Influence of elevation of γ-glutamyl transpeptidase by cholestatic liver disease on bone destruction

Yusuke Kawazoe1, Mutsumi Miyauchi1, Susumu Tazuma2, Hisako Furusyo1,

Keiko Suzuki3, Shumpei Niida4, Takashi Takata1

Department of Oral and Maxillofacial Pathobiology, Hiroshima University1

Division of Clinical Pharmacotherapeutics, Hiroshima University

Department of Pharmacology, Showa University

Department of Geriatric Sciences, National Institute for Longevity Sciences

 

  Patients with cholestatic liver disease show the elevation of serum γ-glutamyl transpeptidase (sGGT). It is generally accepted that GGT is an escape enzyme and has no effect on bone metabolism. We identified GGT as a novel bone resorbing factor. The elevation of sGGT may be responsible for reduction of bone mass. Influences of elevated sGGT on bone metabolism were analyzed using rat bile duct ligation (BDL) model. In BDL-animals, sGGT level and number of osteoclasts were significantly increased. Bone mineral density and bone mass were markedly reduced. They were improved by anti-GGT antibody treatment.

These findings indicated that the elevation of sGGT might be a critical causative factor of osteoporosis in patients with cholestatic liver disease.