Dual Energy X-ray Absorptiometry (DXA)-based finite element (FE) modelling has emerged as a potential tool for better assessment of osteoporotic hip fracture risk. Automation of this complex and computationally-intense procedure is the prime requirement for its clinical applicability. The aim of this study was to develop a fully automatic DXA-based finite element tool and assess its discrimination ability and short-term repeatability. The proximal femur was automatically segmented from clinical hip DXA scan and the subject-specific FE model was constructed for simulating sideways fall. Hip fracture risk indices (HFRIs) were calculated using two ways (along a femur cross-section and over a region of interest, ROI). Hip fracture discriminability increased when moved from femur cross-section based to ROI based HFRI calculation. A significant increase in hip fracture discriminability from baseline femoral neck and total hip bone mineral density (BMD) was achieved with ROI based HFRIs. Promising short-term repeatability was observed for HFRIs (coefficient of variation, CV, 3~3.5%). After removing representative poor cases, CVs were less than 3%. These preliminary results establish the potential of the proposed automatic tool for hip fracture risk assessment and justify large-scale clinical evaluation of its ability to predict incident hip fractures. / February 2017

Osteoporosis and depression are prevalent among older postmenopausal women 65 years or older. Bisphosphonates (BPs) and selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) are commonly used medications to treat these conditions. Inhibitory effects of BPs on osteoclasts are responsible for the reduction in fracture risk. SSRIs, however, are associated with increased fracture risk through decreasing osteoblasts and increasing osteoclastic activity. These effects of SSRIs could attenuate the beneficial effects of BPs. This dissertation describes the concomitant use of BPs and SSRIs among postmeopausa women and reports findings from examining the association between concomitant use of BPs and SSRIs and fracture risk. Separate cross-sectional analyses were performed using data from the 2004-2008 Medical Expenditure Panel Survey (MEPS) and Medicare Part D prescriptions claims data (2008-2010) to examine usage patterns of BPs and SSRIs/SNRIs for women aged ≥45 years and ≥65 years, respectively. For our second objective, a nested-case control was conducted using Medicare claims data (2008-2010). Data from Medicare inpatient claims were linked to Medicare Part D data for all female BP users 65 years or older. We used Cox proportional hazards model to assess the increased risk of osteoporotic-related fractures among propensity score matched (1:1 ratio) cohorts of concomitant users of BPs and SSRIs and BP alone users. Concomitant use of BPs and SSRIs was prevalent and increased with age for each timeframe examined. Findings showed that approximately 12% (using MEPS) and 28% (using Medicare data) of women on BPs were also on SSRIs. For the second objective, 4,214 propensity score matched pairs (average age=80.4 years) of subjects were analyzed. Findings showed that concomitant use of BPs and SSRIs was associated with statistically significant increased risk for any fracture (HR=1.29, 95% CI, 1.07-1.57), but statistically non-significant increased risk for hip (HR=1.16, 95% CI, 0.92-1.47) and vertebral fractures (HR=1.55, 95% CI, 0.97-2.48). Current findings indicate that concomitant use of BPs and SSRIs is not uncommon among postmenopausal women and suggest potential attenuation of antifracture efficacy of BPs by SSRIs. Further studies are needed to understand the clinical impact of concomitant use of these medications among older postmenopausal women.