PROSTAGLANDIN-E(2) ADMINISTERED BY SUBCUTANEOUS PELLETS CAUSES LOCAL INFLAMMATION AND SYSTEMIC BONE LOSS - A MODEL FOR INFLAMMATION-INDUCEDBONE-DISEASE

The effects of prostaglandin E2 (PGE2) given in controlled-release pel lets or by daily se injection for 21 days on mineral homeostasis and b one histomorphometry were compared in 7-week-old female rats. Sham ope ration 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 experiment s, and the tibiae were removed for histomorphometric analysis of the d iaphysis and metaphysis. When administered by pellets in experiment 1, PGE2 lowered serum 1,25-dihydroxyvitamin D and did not influence weig ht gain, serum calcium, phosphorus, or magnesium, cross-sectional or m edullary areas, periosteal bone formation and apposition rates, endost eal bone formation and apposition rates, or endosteal tetracycline-lab eled perimeter. PGE2 lowered cancellous bone area and cancellous bone perimeter in both the sham-operated and ovariectomized rats. In contra st, when administered by sc injection in experiment 2, PGE2 reduced we ight gain, increased serum magnesium, increased cortical area, and red uced medullary area without changing cross-sectional area, increased p eriosteal bone formation and apposition rates and endosteal bone and a pposition rates, did not alter endosteal tetracycline-labeled perimete r, and increased cancellous bone area and cancellous bone perimeter in both sham-operated and ovariectomized animals. PGE2 produced local in flammation when given by pellets, and the serum concentration of 13,14 -dihydro-15-ketoprostaglandin E2, the major metabolite of PGE2, increa sed when PGE2 was given by sc injection but not when administered by p ellets. Thus, PGE2 given sc by controlled-release pellets (1) produces local inflammation and systemic bone loss without increasing PGE2 sys temically and (2) provides a model for inflammation-induced loss of ca ncellous bone. The results also indicate that the pellet is not a vali d means for the delivery of PGE2 to the general circulation.