Human parathyroid hormone (1-34) and salmon calcitonin do not reverse impaired mineralization produced by high doses of 1,25 dihydroxyvitamin D3.
We have reported recently that pharmacologic doses of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) stimulated bone matrix formation but impaired mineralization. The objective of this study was to determine if parathyroid hormone (hPTH 1-34) or calcitonin (sCT) would mineralize the osteoid induced by 1,25(OH)2D3 in rat long bones. In one experiment, male Sprague-Dawley rats were given daily subcutaneous injections of vehicle: 8 micrograms hPTH(1-34); 125 ng 1,25(OH)2D3; or both 8 micrograms hPTH and 125 ng 1,25(OH)2D3 per 100 g body weight for 12 days. In a second experiment, rats received daily injections of vehicle: 2 U sCT; 125 ng 1,25(OH)2D3; or both 2 U sCT and 125 ng 1,25(OH)2D3 per 100 g body weight for 18 days. Calcium (Ca), hydroxyproline (Hyp), and dry weight (DW) of the distal femur and serum calcium, phosphate, and serum bone Gla protein (BGP) were measured. In rats given both 1,25(OH)2D3 and hPTH, total bone DW and Hyp increased (P less than .01) without a corresponding increase in bone Ca so that Ca/Hyp decreased 47% (P less than .01) from control and remained comparable to values for rats treated with 1,25(OH)2D3 alone. In rats treated with both 1,25(OH)2D3 and sCT, total bone DW and Hyp increased while Ca decreased so that Ca/Hyp decreased 38% from control (P less than .05), and remained comparable to values for rats treated with 1,25(OH)2D3 alone. These results indicate that hPTH or sCT, given by intermittent injection to rats for 12 or 18 days respectively, failed to mineralize the osteoid induced by high doses of 1,25(OH)2D3.
D000818:Animals; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002116:Calcitonin / Q000494:pharmacology*; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D015675:Osteocalcin; D010012:Osteogenesis / Q000187:drug effects; D010018:Osteomalacia / Q000139:chemically induced; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D019379:Teriparatide
D002135:Calcium-Binding Proteins; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D015675:Osteocalcin; D019379:Teriparatide; C028815:salmon calcitonin; D002116:Calcitonin; D002117:Calcitriol; D006909:Hydroxyproline; D002118:Calcium