EFFECTS OF COMBINED PROSTAGLANDIN AND ALENDRONATE TREATMENT ON THE HISTOMORPHOMETRY AND BIOMECHANICAL PROPERTIES OF BONE IN OVARIECTOMIZED RATS

Prostaglandin E2 (PGE2) has been shown to stimulate both bone resorpti on and formation in experimental animals, leading to augmentation of t rabecular and cortical bone. The amino bisphosphonate alendronate (ALN ) is a potent inhibitor of bone resorption. The objectives of this stu dy were to examine if PGE2 StiMUlation of bone formation was dependent on bone resorption and if the bone accrued as a result of PGE2 treatm ent contributed to bone strength. The 48 female Sprague-Dawley rats we re assigned to six groups as follows: five groups (8/group) were ovari ectomized at the age of 6 months. One group was sacrificed 2 months la ter to establish baseline conditions, and four groups were treated for 25 days with (1) vehicle, (2) PGE2 at 3 mg/kg/day, (3) ALN sc at 0.8 mug/kg/day, and (4) PGE2 + ALN at the respective doses. The sixth grou p served as nonovariectomized untreated controls. Histomorphometric an alysis of 6-10 mum thick tibial sections after in vivo fluorochrome do uble labeling showed that treatment with PGE2 alone increased endocort ical mineral apposition rate and bone formation rate, stimulated produ ction of bone trabeculae in the marrow cavity, and increased cortical porosity. Combined ALN + PGE2 treatment prevented the resorption induc ed by PGE2 but not the stimulation of bone formation on endocortical a nd periosteal surfaces and resulted in a significant increase in corti cal thickness. Consistent with these observations, the femoral midshaf t tested to failure in three-point bending showed a significant increa se in strength in the PGE2 + ALN group (181 +/- 15 N) compared to time 0 controls (145 +/- 23 N) or to the ovariectomized vehicle-treated gr oup (141 +/- 28 N). Similarly, there was a statistically significant i ncrease in femoral midshaft stiffness. There was also a statistically significant increase in the ash content of bones from animals treated with PGE2 + ALN relative to vehicle-treated animals. No statistically significant differences among groups were observed in femoral neck or vertebral strength or stiffness. These findings show that PGE2 stimula tion of bone formation is not blocked by inhibition of bone resorption and that combined treatment with PGE2 and the bone resorption inhibit or ALN increased the mechanical strength of ovariectomized rat femoral shaft compared to nonovariectomized animals.