National Estimates of Serum Total 25-Hydroxyvitamin D and Metabolite Concentrations Measured by Liquid Chromatography-Tandem Mass Spectrometry in the US Population during 2007-2010.

BACKGROUND: The 2007-2010 NHANES provides the first US nationally representative serum 25-hydroxyvitamin D [25(OH)D] concentrations measured by standardized liquid chromatography-tandem mass spectrometry. OBJECTIVE: We describe patterns for total 25(OH)D and individual metabolites in persons aged ≥1 y stratified by race-ethnicity and grouped by demographic, intake, physiologic, and lifestyle variables. METHODS: We measured 25-hydroxycholecalciferol [25(OH)D3], 25-hydroxyergocalciferol [25(OH)D2], and C3-epimer of 25(OH)D3 [C3-epi-25(OH)D3] in serum samples (n = 15,652) from the 2007-2010 cross-sectional NHANES [total 25(OH)D = 25(OH)D3 + 25(OH)D2]. RESULTS: Concentrations (median, detection rate) of 25(OH)D3 (63.6 nmol/L, 100%) and C3-epi-25(OH)D3 (3.40 nmol/L, 86%) were generally detectable; 25(OH)D2 was detectable in 19% of the population. Total 25(OH)D, 25(OH)D3, and C3-epi-25(OH)D3 displayed similar demographic patterns and were strongly correlated (Spearman's r > 0.70). Concentrations of 25(OH)D2 (90th percentile) were much higher in persons aged ≥60 y (17.3 nmol/L) than in younger age groups (≤4.88 nmol/L). We noted significant race-ethnicity differences in mean total 25(OH)D [non-Hispanic blacks (NHBs), Hispanics, and non-Hispanic whites (NHWs): 46.6, 57.2, and 75.2 nmol/L, respectively] and in the prevalence of total 25(OH)D <30 nmol/L overall (24% of NHBs, 6.4% of Hispanics, and 2.3% of NHWs) as well as stratified by season (winter months: 30% of NHBs, 7.5% of Hispanics, and 3.8% of NHWs; summer months: 17% of NHBs, 4.4% of Hispanics, and 1.6% of NHWs). Persons with higher vitamin D intakes (diet, supplements, or both) and those examined during May-October had significantly higher total 25(OH)D. Significant race-ethnicity interactions in a multiple linear regression model confirmed the necessity of providing race-ethnicity-specific estimates of total 25(OH)D. CONCLUSIONS: Race-ethnicity differences in the prevalence of low total 25(OH)D remained strong even after adjustment for season to account for the NHANES design imbalance between season, latitude, and race-ethnicity. The strong correlation between C3-epi-25(OH)D3 and 25(OH)D3 may be because the epimer is a metabolite of 25(OH)D3. The presence of 25(OH)D2 mainly in older persons is likely a result of high-dose prescription vitamin D2.

Long-term precision of dual-energy X-ray absorptiometry body composition measurements and association with their covariates.

Few studies have described the long-term repeatability of dual-energy X-ray absorptiometry scans. Even fewer studies have been performed with enough participants to identify possible precision covariates such as sex, age, and body mass index (BMI). Our objective was to investigate the long-term repeatability of both total and subregional body composition measurements and their associations with covariates in a large sample. Two valid whole-body dual-energy X-ray absorptiometry scans were available for 609 participants in the National Health and Nutrition Examination Survey 2000-2002. Participants with scan-quality issues were excluded. Participants varied in race and ethnicity, sex, age (mean 38.8±17.5; range 16-69 yr), and BMI (mean, 26.9±5.2; range 14.1-43.5 kg/m2). The length of time between scans ranged from 3 to 51 days (mean, 18.7±8.4). Precision error estimates for total body measures (bone mineral density, bone mineral content, lean mass, total mass, fat mass, and percent body fat) were calculated as root mean square percent coefficients of variation and standard deviations. The average root mean square percent coefficients of variation and root mean square standard deviations of the precision error for total body variables were 1.12 and 0.01 g/cm2 for bone mineral density, 1.14 and 27.3 g for bone mineral content, 1.97 and 505 g for fat mass, 1.46 and 760 g for lean mass, 1.10 and 858 g for total mass, and 1.80 and 0.59 for percent body fat. In general, only fat and lean masses were impacted by participant and scan qualities (obesity category, sex, the magnitude of the body composition variables, and time between scans). We conclude that long-term precision error values are impacted by BMI, and sex. Our long-term precision error estimates may be more suitable than short-term precision for calculating least significant change and monitoring time intervals.

Multiple imputation of missing dual-energy X-ray absorptiometry data in the National Health and Nutrition Examination Survey.

In 1999, dual-energy x-ray absorptiometry (DXA) scans were added to the National Health and Nutrition Examination Survey (NHANES) to provide information on soft tissue composition and bone mineral content. However, in 1999-2004, DXA data were missing in whole or in part for about 21 per cent of the NHANES participants eligible for the DXA examination; and the missingness is associated with important characteristics such as body mass index and age. To handle this missing-data problem, multiple imputation of the missing DXA data was performed. Several features made the project interesting and challenging statistically, including the relationship between missingness on the DXA measures and the values of other variables; the highly multivariate nature of the variables being imputed; the need to transform the DXA variables during the imputation process; the desire to use a large number of non-DXA predictors, many of which had small amounts of missing data themselves, in the imputation models; the use of lower bounds in the imputation procedure; and relationships between the DXA variables and other variables, which helped both in creating and evaluating the imputations. This paper describes the imputation models, methods, and evaluations for this publicly available data resource and demonstrates properties of the imputations via examples of analyses of the data. The analyses suggest that imputation helps to correct biases that occur in estimates based on the data without imputation, and that it helps to increase the precision of estimates as well. Moreover, multiple imputation usually yields larger estimated standard errors than those obtained with single imputation.

Three-phase model harmonizes estimates of the maximal suppression of parathyroid hormone by 25-hydroxyvitamin D in persons 65 years of age and older.

The concentration or threshold of 25-hydroxyvitamin D [25(OH)D] needed to maximally suppress intact serum parathyroid hormone (iPTH) has been suggested as a measure of optimal vitamin D status. Depending upon the definition of maximal suppression of iPTH and the 2-phase regression approach used, 2 distinct clusters for a single 25(OH)D threshold have been reported: 16-20 ng/mL (40-50 nmol/L) and 30-32 ng/mL (75-80 nmol/L). To rationalize the apparently disparate published results, we compared thresholds from several regression models including a 3-phase one to estimate simultaneously 2 thresholds before and after adjusting for possible confounding for age, BMI, glomerular filtration rate, dietary calcium, and season (April-September vs. October-March) within a single data set, i.e. data from the Tufts University Sites Testing Osteoporosis Prevention/Intervention Treatment study, consisting of 181 men and 206 women (total n = 387) ages 65-87 y. Plasma 25(OH)D and serum iPTH concentrations were (mean +/- SD) 22.1 +/- 7.44 ng/mL (55.25 +/- 18.6 nmol/L) and 36.6 +/- 16.03 pg/mL (3.88 +/- 1.7 pmol/L), respectively. The 3-phase model identified 2 thresholds of 12 ng/mL (30 nmol/L) and 28 ng/mL (70 nmol/L); similar results were found from the 2-phase models evaluated, i.e. 13-20 and 27-30 ng/mL (32.5-50 and 67.5-75 nmol/L) and with previous results. Adjusting for confounding did not change the results substantially. Accordingly, the 3-phase model appears to be superior to the 2-phase approach, because it simultaneously estimates the 2 threshold clusters found from the 2-phase approaches along with estimating confidence limits. If replicated, it may be of both clinical and public health importance.

NHANES monitoring of serum 25-hydroxyvitamin D: a roundtable summary.

A roundtable to discuss monitoring of serum 25-hydroxyvitamin D [25(OH)D] in the NHANES was held in late July 2009. Topics included the following: 1) options for dealing with assay fluctuations in serum 25(OH)D in the NHANES conducted between 1988 and 2006; 2) approaches for transitioning between the RIA used in the NHANES between 1988 and 2006 to the liquid chromatography tandem MS (LC-MS/MS) measurement procedure to be used in NHANES 2007 and later; 3) approaches for integrating the recently available standard reference material for vitamin D in human serum (SRM 972) from the National Institute of Standards and Technology (NIST) into the NHANES; 4) questions regarding whether the C-3 epimer of 25-hydroxyvitamin D3 [3-epi-25(OH)D3] should be measured in NHANES 2007 and later; and 5) identification of research and educational needs. The roundtable experts agreed that the NHANES data needed to be adjusted to control for assay fluctuations and offered several options for addressing this issue. The experts suggested that the LC-MS/MS measurement procedure developed by NIST could serve as a higher order reference measurement procedure. They noted the need for a commutability study for the recently released NIST SRM 972 across a range of measurement procedures. They suggested that federal agencies and professional organizations work with manufacturers to improve the quality and comparability of measurement procedures across all laboratories. The experts noted the preliminary nature of the evidence of the 3-epi-25(OH)D3 but felt that it should be measured in 2007 NHANES and later.

Serum 25-hydroxyvitamin D and hip fracture risk in older U.S. white adults.

UNLABELLED: We used serum 25(OH)D data from NHANES III and incident hip fracture cases identified using linked mortality and Medicare records, and found that serum 25(OH)D was significantly related to reduced hip fracture risk in non-Hispanic white adults >or=65 yr of age. INTRODUCTION: The role of vitamin D status in reducing fracture risk is unclear. We examined the relationship between serum 25 hydroxyvitamin D [25(OH)D] and incident hip fracture risk in older non-Hispanic white adults. MATERIALS AND METHODS: The study sample consisted of 1917 white men and women >or=65 yr of age who were examined in the third National Health and Nutrition Examination Survey (NHANES III, 1988-1994), a nationally representative survey. Incident hip fractures were ascertained using linked mortality and Medicare records that were obtained for NHANES III participants. Serum 25(OH)D values were measured with a radioimmunoassay kit. Cox proportional hazards models were used to estimate the relative risk (RR) of hip fracture by serum 25(OH)D level. RESULTS: There were 156 incident hip fracture cases in the sample. Cases were older, had lower BMD and body mass index, more prevalent spine or wrist fractures and weight loss before baseline, and ate fewer kilocalories and less calcium than noncases. After adjusting for these differences, serum 25(OH)D values exceeding 60 nM were significantly related to hip fracture risk. For example, the multivariate-adjusted RR was 0.64 (95% CI, 0.46-0.89) among individuals with serum 25(OH)D values >or=62.5 nM compared with those with values below this level. When grouped into quartiles, the multivariate-adjusted RR for the second, third, and fourth versus the first quartile of serum 25(OH)D were 0.50 (95% CI, 0.25-1.00), 0.41 (95% CI, 0.24-0.70), and 0.50 (95% CI, 0.29-0.86), respectively. CONCLUSIONS: Serum 25(OH)D was related to a significantly lower hip fracture risk in this cohort of older white adults, even after adjusting for several relevant confounding variables. The relationship did not seem to be linear across all values. Our results support other studies suggesting that serum 25(OH)D values exceeding 60 nM are associated with health benefits.

Prevalence, family history, and prevention of reported osteoporosis in U.S. women.

BACKGROUND: Osteoporosis is a major public health concern and has been associated with a family history positive for the condition. However, data on the behaviors of individuals with such a family history are scarce. The objectives of this study were to assess the relationship between the prevalence of reported physician-diagnosed osteoporosis and family history in a representative sample of U.S. women, examine whether osteoporosis risk factors account for this relationship, and evaluate the likelihood that women at high risk of osteoporosis due to family history report preventive behaviors. METHODS: The prevalence of reported osteoporosis was estimated in 8073 women aged>or=20 years in the National Health and Nutrition Examination Survey, 1999-2004. Information on osteoporosis in first-degree relatives and grandparents was obtained during interviews. RESULTS: The prevalence of osteoporosis in participants was 7.94%. In 19.8% of them, a positive family history was reported and was significantly and independently associated with osteoporosis (AOR 2.35, 95% CI=1.87, 2.96). This association was stronger when two or more relatives were affected (AOR 8.48, 95% CI=4.50, 15.99). After stratification by age, the association was observed only in women aged>or=35 years. Women with a family history of osteoporosis were more likely than those with none to report preventive behavior, such as taking supplements of calcium, vitamin D, or both; physical activity; and estrogen use. CONCLUSIONS: These findings indicate that family history is a significant, independent risk factor for osteoporosis in U.S. women aged>or=35 years. Further studies are warranted to evaluate family history as a convenient and inexpensive tool for identifying women at risk of osteoporosis and for promoting the adoption of preventive behaviors.

Evaluation of an automated soluble transferrin receptor (sTfR) assay on the Roche Hitachi analyzer and its comparison to two ELISA assays.

BACKGROUND: Soluble transferrin receptor (sTfR) assays are currently not standardized. This hinders data comparison between studies and also affects the use of a recently proposed model to estimate body iron. METHODS: We evaluated the analytical performance of a fully automated sTfR immunoturbidimetric assay (Roche Diagnostics) and compared it with two ELISA assays (Ramco Laboratories and an in-house ELISA assay used in the body iron model). RESULTS: The Roche assay showed excellent intra- and inter-assay precision (CV<5%). Prolonged exposure of serum samples to room temperature and multiple freeze-thaw cycles did not affect sTfR concentrations. Receiver-operator characteristic curve analysis demonstrated that the Roche assay (area-under-the-curve (AUC)=0.882) was superior to the Ramco assay (AUC=0.794) in predicting iron deficiency (defined as serum ferritin <10 microg/L; P=0.013). Method comparison between the Roche and the two ELISA assays showed good correlations (r>0.8); however, sTfR values by the Roche assay were on average 30% lower than values obtained with the two ELISA assays. CONCLUSIONS: sTfR data measured with an immunoturbidimetric assay can be compared to a commonly used ELISA assay, and can be used in the body iron model through regression equations obtained in the present study.

Laboratory methodologies for indicators of iron status: strengths, limitations, and analytical challenges.

Biochemical assessment of iron status relies on serum-based indicators, such as serum ferritin (SF), transferrin saturation, and soluble transferrin receptor (sTfR), as well as erythrocyte protoporphyrin. These indicators present challenges for clinical practice and national nutrition surveys, and often iron status interpretation is based on the combination of several indicators. The diagnosis of iron deficiency (ID) through SF concentration, the most commonly used indicator, is complicated by concomitant inflammation. sTfR concentration is an indicator of functional ID that is not an acute-phase reactant, but challenges in its interpretation arise because of the lack of assay standardization, common reference ranges, and common cutoffs. It is unclear which indicators are best suited to assess excess iron status. The value of hepcidin, non-transferrin-bound iron, and reticulocyte indexes is being explored in research settings. Serum-based indicators are generally measured on fully automated clinical analyzers available in most hospitals. Although international reference materials have been available for years, the standardization of immunoassays is complicated by the heterogeneity of antibodies used and the absence of physicochemical reference methods to establish "true" concentrations. From 1988 to 2006, the assessment of iron status in NHANES was based on the multi-indicator ferritin model. However, the model did not indicate the severity of ID and produced categorical estimates. More recently, iron status assessment in NHANES has used the total body iron stores (TBI) model, in which the log ratio of sTfR to SF is assessed. Together, sTfR and SF concentrations cover the full range of iron status. The TBI model better predicts the absence of bone marrow iron than SF concentration alone, and TBI can be analyzed as a continuous variable. Additional consideration of methodologies, interpretation of indicators, and analytic standardization is important for further improvements in iron status assessment.

FRAX-based Estimates of 10-year Probability of Hip and Major Osteoporotic Fracture Among Adults Aged 40 and Over: United States, 2013 and 2014.

BACKGROUND: The FRAX algorithm estimates the 10-year probability of hip and major osteoporotic (clinical spine, forearm, hip, or humerus) fracture for adults aged 40 and over. An expert panel developed criteria to define elevated FRAX probabilities for U.S. adults aged 50 and over. This report uses FRAX estimates from the National Health and Nutrition Examination Survey 2013-2014 to describe the hip and major osteoporotic fracture probability distribution (for adults aged 40 and over) and prevalence of elevated probabilities (for adults aged 50 and over) in the United States. METHODS: FRAX U.S. version 3.05 was used to calculate fracture probability from risk factors that were measured (i.e., femur neck bone mineral density, height, and weight) or self-reported (i.e., fracture history, glucocorticoid use, rheumatoid arthritis, smoking, and alcohol intake). Among adults aged 50 and over, elevated probabilities were defined as 3% or greater for hip fracture and 20% or greater for major osteoporotic fracture. RESULTS: Mean skew-adjusted fracture probabilities were 0.5% for hip fracture and 5.3% for major osteoporotic fracture among adults aged 40 and over, and 0.9% and 7.4%, respectively, among adults aged 50 and over. The percentages of adults aged 50 and over with an elevated hip or major osteoporotic fracture probability were 19% and 8%, respectively. Fracture probabilities varied significantly by age (older groups had higher probabilities than younger groups), sex (women had higher probabilities than men), and race and Hispanic origin (non-Hispanic white persons had higher probabilities than all other race and Hispanic groups) (p < 0.001). An estimated 95%-97% of adults aged 50 and over with an elevated probability of either fracture type had femoral neck osteoporosis or low bone mass. CONCLUSIONS: Mean hip and major osteoporotic fracture probabilities were 0.5% and 5.3%, respectively, for adults aged 40 and over. Among adults aged 50 and over, mean hip and major osteoporotic fracture probabilities were 0.9% (19% with elevated values) and 7.4% (8% with elevated values), respectively.

Age trends in femur stresses from a simulated fall on the hip among men and women: evidence of homeostatic adaptation underlying the decline in hip BMD.

UNLABELLED: Age trends in proximal femur stresses were evaluated by simulating a fall on the greater trochanter using femur geometry from hip DXA scans of 5334 white men and women in the NHANES III survey. Expansion of femur outer diameter seems to counter net bone loss so that stresses remain similar across age groups, but stresses are higher in older women than in older men. INTRODUCTION: The age decline in hip BMD is caused by both bone loss and expansion of outer diameter that increases the region size over which mass is measured in a DXA scan. Because expansion has an opposing effect on structural strength, it may be a homeostatic adaptation to net bone loss to ensure that load stresses are kept within a narrow range. MATERIALS AND METHODS: Age trends in femur stresses were evaluated with an engineering beam simulation of a fall on the greater trochanter. Hip geometry was extracted from hip DXA scans using the Hip Structure Analysis (HSA) software on 2613 non-Hispanic white men and 2721 women from the third National Health and Nutrition Examination Survey (NHANES III). Using body weight as load, stresses were computed on the inferior-medial and superior-lateral femur neck at its narrowest point and the medial and lateral shaft 2 cm distal to the midpoint of the lesser trochanter. Stresses and the underlying geometries in men and women >50 years oaf age were compared with those 20-49 years of age. RESULTS: Compared with men <50 years of age, stresses in older men were 6% lower on both surfaces of the shaft, 4% lower on the inferior-medial neck, and not different on the superior-lateral neck. In women >50 years of age, stresses on the proximal shaft and inferior-medial neck remained within 3% of young values but were 13% greater on the superior-lateral neck. Neck stresses in young women were lower on the superior-lateral than the inferior-medial neck, but lateral stress increased to the level on the medial surface in older women. Stresses were higher in women than in men, with a greater gender difference in those >50 years of age. CONCLUSIONS: We conclude that femur expansion has a homeostatic effect in men and women that opposes bone loss so that stresses change little with age. Because expansion preserves stresses with progressively less bone mass, the process may reduce structural stability in the femoral neck under fall conditions, especially in the elderly female.

Diabetes and fracture risk in older U.S. adults.

OBJECTIVE: We examined the diabetes-fracture relationship by race/ethnicity, including the link between pre-diabetes and fracture. RESEARCH DESIGN AND METHODS: We used Medicare- and mortality-linked data for respondents aged 65years and older from the third National Health and Nutrition Examination Survey (NHANES III) and NHANES 1999-2004 for three race/ethnic groups: non-Hispanic whites (NHW), non-Hispanic blacks (NHB), and Mexican Americans (MA). Diabetes was defined as diagnosed diabetes (self-reported) and diabetes status: diagnosed and undiagnosed diabetes (positive diagnosis or hemoglobin A1c (A1C)≥6.5%); pre-diabetes (no diagnosis and A1C between 5.7% and 6.4%); and no diabetes (no diagnosis and A1C<5.7%). Non-skull fractures (n=750) were defined using published algorithms. Hazards ratios (HRs) were calculated using Cox proportional hazards models. RESULTS: The diabetes-fracture relationship differed significantly by race/ethnicity (pinteraction<0.05). Compared to those without diagnosed diabetes, the HRs for those with diagnosed diabetes were 2.37 (95% CI 1.49-3.75), 1.87 (95% CI 1.02-3.40), and 1.22 (95% CI 0.93-1.61) for MA, NHB, and NHW, respectively, after adjusting for significant confounders. HRs for diagnosed and undiagnosed diabetes were similar to those for diagnosed diabetes alone. Pre-diabetes was not significantly related to fracture risk, however. Compared to those without diabetes, adjusted HRs for those with pre-diabetes were 1.42 (95% CI 0.72-2.81), and 1.20 (95% CI 0.96-1.51) for MA and NHW, respectively. There were insufficient fracture cases to examine detailed diabetes status in NHB. CONCLUSIONS: The diabetes-fracture relationship was stronger in MA and NHB. Pre-diabetes was not significantly associated with higher fracture risk, however.

The vitamin D status of the US population from 1988 to 2010 using standardized serum concentrations of 25-hydroxyvitamin D shows recent modest increases.

BACKGROUND: Temporal trends in the US population's vitamin D status have been uncertain because of nonstandardized serum 25-hydroxyvitamin D [25(OH)D] measurements. OBJECTIVE: To accurately assess vitamin D status trends among those aged ≥12 y, we used data from the cross-sectional NHANESs. DESIGN: A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring 25(OH)D (sum of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3), calibrated to standard reference materials, was used to predict LC-MS/MS-equivalent concentrations from radioimmunoassay data (1988-2006 surveys; n = 38,700) and to measure LC-MS/MS concentrations (2007-2010 surveys; n = 12,446). Weighted arithmetic means and the prevalence of 25(OH)D above or below cutoff concentrations were calculated to evaluate long-term trends. RESULTS: Overall, mean predicted 25(OH)D showed no time trend from 1988 to 2006, but during 2007-2010 the mean measured 25(OH)D was 5-6 nmol/L higher. Those groups who showed the largest 25(OH)D increases (7-11 nmol/L) were older, female, non-Hispanic white, and vitamin D supplement users. During 1988-2010, the proportions of persons with 25(OH)D <40 nmol/L were 14-18% (overall), 46-60% (non-Hispanic blacks), 21-28% (Mexican Americans), and 6-10% (non-Hispanic whites). CONCLUSIONS: An accurate method for measuring 25(OH)D showed stable mean concentrations in the US population (1988-2006) and recent modest increases (2007-2010). Although it is unclear to what extent supplement usage compared with different laboratory methods explain the increases in 25(OH)D, the use of higher vitamin D supplement dosages coincided with the increase. Marked race-ethnic differences in 25(OH)D concentrations were apparent. These data provide the first standardized information about temporal trends in the vitamin D status of the US population.

A Method-bridging Study for Serum 25-hydroxyvitamin D to Standardize Historical Radioimmunoassay Data to Liquid Chromatography-Tandem Mass Spectrometry.

BACKGROUND: Serum concentrations of 25-hydroxyvitamin D (25OHD) were measured for the National Health and Nutrition Examination Survey (NHANES) over the 1988-2006 period using a radioimmunoassay (RIA). In 2010, the Centers for Disease Control and Prevention (CDC) reissued RIA-harmonized 25OHD for NHANES 2004 and 2006, and advised users to adjust the original RIA data from 1988-1994 by using an equation. Beginning with NHANES 2007-2008, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method measured 25OHD. METHODS: A method comparison (bridging) study was designed to convert original RIA 25OHD to LC­MS/MS-equivalents. This report compares the predictive ability of a competitor regression model (Model 2) to the equations that CDC publicly released in 2015 (Model 1). The models differ by time period variable and use of transformations. RESULTS: The two models provided similar adjusted R(2) (Model 1: 88.9%, Model 2: 90.4%) and root mean square error of prediction (plus or minus 9 to 10 nanomoles per liter [nmol/L]). Applying these models to NHANES 1988­2006 RIA 25OHD, the Pearson correlation of LC­MS/MS-equivalent concentrations was 0.99; the median difference between models was 0 nmol/L (interquartile range: ­2.8 to 1 nmol/L). In contrast to declining RIA-harmonized 25OHD, both models showed little change in LC­MS/MS-predicted 25OHD over the 1988­2006 period. For 2001­2006, both models predicted similar prevalences of 25OHD less than 30 nmol/L, which were lower than the prevalence estimates based on RIA-harmonized data. Mean weighted LC­MS/MS-equivalent concentrations based on either model were about 3 nmol/L lower for the 1988­1994 survey and about 3 nmol/L higher for the 2001­2006 surveys, effectively smoothing out temporal trends observed using the harmonized RIA data. CONCLUSIONS: Given minimal differences between models, final selection was based on public availability of the regression data. The bridging equations provide a way to use the previous RIA results to obtain LC­MS/MS-equivalent concentrations and evaluate temporal trends in vitamin D status.

Body fat and vitamin D status in black versus white women.

Obesity has been linked to lower serum 25-hydroxyvitamin D [25(OH)D] values, but whether this relationship plays a role in the poorer vitamin D status observed in blacks vs. whites is not clear. This study examines the relationship between serum 25(OH)D and percent body fat (%BF) by race in 6042 women (3567 non-Hispanic whites and 2475 non-Hispanic blacks), aged 12+ yr, from the third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). Serum 25(OH)D values were measured with an RIA kit (DiaSorin), and %BF was calculated from bioelectrical impedance analysis. Adjusting for %BF only slightly reduced differences in mean serum 25(OH)D by race. The negative relationship between serum 25(OH)D and %BF was noticeably stronger in whites than in blacks of the same age. Within race, the relationship was stronger in younger than older individuals. Adjusting for confounders reduced, but did not remove, these differences in relationship strength. In conclusion, the serum 25(OH)D-%BF relationship in women varies both by race (stronger in whites than blacks) and age (stronger in younger than older persons). This complex relationship may explain why differences in obesity do not appear to play a major role in explaining variation in serum 25(OH)D by race.

Prevalence of reduced muscle strength in older U.S. adults: United States, 2011-2012.

Five percent of adults aged 60 and over had weak muscle strength and 13% had intermediate muscle strength, as defined by the new FNIH criteria. Weak muscle strength is clinically relevant because it is associated with slow gait speed, an important mobility impairment. It is also linked to an increased risk of death. The prevalence of reduced muscle strength increased with age and was higher in non-Hispanic Asian and Hispanic persons than in non-Hispanic white or non-Hispanic black persons. Decreasing muscle strength was linked with increased difficulty in rising from an armless chair, which is another important type of mobility impairment.

B-vitamin status and bone mineral density and risk of lumbar osteoporosis in older females in the United States.

BACKGROUND: Previous data suggest that elevated serum total homocysteine (tHcy) may be a risk factor for bone fracture and osteoporosis. Nutritional causes of elevated tHcy are suboptimal B-vitamin status. To our knowledge, this is the first nationally representative report on the relation of B vitamins and bone health from a population with folic acid fortification. OBJECTIVE: The purpose of this analysis was to examine the relation between B-vitamin status biomarkers and bone mineral density (BMD), risk of osteoporosis, and biomarkers of bone turnover. DESIGN: We examined the relation of tHcy, methylmalonic acid (MMA), and serum/red blood cell folate and total-body and lumbar spine BMD in women aged ≥50 y participating in the NHANES 1999-2004 (n = 2806), a nationally representative cross-sectional survey. These are the only years with concurrent measurement of tHcy and whole-body dual-energy X-ray absorptiometry. We also examined B-vitamin biomarkers relative to bone turnover markers, bone alkaline phosphatase, and urinary N-terminal cross-linked telopeptide of type I collagen in a 1999-2002 subset with available data (n = 1813). RESULTS: In comparison with optimal concentrations, women with elevated tHcy were older with lower serum vitamin B-12, red blood cell folate, and dietary micronutrient intakes and had significantly higher mean ± SE markers of bone turnover (bone alkaline phosphatase: 15.8 ± 0.59 compared with 14.0 ± 0.25 µg/L; urinary N-terminal cross-linked telopeptide of type I collagen: 48.2 ± 2.9 compared with 38.9 ± 0.90 nmol bone collagen equivalents per mmol creatinine/L). Elevated MMA (OR: 1.88; 95% CI: 1.10, 3.18) and tHcy (OR: 2.17; 95% CI: 1.14, 4.15) were related to increased risk of lumbar osteoporosis. When examined as a continuous variable, tHcy was negatively associated, serum folates were positively associated, and MMA and vitamin B-12 were not significantly associated with lumbar and total-body BMD. CONCLUSION: In this nationally representative population of older US women with high exposure to B vitamins through food fortification and dietary supplements, only elevated tHcy and MMA were independently associated with risk of lumbar spine osteoporosis.

Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988-1994.

BACKGROUND: Recent reports of rickets among African American children drew attention to the vitamin D status of these infants and their mothers. African American women are at higher risk of vitamin D deficiency than are white women, but few studies have examined determinants of hypovitaminosis D in this population. OBJECTIVE: We examined the prevalence and determinants of hypovitaminosis D among African American and white women of reproductive age. DESIGN: We examined 1546 African American women and 1426 white women aged 15-49 y who were not pregnant and who participated in the third National Health and Nutrition Examination Survey (1988-1994). Hypovitaminosis D was defined as a serum 25-hydroxyvitamin D concentration < or =37.5 nmol/L. Multiple logistic regression was used to examine the independent association of dietary, demographic, and behavioral determinants of hypovitaminosis D. RESULTS: The prevalence of hypovitaminosis D was 42.4 +/- 3.1% ( +/- SE) among African Americans and 4.2 +/- 0.7% among whites. Among African Americans, hypovitaminosis D was independently associated with consumption of milk or breakfast cereal <3 times/wk, no use of vitamin D supplements, season, urban residence, low body mass index, and no use of oral contraceptives. Even among 243 African Americans who consumed the adequate intake of vitamin D from supplements (200 IU/d), 28.2 +/- 2.7% had hypovitaminosis D. CONCLUSIONS: The high prevalence of hypovitaminosis D among African American women warrants further examination of vitamin D recommendations for these women. The determinants of hypovitaminosis D among women should be considered when these women are advised on dietary intake and supplement use.

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.

Depression and bone mineral density in young adults: results from NHANES III.

OBJECTIVE: The purpose of this cross-sectional population-based study was to assess the association of major depressive episode (MDE) and dysthymia with bone mineral density (BMD) in young adults. METHODS: Data are from a nationally representative sample of 5,171 people aged 20 to 39 years from the Third National Health and Nutrition Examination Survey. Total proximal femoral BMD was measured using dual energy x-ray absorptiometry. MDE and dysthymia were measured using the Diagnostic Interview Schedule. RESULTS: MDE was associated with lower BMD in multivariate models in men (mean BMD = 1.038 vs. 1.068 g/cm(2); odds ratio (OR) per 1 SD decline in BMD = 1.65, 95% confidence interval (CI) = 1.08-2.52; p = 0.02) but not in women (mean BMD = 0.982 vs. 0.979 g/cm(2); OR = 0.96, 95% CI = 0.71-1.30; p =.79). The same divergence by gender was seen for dysthymia. CONCLUSION: The relationship between BMD and MDE or dysthymia in young adults varies by gender.