Contrasting effects of parathyroid hormone and insulin-like growth factor I in an aged ovariectomized rat model of postmenopausal osteoporosis

Abstract

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.