The NHANES are conducted by the National Center for Health Statistics (NCHS), Centers for Disease Control and Prevention, to assess the health and nutritional status of large representative cross-sectional samples of the noninstitutionalized civilian US population. In NHANES III, a nationally representative sample was obtained in two 3-year cycles between 1988 and 1994. Starting in 1999, data from a nationally representative sample have been collected each year, but data are released for 2-year periods to protect confidentiality and increase statistical reliability. The present study was based on data collected in NHANES 2005–2006. In each NHANES, data were collected via household interviews and direct standardized physical examinations conducted in specially equipped mobile examination centers.7, 8 All procedures in both surveys were approved by the NCHS Institutional Review Board, and written informed consent was obtained from all subjects.
NHANES III and NHANES 2005–2006 were designed to provide reliable estimates for three race/ethnic groups: non-Hispanic whites, non-Hispanic blacks, and Mexican Americans. Race and ethnicity were self-reported by the participants. A total of 10,995 adults age 50 years and older were eligible to participate in NHANES III. Of the eligible sample, 8654 (79%) were interviewed, and 7155 (65%) were examined. The present study uses data for 6401 adults age 50 years and older with valid nonmissing femur BMD data from NHANES III, which represents 58% of the sample in this age range who were originally selected for NHANES III, 74% of the participants in this age range who were interviewed, and 89% of those who received physical examinations. A total of 3157 adults age 50 years and older were eligible to participate in NHANES 2005–2006. Of these, 2214 (70%) were interviewed, and 2119 (68%) were examined. The analytic sample from NHANES 2005–2006 was limited to 1614 adults age 50 years and older with valid, nonmissing femur BMD data, which represents 51% of the participants in this age range who were eligible to participate in the survey, 73% of the interviewed participants, and 76% of those who received physical examinations.
As described elsewhere,9 femur BMD was measured in NHANES 2005–2006 with Hologic QDR 4500A fan-beam densitometers (Hologic, Inc., Bedford, MA, USA) using Discovery version 12.4 software. Scanning was done in the fast mode. In NHANES III, femur BMD was measured with Hologic QDR 1000 pencil-beam densitometers.10 Rigorous quality-control (QC) programs were employed in both surveys, which included use of anthropomorphic phantoms and review of each QC and respondent scan at a central site (Department of Radiology, University of California San Francisco in NHANES 2005–2006 and Department of Diagnostic Radiology, Mayo Clinic in NHANES III).9, 10 In both surveys, the left hip was scanned unless there was a history of previous fracture or surgery.
To address the potential impact of the change in DXA methodology between surveys, a literature search was performed to identify the magnitude of the difference that might be expected when the same individuals were measured on both scanner types.18–21 The largest discrepancy between the two scanners found in published studies was a difference of ± 3% at either the femur neck or total hip.18, 21 Accordingly, the BMD values of each respondent from NHANES 2005–2006 were raised or lowered by 3%. Estimates of osteoporosis, as defined below, that were based on the adjusted BMD values from NHANES 2005–2006 then were calculated and compared with the prevalence estimates from NHANES III (data not shown). Although the magnitude of the prevalence estimates was altered by this adjustment, conclusions regarding the differences in prevalence between surveys were the same as when based on the observed BMD values except in one case (when BMD was lowered by 3% in men). As a result, the observed BMD values from both surveys were used in the present study without adjustment for the difference in DXA methods.
In the present study, BMD data at the femur neck and total hip were analyzed. The femur neck was chosen because it has been proposed as the reference skeletal site for defining osteoporosis in epidemiologic studies.5 The total hip was included because it is the skeletal site used in the Healthy People 2010 objective related to osteoporosis.6 Definitions of osteopenia and osteoporosis were based on criteria outlined by WHO in 199411:
Osteopenia: BMD between 1 standard deviation (SD) and 2.5 SD below the mean of the young reference group.
Osteoporosis: BMD 2.5 SD or more below the mean of the young reference group.
As recommended more recently by the WHO,5 20- to 29-year-old non-Hispanic white women from NHANES III3 were used as the reference group to derive these cutoff values for men and women in both surveys. The specific NHANES III cutoff values used to define osteopenia were 0.561 to 0.74 g/cm2 and 0.641 to 0.82 g/cm2 for the femur neck and total hip, respectively.3 The thresholds for osteoporosis were 0.56 g/cm2 or less and 0.64 g/cm2 or less for the femur neck and total hip, respectively.3
Two potential explanatory factors related to secular trends in BMD were examined in the present study: body mass index (BMI) and use of osteoporosis medications. These variables were chosen because they have been shown to be strongly related to BMD,12, 13 and there is also evidence that changes have occurred in the population since NHANES III.14–16 BMI was calculated as body weight (kilograms) divided by height (meters squared). In both surveys, body weight was measured to the nearest 0.01 kg using an electronic load-cell scale, and standing height was measured with a fixed stadiometer.
Osteoporosis medication users were defined as those who self-reported having been treated for osteoporosis and/or were currently taking the prescription medications described below. Data to define users of osteoporosis medications were collected in a comparable manner in both surveys. Respondents who self-reported having been diagnosed with osteoporosis by a physician were asked if they had been treated for it. In addition, all respondents, regardless of whether they had self-reported having been diagnosed with osteoporosis, showed the containers for all current prescription medications to the interviewer, who recorded the name of the product. Medications were assigned standard generic names and four-digit generic codes using the Physicians' GenRx17 in NHANES III. The December 2007 Multum Lexicon Drug Database (Cerner Multum, Inc., Denver CO; www.multum.com/Lexicon.htm) was used to assign generic drug names and codes in NHANES 2005–2006.
Osteoporosis medications were defined as medications included in a recent systematic review of the comparative effectiveness of treatments to prevent osteoporotic fractures.13 In NHANES III, these included calcitonin, calcitriol, ergocalciferol, etidronate, sodium fluoride, tamoxifen, calcium acetate, and sex hormones (i.e., estrogen and testosterone, as defined below). In NHANES 2005–2006, they included bisphosphonates (e.g., alendronate, risedronate, etidronate, pamidronate, tiludronate, ibandronate, and zolendronate), calcitonin, calcitriol, fluoride, raloxifene, tamoxifen, tibolone, strontium ranelate, parathyroid hormone, teriparatide, and sex hormones (i.e., estrogen and testosterone). The Multum drug therapeutic category codes for estrogen and testosterone were used to identify the relevant sex hormone treatments in NHANES 2005–2006. Generic drugs corresponding to these Multum drug therapeutic codes were considered to be in these categories in NHANES III as well. “Estrogens” included estradiol, estradiol valerate, estrogenic substances, conjugated estrogens, esterified estrogens (alone and with methyltestosterone), estropipate, ethinyl estradiol (alone or with ethynodiol diacetate, levonorgestrel, norethindrone, norethindrone acetate, or desogestrel), diethylstilbesterol (alone or with disphosphate), fluoxymesterone, and quinestrol. “Testosterones” included testosterone, testosterone cypionate, stanozolol, and nandrolone decanoate.
Education was included as a variable in order to make comparisons with subgroups identified in the osteoporosis objective in Healthy People 2010.6 Education was defined as numbers of years of schooling completed and was categorized as less than high school, high school, and more than high school to be consistent with categories used in the Healthy People 2010 osteoporosis objective.
Analyses were conducted with PC-SAS (version 9.1, SAS Institute, Cary, NC, USA) and SUDAAN (version 9.03, Research Triangle Institute, NC, USA). All analyses used sample weights and took into account the complex design of the survey. When multiple comparisons of estimates between groups were made, a Bonferoni correction was used.
BMD means by age and race/ethnicity were calculated for NHANES 2005–2006 using linear regression and adjusting for the other characteristic in the model. The prevalence of low BMD at the femur neck and total hip in 2005–2006 was calculated by sex and age group, and differences by age and sex were tested using logistic regression. Prevalence estimates for the total population and by race/ethnicity were age standardized to the US Census 2000 population estimates when not provided by detailed age groups. Estimates of the number of older US adults with poor skeletal status were calculated by multiplying the unadjusted prevalences for age 50+ by Census Current Population Survey estimates of the noninstitutionalized US population for 2005–2006 (www.cdc.gov/nchs/about/major/nhanes/nhanes_cps_totals.htm).
Changes in the prevalence of low femur BMD between NHANES III and NHANES 2005–2006 were examined by calculating the age-standardized prevalence in each survey for the total population age 50 years and older and by sex and race/ethnicity. Differences between age-standardized prevalences were tested using a t test. Differences between the two surveys also were tested using logistic regression models that included age and the survey time period.
Secondary analyses were done to assess the potential impact of changes in BMI and osteoporosis medications on the observed difference in prevalence of femur neck osteoporosis. These analyses were stratified by race/ethnicity in order to avoid potential confounding by this variable in the relationships. The analyses were limited to non-Hispanic whites owing to statistically unreliable prevalence estimates of osteoporosis and/or medication use in the other groups. To assess the potential impact of differences in BMI and medication use, the prevalences before and after adjusting for those two factors were calculated using logistic regression models that also included age and the survey time period as variables.