Osteopenia in rats with liver cirrhosis: beneficial effects of IGF-I treatment.
OBJECTIVE
Liver cirrhosis is associated with osteopenia and also with low levels of IGF-I. This hormone has been reported to stimulate bone formation in states of undernutrition and low bone turnover. Our aims were to evaluate whether osteopenia develops in male Wistar rats with CCl4-induced cirrhosis and whether IGF-I is effective in the restoration of bone mass in these animals.


METHODS
Cirrhotic rats were distributed into two groups: group CI (n = 12) which received placebo and group CI + IGF (n = 12) which was treated with human recombinant IGF-I (2 microg/100 g bw/day, s.c., 21 days). Twelve normal animals which received placebo constituted the control group. On the 22nd day, the animals were sacrificed, and bone parameters were analyzed in femur and/or tibia.


RESULTS
Posterior-anterior and latero-medial diameters were similar in all groups. Also, no significant differences were observed in bone contents of calcium, total proteins, collagen and hydroxyapatite in CI rats as compared with controls. However, CI rats showed significant reductions in bone weight (-13.5%, p < 0.001), total bone density (-9.28%, p < 0.001), and increased perimedullar bone resorption and urinary levels of deoxypyridinoline (a marker of bone resorption). In CI + IGF rats these parameters improved significantly as compared with CI animals.


CONCLUSIONS
Osteopenia characterized by loss of bone mass and preserved bone composition is found in rats with CCl4-induced cirrhosis. This bone disorder is partially corrected by treatment with low doses of IGF-I. Since osteoporosis seems to be the predominant form of osteopenia in patients with cirrhosis, IGF-I should be considered as a possible therapy for this disorder.
Cemborain
A
A
Department of Human Physiology, School of Medicine, University of Navarra, Pamplona, Spain.
Castilla-Cortázar
I
I
García
M
M
Quiroga
J
J
Muguerza
B
B
Picardi
A
A
Santidrián
S
S
Prieto
J
J
D000410:Alanine Transaminase / Q000097:blood; D000596:Amino Acids / Q000652:urine; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000652:urine; D001798:Blood Proteins / Q000032:analysis; D015519:Bone Density / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000209:etiology* / Q000473:pathology / Q000628:therapy*; D001862:Bone Resorption; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002252:Carbon Tetrachloride Poisoning / Q000150:complications; D003094:Collagen / Q000378:metabolism; D017886:Durapatite / Q000032:analysis; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D008106:Liver Cirrhosis, Experimental / Q000150:complications* / Q000473:pathology / Q000628:therapy*; D008297:Male; D010710:Phosphates / Q000378:metabolism; D010919:Placebos; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values
D000596:Amino Acids; D015415:Biomarkers; D001798:Blood Proteins; D010710:Phosphates; D010919:Placebos; D007334:Insulin-Like Growth Factor I; C036020:deoxypyridinoline; D003094:Collagen; D017886:Durapatite; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002118:Calcium