Human parathyroid hormone-(1-38) restores cancellous bone to the immobilized, osteopenic proximal tibial metaphysis in rats.
The purpose of this study was to determine if human parathyroid hormone-(1-38) (hPTH(1-38)) can restore cancellous bone mass to the established osteopenic, immobilized proximal tibial metaphyses of female rats. The right hindlimbs of 6-month-old female Sprague-Dawley rats were immobilized by bandaging the right hindlimbs to the abdomen. After 30 days of right hindlimb immobilization, the rats were subcutaneously injected with 200 micrograms hPTH(1-38)/kg/day for 15 days (short-term treatment) or 75 days (longer-term treatment). Static bone histomorphometry was performed on the primary spongiosa, and both static and dynamic histomorphometry were performed on the secondary spongiosa of the right proximal tibial metaphyses. Immobilization for 30 days without treatment decreased trabecular bone area, number, and thickness in both primary and secondary spongiosa, and induced an increase in eroded perimeter and a decrease in tissue referent-bone formation rate in the secondary spongiosa. These changes reached a new steady state thereafter. Treatment with 200 micrograms hPTH(1-38)/kg/day for 15 days, beginning 30 days after immobilization, significantly increased trabecular bone area, thickness, and number in both primary and secondary spongiosa despite continuous immobilization when compared with controls. The short-term PTH treatment (15 days) significantly increased labeling perimeter, mineral apposition rate, and tissue referent-bone formation rate in the secondary spongiosa and stimulated longitudinal bone growth as compared with the controls. Longer PTH treatment (75 days) further increased trabecular bone area, thickness, and number as compared with controls and groups given short-term PTH treatment (15 days). The bone formation indices in the secondary spongiosa of the longer-term treated rats were lower than those of the short-term treated group, but they were still higher than those of controls. Our findings indicate that PTH treatment stimulates cancellous bone formation, and restores and adds extra cancellous bone to the established, disuse-osteopenic proximal tibial metaphysis of female rats with continuously immobilized right hindlimbs. These results suggest that PTH may be useful in treating disuse-induced osteoporosis in humans.
Ma
Y F
YF
Division of Radiobiology, University of Utah School of Medicine, Salt Lake City 84112, USA.
Jee
W S
WS
Ke
H Z
HZ
Lin
B Y
BY
Liang
X G
XG
Li
M
M
Yamamoto
N
N
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007103:Immobilization; D007279:Injections, Subcutaneous; D018482:Muscle, Skeletal / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure
D010281:Parathyroid Hormone; D010446:Peptide Fragments; C035747:parathyroid hormone (1-38)