Clinical studies often face the difficult problem of how to account for participants who die without experiencing the study outcome of interest. In a geriatric population with considerable comorbidities, the competing risk of death is especially high. Traditional approaches to describe risk of disease include Kaplan-Meier survival analysis and Cox proportional hazards regression, but these methods can overestimate risk of disease by failing to account for the competing risk of death. This report discusses traditional survival analysis and competing risk analysis as used to estimate risk of disease in geriatric studies. Furthermore, it illustrates a competing risk approach to estimate risk of second hip fracture in the Framingham Osteoporosis Study and compares the results with traditional survival analysis. In this example, survival analysis overestimated the 5-year risk of second hip fracture by 37% and the 10-year risk by 75% compared with competing risk estimates. In studies of older individuals in which a substantial number of participants die during a long follow-up, the cumulative incidence competing risk estimate and competing risk regression should be used to determine incidence and effect estimates. Use of a competing risk approach is critical to accurately determining disease risk for elderly individuals and therefore best inform clinical decision-making. J Am Geriatr Soc 58: 783-787, 2010.

These findings suggest that the homocysteine concentration, which is easily modifiable by means of dietary intervention, is an important risk factor for hip fracture in older persons.

Background: Although dual-energy x-ray absorptiometry (DXA) assessed areal bone density (aBMD) is the clinical standard for determining fracture risk, the majority of older adults who sustain a fracture do not have osteoporosis (T-score < −2.5). Importantly, bone fragility results not only from low BMD, but also from deterioration in bone structure. We used high-resolution peripheral quantitative computed tomography (HR-pQCT) data from eight cohorts to evaluate whether HR-pQCT indices were associated with fracture risk independently of femoral neck (FN) aBMD and FRAX (Fracture Risk Assessment Tool) score. Methods: Participants included 7,254 individuals (66% women) from cohorts in the USA (Framingham, Mayo Clinic), France (QUALYOR, STRAMBO, OFELY), Switzerland (GERICO), Canada (CaMos), and Sweden (MrOS). We used Cox proportional hazards models to estimate hazards ratios (HRs) for the association between bone parameters (per standard deviation, SD, deficit) and incident fracture, adjusting for age, sex, height, weight and cohort. Findings: Mean baseline age was 69 (±9) years (range, 40 to 96). Cumulative incidence of fracture was 11% (n=765) over a mean follow-up time of 4.6 (± 2.4) years. The majority of participants (92%) had a femoral neck T-score >−2.5, and thus did not meet diagnostic criteria for osteoporosis. Failure load was the bone measure most strongly associated with risk of fracture: tibia HR=2.40 (1.98-2.91), radius HR=2.13 (1.77-2.56), per SD decrease in failure load. HRs for other bone indices ranged from HR=1.12 (1.03-1.23) per SD increase in tibia cortical porosity to HR=1.58 (1.45-1.72) per SD decrease in radius trabecular volumetric bone density (vBMD). After further adjustment for FN aBMD or FRAX, HRs were attenuated, but most bone parameters remained significantly associated with fracture. Cortical density, trabecular number, and trabecular thickness at the distal radius were the best set of predictors of fracture; while the same indices plus cortical area were identified for the tibia. These HR-pQCT indices and failure load improved prediction of fracture, beyond FN aBMD alone or FRAX. Interpretation: Results from this large international cohort of women and men confirm prior studies showing that deficits in trabecular and cortical bone density and structure contribute to fracture risk independently of aBMD and FRAX. Measurements of cortical and trabecular bone density and morphology at the peripheral skeleton may improve identification of those at highest risk for fracture. Funding: National Institutes of Health, National Institute of Arthritis Musculoskeletal and Skin Diseases, R01AR061445

Background: Older persons with hip fractures remain at increased risk of subsequent hip fractures. However, little is known about the frequency and characteristics of persons who sustain a second hip fracture. Methods: Participants included 481 members of the Framingham Heart Study who sustained an initial hip fracture between April 1952 and December 31, 2003. Participants were followed up until a second hip fracture, death, dropout, or study completion. Age, sex, falls, stroke, dementia, residence, recent weight change, body mass index, and functional status were considered potential predictors of a second hip fracture. Results: During a median of 4.2 years of follow-up, 71 subjects (14.8%) experienced a second hip fracture. Following a first hip fracture, 2.5% of subjects experienced a second hip fracture within 1 year, and 8.2% of subjects (9.7% of women) experienced a second hip fracture within 5 years. One-year mortality following an ini