Sequential treatment with basic fibroblast growth factor and parathyroid hormone restores lost cancellous bone mass and strength in the proximal tibia of aged ovariectomized rats

This study was designed to determine whether sequential treatment with basi c fibroblast growth factor (bFGF) and parathyroid hormone (PTH) can restore lost cancellous bone mass and strength at a severely osteopenic skeletal s ite in aged ovariectomized (OVX) rats. Female Sprague-Dawley rats were subj ected to sham surgery or ovariectomy at 3 months of age and maintained untr eated for the first year after surgery. At 15 months of age, groups of base line control and OVX rats were killed and catheters were inserted in the ju gular veins of all remaining rats. Two groups of OVX rats were injected int ravenously (iv) daily with bFGF for 14 days at a dose of 200 mug/kg body we ight. At the end of bFGF treatment, one group was killed whereas the other group was subjected to 8 weeks of treatment with synthetic human PTH 1-34 [ hPTH(1-34)] consisting of subcutaneous (sc) injections 5 days/week at a dos e of 80 mug/kg. Another group of OVX rats was treated iv with vehicle for 2 weeks followed by treatment with PTH alone for 8 weeks. Other groups of sh am-operated control rats and OVX rats were treated iv and sc with vehicle a lone. The right proximal tibia from each rat was processed undecalcified fo r quantitative bone histomorphometry and the left proximal tibia was subjec ted to biomechanical testing. Baseline and vehicle-treated OVX rats were se verely osteopenic because their tibial cancellous bone volumes were less th an 5% compared with mean values of 20.3% and 15.0% in baseline and vehicle- treated control rats, respectively. Treatment of OVX rats for 2 weeks with bFGF alone did not significantly increase, tibial cancellous bone volume bu t induced marked increases in osteoid volume, osteoblast surface, and osteo id surface. Sequential treatment of aged OVX rats with bFGF and PTH increas ed tibial cancellous bone volume (15.1%) and load to failure to at least th e level of vehicle-treated control rats. Tibial cancellous bone volume (10. 8%) and load to failure also were significantly increased by treatment with PTH alone, and these variables were not significantly different from those of OVX rats treated with bFGF + PTH. However, tibial ash density was signi ficantly greater in OVX rats treated sequentially with bFGF and PTH compare d with OVX rats treated with PTH:, alone. Our findings suggest that sequent ial treatment with bFGF and PTH may be useful for restoration of lost cance llous bone in the severely osteopenic, estrogen-deplete skeleton, but it ca nnot lie concluded with certainty that this sequential treatment has a grea ter bone restorative effect than treatment with PTH alone.