Relationships between OPG, RANKL, bone metabolism, and bone mineral density in biliary atresia.
OBJECTIVE
Osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) have been implicated in osteoclastogenesis. However, the relationship between the OPG-RANKL system and bone status in biliary atresia (BA) has not, as yet, been clarified. Thus, the aim of this study has been to evaluate the relationship between the OPG-RANKL system and bone mineral metabolism in patients with BA.


METHODS
Fifty patients with BA and 13 healthy controls were investigated. The mean age of BA patients and controls was 7.3 +/- 0.6 and 8.0 +/- 1.1 years, respectively. Serum levels of OPG, RANKL, osteocalcin, and C-terminal telopeptide of type I collagen (CTX) were measured by sandwich enzyme-linked immunosorbent assay. Bone mineral density (BMD) of the lumbar spine was determined by dual energy X-ray absorptiometry.


RESULTS
Biliary atresia patients had significantly elevated serum OPG levels compared with controls (4.0 +/- 0.3 vs. 3.0 +/- 0.3 pmol/L, P = 0.02) and serum OPG levels in BA patients with jaundice were higher than in those without jaundice (4.6 +/- 0.4 vs. 3.6 +/- 0.4 pmol/L, P = 0.04). Likewise, serum RANKL levels were significantly higher in BA patients than in controls (2.9 +/- 0.2 vs. 1.2 +/- 0.7 pmol/L, P = 0.001). In addition, serum RANKL levels were increased in BA patients with jaundice compared to those without jaundice, but this difference was not statistically significant (3.2 +/- 0.3 vs. 2.7 +/- 0.2 pmol/L, P = 0.2). The serum osteocalcin levels in BA patients were not significantly different from those in the healthy controls, whereas the serum CTX levels were elevated in BA patients compared with the controls (0.4 +/- 0.1 vs. 0.2 +/- 0.1 ng/mL, P = 0.02). Furthermore, BMD of BA children with jaundice was significantly lower than that of BA children without jaundice (P = 0.0005). BMD of BA patients was inversely correlated with serum levels of OPG (r = -0.452, P < 0.001).


CONCLUSIONS
Elevated serum OPG levels are associated with reduced BMD and the outcome of BA. The increase of serum OPG in BA patients with severe disease could reflect a compensatory response to bone loss.
Honsawek
Sittisak
S
Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Chaiwatanarat
Tawatchai
T
Vejchapipat
Paisarn
P
Chongsrisawat
Voranush
V
Thawornsuk
Nutchanart
N
Poovorawan
Yong
Y
D001656:Biliary Atresia / Q000097:blood* / Q000150:complications / Q000378:metabolism*; D015519:Bone Density; D001851:Bone Diseases, Metabolic / Q000097:blood* / Q000209:etiology; D001842:Bone and Bones / Q000378:metabolism*; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D053244:Osteoprotegerin / Q000097:blood*; D053245:RANK Ligand / Q000097:blood*
D053244:Osteoprotegerin; D053245:RANK Ligand; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human