Effects of combined and separate intermittent administration of low-dose human parathyroid hormone fragment (1-34) and 17 beta-estradiol on bone histomorphometry in ovariectomized rats with established osteopenia.
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 micrograms/kg/day) (Ovx + P), 17 beta-estradiol (50 micrograms/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.(ABSTRACT TRUNCATED AT 250 WORDS)
Shen
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Regional Bone Center, Helen Hayes Hospital, Haverstraw, New York 10993.
Dempster
D W
DW
Mellish
R W
RW
Birchman
R
R
Horbert
W
W
Lindsay
R
R
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000188:drug therapy*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005269:Femur / Q000187:drug effects / Q000473:pathology; D006801:Humans; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000494:pharmacology* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D010710:Phosphates / Q000097:blood / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D019379:Teriparatide
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D010710:Phosphates; D019379:Teriparatide; D004958:Estradiol