Quantitive bone histomorphometry
Springer Online Journal Archives 1860-2000
Summary To evaluate the potential use of a combination of parathyroid hormone (PTH) and estrogen as therapy for osteoporosis, we examined the effects of combined and separate administration of low-dose PTH and estradiol in ovariectomized rats with established osteopenia. Ovariectomized rats were untreated for 5 weeks after surgery and then injected s.c. with vehicle (Ovx+V), 1–34 hPTH (2.5 μg/kg/day) (Ovx+P), 17β-estradiol (50 μg/kg/day) (Ovx+E), or a combination of these (Ovx+P+E), for a further 4 weeks. We found no differences in serum calcium, tubular reabsorption of phosphate, or 25OHD. 1,25(OH)2D levels were significantly higher in Ovx+P and lower in Ovx+E, when compared with Ovx+V. Though there was no change in bone mineral density (BMD) in the diaphysis region of femurs, reduction of BMD in the distal region of the femurs in Ovx+V was reversed in Ovx+E and Ovx+P+E. Compared with Ovx+V, Ovx+P and Ovx+P+E had significantly higher cancellous bone volume (Cn-BV/TV) whereas Ovx+E showed a nonsignificant increase. When indices of bone turnover were examined, PTH alone showed a small but not significant improvement in bone formation rate (BFR). Increased osteoclast surface (OCS), as the result of ovariectomy, was inhibited in Ovx+E and Ovx+P+E. Estrogen alone (Ovx+E) severely inhibited BFR, but co-administration of PTH and estrogen (Ovx+P+E) showed an impressive reversal of such inhibition. The changes in BFR were mainly derived from changes in double-labeled surface (dLS), except a small increase in mineral apposition rate was also observed in Ovx+P+E. These results suggest that, after extensive cancellous bone loss in the rat tibia, low doses of PTH function anabolically, especially in situations where the bone formation rate is low. A combination of both estrogen and PTH may provide the best treatment for improving bone mass by decreasing resorption and maintaining a high bone formation rate.
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