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

J Intern Med. 2007 Jun;261(6):587-96. doi: 10.1111/j.1365-2796.2007.01784.x.

Abstract

Objectives: To investigate the relationship of 8-iso-prostaglandin (PG) F(2alpha) 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(2alpha) 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(2alpha) 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(2alpha) 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(2alpha) 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(2alpha) 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.

MeSH terms

  • Adult
  • Alkaline Phosphatase / blood
  • Biomarkers / blood
  • Bone Density
  • Bone and Bones / metabolism*
  • Bone and Bones / physiopathology
  • Cross-Sectional Studies
  • Dinoprost / analogs & derivatives*
  • Dinoprost / metabolism
  • Female
  • Femur Neck / metabolism
  • Femur Neck / physiopathology
  • Humans
  • Hypercholesterolemia / metabolism*
  • Hypercholesterolemia / physiopathology
  • Lipid Peroxidation
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Osteocalcin / blood
  • Osteoprotegerin / blood
  • Oxidative Stress
  • RANK Ligand / blood
  • Statistics, Nonparametric

Substances

  • Biomarkers
  • Osteoprotegerin
  • RANK Ligand
  • Osteocalcin
  • 8-epi-prostaglandin F2alpha
  • Dinoprost
  • Alkaline Phosphatase