Risk factors for prevalent vertebral fractures in black and white female densitometry patients.

This cross-sectional study compared risk factors for prevalent vertebral fractures (diagnosed using densitometric spine image Vertebral Fracture Assessment [VFA]) in 176 black and 345 white women recruited during their clinical bone mineral density (BMD) testing at the University of Chicago Hospitals. We used logistic regression to assess the association of prevalent vertebral fractures and risk factors (age, height loss, history of nonvertebral fractures, BMD, and use of corticosteroids). The prevalence of vertebral fractures was 21% for both races. All risk factors of interest were significantly associated with vertebral fractures in white women. Among black women, only age and corticosteroid use were found to be significant predictors of presence of vertebral fracture(s). In women without history of corticosteroid use, the probability of having vertebral fracture(s) given age was lower (p=0.02) in black subjects. In 77 patients with a history of corticosteroid use, the probability of having vertebral fracture(s) was higher in black than in white women after adjustment for age (p=0.045), BMD (p=0.045), or cumulative corticosteroid dose (p=0.08). Fewer black women were prescribed pharmacologic therapy for osteoporosis, regardless of their BMD level and corticosteroid use. We conclude that use of corticosteroids may be associated with relatively greater vertebral fracture risk in blacks than in whites.

NuRD complex component Mi-2beta binds to and represses RORgamma-mediated transcriptional activation.

RORgamma is a nuclear receptor that binds to DNA motifs as a monomer to constitutively activate target genes. RORgamma plays an important role in thymocyte development and lymph node organogenesis, while the regulation of RORgamma-mediated transcriptional activation is currently unclear. The purpose of this study was to identify other nuclear proteins that interact with RORgamma. A yeast two-hybrid screen with Y190 yeast cells under stringent conditions resulted in the identification of CHD4, also known as Mi-2beta, as a RORgamma-interacting protein. This interaction was confirmed by GST pull-down assays. This interaction occurred within the middle regulatory region (amino acids 719-1164) of Mi-2beta. Transfection of Gal4-RORgamma into HeLa cells resulted in constitutive transactivation of the MH100-tk-luc reporter. The addition of Mi-2beta resulted in a dramatic 50% decrease in Gal4-RORgamma-mediated transactivation. These data demonstrate that RORgamma forms a protein-protein interaction with the regulatory region of Mi-2beta, resulting in inhibition of RORgamma transcriptional activity. These results may provide evidence as to how RORgamma-mediated transactivation is regulated by other nuclear proteins.