Increased formation of 8-iso-prostaglandin F(2alpha) is associated with altered bone metabolism and lower bone mass in hypercholesterolaemic subjects

Objectives. To investigate the relationship of 8-iso-prostaglandin (PG) F-2 alpha levels, a reliable marker of in vivo oxidative stress and lipid peroxidation, with bone mineral density (BMD), bone turnover markers, osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa B ligand (RANKL) in hypercholesterolaemia. Design. Cross-sectional study Setting. University hospital centre Methods. Serum 8-iso-PGF(2 alpha) levels were measured in 173 hypercholesterolaemic subjects and in 152 age- and sex-matched normocholesterolaemic controls. Femoral neck and lumbar spine BMD, serum bone-specific alkaline phosphatase (BAP), osteocalcin (OC), OPG and RANKL levels, as well as urinary levels of C-terminal telopeptides of type I collagen (CTX-I), were also assessed. Results. Hypercholesterolaemic subjects showed higher (P < 0.0001) serum 8-iso-PGF(2 alpha) levels than controls. They also had decreased (P < 0.0001) femoral neck and lumbar spine BMD, and lower (P < 0.0001) serum BAP and OC levels. No significant differences between hypercholesterolaemic and control subjects were found when comparing urinary CTX-I levels, or serum OPG and RANKL levels. In multivariate linear regression analysis, serum 8-iso-PGF(2 alpha) was the only negative predictor for femoral neck BMD and serum BAP and OC levels in hypercholesterolaemic subjects. No significant correlation (all P > 0.25) was present between serum 8-iso-PGF(2 alpha) levels and urinary CTX-I levels, or serum OPG and RANKL levels, in hypercholesterolaemic subjects. Conclusions. We found an association between increased serum 8-iso-PGF(2 alpha) levels and lower bone mass and reduced serum BAP and OC concentrations in hypercholesterolaemic subjects. These results would suggest a possible role for oxidative stress in the development of lower bone mass in hypercholesterolaemia