Loss of the anabolic effect of parathyroid hormone on bone after discontinuation of hormone in rats.
We have previously reported that low doses of hPTH 1-34 given daily to rats exert an anabolic effect on bone. The objective of this study was to determine if the anabolic effect of PTH was dependent upon continued daily administration of the hormone. Young, male rats were given daily subcutaneous injections of either vehicle or 8 micrograms/100g bw hPTH 1-34 for 12, 16, 20, or 24 days. Additional groups were treated with 8 micrograms/100g bw hPTH for 12 days followed by vehicle for the next 4, 8, or 12 days; or 8 micrograms/100g bw hPTH 1-34 for 16 days followed by 4 days of vehicle. We measured calcium (Ca), dry weight (DW), and hydroxyproline (Hyp) of the distal femur; percent of osteoblast (Ob.S/BS) and osteoclast (Oc.S/BS) surface, mineral apposition rate (MAR), double label surface (DLS/BS), and bone formation rate (BFR) in the metaphysis of the proximal tibia, and serum calcium and phosphate. Trabecular and cortical bone Ca and DW and the histologic measures of bone formation increased in all PTH-treated rats. Serum calcium and phosphate were comparable in all rats. The PTH-stimulated bone mass was lost 12 days after discontinuation of PTH. Discontinuation of PTH administration for 4, 8, or 12 days, respectively, resulted in a 72%, 68%, or 50% decrease in Ob.S/BS from the 2- to 3-fold increase associated with PTH treatment (p less than .05). Oc.S/BS increased compared to controls after 4 days of PTH withdrawal (NS), but was comparable to controls 8 days after withdrawal of PTH.(ABSTRACT TRUNCATED AT 250 WORDS)
Gunness-Hey
M
M
School of Medicine, University of Connecticut Health Center, Farmington 06032.
Hock
J M
JM
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects*; D006909:Hydroxyproline / Q000032:analysis; D007279:Injections, Subcutaneous; D008297:Male; D010012:Osteogenesis / Q000187:drug effects; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011859:Radiography; D051381:Rats; D011919:Rats, Inbred Strains
D010281:Parathyroid Hormone; D006909:Hydroxyproline