title: Increased RANKL/OPG mRNA ratio in iliac bone biopsies from women with hip fractures.
abstract: RANKL (receptor activator of NF-kappaB) is a potent physiological inducer of osteoclastogenesis. Its actions are blocked by the decoy receptor osteoprotegerin (OPG), and treatment with OPG blocks bone resorption in postmenopausal women. Both positive and negative associations between serum OPG and bone mineral density (BMD) have been reported in the literature. We hypothesized that decreased OPG production relative to RANKL within bone itself could lead to increased risk of osteoporotic fracture. We included ten women with hip fracture (age 76.3 +/- 8.0 years, N.S, : hip BMD 0.686 +/- 1.3 g/cm2, P < 0.05) and 24 women with osteoarthrosis of the hip (age 72.8 +/- 7.2 years, hip BMD 0.832 +/- 1.1 g/cm(2)). Transiliac biopsies were obtained at the time of surgery. Total RNA was extracted from biopsies and reverse-transcribed. Real-time quantification of mRNA was performed with a SYBR Green I real time PCR assay, calculating relative gene expression with normalization of results for beta actin mRNA. Actin normalized mRNA levels for OPG and interleukin (IL)-6 were significantly lower in fracture patients, with a significantly higher RANKL/OPG ratio in patients with fractures. There was no significant difference in tumor necrosis factor (TNF), IL-1, IL-1ra, or IL-7 expression. IL-6 mRNA levels were lower in fracture patients (P < 0.05). The effect of increased RANKL/OPG ratio (Z = 2.08, P < 0.05) on fracture risk was additive to that of hip BMD T score (Z = -1.95, P < 0.05) when assessed using logistic regression. Elderly women with hip fractures exhibit an increased RANKL/OPG mRNA content of iliac bone. This is associated with increased fracture susceptibility, which is not in itself explained by low BMD.
authors.affiliation: Clinic for Molecular Endocrine Treatment KMEB, Odense University Hospital, Winsloewparken 15, 111, DK-5000 Odense C, Denmark.
authors.forename: Basem M
authors.initials: BM
authors.lastname: Abdallah
authors.forename: Lis S
authors.initials: LS
authors.lastname: Stilgren
authors.forename: Nis
authors.initials: N
authors.lastname: Nissen
authors.forename: Moustapha
authors.initials: M
authors.lastname: Kassem
authors.forename: Hans R I
authors.initials: HR
authors.lastname: Jørgensen
authors.forename: Bo
authors.initials: B
authors.lastname: Abrahamsen
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D015519:Bone Density; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D006620:Hip Fractures / Q000378:metabolism*; D006801:Humans; D007085:Ilium / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D053245:RANK Ligand; D012333:RNA, Messenger / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D016207:Cytokines; D017931:DNA Primers; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human