The effects of
prostaglandin E2 (
PGE2) given in controlled-release pellets or by daily sc injection for 21 days on
mineral homeostasis and bone histomorphometry were compared in 7-week-old female rats.
Sham operation and
ovariectomy were performed at the beginning of the studies. In experiment 1, 7.5 mg
PGE2 or
drug-free, controlled-release pellets were implanted sc at the back of the neck on day 7. In experiment 2, 3 mg/kg
body weight of
PGE2 or vehicle was injected sc daily beginning on day 7. The animals were sacrificed on day 28 of the two experiments, and the tibiae were removed for histomorphometric analysis of the diaphysis and metaphysis. When administered by pellets in experiment 1,
PGE2 lowered serum
1,25-dihydroxyvitamin D and did not influence
weight gain, serum
calcium,
phosphorus, or
magnesium, cross-sectional or medullary areas, periosteal bone formation and apposition rates, endosteal bone formation and apposition rates, or endosteal
tetracycline-labeled perimeter.
PGE2 lowered cancellous bone area and cancellous bone perimeter in both the
sham-operated and ovariectomized rats. In contrast, when administered by sc injection in experiment 2,
PGE2 reduced
weight gain, increased serum
magnesium, increased cortical area, and reduced medullary area without changing cross-sectional area, increased periosteal bone formation and apposition rates and endosteal bone and apposition rates, did not alter endosteal
tetracycline-labeled perimeter, and increased cancellous bone area and cancellous bone perimeter in both
sham-operated and ovariectomized animals.
PGE2 produced local
inflammation when given by pellets, and the serum concentration of
13,14-dihydro-15-ketoprostaglandin E2, the major metabolite of
PGE2, increased when
PGE2 was given by sc injection but not when administered by pellets. Thus,
PGE2 given sc by controlled-release pellets (1) produces local
inflammation and systemic bone loss without increasing
PGE2 systemically and (2) provides a model for
inflammation-induced loss of cancellous bone. The results also indicate that the pellet is not a valid means for the delivery of
PGE2 to the general circulation.