Altered RANKLOPG system in hepatic osteodystrophy

Abstract EN

Hypothesis : the coexistence of liver disease and metabolic bone disease has been recognized for many years and is now the subject of increasing attention.

Hepatic Osteodystrophy was established in patients with cholestasis liver disease, but new research suggests that it is prevalent in patients with other chronic liver diseases.

Its etiology is complex and multifactorial.

Receptor activator of nuclear factor Kb ligand (RANKL) plays a role in the differentiation and activation of bone resorbing osteoclasts by binding to its high affinity receptor (RANK) located on the surface of osteoclasts.

This effect is counterbalanced by osteoprotegren (OPG), which acts as a decoy receptor competing with RANKL for RANK.

Objective : to evaluate bone mineral density (BMD) and OPG / RANKL system in cirrhotic patients with backache.

Methodology : this study included 50 subjects suffering from backache, divided into 4 groups as follows : Group I : 10 subjects with normal BMD, Group II : 10 patients with pathological BMD but otherwise healthy considered as control, Group III: 15 patients with cirrhosis and normal BMD, Group IV : 15 patients with cirrhosis and pathological BMD.

All patients underwent clinical examination, routine liver function tests, alkaline phosphatase, total calcium, serum OPG, serum RANKL, added to BMD.

Results : the lowest BMD values are estimated at the lumber spine, femoral neck, and lastly lower end of radius.

There was a significant decrease in OPG in osteopenia / osteoporotic non-cirrhotic patients compared to control group, while it is significantly higher than control in both osteopenia /osteoporotic and patients with normal BMD of cirrhotic groups.

RANKL was significantly higher in non-cirrhotic patients with pathological BMD compared to control group, but lower than control in cirrhotic groups both with normal and pathological BMD, with significant difference in cirrhotic with pathological BMD and non-significant in those with normal BMD compared to controls.

Serum OPG was negatively correlated to serum calcium, albumin, and International Normalized Ratio (INR), but positively correlated to bone alkaline phosphatase, and AST in cirrhotic patients of both groups.

Conclusion : in cirrhotic patients, low BMD has tendency to affect axial bone early, which is similar to postmenopausal osteoporosis.

On the contrary, higher OPG and lower RANKL levels are opposite to postmenopausal osteoporosis.

This difference indicates that: OPG / RANKL system is activated in a different way in cirrhosis, suggesting a role for OPG / RANKL system in pathogenesis of hepatic osteodystrophy.