. In summary, PTH increased bone mass by stimulating bone formation in aged rats irrespective of diet, and supplementation with GH or IGF-I did not modify the response of bone to PTH.
Gunness
M
M
Pathology & Laboratory Medicine Service (113), VA Medical Center, Portland, OR 97207, USA.
Hock
J M
JM
D000375:Aging / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001846:Bone Development / Q000187:drug effects; D004032:Diet; D004347:Drug Interactions; D002149:Energy Intake / Q000502:physiology*; D004734:Energy Metabolism; D005260:Female; D013006:Growth Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000494:pharmacology*; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000502:physiology; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN; D019379:Teriparatide
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D019379:Teriparatide; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone