Elizabeth J. Samelson

Competing Risk of Death: An Important Consideration in Studies of Older Adults

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.

The MOBILIZE Boston Study: Design and methods of a prospective cohort study of novel risk factors for falls in an older population

BackgroundFalls are the sixth leading cause of death in elderly people in the U.S. Despite progress in understanding risk factors for falls, many suspected risk factors have not been adequately studied. Putative risk factors for falls such as pain, reductions in cerebral blood flow, somatosensory deficits, and foot disorders are poorly understood, in part because they pose measurement challenges, particularly for large observational studies.MethodsThe MOBILIZE Boston Study (MBS), an NIA-funded Program Project, is a prospective cohort study of a unique set of risk factors for falls in seniors in the Boston area. Using a door-to-door population-based recruitment, we have enrolled 765 persons aged 70 and older. The baseline assessment was conducted in 2 segments: a 3-hour home interview followed within 4 weeks by a 3-hour clinic examination. Measures included pain, cerebral hemodynamics, and foot disorders as well as established fall risk factors. For the falls follow-up, participants return fall calendar postcards to the research center at the end of each month. Reports of falls are followed-up with a telephone interview to assess circumstances and consequences of each fall. A second assessment is performed 18 months following baseline.ResultsOf the 2382 who met all eligibility criteria at the door, 1616 (67.8%) agreed to participate and were referred to the research center for further screening. The primary reason for ineligibility was inability to communicate in English. Results from the first 600 participants showed that participants are largely representative of seniors in the Boston area in terms of age, sex, race and Hispanic ethnicity. The average age of study participants was 77.9 years (s.d. 5.5) and nearly two-thirds were women. The study cohort was 78% white and 17% black. Many participants (39%) reported having fallen at least once in the year before baseline.ConclusionOur results demonstrate the feasibility of conducting comprehensive assessments, including rigorous physiologic measurements, in a diverse population of older adults to study non-traditional risk factors for falls and disability. The MBS will provide an important new data resource for examining novel risk factors for falls and mobility problems in the older population.

Plasma B Vitamins, Homocysteine, and Their Relation with Bone Loss and Hip Fracture in Elderly Men and Women

CONTEXT Elevated homocysteine is a strong risk factor for osteoporotic fractures among elders, yet it may be a marker for low B-vitamin status. OBJECTIVE Our objective was to examine the associations of plasma concentrations of folate, vitamin B12, vitamin B6, and homocysteine with bone loss and hip fracture risk in elderly men and women. DESIGN This was a longitudinal follow-up study of the Framingham Osteoporosis Study. SETTING Community dwelling residents of Framingham, MA, were included in the study. PARTICIPANTS A total of 1002 men and women (mean age 75 yr) was included in the study. MAIN OUTCOME MEASURES Baseline (1987-1989) blood samples were used to categorize participants into plasma B-vitamin (normal, low, deficient) and homocysteine (normal, high) groups. Femoral neck bone mineral density (BMD) measured at baseline and 4-yr follow-up was used to calculate annual percent BMD change. Incident hip fracture was assessed from baseline through 2003. RESULTS Multivariable-adjusted mean bone loss was inversely associated with vitamin B6 (P for trend 0.01). Vitamins B12 and B6 were inversely associated with hip fracture risk (all P for trend < 0.05), yet associations were somewhat attenuated and not significant after controlling for baseline BMD, serum vitamin D, and homocysteine. Participants with high homocysteine (>14 micromol/liter) had approximately 70% higher hip fracture risk after adjusting for folate and vitamin B6, but this association was attenuated after controlling for vitamin B12 (hazard ratio = 1.49; 95% confidence interval 0.91, 2.46). CONCLUSIONS Low B-vitamin concentration may be a risk factor for decreased bone health, yet does not fully explain the relation between elevated homocysteine and hip fracture. Thus, homocysteine is not merely a marker for low B-vitamin status.

Incidence and Risk Factors for Vertebral Fracture in Women and Men: 25‐Year Follow‐Up Results From the Population‐Based Framingham Study

This study evaluates baseline characteristics of 704 women and men in the Framingham Study with respect to long‐term risk of incident vertebral fracture. Incidence was 24% in women and 10% in men. Few factors in middle‐aged persons, except prevalent (moderate) fracture and alcohol consumption (in men), predicted long‐term incidence of vertebral fracture.

Effect of Birth Cohort on Risk of Hip Fracture: Age-Specific Incidence Rates in the Framingham Study

OBJECTIVES This study examined the effect of birth cohort on incidence rates of hip fracture among women and men in the Framingham Study. METHODS Age-specific incidence rates of first hip fracture were presented according to tertile of year of birth for 5209 participants of the Framingham Study, a population-based cohort followed since 1948. Sex-specific incidence rate ratios were calculated by Cox regression to assess the relation between birth cohort and hip fracture incidence. RESULTS An increasing trend in hip fracture incidence rates was observed with year of birth for women (trend, P =.05) and men (trend, P =.03). Relative to those born from 1887 to 1900 (incidence rate ratio [IRR] = 1.0), age-specific incidence rates were greatest in the most recent birth cohort, born from 1911 to 1921 (IRR = 1.4 for women, IRR = 2.0 for men), and intermediate in those born from 1901 to 1910 (IRR = 1.2 for women, IRR = 1.5 for men). CONCLUSIONS Results suggest risk of hip fracture is increasing for successive birth cohorts. Projections that fail to account for the increase in rates associated with birth cohort underestimate the future public health impact of hip fracture in the United States.

Issues in Conducting Epidemiologic Research Among Elders: Lessons From The MOBILIZE Boston Study

Conducting research in elderly populations is important, but challenging. In this paper, the authors describe specific challenges that have arisen and solutions that have been used in carrying out The MOBILIZE Boston Study, a community-based, prospective cohort study in Massachusetts focusing on falls among 765 participants aged 70 years or older enrolled during 2005-2007. To recruit older individuals, face-to-face interactions are more effective than less personal approaches. Use of a board of community leaders facilitated community acceptance of the research. Establishing eligibility for potential participants required several interactions, so resources must be anticipated in advance. Assuring a safe and warm environment for elderly participants and offering a positive experience are a vital priority. Adequate funding, planning, and monitoring are required to provide transportation and a fully accessible environment in which to conduct study procedures as well as to select personnel highly skilled in interacting with elders. It is hoped that this paper will encourage and inform future epidemiologic research in this important segment of the population.

Vascular calcification in middle-age and long term risk of hip fracture: The Framingham Study

Osteoporosis and atherosclerosis frequently occur in the same individuals and may share similar pathogenic mechanisms. This study examined the relation between severity of aortic calcification in middle‐age years and subsequent risk of hip fracture in women and men in the population‐based Framingham Study.

Survival of Aged Nursing Home Residents With Hip Fracture

BACKGROUND Little is known about mortality in nursing home residents with hip fracture. This study examined the effect of pre-fracture characteristics, hospital complications, and post-fracture complications on mortality in residents with hip fracture. METHODS This is a retrospective cohort study of 195 long-term care residents (153 women, 42 men) with hip fracture (1999-2006) followed for mortality until June 30, 2007. Pre-fracture characteristics (age, sex, cognition, functional status, comorbidities, body mass index), hospital complications (acute myocardial infarction, congestive heart failure, delirium, infection) and 6-month complications (delirium, pneumonia, pressure ulcer, urinary tract infection [UTI]) were evaluated as potential predictors of mortality. RESULTS During a median follow-up of 1.4 years, 150 participants (76.9%) died. Male residents were nearly twice as likely to die compared with female residents (hazard ratio [HR] = 1.9, 95% confidence interval [CI] 1.2-3.0). Other pre-fracture characteristics associated with increased mortality included older age (HR per 5 years = 1.3, 95% CI 1.1-1.6), low functional status (HR = 1.7, 95% CI 1.0-3.0), anemia (HR = 1.6, 95% CI 1.1-2.5), and coronary artery disease (HR = 2.0, 95% CI 1.3-2.9). Mortality was 70% greater among residents with a pressure ulcer or pneumonia within 6 months of hip fracture (pressure ulcer, HR = 1.7, 95% CI 1.2-2.6; pneumonia, HR = 1.7, 95% CI 1.1-2.7). Individual hospital complications and post-fracture delirium and UTI were not significant predictors of mortality. CONCLUSIONS In addition to pre-fracture characteristics, potentially modifiable post-fracture complications including pressure ulcer and pneumonia were associated with increased mortality in nursing home residents with hip fracture. Prevention strategies to reduce pressure ulcers and pneumonia may help reduce mortality in this frail population.

Calcium intake is not associated with increased coronary artery calcification: the Framingham Study

BACKGROUND Adequate calcium intake is known to protect the skeleton. However, studies that have reported adverse effects of calcium supplementation on vascular events have raised widespread concern. OBJECTIVE We assessed the association between calcium intake (from diet and supplements) and coronary artery calcification, which is a measure of atherosclerosis that predicts risk of ischemic heart disease independent of other risk factors. DESIGN This was an observational, prospective cohort study. Participants included 690 women and 588 men in the Framingham Offspring Study (mean age: 60 y; range: 36-83 y) who attended clinic visits and completed food-frequency questionnaires in 1998-2001 and underwent computed tomography scans 4 y later in 2002-2005. RESULTS The mean age-adjusted coronary artery-calcification Agatston score decreased with increasing total calcium intake, and the trend was not significant after adjustment for age, BMI, smoking, alcohol consumption, vitamin D-supplement use, energy intake, and, for women, menopause status and estrogen use. Multivariable-adjusted mean Agatston scores were 2.36, 2.52, 2.16, and 2.39 (P-trend = 0.74) with an increasing quartile of total calcium intake in women and 4.32, 4.39, 4.19, and 4.37 (P-trend = 0.94) in men, respectively. Results were similar for dietary calcium and calcium supplement use. CONCLUSIONS Our study does not support the hypothesis that high calcium intake increases coronary artery calcification, which is an important measure of atherosclerosis burden. The evidence is not sufficient to modify current recommendations for calcium intake to protect skeletal health with respect to vascular calcification risk.

Increased bone resorption is associated with increased risk of cardiovascular events in men: the MINOS study.

Better assessment of the association between cardiovascular disease and osteoporosis in older men may help identify shared etiologies for bone and heart health in this population. We assessed the association of BMD and bone turnover markers (BTMs) with risk of cardiovascular events (myocardial infarction or stroke) in 744 men ≥50 yr of age. During the 7.5‐yr prospective follow‐up, 43 strokes and 40 myocardial infarctions occurred in 79 men. After adjustment for confounders (age, weight, height, smoking, education, physical activity, self‐reported history of diabetes, hypertension, and prevalent ischemic heart disease), men in the lowest quartile of BMD at the spine, whole body, and forearm had a 2‐fold increased risk of cardiovascular events. Men in the highest quartile of bone resorption markers (deoxypyridinoline [DPD], C‐telopeptide of type I collagen) had a 2‐fold increased risk of cardiovascular events (e.g., multivariable‐adjusted hazard ratio [including additional adjustment for BMD] was 2.11 [95% CI: 1.26–3.56], for the highest quartile of free DPD relative to the lowest three quartiles). The results were similar for men without prevalent ischemic heart disease and for myocardial infarction and stroke analyzed separately. Our data suggest that men with low BMD or high bone resorption may be at increased risk of myocardial infarction and stroke in addition to fracture. Thus, men with osteoporosis may benefit from screening for cardiovascular disease. Further study to elucidate the biological mechanism shared by bone and vascular disease may help efforts to identify men at risk or develop treatment.