Tamsen Bassford

Validity of self-report for fractures among a multiethnic cohort of postmenopausal women: results from the Women's Health Initiative observational study and clinical trials.

Objective:The purpose of this study is to examine the validity of, and factors associated with, the accuracy of self-report (participant-report and proxy-report) for fractures. Design:Study participants were from the Womens Health Initiative Clinical Trial and Observational Study cohorts. All women were postmenopausal; populations included American Indian, Asian/Pacific Islander, black, Hispanic, and non-Hispanic white. The average length of follow-up was 4.3 years. Self-reported fractures were adjudicated by reviewing medical records. The first adjudicated self-report of fractures for each participant was included in the analysis (n = 6,652). Results:We found substantial variations in validity of self-report by the fracture site. Agreements between self-reports for single-site fractures and medical records were high for hip (78%) and forearm/wrist (81%) but relatively lower for clinical spine fractures (51%). The average confirmation rate for all single-site fractures was 71%. Misidentification of fracture sites by participants or proxy-reporters seemed to be a cause of unconfirmed self-reports. Higher confirmation rates were observed in participant-reports than in proxy-reports. Results of the multivariate analysis indicated that multiple factors, such as ethnicity, a history of osteoporosis or fractures, body mass index, years since menopause, smoking status, and number of falls in the past year were significantly (P < 0.05) related to the validity of self-report. Conclusion:The validity of self-reports for fracture varies by fracture sites and many other factors. The assessed validity in this study is likely conservative because some of the unconfirmed self-reports may be due to poor medical record systems. The validity of self-reports for hip and forearm/wrist fractures is high in this study, supporting their use in epidemiological studies among postmenopausal women.

Effects of conjugated equine estrogen on risk of fractures and BMD in postmenopausal women with hysterectomy: Results from the women's health initiative randomized trial

Further analyses from the Womens Health Initiative estrogen trial shows that CEE reduced fracture risk. The fracture reduction at the hip did not differ appreciably among risk strata. These data do not support overall benefit over risk, even in women at highest risk for fracture.

Postmenopausal hormone therapy and body composition—a substudy of the estrogen plus progestin trial of the Women's Health Initiative

BACKGROUND It has been suggested that hormone therapy may help counter undesirable changes in body composition in older women. OBJECTIVE This study was designed to test whether estrogen plus progestin (E+P) therapy favorably affects age-related changes in body composition in postmenopausal women. DESIGN The substudy was composed of 835 women from the estrogen plus progestin trial of the Womens Health Initiative who were randomly assigned to receive either E+P therapy (n = 437) or placebo (n = 398). The women had a mean age of 63.1 y and, on average, were 13.8 y past menopause. More than 17% of the participants were from an ethnic minority. No significant differences in baseline body composition (measured with dual-energy X-ray absorptiometry) by intervention assignment were observed. RESULTS After 3 y of intervention, the women who received active E+P therapy lost less lean soft tissue mass (-0.04 kg) than did the women who received placebo (-0.44 kg; P = 0.001). Additionally, the women in the E+P group had less upper-body fat distribution than did the women in the placebo group (change in ratio of trunk to leg fat mass: -0.025 for the E+P group and 0.004 for the placebo group; P = 0.003). A sensitivity analysis, which was conducted on the women who took > or = 80% of the study medication during the intervention period, corroborated the findings from the intent-to-treat analysis. CONCLUSIONS A 3-y E+P intervention significantly reduced both the loss of lean soft tissue mass and the ratio of trunk to leg fat mass in postmenopausal women. However, the effect sizes were small, and whether these changes in body composition lead to significant health benefits remains to be confirmed.

Arthritis Increases the Risk for Fractures---Results from the Women’s Health Initiative

Objective. To examine the relationship between arthritis and fracture. Methods. Women were classified into 3 self-reported groups at baseline: no arthritis (n = 83,295), osteoarthritis (OA; n = 63,402), and rheumatoid arthritis (RA; n = 960). Incident fractures were self-reported throughout followup. Age-adjusted fracture rates by arthritis category were generated, and the Cox proportional hazards model was used to test the association between arthritis and fracture. Results. After an average of 7.80 years, 24,137 total fractures were reported including 2559 self-reported clinical spinal fractures and 1698 adjudicated hip fractures. For each fracture type, age-adjusted fracture rates were highest in the RA group and lowest in the nonarthritic group. After adjustment for several covariates, report of arthritis was associated with increased risk for spine, hip, and any clinical fractures. Compared to the nonarthritis group, the risk of sustaining any clinical fracture in the OA group was HR 1.09 (95% CI 1.05, 1.13; p < 0.001) and HR 1.49 (95% CI 1.26, 1.75; p < 0.001) in the RA group. The risk of sustaining a hip fracture was not statistically increased in the OA group (HR 1.11; 95% CI 0.98, 1.25; p = 0.122) compared to the nonarthritis group; however, the risk of hip fracture increased significantly (HR 3.03; 95% CI 2.03, 4.51; p < 0.001) in the RA group compared to the nonarthritis group. Conclusion. The increase in fracture risk confirms the importance of fracture prevention in patients with RA and OA.

Recruitment of Hispanic women to the Women's Health Initiative: the case of Embajadoras in Arizona

This study examined the use of lay advocates (i.e., women enrolled in a study who advocate to others) to improve recruitment among Hispanic women in the Arizona recruitment sites for a large-scale, national prevention study, the Womens Health Initiative (WHI). We examined whether trained, Hispanic lay advocates (called Embajadoras) brought more women into the study than a matched group of Hispanic and Anglo enrollees in the WHI who were supplied with brochures. Fifty-six Hispanic participants in the WHI were randomized to receive training or no training on advocacy, and continued to meet quarterly for 18 months. Also, 42 Anglo women were assigned to control. All groups received brochures to use for advocating the WHI. The number of women referred and enrolled was tracked as well as other factors expected to influence outcomes. Embajadoras were more successful at referral and enrollment than untrained Hispanic women and more successful at enrollment than untrained Anglo controls. Embajadoras were also found to distribute significantly more brochures than control groups. Therefore, a culturally aligned training program to encourage current Hispanic participants in a clinical trial to advocate the study to others may be an effective way to boost referrals and enrollments. Other potential influences on enrollment or referral success could not be determined due to the small sample size. Further study is needed to examine the best methods to encourage enrollment for women referred to the study.

Ethnic differences in femur geometry in the women's health initiative observational study

SummaryParticipants in the observational study of the Womens Health Initiative (WHI) were studied to determine if ethnic differences in femur geometry can help to explain differences in hip fracture rates. Structural differences in femurs of African and Mexican-American women appear to be consistent with lower rates of hip fractures vs. whites.IntroductionEthnic origin has a major influence on hip fractures, but the underlying etiology is unknown. We evaluated ethnic differences in hip fracture rates among 159,579 postmenopausal participants in the WHI then compared femur bone mineral density (BMD) and geometry among a subset with dual X-ray absorptiometry (DXA) scans of the hip and total body.MethodsThe subset included 8,206 non-Hispanic whites, 1,476 African-American (AA), 704 Mexican-American (MA), and 130 Native Americans (NA). Femur geometry derived from hip DXA using hip-structure analysis (HSA) in whites was compared to minority groups after adjustment for age, height, weight, percent lean mass, neck-shaft angle and neck length, hormone use, chronic disease (e.g., diabetes, rheumatoid arthritis, cancer), bone active medications (e.g., corticosteroids, osteoporosis therapies), and clinical center.ResultsBoth AA and MA women suffered hip fractures at half the rate of whites while NA appeared to be similar to whites. The structural advantage among AA appears to be due to a slightly narrower femur that requires more bone tissue to achieve similar or lower section moduli (SM) vs. whites. This also underlies their higher BMD (reduces region area) and lower buckling ratios (buckling susceptibility). Both MA and NA women had similar advantages vs. whites at the intertrochanter region where cross-sectional area and SM were higher but with no differences at the neck. NA and MA had smaller bending moments vs. whites acting in a fall on the hip (not significant in small NA sample). Buckling ratios of MA did not differ from whites at any region although NA had 4% lower values at the IT region.ConclusionDifferences in the geometry at the proximal femur are consistent with the lower hip fracture rates among AA and MA women compared to whites.

The Relationship Between Incidence of Fractures and Anemia in Older Multiethnic Women

OBJECTIVES: To prospectively examine the relationship between anemia and incident fractures of the hip, spine, and all skeletal sites in women from diverse racial and ethnic backgrounds enrolled in the Womens Health Initiative (WHI) Observational Study and Clinical Trials.

Hormone Therapy Improves Femur Geometry Among Ethnically Diverse Postmenopausal Participants in the Women's Health Initiative Hormone Intervention Trials

Loss of bone strength underlies osteoporotic fragility fractures. We hypothesized that hormone interventions significantly improve the structural geometry of proximal femur cross‐sections. Study participants were from the Womens Health Initiative hormone intervention trials: either the conjugated equine estrogen (CEE) only (Nplacebo = 447, NCEE = 422) trial or the estrogen (E) plus progestin (P) (Nplacebo = 441, NE+P = 503) trial, who were 50–79 yr old at baseline and were followed up to 6 yr. BMD scans by DXA were conducted at baseline, year 1, year 3, and year 6. Femur geometry was derived from hip DXA scans using the hip structural analysis (HSA) method. Mixed effects models with the intent‐to‐treat analysis approach were used. There were no significant differences in treatment effects between the E‐alone and the E + P trial, so the analyses were conducted with participants combined from both trials. Treatment benefits (p < 0.05) on femur geometry were observed as early as 1 yr after the intervention. From baseline to year 6, section modulus (a measure of maximum bending stress) was preserved, and buckling ratio (an index of cortical instability under compression) was reduced by hormone interventions (p < 0.05); the differences in the percent changes from baseline to year 6 between women on hormone intervention versus women on placebo were 2.3–3.6% for section modulus and –5.3% to – 4.3% for buckling ratio. Hormone interventions led to favorable changes in femur geometry, which may help explain the reduced fracture risk observed in hormone interventions.

Effect of hormone therapy on lean body mass, falls, and fractures: 6-year results from the Women's Health Initiative hormone trials

Objective:Loss of lean body mass with aging may contribute to falls and fractures. The objective of this analysis was to determine if taking postmenopausal hormone therapy (or HT: estrogen plus progestogen therapy or estrogen therapy alone) favorably affects age-related changes in lean body mass and if these changes partially account for decreased falls or fractures with HT. Methods:Participants randomly assigned to either estrogen plus progestogen therapy (n = 543) or control (n = 471) and estrogen therapy alone (n = 453) or control (n = 474) and receiving dual-energy x-ray absorptiometry scans to estimate body composition during the Womens Health Initiative were evaluated. Falls and fracture occurrence were obtained by annual self-report. Fractures were confirmed by a clinical chart review. Results:At 6 years postrandomization, lean body mass was not different between HT and control groups. Although lean body mass positively influenced bone mineral density, independent of HT status, the preserved lean body mass observed in the HT arms in the first 3 years did not significantly contribute to models evaluating HT influence on falls and fractures between years 3 and 6. Women taking at least 80% of their medication in the HT arms demonstrated fewer falls compared with placebo; this difference was not attributable to change in lean body mass. Conclusions:Despite early preservation of lean body mass with HT (3 y), HT did not ameliorate long-term (6 y) loss in lean body mass with aging.

Benchmarks for designing two-stage studies using modified mini-mental state examinations: Experience from the Women's Health Initiative Memory Study

Background The most efficient approach for studies examining the incidence of dementia involves a brief screening instrument to identify participants for more extensive testing to identify cognitive impairment. The modified mini-mental state examination (3MS) is commonly used as this initial screen in such two-stage designs, however its properties for this role require further study. Purpose We use data from the Womens Health Initiative Memory Study to contrast design options in two-stage designs. Methods This trial enrolled 7251 participants with nine or more years of education who were aged 65–79 and followed an average of four to five years. Logistic regression was used to examine the case yields at varying two-stage 3MS cutpoints. The efficiency of using different examination schedules and restricting enrollment to higher risk women was examined. Results Probable dementia is associated with marked decline in 3MS scores. The percentages of women classified with probable dementia ranged from 7.95% (3MS 85–88) to 50.0% (3MS = 70). The numbers [95% confidence interval] of enrolled women necessary to detect one case of probable dementia (four-year follow-up) for baseline 3MS scores of 100, 95, 90 and 85 were estimated as 1477 [389, 5618], 253 [134, 481], 53 [34, 85], and 14 [9, 23], respectively. Compared to annual testing, administration every two years increased the number of required enrollees by 11%, but decreased the number of test administrations by 46%. Limitations Our findings are influenced by the characteristics of our study group, its rates of retention, and the study protocol, and may not fully generalize to other settings. Conclusions The 3MS can serve as an efficient basis for two-stage study designs and a cutpoint of 88 is reasonable for populations with similar characteristics. Studies may improve efficiency by using the 3MS during screening to eliminate women with low risk for dementia and by conducting testing every two years.