The effect of gallium nitrate on healing of vitamin D- and phosphate-deficient rickets in the immature rat.
The effect of gallium on rapid in vivo mineralization was studied in a rachitic rat model in which rickets were induced in immature rats then reversed ("healed") with repletion of vitamin D and phosphate. Gallium was administered to selected groups of animals before and during the healing phase. In nonrachitic animals and rachitic animals before healing, the mineral content of diaphyseal and metaphyseal bone was increased, and the crystal size was decreased in those animals that received gallium compared with those that did not. Mineralization of the undermineralized osteoid appeared histologically normal by 72 hours in all animals. However, animals that received gallium both before and during the healing phase had less well-mineralized bones at 18 hours, and by 72 hours, they had lesser increases in osteocalcin and mineral content, which was associated with smaller crystal sizes, than did any animal that did not receive gallium at any time. Prior to the healing phase, the ratio of gallium to hydroxyproline in the metaphyses of rachitic animals was similar to that in nonrachitic animals. Likewise, this ratio did not change in the animals receiving gallium both before and during the healing phase. The ratio of gallium to calcium was higher in rachitic animals compared with controls, and this ratio lowered significantly by the end of the healing phase. Results may be explained in part by direct effect of gallium on the physical process of mineral formation during the rapid healing phase as well as by effects of gallium on osteoblasts and osteoclasts during the induction of rickets.
Donnelly
R
R
Hospital for Special Surgery, New York, New York 10021.
Bockman
R
R
DiCarlo
E
E
Betts
F
F
Boskey
A
A
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000737:chemistry; D002113:Calcification, Physiologic / Q000187:drug effects*; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000032:analysis / Q000097:blood; D005708:Gallium / Q000032:analysis / Q000494:pharmacology*; D006887:Hydroxycholecalciferols / Q000097:blood; D007279:Injections, Subcutaneous; D008297:Male; D015675:Osteocalcin / Q000032:analysis; D010710:Phosphates / Q000008:administration & dosage / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012279:Rickets / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D014807:Vitamin D / Q000008:administration & dosage
D006887:Hydroxycholecalciferols; D010710:Phosphates; D015675:Osteocalcin; D014807:Vitamin D; D005708:Gallium; D000469:Alkaline Phosphatase; D002117:Calcitriol; D002118:Calcium; C027235:gallium nitrate