title: Molecular mechanisms of osteoporotic hip fractures in elderly women.
abstract: A common manifestation of age-related bone loss and resultant osteoporosis are fractures of the hip. Age-related osteoporosis is thought to be determined by a number of intrinsic factors including genetics, hormonal changes, changes in levels of oxidative stress, or an inflammatory status associated with the aging process. The aim of this study was to investigate gene expression and bone architecture in bone samples derived from elderly osteoporotic women with hip fractures (OP) in comparison to bone samples from age matched women with osteoarthritis of the hip (OA). Femoral heads and adjacent neck tissue were collected from 10 women with low-trauma hip fractures (mean age 83±6) and consecutive surgical hip replacement. Ten bone samples from patients undergoing hip replacement due to osteoarthritis (mean age 80±5) served as controls. One half of each bone sample was subjected to gene expression analysis. The second half of each bone sample was analyzed by microcomputed tomography. From each half, samples from four different regions, the central and subcortical region of the femoral head and neck, were analyzed. We could show a significantly decreased expression of the osteoblast related genes RUNX2, Osterix, Sclerostin, WNT10B, and Osteocalcin, a significantly increased ratio of RANKL to Osteoprotegerin, and a significantly increased expression of the enzymes superoxide dismutase 2 (SOD2) and glutathione peroxidase GPX3, and of the inflammatory cytokine IL6 in bone samples from hip fracture patients compared to controls. Major microstructural changes in OP bone were seen in the neck and were characterized by a significant decrease of bone volume, trabecular number, and connectivity density and a significant increase of trabecular separation. In conclusion, our data give evidence for a decreased expression of osteoblast related genes and increased expression of osteoclast related genes. Furthermore, increased expression of SOD2 and GPX3 suggest increased antioxidative activity in bone samples from elderly osteoporotic women with hip fractures.
authors.affiliation: Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria. Electronic address: ursula.foeger-samwald@meduniwien.ac.at.
authors.forename: Ursula
authors.initials: U
authors.lastname: Föger-Samwald
authors.affiliation: Department of Trauma Surgery, Danube Hospital, Langobardenstrasse 122, A-1220, Vienna, Austria. Electronic address: vekszler@sportchirurgie-wien.at.
authors.forename: György
authors.initials: G
authors.lastname: Vekszler
authors.affiliation: Department of Orthopaedics, St. Vincent Hospital, Stumpergasse 13, A-1060, Vienna, Austria. Electronic address: edith.hoerz-schuch@bhs.at.
authors.forename: Edith
authors.initials: E
authors.lastname: Hörz-Schuch
authors.affiliation: Department of Orthopaedics, St. Vincent Hospital, Stumpergasse 13, A-1060, Vienna, Austria. Electronic address: sylvia.salem@bhs.at.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Salem
authors.affiliation: Department of Orthopaedics, Orthopaedic Hospital Gersthof, Wielemansgasse 28, A-1180, Vienna, Austria. Electronic address: markus.wipperich@wienkav.at.
authors.forename: Markus
authors.initials: M
authors.lastname: Wipperich
authors.affiliation: Department of Orthopaedics, Orthopaedic Hospital Gersthof, Wielemansgasse 28, A-1180, Vienna, Austria. Electronic address: peter.ritschl@wienkav.at.
authors.forename: Peter
authors.initials: P
authors.lastname: Ritschl
authors.affiliation: Department of Trauma Surgery, Danube Hospital, Langobardenstrasse 122, A-1220, Vienna, Austria. Electronic address: mehdi.mousavi@wienkav.at.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mousavi
authors.affiliation: Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria. Electronic address: peter.pietschmann@meduniwien.ac.at.
authors.forename: Peter
authors.initials: P
authors.lastname: Pietschmann
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005272:Femur Neck / Q000000981:diagnostic imaging / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000502:physiology; D020022:Genetic Predisposition to Disease; D006620:Hip Fractures / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D006801:Humans; D015207:Osteoarthritis, Hip / Q000235:genetics / Q000473:pathology; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology; D058866:Osteoporotic Fractures / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D055114:X-Ray Microtomography
chemical_list: D012333:RNA, Messenger
keywords: Bone formation; Gene expression; Hip fracture; Osteoporosis; Oxidative stress