Comparison of the effects of intermittent and continuous administration of human parathyroid hormone(1-34) on rat bone.
We compared the effects of synthetic human parathyroid hormone (1-34) (hPTH[1-34]) on rat bones when administered by intermittent injection and by continuous infusion for 4 weeks. Continuous infusion of hPTH(1-34) caused a dose-dependent decrease in the dry weight of the femur and a hyperparathyroidism-like condition in the high-dose group (214 ng/kg/h). In this group, although bone morphology was quite abnormal, the metaphyseal trabecular bone volume increased, whereas the epiphyseal trabecular bone volume tended to decrease, enhancing both bone resorption and formation. The diaphyseal cortical bone of the tibia became markedly porous, and this appeared to be the main cause of the decrease in total bone weight. Conversely, the dry weight of the femur increased in a dose-dependent manner in the intermittent-injection groups. Neither porosity of the cortical bone nor abnormal morphology of the trabecular bone was observed. The volume of the metaphyseal trabecular bone increased while retaining its normal morphology. The epiphyseal trabecular bone formation obviously increased without increase in the number of osteoclasts. In other words, it was postulated that the total weight of bone increased because intermittent injection of hPTH(1-34) increased the trabecular bone volume without loss of the cortical bone volume. These results show that either mode of treatment with hPTH(1-34) continuously accelerated bone formation, whereas the continuous infusion was essential for persistently and markedly enhanced acceleration of bone resorption. It appears that the increase in bone volume with intermittent injection of hPTH(1-34) resulted from the prominent manifestation of its bone-formative action rather than from its bone-resorptive action.(ABSTRACT TRUNCATED AT 250 WORDS)
Uzawa
T
T
Laboratory for Life Science Research, Asahi Chemical Industry Co., Ltd., Shizuoka-ken, Japan.
Hori
M
M
Ejiri
S
S
Ozawa
H
H
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D002118:Calcium / Q000097:blood; D004334:Drug Administration Schedule; D005269:Femur; D006909:Hydroxyproline / Q000652:urine; D015918:Infusion Pumps, Implantable; D007279:Injections, Subcutaneous; D008297:Male; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D010758:Phosphorus / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D019379:Teriparatide; D013977:Tibia
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D019379:Teriparatide; D010758:Phosphorus; D000469:Alkaline Phosphatase; D006909:Hydroxyproline; D002118:Calcium