Experimental cholestatic liver disease through bile-duct ligation in rats results in skeletal fragility and impaired osteoblastogenesis.
OBJECTIVE
Patients with cholestatic liver disease have 'low-turnover' osteoporosis. Since we reported that bile-duct ligated (BDL) rats develop bone disease with low bone formation and mass, we examined whether their reduced bone mass results in skeletal fragility, and whether the reduction in osteoprogenitor cells could explain the depressed bone formation.


METHODS
Four-week-old rats were pair-fed and subjected to BDL or sham surgery. After 4 weeks, ex vivo bone marrow stromal cell cultures were used to estimate the number of osteoprogenitors and tibial strength was measured by mechanical testing. The serum levels of albumin, bilirubin, alanine amino-transferase (ALT), alkaline phosphatase (ALP) and nitrite were measured.


RESULTS
BDL rats had elevated levels of bilirubin, ALT, ALP and nitrite. Tibiae of BDL rats were weaker than those of sham rats, exhibiting lower maximal force (-34%) and stiffness (-37%). The number of mineralized bone-like nodules in cultures from BDL rats was 65% lower than that in cultures from sham-operated rats, attesting to a diminished number of osteoprogenitors.


CONCLUSIONS
Skeletal fragility diminished osteoprogenitor pool and elevated plasma levels of nitrite are three additional characteristics of the bone disease that develops in BDL rats, thus increasing the validity of this animal model as representing the human bone disease in patients with cholestatic liver disease.
Weinreb
Miron
M
Department of Oral Biology, Goldschleger School of Dental Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel. weinreb@post.tau.ac.il
Pollak
Rivka Dresner
RD
Ackerman
Zvi
Z
D000818:Animals; D001652:Bile Ducts; D015519:Bone Density; D001854:Bone Marrow Cells / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D002780:Cholestasis, Intrahepatic / Q000150:complications* / Q000209:etiology; D004195:Disease Models, Animal; D050723:Fractures, Bone / Q000209:etiology; D008026:Ligation; D008297:Male; D009573:Nitrites / Q000097:blood; D010006:Osteoblasts / Q000473:pathology*; D010024:Osteoporosis / Q000150:complications / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013718:Tensile Strength; D013977:Tibia / Q000503:physiopathology
D009573:Nitrites