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Keywords:

  • bile acids;
  • bone mass;
  • cholestasis;
  • osteoporosis;
  • primary biliary cirrhosis

Abstract

Background

Osteoporosis resulting from decreased bone formation is a common complication in patients with chronic cholestasis. Lithocholic acid (LCA) and bilirubin may play a role in osteoporosis given that both substances have detrimental effects on survival of human osteoblasts, the cells involved in bone formation.

Aims

As ursodeoxycholic acid (UDCA) improves cholestasis, we have assessed if this bile acid may neutralize the harmful effects of LCA, bilirubin and sera from jaundiced patients on osteoblastic cells.

Methods

The experiments were performed in primary human osteoblasts and human osteosarcoma cell line (Saos-2) at different times and concentrations of UDCA, LCA, cholic acid (CA), bilirubin and sera from jaundiced patients to assess cell viability, differentiation and mineralization.

Results

UDCA significantly decreased cell survival at concentrations 10 times higher (1 mM) than that observed with LCA, whereas CA did not decrease osteoblast survival. UDCA (100 μM) neutralized the damaging effects of bilirubin (50 μM) and sera from jaundiced patients on survival. Moreover, UDCA (1 μM and 10 μM) increased osteoblast differentiation in cells treated with harmful concentrations of LCA or bilirubin. UDCA (100 μM) increased cell differentiation in osteoblasts cultured with a mix of serum from cholestatic patients by 23%. Furthermore, UDCA increased osteoblast mineralization by 35% and neutralized the negative consequences of 50 μM bilirubin.

Conclusions

UDCA increases osteoblast differentiation and mineralization, and neutralizes the detrimental effects of lithocholic acid, bilirubin and sera from jaundiced patients on osteoblastic cells. Therefore, UDCA may exert a favourable effect on bone in patients which chronic cholestasis.