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

To clarify the effects of 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) on bone growth, strength, and turnover in growing rats with liver cirrhosis induced by carbon tetrachloride (CCl4) injection, groups of 4-week-old male Wistar rats (n = 10, each) were injected intraperitoneally with CCl4 twice weekly for 7 weeks. One group was treated with the vehicle alone (Group 1). Three CCl4-injected groups were orally administered 1,25(OH)2D3 at doses of 0, 0.05, and 0.1 μg/kg, respectively (Groups 2, 3, and 4). At the end, serum levels of 1,25(OH)2D3, 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 CCl4-injected rats was associated with reduced serum 1,25(OH)2D3 and IGF-I levels. The trabecular bone in the rats exhibited low turnover osteopenia. 1,25(OH)2D3 administration partially prevented the growth disturbance, but did not substantially affect bone turnover. Factors other than 1,25(OH)2D3 and IGF-I appeared to be critical in the low turnover osteopenia evident in liver cirrhosis.