Intravenous 1alpha, 25[OH]2 vitamin D3 (calcitriol) pulse therapy for bone lesions in a murine model of chronic cadmium toxicosis.
The aim of the present study was to clarify the therapeutic effects of 1alpha, 25[OH]2 vitamin D3 (calcitriol) pulse injection on bone lesions induced in a rat model of chronic cadmium toxicosis. Ovariectomized (OVX) and control-operated (sham-OVX) rats were given repeated intravenous injections of 0.5 mg/kg/day CdCl2 for 70 weeks. The rats were then treated intravenously with 0.02 microg/kg/day calcitriol 3 days per week for 8 weeks. CdCl2 treatment induced increases in osteoid volumes of the femur cortex and trabecula. This change was accompanied by an increase in the volume of iron deposition at the mineralization front of the trabeculae and a reduction in mineral density. Abnormalities of bone metabolic parameters, which were increases in the blood calcium, inorganic phosphorous, bone-specific alkaline phosphatase, parathyroid hormone (PTH) and osteocalcin levels, and in the urine deoxypyridinoline (D-PYR) level, were also induced. Calcitriol treatment increased the blood calcium and inorganic phosphorous levels, and reduced the blood PTH level. Decreases in blood tartrate-resistant acid phosphatase and urine d-PYR levels were also induced indicating that bone resorption was suppressed. The findings indicated that the increased osteoid volume of the cortex and Fe-deposition volume of the trabecula were improved. These effects or improvements were observed in the sham-OVX rats but not in the OVX rats.
Kurata
Y
Y
Toxicology Division, Mitsubishi Chemical Safety Institute Ltd, Ibaraki, Japan. kurata@ankaken.co.jp
Katsuta
O
O
Hiratsuka
H
H
Tsuchitani
M
M
Umemura
T
T
D000135:Acid Phosphatase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000652:urine; D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015519:Bone Density; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002104:Cadmium / Q000378:metabolism; D019256:Cadmium Chloride; D002105:Cadmium Poisoning / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002117:Calcitriol / Q000008:administration & dosage*; D002908:Chronic Disease; D004909:Erythrocyte Indices; D005260:Female; D005269:Femur; D006454:Hemoglobins / Q000032:analysis; D007501:Iron / Q000378:metabolism; D023421:Models, Animal; D015675:Osteocalcin / Q000097:blood; D010018:Osteomalacia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010052:Ovariectomy; D020551:Pulse Therapy, Drug; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D015415:Biomarkers; D006454:Hemoglobins; D002104:Cadmium; D015675:Osteocalcin; C036020:deoxypyridinoline; D007501:Iron; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D002117:Calcitriol; D019256:Cadmium Chloride