Effects of 1,25(OH)2D3 on turnover, mineralization, and strength of bone in growing rats with liver cirrhosis induced by administration of carbon tetrachloride

• Published in: Bone (New York, N.Y.) Vol. 32; no. 3; pp. 275 - 283
• Main Authors: TANAKA, Shinya, TSURUKAMI, Hiroshi, SAKAI, Akinori, OKIMOTO, Nobukazu, IKEDA, Satoshi, OTOMO, Hajime, NAKAMURA, Toshitaka
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Science 01-03-2003
• Subjects: Animals; Biological and medical sciences; Biomechanical Phenomena; Bone Development - drug effects; Bones, joints and connective tissue. Antiinflammatory agents; Calcification, Physiologic - drug effects; Calcitriol - pharmacology; Calcium Channel Agonists - pharmacology; Carbon Tetrachloride; Femur - drug effects; Femur - growth & development; Femur - physiology; Liver Cirrhosis - chemically induced; Liver Cirrhosis - pathology; Liver Cirrhosis - physiopathology; Lumbar Vertebrae - drug effects; Lumbar Vertebrae - growth & development; Lumbar Vertebrae - physiology; Male; Medical sciences; Pharmacology. Drug treatments; Rats; Rats, Wistar; Tibia - drug effects; Tibia - growth & development; Tibia - physiology; Animal model; Osteocalcin; Biochemical analysis; Cholecalciferol(1,25-dihydroxy); Growth; Hepatic disease; IGF-1; Bone remodeling; Insulin like growth factor 1; Biological activity; Young animal; Biomechanics; Osteoarticular system; Cirrhosis; Vitamin D; Mineralization; Digestive diseases; Activation frequency; Bone; Strength; Deoxypyridinoline: BMC
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/S8756-3282(02)00977-8

To clarify the effects of 1 alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) on bone growth, strength, and turnover in growing rats with liver cirrhosis induced by carbon tetrachloride (CCl(4)) injection, groups of 4-week-old male Wistar rats (n = 10, each) were injected intraperitoneally with CCl(4) twice weekly for 7 weeks. One group was treated with the vehicle alone (Group 1). Three CCl(4)-injected groups were orally administered 1,25(OH)(2)D(3) at doses of 0, 0.05, and 0.1 micro g/kg, respectively (Groups 2, 3, and 4). At the end, serum levels of 1,25(OH)(2)D(3), IGF-I, and osteocalcin were reduced in Group 2 compared to Group 1, and the corresponding values in Group 4 were larger than those in Group 2. Urinary deoxypyridinoline levels increased in Group 2 compared to Group 1, and did not significantly differ in Groups 2-4. The values for bone sizes, mineral content (BMC) in the lumbar vertebra and femur, and ultimate bending load in the femur were reduced in Group 2 compared to Group 1, and lumbar BMC in Group 3 and bone sizes in Group 4 were larger than those in Group 2. The values for lumbar trabecular bone volume in Group 2 were reduced compared to Group 1, and the corresponding values in Group 4 were larger than those in Group 2. Bone formation rates, reduced in Group 2 compared to Group 1, did not differ in Groups 2-4. Parameters for trabecular osteoclasts did not differ among all groups. In the proximal tibia, the value of activation frequency (Ac.f) in Group 2 significantly decreased compared to Group 1. Ac.f values in Groups 3 and 4 were larger than that in Group 2. These data demonstrated that retardation of bone growth in CCl(4)-injected rats was associated with reduced serum 1,25(OH)(2)D(3) and IGF-I levels. The trabecular bone in the rats exhibited low turnover osteopenia. 1,25(OH)(2)D(3) administration partially prevented the growth disturbance, but did not substantially affect bone turnover. Factors other than 1,25(OH)(2)D(3) and IGF-I appeared to be critical in the low turnover osteopenia evident in liver cirrhosis.