Contrasting effects of parathyroid hormone and insulin-like growth factor I in an aged ovariectomized rat model of postmenopausal osteoporosis.
Agents that exert anabolic effects on bone have generally been tested in young or estrogen-replete animals. It is unclear whether these agents exert similar effects in older ovariectomized (Ovx) animals. In this single study we examined the effects of intermittent (daily) human PTH-(1-34) and continuous infusion of human recombinant IGF-I alone and in combination on bone resorption and formation over a 14 day period in an aged Ovx rat model of postmenopausal osteoporosis (2-year-old rats, Ovx at 1 year). Compared to Ovx controls, PTH treatment increased bone mineral content (BMC) and bone volume and stimulated bone formation but had no effect on bone resorption. In contrast, IGF-I treatment reduced BMC and stimulated resorptive activity as assessed by increases in marrow volume, cortical porosity, osteoclast-positive eroded surfaces, and urinary hydroxyproline excretion. IGF-I had no effect on bone formation, but when combined with PTH, IGF-I blunted the response to PTH on the periosteal and endocortical surfaces. In summary, PTH stimulated bone formation in a manner similar to that observed in younger animals and IGF-I stimulated bone resorption rather than formation and blunted the bone-forming response to PTH. The effects of IGF-I in older Ovx rats may differ from those observed in younger estrogen-replete animals.
Ibbotson
K J
KJ
Bone Metabolism Department, Norwich Eaton Pharmaceuticals, Inc., New York.
Orcutt
C M
CM
D'Souza
S M
SM
Paddock
C L
CL
Arthur
J A
JA
Jankowsky
M L
ML
Boyce
R W
RW
D000375:Aging / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000187:drug effects / Q000473:pathology; D006801:Humans; D015918:Infusion Pumps, Implantable; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000503:physiopathology; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013131:Spine / Q000187:drug effects / Q000473:pathology
D010281:Parathyroid Hormone; D007334:Insulin-Like Growth Factor I