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


METHODS
Cross-sectional study.


METHODS
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.
Mangiafico
R A
RA
Department of Internal Medicine, University of Catania, Catania, Italy. rmangiafico@tiscali.it
Malaponte
G
G
Pennisi
P
P
Li Volti
G
G
Trovato
G
G
Mangiafico
M
M
Bevelacqua
Y
Y
Mazza
F
F
Fiore
C E
CE
D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015519:Bone Density; D001842:Bone and Bones / Q000378:metabolism* / Q000503:physiopathology; D003430:Cross-Sectional Studies; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D005272:Femur Neck / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism* / Q000503:physiopathology; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015675:Osteocalcin / Q000097:blood; D053244:Osteoprotegerin / Q000097:blood; D018384:Oxidative Stress; D053245:RANK Ligand / Q000097:blood; D018709:Statistics, Nonparametric
D015415:Biomarkers; D053244:Osteoprotegerin; D053245:RANK Ligand; D015675:Osteocalcin; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D000469:Alkaline Phosphatase