title: Association of oxidative stress with postmenopausal osteoporosis and the effects of hydrogen peroxide on osteoclast formation in human bone marrow cell cultures.
abstract: 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.
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Ki Hyun
authors.initials: KH
authors.lastname: Baek
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Oh
authors.forename: Won Young
authors.initials: WY
authors.lastname: Lee
authors.forename: Seong Su
authors.initials: SS
authors.lastname: Lee
authors.forename: Mee Kyoung
authors.initials: MK
authors.lastname: Kim
authors.forename: Hyuk Sang
authors.initials: HS
authors.lastname: Kwon
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Rhee
authors.forename: Je Ho
authors.initials: JH
authors.lastname: Han
authors.forename: Ki Ho
authors.initials: KH
authors.lastname: Song
authors.forename: Bong Yun
authors.initials: BY
authors.lastname: Cha
authors.forename: Kwang Woo
authors.initials: KW
authors.lastname: Lee
authors.forename: Moo Il
authors.initials: MI
authors.lastname: Kang
mesh_terms: 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
chemical_list: 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