Preexisting bone loss associated with ovariectomy in rats is reversed by parathyroid hormone.
Previous studies have demonstrated that when parathyroid hormone (PTH) administration to rats is started immediately following ovariectomy, it prevents bone loss due to ovarian hormone deficiency. In this study, we examined whether bone loss induced by ovariectomy could be reversed by parathyroid hormone if hormone therapy is started after the bone loss had already occurred. In the first experiment, two groups of animals were ovariectomized or sham operated, killed after 40 days, and their bones examined to ensure that bone loss occurred. In the second experiment, three groups of rats were studied. Group 1 rats were sham operated, and rats in groups 2 and 3 were ovariectomized. Each rat in group 3 received a single subcutaneous injection of 8 micrograms parathyroid hormone [hPTH-(1-34); Bachem, CA] per 100 g body weight per day, starting 40 days following ovariectomy. Rats in groups 1 and 2 received solvent vehicle, and all animals were sacrificed on day 60. Ovariectomized rats had lost an appreciable amount of bone 40 days after surgery, as indicated by a significant decrease in femoral and vertebral densities and calcium and an over 55% loss of cancellous bone in the tibial metaphysis. The loss of bone was reversed by intermittent PTH administration. Increased cancellous bone in the parathyroid hormone-treated ovariectomized rats was associated with increased trabecular osteoblasts, decreased trabecular osteoclasts, and increased serum osteocalcin and urinary hydroxyproline. Our findings indicate that parathyroid hormone can substantially augment bone mass after the loss due to ovarian hormone deficiency has already occurred. The hormone caused positive bone balance in vivo in ovarian hormone-deficient animals by increasing bone formation and decreasing bone resorption.
Liu
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CC
Research Service, Veterans Administration Medical Center, Tacoma, Washington.
Kalu
D N
DN
Salerno
E
E
Echon
R
R
Hollis
B W
BW
Ray
M
M
D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D001862:Bone Resorption / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology*; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000378:metabolism; D005260:Female; D007279:Injections, Subcutaneous; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy / Q000009:adverse effects*; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D019379:Teriparatide; D014599:Uterus / Q000473:pathology
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D019379:Teriparatide; D002117:Calcitriol; D002118:Calcium