Bone mineral metabolism and histomorphometry in rats with cholestatic liver disease.
BACKGROUND
The etiology of osteopenia in cholestatic liver disease is uncertain. An animal model is needed in order to study the efficacy of therapeutic agents.


OBJECTIVE
In order to characterise the bone disease in rats with cholestatic liver disease.


METHODS
Four-month old male Sprague-Dawley bile duct-ligated (BDL) and sham-operated (SO) rats were studied. Twenty-eight days after surgery serum osteocalcin, a bone-formation marker, urinary deoxypyridinoline (DPD) cross-links, a resorption marker, and 25-hydroxyvitamin D3 were determined. Static and dynamic (tetracycline-based) histomorphometric analysis was performed on femurs and tibiae.


RESULTS
All BDL rats developed biliary cirrhosis. Bile duct-ligated rats had lower bone mass, reflected in statistically significantly 13.5% lower femoral dry-weight, 16% lower femoral ash-weight, 42.7% lower tibial cancellous bone area and 19% lower trabecular thickness, compared with SO rats. Bile duct-ligated rats exhibited decreased bone formation manifested by statistically significantly 70% lower tetracycline double-labelling, 40% lower mineralising surface, 51% lower bone-formation rate and 47% lower osteocalcin compared with SO rats. Deoxypyridinoline levels were 20% lower in BDL rats. Bile duct-ligated rats had 52% lower serum 25-hydroxyvitamin D3 level, but no significant increase in cortical osteoid area.


CONCLUSIONS
Bile duct-ligated rats develop osteopenia characterised by low bone-formation rate, and can be used for studying therapeutic agents for patients with cholestatic liver disease displaying similar bone changes.
Ackerman
Zvi
Z
Department of Medicine, Hadassah University Hospital, Mount Scopus, Hebrew University-Hadassah Medical School, Jerusalem, Israel. zackerman@hadassah.org.il
Weinreb
Miron
M
Amir
Gail
G
Pollak
Rivka D
RD
D000596:Amino Acids / Q000652:urine; D000818:Animals; D001851:Bone Diseases, Metabolic / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002112:Calcifediol / Q000031:analogs & derivatives* / Q000097:blood; D001651:Cholestasis, Extrahepatic / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005269:Femur / Q000378:metabolism / Q000473:pathology; D008297:Male; D015675:Osteocalcin / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000378:metabolism / Q000473:pathology
D000596:Amino Acids; D015675:Osteocalcin; C036020:deoxypyridinoline; C045956:1-25-dihydroxy-23,23-difluorovitamin D3; D002112:Calcifediol