Teresa A. Hillier

Comparison of 2 frailty indexes for prediction of falls, disability, fractures, and death in older women

BACKGROUND Frailty, as defined by the index derived from the Cardiovascular Health Study (CHS index), predicts risk of adverse outcomes in older adults. Use of this index, however, is impractical in clinical practice. METHODS We conducted a prospective cohort study in 6701 women 69 years or older to compare the predictive validity of a simple frailty index with the components of weight loss, inability to rise from a chair 5 times without using arms, and reduced energy level (Study of Osteoporotic Fractures [SOF index]) with that of the CHS index with the components of unintentional weight loss, poor grip strength, reduced energy level, slow walking speed, and low level of physical activity. Women were classified as robust, of intermediate status, or frail using each index. Falls were reported every 4 months for 1 year. Disability (> or =1 new impairment in performing instrumental activities of daily living) was ascertained at 4(1/2) years, and fractures and deaths were ascertained during 9 years of follow-up. Area under the curve (AUC) statistics from receiver operating characteristic curve analysis and -2 log likelihood statistics were compared for models containing the CHS index vs the SOF index. RESULTS Increasing evidence of frailty as defined by either the CHS index or the SOF index was similarly associated with an increased risk of adverse outcomes. Frail women had a higher age-adjusted risk of recurrent falls (odds ratio, 2.4), disability (odds ratio, 2.2-2.8), nonspine fracture (hazard ratio, 1.4-1.5), hip fracture (hazard ratio, 1.7-1.8), and death (hazard ratio, 2.4-2.7) (P < .001 for all models). The AUC comparisons revealed no differences between models with the CHS index vs the SOF index in discriminating falls (AUC = 0.61 for both models; P = .66), disability (AUC = 0.64; P = .23), nonspine fracture (AUC = 0.55; P = .80), hip fracture (AUC = 0.63; P = .64), or death (AUC = 0.72; P = .10). Results were similar when -2 log likelihood statistics were compared. CONCLUSION The simple SOF index predicts risk of falls, disability, fracture, and death as well as the more complex CHS index and may provide a useful definition of frailty to identify older women at risk of adverse health outcomes in clinical practice.

Childhood Obesity and Metabolic Imprinting: The Ongoing Effects of Maternal Hyperglycemia

OBJECTIVE—The purpose of this study was to determine how the range of measured maternal glycemia in pregnancy relates to risk of obesity in childhood. RESEARCH DESIGN AND METHODS—Universal gestational diabetes mellitus (GDM) screening (a 50-g glucose challenge test [GCT]) was performed in two regions (Northwest and Hawaii) of a large diverse HMO during 1995–2000, and GDM was diagnosed/treated using a 3-h 100-g oral glucose tolerance test (OGTT) and National Diabetes Data Group (NDDG) criteria. Measured weight in offspring (n = 9,439) was ascertained 5–7 years later to calculate sex-specific weight-for-age percentiles using U.S. norms (1963–1994 standard) and then classified by maternal positive GCT (1 h ≥ 7.8 mmol/l) and OGTT results (1 or ≥2 of the 4 time points abnormal: fasting, 1 h, 2 h, or 3 h by Carpenter and Coustan and NDDG criteria). RESULTS—There was a positive trend for increasing childhood obesity at age 5–7 years (P < 0.0001; 85th and 95th percentiles) across the range of increasing maternal glucose screen values, which remained after adjustment for potential confounders including maternal weight gain, maternal age, parity, ethnicity, and birth weight. The risk of childhood obesity in offspring of mothers with GDM by NDDG criteria (treated) was attenuated compared with the risks for the groups with lesser degrees of hyperglycemia (untreated). The relationships were similar among Caucasians and non-Caucasians. Stratification by birth weight also revealed these effects in children of normal birth weight (≤4,000 g). CONCLUSIONS—Our results in a multiethnic U.S. population suggest that increasing hyperglycemia in pregnancy is associated with an increased risk of childhood obesity. More research is needed to determine whether treatment of GDM may be a modifiable risk factor for childhood obesity.

Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes.

CONTEXT Type 2 diabetes mellitus (DM) is associated with higher bone mineral density (BMD) and paradoxically with increased fracture risk. It is not known if low BMD, central to fracture prediction in older adults, identifies fracture risk in patients with DM. OBJECTIVE To determine if femoral neck BMD T score and the World Health Organization Fracture Risk Algorithm (FRAX) score are associated with hip and nonspine fracture risk in older adults with type 2 DM. DESIGN, SETTING, AND PARTICIPANTS Data from 3 prospective observational studies with adjudicated fracture outcomes (Study of Osteoporotic Fractures [December 1998-July 2008]; Osteoporotic Fractures in Men Study [March 2000-March 2009]; and Health, Aging, and Body Composition study [April 1997-June 2007]) were analyzed in older community-dwelling adults (9449 women and 7436 men) in the United States. MAIN OUTCOME MEASURE Self-reported incident fractures, which were verified by radiology reports. RESULTS Of 770 women with DM, 84 experienced a hip fracture and 262 a nonspine fracture during a mean (SD) follow-up of 12.6 (5.3) years. Of 1199 men with DM, 32 experienced a hip fracture and 133 a nonspine fracture during a mean (SD) follow-up of 7.5 (2.0) years. Age-adjusted hazard ratios (HRs) for 1-unit decrease in femoral neck BMD T score in women with DM were 1.88 (95% confidence interval [CI], 1.43-2.48) for hip fracture and 1.52 (95% CI, 1.31-1.75) for nonspine fracture, and in men with DM were 5.71 (95% CI, 3.42-9.53) for hip fracture and 2.17 (95% CI, 1.75-2.69) for nonspine fracture. The FRAX score was also associated with fracture risk in participants with DM (HRs for 1-unit increase in FRAX hip fracture score, 1.05; 95% CI, 1.03-1.07, for women with DM and 1.16; 95% CI, 1.07-1.27, for men with DM; HRs for 1-unit increase in FRAX osteoporotic fracture score, 1.04; 95% CI, 1.02-1.05, for women with DM and 1.09; 95% CI, 1.04-1.14, for men with DM). However, for a given T score and age or for a given FRAX score, participants with DM had a higher fracture risk than those without DM. For a similar fracture risk, participants with DM had a higher T score than participants without DM. For hip fracture, the estimated mean difference in T score for women was 0.59 (95% CI, 0.31-0.87) and for men was 0.38 (95% CI, 0.09-0.66). CONCLUSIONS Among older adults with type 2 DM, femoral neck BMD T score and FRAX score were associated with hip and nonspine fracture risk; however, in these patients compared with participants without DM, the fracture risk was higher for a given T score and age or for a given FRAX score.

Hyponatremia: evaluating the correction factor for hyperglycemia.

PURPOSE There are no controlled experimental data that assess the accuracy of the commonly used correction factor of a 1.6 meq/L decrease in serum sodium concentration for every 100 mg/dL increase in plasma glucose concentration. The purpose of this study was to evaluate experimentally the hyponatremic response to acute hyperglycemia. SUBJECTS AND METHODS Somatostatin was infused to block endogenous insulin secretion in 6 healthy subjects. Plasma glucose concentrations were increased to >600 mg/dL within 1 hour by infusing 20% dextrose. The glucose infusion was then stopped and insulin given until the plasma glucose concentration decreased to 140 mg/dL. Plasma glucose and serum sodium concentrations were measured every 10 minutes. RESULTS Overall, the mean decrease in serum sodium concentration averaged 2.4 meq/L for every 100 mg/dL increase in glucose concentration. This value is significantly greater than the commonly used correction factor of 1.6 (P = 0.02). Moreover, the association between sodium and glucose concentrations was nonlinear. This was most apparent for glucose concentrations >400 mg/dL. Up to 400 mg/dL, the standard correction of 1.6 worked well, but if the glucose concentration was >400 mg/dL, a correction factor of 4.0 was better. CONCLUSION These data indicate that the physiologic decrease in sodium concentration is considerably greater than the standard correction factor of 1.6 (meq/L Na per 100 mg/dL glucose), especially when the glucose concentration is >400 mg/dL. Additionally, a correction factor of a 2.4 meq/L decrease in sodium concentration per 100 mg/dL increase in glucose concentration is a better overall estimate of this association than the usual correction factor of 1.6.

Circadian activity rhythms and risk of incident dementia and mild cognitive impairment in older women.

Previous cross‐sectional studies have observed alterations in activity rhythms in dementia patients but the direction of causation is unclear. We determined whether circadian activity rhythms measured in community‐dwelling older women are prospectively associated with incident dementia or mild cognitive impairment (MCI).

The Association between Sleep Duration and Obesity in Older Adults

Background:Reduced sleep has been reported to predict obesity in children and young adults. However, studies based on self-report have been unable to identify an association in older populations. In this study, the cross-sectional associations between sleep duration measured objectively and measures of weight and body composition were assessed in two cohorts of older adults.Methods:Wrist actigraphy was performed for a mean (s.d.) of 5.2 (0.9) nights in 3055 men (age: 67–96 years) participating in the Osteoporotic Fractures in Men Study (MrOS) and 4.1 (0.8) nights in 3052 women (age: 70–99 years) participating in the Study of Osteoporotic Fractures (SOF). A subgroup of 2862 men and 455 women also underwent polysomnography to measure sleep apnea severity.Results:Compared to those sleeping an average of 7–8 h per night, and after adjusting for multiple risk factors and medical conditions, a sleep duration of less than 5 h was associated with a body mass index (BMI) that was on average 2.5 kg/m2 (95% confidence interval (CI): 2.0–2.9) greater in men and 1.8 kg/m2 (95% CI: 1.1–2.4) greater in women. The odds of obesity (BMI ⩾30 kg/m2) was 3.7-fold greater (95% CI: 2.7–5.0) in men and 2.3-fold greater in women (95% CI: 1.6–3.1) who slept less than 5 h. Short sleep was also associated with central body fat distribution and increased percent body fat. These associations persisted after adjusting for sleep apnea, insomnia and daytime sleepiness.Conclusions:In older men and women, actigraphy-ascertained reduced sleep durations are strongly associated with greater adiposity.

Prediction of incident hip fracture risk by femur geometry variables measured by hip structural analysis in the study of osteoporotic fractures.

The role of bone tissues geometric distribution in hip fracture risk requires full evaluation in large population‐based datasets. We tested whether section modulus, a geometric index of bending strength, predicted hip fracture better than BMD. Among 7474 women from the Study of Osteoporotic Fractures (SOF) with hip DXA scans at baseline, there were 635 incident hip fractures recorded over 13 yr. Hip structural analysis software was used to derive variables from the DXA scans at the narrow neck (NN), intertrochanter (IT), and shaft (S) regions. Associations of derived structural variables with hip fracture were assessed using Cox proportional hazard modeling. Hip fracture prediction was assessed using the C‐index concordance statistic. Incident hip fracture cases had larger neck‐shaft angles, larger subperiosteal and estimated endosteal diameters, greater distances from lateral cortical margin to center of mass (lateral distance), and higher estimated buckling ratios (p < 0.0001 for each). Areal BMD, cross‐sectional area, cross‐sectional moment of inertia, section modulus, estimated cortical thickness, and centroid position were all lower in hip fracture cases (p < 0.044). In hip fracture prediction using NN region parameters, estimated cortical thickness, areal BMD, and estimated buckling ratio were equivalent (C‐index = 0.72; 95% CI, 0.70, 0.74), but section modulus performed less well (C‐index = 0.61; 95% CI, 0.58, 0.63; p < 0.0001 for difference). In multivariable models combining hip structural analysis variables and age, effects of bone dimensions (i.e., lateral distance, subperiosteal diameter, and estimated endosteal width) were interchangeable, whereas age and neck‐shaft angle were independent predictors. Several parsimonious multivariable models that were prognostically equivalent for the NN region were obtained combining a measure of width, a measure of mass, age, and neck‐shaft angle (BMD is a ratio of mass to width in the NN region; C‐index = 0.77; 95% CI, 0.75, 0.79). Trochanteric fractures were best predicted by analysis of the IT region. Because section modulus failed to predict hip fracture risk as well as areal BMD, the thinner cortices and wider bones among those who fractured may imply that simple failure in bending is not the usual event in fracture. Fracture might require initiation (e.g., by localized crushing or buckling of the lateral cortex).

Pentosidine and increased fracture risk in older adults with type 2 diabetes

CONTEXT Type 2 diabetes is associated with higher fracture risk at a given bone mineral density. Advanced glycation endproducts (AGEs) accumulate in bone collagen with age and diabetes and may weaken bone. OBJECTIVE The aim was to determine whether urine pentosidine, an AGE, was associated with fractures in older adults with and without diabetes. DESIGN We performed an observational cohort study. SETTING We used data from the Health, Aging and Body Composition prospective study of white and black, well-functioning men and women ages 70-79 yr. PARTICIPANTS Participants with (n = 501) and without (n = 427) diabetes were matched on gender, race, and study site. PREDICTOR Urine pentosidine was assayed from frozen stored baseline specimens. MAIN OUTCOME MEASURES Incident clinical fractures and baseline vertebral fractures were measured. RESULTS Despite higher bone mineral density, clinical fracture incidence (14.8 vs. 12.6%) and vertebral fracture prevalence (2.3 vs. 2.9%) were not lower in those with diabetes (P > 0.05). In multivariable models, pentosidine was associated with increased clinical fracture incidence in those with diabetes [relative hazard, 1.42; 95% confidence interval (CI), 1.10, 1.83, for 1 sd increase in log pentosidine] but not in those without diabetes (relative hazard, 1.08; 95% CI, 0.79, 1.49; P value for interaction = 0.030). In those with diabetes, pentosidine was associated with increased vertebral fracture prevalence (adjusted odds ratio, 5.93; 95% CI, 2.08, 16.94, for 1 sd increase in log pentosidine) but not in those without diabetes (adjusted odds ratio, 0.74; 95% CI, 0.30, 1.83; P value for interaction = 0.005). CONCLUSIONS Higher pentosidine levels are a risk factor for fracture in older adults with diabetes and may account in part for reduced bone strength in type 2 diabetes.

Risk factors for a first-incident radiographic vertebral fracture in women >= 65 years of age: The study of osteoporotic fractures

Vertebral fractures in older women signal an increased risk of additional osteoporotic fractures. To identify risk factors for first vertebral fractures, we studied 5822 women ≥65 years of age who had no fracture on baseline radiographs of the spine. Several modifiable risk factors increased an older womans risk of developing a first vertebral fracture, and women with multiple risk factors and low BMD had the highest risk. Risk factors and low BMD should be useful to help focus efforts to prevent these fractures.

Long-term Risk of Incident Vertebral Fractures

CONTEXT Vertebral fractures are the most common osteoporotic fracture. Women with low bone mineral density (BMD) and prevalent vertebral fractures have a greater risk of incident vertebral fractures over the short-term, but their absolute risk of vertebral fracture over the long-term is uncertain. OBJECTIVE To examine the absolute risk of incident vertebral fracture by BMD and prevalent vertebral fracture status over 15 years. DESIGN, SETTING, AND PARTICIPANTS A total of 9704 white women were recruited at 4 US clinical centers and enrolled in the Study of Osteoporotic Fractures, a longitudinal cohort study. Of these, 2680 attended a clinic visit an average of 14.9 years after baseline; mean age of 68.8 years at entry and 83.8 years at follow-up. Mean Outcome Measure Incident vertebral fractures identified from lateral spinal radiographs defined as a decrease of at least 20% and 4 mm at any vertebral level. Prevalent vertebral fractures were identified on the baseline radiographs using vertebral morphometry. Bone mineral density was measured at the total hip and lumbar spine using dual-energy x-ray absorptiometry. RESULTS Of the 2680 women, 487 (18.2%) had an incident vertebral fracture including 163 of the 394 (41.4%) with a prevalent vertebral fracture at baseline and 324 of the 2286 (14.2%) without a prevalent vertebral fracture at baseline (odds ratio, 4.21; 95% confidence interval, 3.33-5.34). Low BMD was associated with an increased risk of incident vertebral fracture (odds ratio per 1 SD decrease in total hip BMD, 1.78 [95% confidence interval, 1.58-2.00]). The absolute risk of vertebral fracture ranged from 56% among women with total hip BMD T score of -2.5 or less and a prevalent vertebral fracture to 9% in women with normal BMD and no prevalent vertebral fracture. CONCLUSIONS Low BMD and prevalent vertebral fractures are independently related to new vertebral fractures over 15 years of follow-up. Women with a prevalent vertebral fracture have a substantially increased absolute risk of an incident fracture, especially if they have osteoporosis diagnosed by BMD.