Effects of daily administration of prostaglandin E2 and its withdrawal on the lumbar vertebral bodies in male rats

Abstract

The effects of daily prostaglandin E₂ (PGE₂) treatment (on) and PGE₂ treatment followed by withdrawal (on-off) on cancellous bone in lumbar vertebral bodies were studied in 7-month-old male Sprague-Dawley rats. The first groups of rats were given daily subcutaneous injections of 0,1,3, and 6 mg PGE₂ /kg/dfor 60, 120, and 180 days, and the second group of rats were given PGE₂ for 60 days followed by withdrawal for 60 and 120 days. Histomorphometric analyses were performed on double-fluorescent labeled undecalcified sections of fourth lumbar vertebral bodies. Systemic PGE₂ treatment elevated cancellous bone mass of lumbral vertebral bodies 26–60% above control levels within 60 days and continued treatment maintained it for another 120 days, but the excess bone was lost after the treatment was withdrawn. PGE₂ treatment for 60 days increased trabecular bone area, trabecular width, and bone formation parameters, and shortened remodeling periods in a dose-response manner. These changes were sustained at the levels achieved by 60-day treatment in the rats treated for 120 and 180 days. The eroded perimeter increased at day 60 and further at day 120 and then plateaued. In the on-off treated rats, the cancellous bone area, bone formation, and resorption parameters returned to near agerelated controls by 60 days after withdrawal and were maintained there after 120 days of withdrawal. Therefore we conclude that the continuous treatment is needed in order to maintain the PGE₂-induced bone gain. When these findings were compared to those previously reported for the proximal tibial metaphyses, we found that the proximal tibial spongiosa was much more responsive to PGE₂ treatment than the fourth lumbar vertebral body.© Willey-Liss, Inc.