1,25 dihydroxyvitamin D3 alone or in combination with parathyroid hormone does not increase bone mass in young rats.
Parathyroid hormone (PTH) alone is known to increase bone mass, but clinical studies of osteoporotic men suggest that when 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) is given in combination with PTH, the effect on bone growth is enhanced. To determine if 1,25(OH)2D3 alone would stimulate bone growth, young male rats were given daily subcutaneous injections of either vehicle or 2.5, 5, 10, or 20 ng 1,25(OH)2D3 per 100 g body weight for 30 days. To determine if 1,25(OH)2D3 would augment the PTH anabolic response, rats were given daily subcutaneous injections of either vehicle for 12 days; or 4 micrograms/100 g hPTH alone or in combination with 5 ng/100 g 1,25(OH)2D3; or 8 micrograms/100 g hPTH alone or in combination with 5 ng/100 g 1,25(OH)2D3. Calcium (Ca), dry weight (DW), and hydroxyproline (Hyp) of the distal femur; the rate of mineralization in the metaphysis of the proximal tibia; and serum calcium and phosphate were measured. Low normocalcemic doses of 1,25(OH)2D3 did not significantly stimulate bone growth. 1,25(OH)2D3 did not augment the PTH-stimulated anabolic effect in young male rats. Low doses (2.5 and 5 ng) of 1,25(OH)2D3 were not hypercalcemic, and there was no increase in total bone calcium or dry weight although the 5 ng dose increased trabecular bone calcium. 1,25(OH)2D3 at 10 and 20 ng increased trabecular bone DW and Hyp, but mineralization was impaired and rats were hypercalcemic. 1,25(OH)2D3 in combination with PTH did not augment the PTH stimulation of bone growth as trabecular and cortical bone Ca, DW, and HYP were not increased in rats given both hPTH and 1,25(OH)2D3 compared with values for rats treated with hPTH alone.
Gunness-Hey
M
M
School of Medicine, University of Connecticut Health Center, Farmington 06032.
Gera
I
I
Fonseca
J
J
Raisz
L G
LG
Hock
J M
JM
D000818:Animals; D001846:Bone Development / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002117:Calcitriol / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D010281:Parathyroid Hormone; D002117:Calcitriol