Human parathyroid hormone 1-34 prevents bone loss in experimental biliary cirrhosis in rats.
OBJECTIVE
Reduced bone mass and increased fracture rate are complications of primary biliary cirrhosis (PBC). The effect of intermittent administration of human parathyroid hormone (hPTH) 1-34 on bone mass and architecture in bile duct-ligated (BDL) rats was studied.


METHODS
Six-month-old male rats were subjected to BDL or sham operation (SO) and were treated from the second postoperative week intermittently with either hPTH 1-34 40 microg/kg per day, 80 microg/kg per day, or a vehicle for 4 weeks. Femoral and tibial bones were evaluated ex vivo by dual x-ray absorptiometry, microcomputed tomography, and histomorphometry. Serum osteocalcin and urinary deoxypyridinoline cross-links (DPD) were determined.


RESULTS
BDL rats had decreased bone mass compared with SO rats as indicated by a 6% decrease in femoral and tibial bone mineral density (BMD), 18% reduction in femoral trabecular bone volume (bone volume/total volume [BV/TV]), 17% decrease in trabecular thickness, and 10% decrease in tibial cortical thickness. The administration of hPTH 1-34 at 40 microg/kg per day increased femoral and tibial BMD (9% and 9%), femoral trabecular BV/TV (50%), trabecular thickness (50%), tibial cortical thickness (17%), and serum osteocalcin (82%). On the other hand, hPTH 1-34 80 microg/kg per day had no effect on BMD and tibial cortical thickness, was associated with a smaller increase in trabecular BV/TV (24%), and had a higher osteoclast number and DPD compared with untreated BDL rats and the lower hPTH 1-34 dose treatment group.


CONCLUSIONS
BDL rats exhibit loss of bone mass and structure, which can be prevented by the intermittent administration of hPTH 1-34, a potential therapy for osteoporosis in PBC.
Endocrinology and Metabolism Service, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Rivka
R
Dresner-Pollak
Yankel
Y
Gabet
Arza
A
Steimatzky
Gilad
G
Hamdani
Itai
I
Bab
Zvi
Z
Ackerman
Miron
M
Weinreb
D000818:Animals; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000502:physiology; D004195:Disease Models, Animal; D005269:Femur; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000150:complications* / Q000503:physiopathology; D008297:Male; D010024:Osteoporosis / Q000209:etiology* / Q000517:prevention & control*; D051381:Rats; D019379:Teriparatide / Q000627:therapeutic use*; D013977:Tibia
D050071:Bone Density Conservation Agents; D019379:Teriparatide