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1.
Clin Radiol ; 67(9): 840-2, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22841371

ABSTRACT

AIM: To determine whether the presence of bone bars (BB) identified on anteroposterior hip radiographs are more prevalent in patients that have had a hip fracture as compared to patients without a fracture. MATERIALS AND METHODS: Ninety-two Caucasian women with a unilateral proximal femur fracture were retrospectively evaluated and randomly selected using radiology database records to comprise the investigational group. Ninety-eight age-matched Caucasian women without hip fracture were selected as a control group. Anteroposterior hip radiographs were evaluated for the presence of BBs by two musculoskeletal radiologists. Chi-square tests were used to assess whether fractures were more prevalent in patients with BB than those without BB. RESULTS: The patient population was comprised Caucasian women with a mean age of 79.8 ± 6.4 years in the control group and 79.9 ± 6.6 years in the investigational group. Regardless of the reader, BB were identified in a significantly higher percentage of women with a fracture (75 versus 39%, p < 0.001 or 53 versus 38%, p = 0.041) as compared to those without a fracture. CONCLUSION: BB are associated with hip fracture. Their presence is a trigger for requesting a dual-energy x-ray absorptiometry (DXA) examination to confirm or refute a diagnosis of low bone mineral density (BMD) and a subsequent increased risk of fracture.


Subject(s)
Hip Fractures/diagnostic imaging , Hip Fractures/ethnology , Osteoporosis, Postmenopausal/diagnostic imaging , Osteoporosis, Postmenopausal/ethnology , White People/statistics & numerical data , Aged , Bone Density , Cohort Studies , Comorbidity , Female , Hip/diagnostic imaging , Humans , Observer Variation , Postmenopause , Prevalence , Radiography , Retrospective Studies , Risk Factors
2.
Cancer Gene Ther ; 17(12): 893-905, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20798695

ABSTRACT

Most patients with advanced breast cancer develop osteolytic bone metastases, which have numerous complications. Because current therapies are not curative, new treatments are needed. Conditionally replicating adenoviruses (CRAds) are anticancer agents designed to infect and lyse tumor cells. However, in spite of their promise as selective cancer therapeutics, replicating adenoviruses have shown limited efficacy in the clinical setting. We hypothesized that a CRAd armed with osteoprotegerin (OPG) would eradicate bone metastases of breast cancer both directly, by oncolysis, and indirectly, by inhibiting osteoclastic bone resorption, and thus reducing the tumor burden. We constructed an armed CRAd (Ad5-Δ24-sOPG-Fc-RGD) by replacing viral E3B genes with a fusion of the ligand-binding domains of OPG and the Fc portion of human IgG1. Conditional replication was conferred by a 24-base pair deletion within E1A (Δ24), which prevents the binding of E1A to the retinoblastoma tumor suppressor/cell cycle regulator protein and limits replication in normal cells. Enhanced infection of cells expressing low levels of the primary Ad5 receptor was conferred by incorporating an arginine-glycine-aspartic acid (RGD) peptide sequence into the fiber knob to mediate binding to α(v) integrins. After characterization of the armed CRAd, we demonstrated that infection of breast cancer cells by Ad5-Δ24-sOPG-Fc-RGD both killed the infected cells by oncolysis and inhibited the formation of osteoclasts in an in vitro co-culture model. In a murine model of osteolytic bone metastases of breast cancer, the CRAd armed with shortened OPG (sOPG)-Fc reduced tumor burden in the bone and inhibited osteoclast formation more effectively than an unarmed CRAd.


Subject(s)
Adenoviridae/genetics , Bone Neoplasms/secondary , Breast Neoplasms/therapy , Osteoprotegerin/genetics , Animals , Bone Neoplasms/pathology , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Carrier Proteins/genetics , Carrier Proteins/metabolism , Cell Line, Tumor , Female , Humans , Mice , Osteoprotegerin/metabolism , Tumor Burden/genetics , Virus Replication
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