Anne C. Looker

Prevalence of Low Femoral Bone Density in Older U.S. Adults from NHANES III

Most estimates of osteoporosis in older U.S. adults have been based on its occurrence in white women, even though it is known to affect men and minority women. In the present study, we used dual‐energy X‐ray absorptiometry measurements of femoral bone mineral density (BMD) from the third National Health and Nutrition Examination Survey (NHANES III, 1988–1994) to estimate the overall scope of the disease in the older U.S. population. Specifically, we estimate prevalences of low femoral BMD in women 50 years and older and explore different approaches for defining low BMD in older men in that age range. Low BMD levels were defined in accordance with an approach proposed by an expert panel of the World Health Organization and used BMD data from 382 non‐Hispanic white (NHW) men or 409 NHW women ages 20–29 years from the NHANES III dataset. For women, estimates indicate 13–18%, or 4–6 million, have osteoporosis (i.e., BMD >2.5 standard deviations [SD] below the mean of young NHW women) and 37–50%, or 13–17 million, have osteopenia (BMD between 1 and 2.5 SD below the mean of young NHW women). For men, these numbers depend on the gender of the reference group used to define cutoff values. When based on male cutoffs, 3–6% (1–2 million) of men have osteoporosis and 28–47% (8–13 million) have osteopenia; when based on female cutoffs, 1–4% (280,000–1 million) have osteoporosis and 15–33% (4–9 million) have osteopenia. Most of the older U.S. adults with low femur BMD are women, but, regardless of which cutoffs are used, the number of men is substantial.

Updated Data on Proximal Femur Bone Mineral Levels of US Adults

Abstract: This paper describes data on bone mineral levels in the proximal femur of US adults based on the nationally representative sample examined during both phases of the third National Health and Nutrition Examination Survey (NHANES III, 1988–94), and updates data previously presented from phase 1 only. The data were collected from 14646 men and women aged 20 years and older using dual-energy X-ray absorptiometry, and included bone mineral density (BMD), bone mineral content (BMC) and area of bone scanned in four selected regions of interest (ROI) in the proximal femur: femur neck, trochanter, intertrochanter and total. These variables are provided separately by age and sex for non-Hispanic whites (NHW), non-Hispanic blacks (NHB) and Mexican Americans (MA). NHW in the southern United States had slightly lower BMD levels than NHW in other US regions, but these differences were not sufficiently large to prevent pooling of the data. The updated data provide valuable reference data on femur bone mineral levels of noninstitutionalized adults. The updated data on BMD for the total femur ROI of NHW have been selected as the reference database for femur standardization efforts by the International Committee on Standards in Bone Measurements.

Serum 25-hydroxyvitamin D status of adolescents and adults in two seasonal subpopulations from NHANES III.

Subclinical vitamin D deficiency may be common in certain subgroups in the U.S., but to date vitamin D data from other groups in the population have not been available. We used serum 25-hydroxyvitamin D (25-OHD) data from 18,875 individuals examined in the Third National Health and Nutrition Examination Survey (NHANES III 1988-1994) to assess the vitamin D status of selected groups of the noninstitutionalized U.S. adolescent and adult population. Serum 25-OHD levels were measured by a radioimmunoassay kit (DiaSorin, Inc., Stillwater, MN; normal range 22.5-94 nmol/L). Because physical exams are performed in mobile vans in NHANES, data could not be collected in northern latitudes during the winter; instead data were collected in northern latitudes during summer and in southern latitudes in winter. To address this season-latitude aspect of the NHANES design, we stratified the sample into two seasonal subpopulations (winter/lower latitude and summer/higher latitude) before examining vitamin D status. Less than 1% of the winter/lower latitude subpopulation had vitamin D deficiency (25-OHD <17.5 nmol/L). However, the prevalence of vitamin D insufficiency in this group ranged from 1%-5% with 25-OHD <25 nmol/L to 25%-57% with 25-OHD <62.5 nmol/L, even though the median latitude for this subsample (32 degrees N) was considerably lower than the latitude at which vitamin D is not synthesized during winter months (approximately 42 degrees N). With the exception of elderly women, prevalence rates of vitamin D insufficiency were lower in the summer/higher latitude subpopulation (<1%-3% with 25-OHD <25 nmol/L to 21%-49% with 25-OHD <62.5 nmol/L). Mean 25-OHD levels were highest in non-Hispanic whites, intermediate in Mexican Americans, and lowest in non-Hispanic blacks. Our findings suggest that vitamin D deficiency is unlikely in the two seasonal subpopulations of noninstitutionalized adolescents and adults that can be validly assessed in NHANES III. However, vitamin D insufficiency is more common in these two seasonal subpopulations. Of particular interest is that insufficiency occurred fairly frequently in younger individuals, especially in the winter/lower latitude subsample. Our findings support continued monitoring of this vitamin in the U.S. population.

Serum 25-hydroxyvitamin D status of the US population: 1988–1994 compared with 2000–2004

BACKGROUND Changes in serum 25-hydroxyvitamin D [25(OH)D] concentrations in the US population have not been described. OBJECTIVE We used data from the National Health and Nutrition Examination Surveys (NHANES) to compare serum 25(OH)D concentrations in the US population in 2000-2004 with those in 1988-1994 and to identify contributing factors. DESIGN Serum 25(OH)D was measured with a radioimmunoassay kit in 20 289 participants in NHANES 2000-2004 and in 18 158 participants in NHANES III (1988-1994). Body mass index (BMI) was calculated from measured height and weight. Milk intake and sun protection were assessed by questionnaire. Assay differences were assessed by re-analyzing 150 stored serum specimens from NHANES III with the current assay. RESULTS Age-adjusted mean serum 25(OH)D concentrations were 5-20 nmol/L lower in NHANES 2000-2004 than in NHANES III. After adjustment for assay shifts, age-adjusted means in NHANES 2000-2004 remained significantly lower (by 5-9 nmol/L) in most males, but not in most females. In a study subsample, adjustment for the confounding effects of assay differences changed mean serum 25(OH)D concentrations by approximately 10 nmol/L, and adjustment for changes in the factors likely related to real changes in vitamin D status (ie, BMI, milk intake, and sun protection) changed mean serum 25(OH)D concentrations by 1-1.6 nmol/L. CONCLUSIONS Overall, mean serum 25(OH)D was lower in 2000-2004 than 1988-1994. Assay changes unrelated to changes in vitamin D status accounted for much of the difference in most population groups. In an adult subgroup, combined changes in BMI, milk intake, and sun protection appeared to contribute to a real decline in vitamin D status.

Comparisons of percentage body fat, body mass index, waist circumference, and waist-stature ratio in adults

BACKGROUND Body mass index (BMI), waist circumference (WC), and the waist-stature ratio (WSR) are considered to be possible proxies for adiposity. OBJECTIVE The objective was to investigate the relations between BMI, WC, WSR, and percentage body fat (measured by dual-energy X-ray absorptiometry) in adults in a large nationally representative US population sample from the National Health and Nutrition Examination Survey (NHANES). DESIGN BMI, WC, and WSR were compared with percentage body fat in a sample of 12,901 adults. RESULTS WC, WSR, and BMI were significantly more correlated with each other than with percentage body fat (P < 0.0001 for all sex-age groups). Percentage body fat tended to be significantly more correlated with WC than with BMI in men but significantly more correlated with BMI than with WC in women (P < 0.0001 except in the oldest age group). WSR tended to be slightly more correlated with percentage body fat than was WC. Percentile values of BMI, WC, and WSR are shown that correspond to percentiles of percentage body fat increments of 5 percentage points. More than 90% of the sample could be categorized to within one category of percentage body fat by each measure. CONCLUSIONS BMI, WC, and WSR perform similarly as indicators of body fatness and are more closely related to each other than with percentage body fat. These variables may be an inaccurate measure of percentage body fat for an individual, but they correspond fairly well overall with percentage body fat within sex-age groups and distinguish categories of percentage body fat.

Structural Trends in the Aging Femoral Neck and Proximal Shaft: Analysis of the Third National Health and Nutrition Examination Survey Dual‐Energy X‐Ray Absorptiometry Data

Hip scans of U.S. adults aged 20–99 years acquired in the Third National Health and Nutrition Examination Survey (NHANES III) using dual‐energy X‐ray absorptiometry (DXA) were analyzed with a structural analysis program. The program analyzes narrow (3 mm wide) regions at specific locations across the proximal femur to measure bone mineral density (BMD) as well as cross‐sectional areas (CSAs), cross‐sectional moments of inertia (CSMI), section moduli, subperiosteal widths, and estimated mean cortical thickness. Measurements are reported here on a non‐Hispanic white subgroup of 2719 men and 2904 women for a cortical region across the proximal shaft 2 cm distal to the lesser trochanter and a mixed cortical/trabecular region across the narrowest point of the femoral neck. Apparent age trends in BMD and section modulus were studied for both regions by sex after correction for body weight. The BMD decline with age in the narrow neck was similar to that seen in the Hologic neck region; BMD in the shaft also declined, although at a slower rate. A different pattern was seen for section modulus; furthermore, this pattern depended on sex. Specifically, the section modulus at both the narrow neck and the shaft regions remains nearly constant until the fifth decade in females and then declined at a slower rate than BMD. In males, the narrow neck section modulus declined modestly until the fifth decade and then remained nearly constant whereas the shaft section modulus was static until the fifth decade and then increased steadily. The apparent mechanism for the discord between BMD and section modulus is a linear expansion in subperiosteal diameter in both sexes and in both regions, which tends to mechanically offset net loss of medullary bone mass. These results suggest that aging loss of bone mass in the hip does not necessarily mean reduced mechanical strength. Femoral neck section moduli in the elderly are on the average within 14% of young values in females and within 6% in males.

The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine.

The goal of our study was to estimate the prevalence of osteoporosis and low bone mass based on bone mineral density (BMD) at the femoral neck and the lumbar spine in adults 50 years and older in the United States (US). We applied prevalence estimates of osteoporosis or low bone mass at the femoral neck or lumbar spine (adjusted by age, sex, and race/ethnicity to the 2010 Census) for the noninstitutionalized population aged 50 years and older from the National Health and Nutrition Examination Survey 2005–2010 to 2010 US Census population counts to determine the total number of older US residents with osteoporosis and low bone mass. There were more than 99 million adults aged 50 years and older in the US in 2010. Based on an overall 10.3% prevalence of osteoporosis, we estimated that in 2010, 10.2 million older adults had osteoporosis. The overall low bone mass prevalence was 43.9%, from which we estimated that 43.4 million older adults had low bone mass. We estimated that 7.7 million non‐Hispanic white, 0.5 million non‐Hispanic black, and 0.6 million Mexican American adults had osteoporosis, and another 33.8, 2.9, and 2.0 million had low bone mass, respectively. When combined, osteoporosis and low bone mass at the femoral neck or lumbar spine affected an estimated 53.6 million older US adults in 2010. Although most of the individuals with osteoporosis or low bone mass were non‐Hispanic white women, a substantial number of men and women from other racial/ethnic groups also had osteoporotic BMD or low bone mass.

Proximal femur bone mineral levels of US adults.

This paper describes bone mineral levels in the proximal femur of US adults based on a nationally representative sample of 7116 men and women aged 20 years and older. The data were collected in phase 1 of the third National Health and Nutrition Examination Survey (NHANES III, 1988–1991) using dual-energy X-ray absorptiometry, and included bone mineral density (BMD), bone mineral content (BMC) and area of bone scanned in five selected regions of interest (ROI) in the proximal femur: femur neck, trochanter, intertrochanter, Wards triangle and total. These variables are provided separately by age and sex for non-Hispanic whites (NHW), non-Hispanic blacks (NHB) and Mexican Americans (MA). BMD and BMC in the five ROI tended to decline with age, whereas area did not. BMD and BMC were highest in NHB, intermediate in MA and lowest in NHW, but areas were highest in NHW, intermediate in NHB and lowest in MA. Men had greater BMD, BMC and area than women in all three race/ethnic groups. Differences by age, sex or race/ethnicity tended to be the largest in Wards triangle, followed by the femur neck; patterns in the trochanter, intertrochanter and total ROI were reasonably similar to each other. This report provides extensive data on femur bone mineral levels of adults from one of the largest samples available to date and should be valuable as reference data for other studies which examine this skeletal site in adults.

Body Iron Stores and the Risk of Coronary Heart Disease

BACKGROUND Recent studies have suggested an association between higher body iron stores and the risk of coronary heart disease. To assess these findings, we examined the association between transferrin saturation and the risk of coronary heart disease, myocardial infarction, overall mortality, and mortality from cardiovascular causes in a large population. METHODS We studied a total of 4518 men and women from the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study, using a multivariate Cox proportional-hazards model. Base-line data were collected from 1971 to 1974, with follow-up through 1987. Transferrin saturation (serum iron concentration divided by total iron-binding capacity) was used as a measure of the amount of circulating iron available to tissues. RESULTS The risk of coronary heart disease was not related to transferrin-saturation levels in white men or women. Estimates of the relative risk of coronary heart disease for the fifth quintile of transferrin saturation as compared with the first quintile were 0.72 (95 percent confidence interval, 0.51 to 1.00) for men and 0.85 (95 percent confidence interval, 0.60 to 1.21) for women. The results were similar for myocardial infarction. A significant inverse association with transferrin saturation was found for overall mortality and for mortality from cardiovascular causes in white men and women. Transferrin saturation was not associated with any of the clinical outcomes in blacks, possibly owing to the small sample. CONCLUSIONS Higher transferrin-saturation levels were not associated with an increased risk of coronary heart disease or myocardial infarction. On the contrary, the results indicate that there may be an inverse association of iron stores with overall mortality and with mortality from cardiovascular causes.

Clinical Use of Biochemical Markers of Bone Remodeling: Current Status and Future Directions

Abstract: Biochemical markers of bone turnover provide a means of evaluating skeletal dynamics that complements static measurements of bone mineral density (BMD). This review evaluates the use of commercially available bone turnover markers as aids in diagnosis and monitoring response to treatment in patients with osteoporosis. High within-person variability complicates but does not preclude their use. Elevated bone resorption markers appear to be associated with increased fracture risk in elderly women, but there is less evidence of a relationship between bone formation markers and fracture risk. The critical question of predicting fracture efficacy with treatment has not been answered. Changes in bone markers as currently determined do not predict BMD response to either bisphosphonates or hormone replacement therapy. Single measurements of markers do not predict BMD cross-sectionally (except possibly in the very elderly), or change in BMD in individual patients, either treated or untreated. On the other hand, research applications of bone turnover markers are of value in investigating the pathogenesis and treatment of bone diseases. Markers have potential in the clinical management of osteoporosis, but their use in this regard is not established. Additional studies with fracture endpoints and information on negative and positive predictive value are needed to evaluate fully the utility of bone turnover markers in individual patients.