Association of oxidative stress with postmenopausal osteoporosis and the effects of hydrogen peroxide on osteoclast formation in human bone marrow cell cultures.
It has been suggested that oxidative stress is associated with the pathogenesis of osteoporosis. The objective of this study was to explore the association between a marker of oxidative stress and either bone turnover markers or bone mineral density (BMD) in postmenopausal women. In addition, the effects of oxidative stress on the formation of osteoclasts in human bone marrow cell culture were examined. We performed a cross-sectional analysis in healthy postmenopausal women aged 60-78 years (n = 135, 68.2 +/- 4.9). Oxidative stress was evaluated in the serum by measuring 8-hydroxy-2'-deoxyguanosine (8-OH-dG) levels. The biochemical markers of bone turnover and areal BMD were measured in all participants. Multivariate linear regression analysis revealed a negative association between 8-OH-dG levels and BMD of the lumbar spine, total hip, femoral neck, and trochanter and positive association with type I collagen C-telopeptide (ICTP) levels. The odds ratio of 8-OH-dG for osteoporosis was 1.54 (1.14-2.31, P = 0.003). In cultures of primary human marrow cells, H2O2 caused concentration-dependent activation of TRAP-positive multinucleated giant cells. H2O2 also increased the area of pits per osteoclast activity assay substrate. RT-PCR showed that H2O2 stimulated the expression of M-CSF and RANKL and increased the RANKL/OPG ratio. The data support the view that oxidative stress is associated with increased bone resorption and low bone mass in otherwise healthy women. In addition, RANKL and M-CSF stimulation induced by oxidative stress may participate in osteoclastogenesis in human bone.
Baek
Ki Hyun
KH
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Oh
Ki Won
KW
Lee
Won Young
WY
Lee
Seong Su
SS
Kim
Mee Kyoung
MK
Kwon
Hyuk Sang
HS
Rhee
Eun Jung
EJ
Han
Je Ho
JH
Song
Ki Ho
KH
Cha
Bong Yun
BY
Lee
Kwang Woo
KW
Kang
Moo Il
MI
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D015519:Bone Density; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D003430:Cross-Sectional Studies; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D015726:Giant Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008875:Middle Aged; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D018384:Oxidative Stress; D053245:RANK Ligand / Q000378:metabolism
D024042:Collagen Type I; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D016173:Macrophage Colony-Stimulating Factor; D000080242:8-Hydroxy-2'-Deoxyguanosine; D006861:Hydrogen Peroxide; D003849:Deoxyguanosine