Increased formation of 8‐iso‐prostaglandin F2α is associated with altered bone metabolism and lower bone mass in hypercholesterolaemic subjects

Abstract.Objectives. To investigate the relationship of 8‐iso‐prostaglandin (PG) F2α 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 studySetting.  University hospital centreMethods.  Serum 8‐iso‐PGF2α 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‐PGF2α 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‐PGF2α 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‐PGF2α 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‐PGF2α 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.