Role of iron metabolism and oxidative damage in postmenopausal bone loss.
It has been suggested that iron-deficient rats have lower bone mass than iron-replete animals, but a clear association between bone and iron repletion has not been demonstrated in humans. A growing body of evidences also suggests a relation between lipid oxidation and bone metabolism and between iron metabolism and LDL oxidation. Iron availability to cells also depends on haptoglobin (Hp) phenotypes. Hp has also important antioxidant properties according to its phenotype, hence we evaluate whether Hp phenotype could influence bone density, iron metabolism and lipid oxidation. This cross-sectional study enrolled 455 postmenopausal women affected by osteoporosis (260) or not (195). Bone mineral density, markers of bone and iron metabolism, levels of oxidized LDL (oxLDL) and Hp phenotype were measured in all the subjects. Hp 1.1 and 2.2 frequency was higher and Hp 2.1 was lower in the patients with fragility fractures (80) compared with the controls. We therefore evaluate different Hp phenotypes as risk or protective factors against fragility fracture: Hp 2.1 is a protective factor against fracture while 1.1 is an important and 2.2 a moderate risk factor for fragility fractures. Lower serum iron was associated with elevated transferrin in patients with Hp 1.1; moreover patients had relative iron deficiency compared with the controls and fractured patients had higher level of oxLDL. We found that both iron metabolism and oxLDL varies according to Hp phenotypes and are predictive of bone density. Our data indicate that Hp 2.1 is a protective factor for fragility fractures, depending on its role on iron metabolism and its antioxidant properties.
D'Amelio
Patrizia
P
Department of Internal Medicine, University of Torino, Torino, Italy. patrizia.damelio@unito.it
Cristofaro
Maria A
MA
Tamone
Cristina
C
Morra
Emanuella
E
Di Bella
Stefania
S
Isaia
Gianluca
G
Grimaldi
Anastasia
A
Gennero
Luisa
L
Gariboldi
Angela
A
Ponzetto
Antonio
A
Pescarmona
Gian Piero
GP
Isaia
Giovanni Carlo
GC
D000368:Aged; D015153:Blotting, Western; D015519:Bone Density; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008875:Middle Aged; D010024:Osteoporosis / Q000378:metabolism*; D018384:Oxidative Stress; D017698:Postmenopause; D012307:Risk Factors
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D007501:Iron