Evolutionary Origins of the Differences in Osteoporosis Risk in US Populations.

Over the past 50 years, it has been increasingly evident that there are population differences in bone mass and the risk of osteoporosis. In the United States, many studies have reported a lower prevalence of osteoporosis in African Americans compared with people of European descent. If we trace the trajectory of changes in lifeways from the earliest migrations of early Homo out of Africa over the past two million years or so, to include lower vitamin D levels in higher latitudes; more meat in the diet; increasing sedentism; and a longer lifespan/longer postmenopausal period, it is not surprising that osteoporosis occurs more frequently in populations of European descent. While many scholars have explored the apparent "paradox" of higher bone mass, lower vitamin D levels, and higher parathyroid hormone levels among African Americans, this brief review of evolutionary shifts that affected our species may change the approach to understanding the current population differences in the United States.

Accuracy of self-reported weight in the Women's Health Initiative.

OBJECTIVE: To assess the extent of error present in self-reported weight data in the Women's Health Initiative, variables that may be associated with error, and to develop methods to reduce any identified error. DESIGN: Prospective cohort study. SETTING: Forty clinical centres in the USA.ParticipantsWomen (n 75 336) participating in the Women's Health Initiative Observational Study (WHI-OS) and women (n 6236) participating in the WHI Long Life Study (LLS) with self-reported and measured weight collected about 20 years later (2013-2014). RESULTS: The correlation between self-reported and measured weights was 0·97. On average, women under-reported their weight by about 2 lb (0·91 kg). The discrepancies varied by age, race/ethnicity, education and BMI. Compared with normal-weight women, underweight women over-reported their weight by 3·86 lb (1·75 kg) and obese women under-reported their weight by 4·18 lb (1·90 kg) on average. The higher the degree of excess weight, the greater the under-reporting of weight. Adjusting self-reported weight for an individual's age, race/ethnicity and education yielded an identical average weight to that measured. CONCLUSIONS: Correlations between self-reported and measured weights in the WHI are high. Discrepancies varied by different sociodemographic characteristics, especially an individual's BMI. Correction of self-reported weight for individual characteristics could improve the accuracy of assessment of obesity status in postmenopausal women.

Cabbage and Sauerkraut Consumption in Adolescence and Adulthood and Breast Cancer Risk among US-Resident Polish Migrant Women.

BACKGROUND: Breast cancer (BC) incidence and mortality are lower in Poland than in the United States (US). However, Polish-born migrant women to US approach the higher BC mortality rates of US women. We evaluated the association between consumption of cabbage/sauerkraut foods and BC risk in Polish-born migrants to US. METHODS: We conducted a case-control study of BC among Polish-born migrants in Cook County and the Detroit Metropolitan Area. Cases (n = 131) were 20-79 years old with histological/cytological confirmation of invasive BC. Population-based controls (n = 284) were frequency matched to cases on age and residence. Food frequency questionnaires assessed diet during adulthood and age 12-13 years. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated with conditional logistic regression. Consumption of total, raw/short-cooked, and long-cooked cabbage/sauerkraut foods was categorized as low, medium, or high (frequency of servings/week). RESULTS: Higher consumption of total and raw/short-cooked cabbage/sauerkraut foods, during both adolescence and adulthood, was associated with a significantly lower BC risk. Consumption of long-cooked cabbage/sauerkraut foods was low and not significantly associated with risk. The multivariate OR for total cabbage/sauerkraut consumption, high vs. low (>4 vs. ≤2 servings/week) during adolescence was 0.36 (95% CI = 0.18-0.71, ptrend < 0.01) and 0.50 (95% CI = 0.23-1.06, ptrend = 0.08) during adulthood. For raw/short-cooked cabbage/sauerkraut (>3 vs. ≤1.5 servings/week), the ORs were 0.35 (95% CI = 0.16-0.72, ptrend < 0.01) during adolescence and 0.37 (95% CI = 0.17-0.78, ptrend < 0.01) during adulthood. For joint adolescent/adult consumption of raw/short-cooked cabbage/sauerkraut foods, (high, high) vs. (low, low), the OR was 0.23 (95% CI = 0.07-0.65). The significant association for high adolescent consumption of raw/short-cooked cabbage/sauerkraut foods and reduced BC risk was consistent across all levels of consumption in adulthood. CONCLUSION: Greater consumption of total and raw/short-cooked cabbage/sauerkraut foods either during adolescence or adulthood was associated with significantly reduced BC risk among Polish migrant women. These findings contribute to the growing literature suggesting a protective effect of a potentially modifiable factor, cruciferous vegetable intake, on breast cancer risk.

Racial and Ethnic Differences in Anthropometric Measures as Risk Factors for Diabetes.

OBJECTIVE: The study objective was to examine the impact of race/ethnicity on associations between anthropometric measures and diabetes risk. RESEARCH DESIGN AND METHODS: A total of 136,112 postmenopausal women aged 50-79 years participating in the Women's Health Initiative without baseline cancer or diabetes were followed for 14.6 years. BMI, waist circumference (WC), and waist-to-hip ratio (WHR) were measured in all participants, and a subset of 9,695 had assessment of whole-body fat mass, whole-body percent fat, trunk fat mass, and leg fat mass by DXA. Incident diabetes was assessed via self-report. Multivariate Cox proportional hazards regression models were used to assess associations between anthropometrics and diabetes incidence. RESULTS: During follow-up, 18,706 cases of incident diabetes were identified. BMI, WC, and WHR were all positively associated with diabetes risk in each racial and ethnic group. WC had the strongest association with risk of diabetes across all racial and ethnic groups. Compared with non-Hispanic whites, associations with WC were weaker in black women (P < 0.0001) and stronger in Asian women (P < 0.0001). Among women with DXA determinations, black women had a weaker association with whole-body fat (P = 0.02) but a stronger association with trunk-to-leg fat ratio (P = 0.03) compared with white women. CONCLUSIONS: In postmenopausal women across all racial/ethnic groups, WC was a better predictor of diabetes risk, especially for Asian women. Better anthropometric measures that reflect trunk-to-leg fat ratio may improve diabetes risk assessment for black women.

Longitudinal study of depot medroxyprogesterone acetate (Depo-Provera) effects on bone health in adolescents: study design, population characteristics and baseline bone mineral density.

BACKGROUND: This analysis was conducted to assess the baseline data and design methodology within an observational longitudinal comparison of use vs. nonuse of the injectable (intramuscular) contraceptive depot medroxyprogesterone acetate (DMPA-IM) and its effect on bone mass in adolescent women. STUDY DESIGN: A prospective, observational, open-label, unmatched-cohort, safety study in females aged 11-18 years. Participants either self-selected DMPA-IM (Depo-Provera) 150 mg to be administered every 12 weeks for up to 240 weeks with a 120-week post-treatment follow-up or were nonusers (users of nonhormonal contraception or sexually abstinent) who were to be followed up for up to 360 weeks. As each participant entered the study, bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at the lumbar spine, hip and femoral neck regions, along with total body bone mineral content; serum and urine specimens were obtained for assay of bone metabolism markers and participants' histories of parity and tobacco and alcohol use were obtained. RESULTS: A total of 389 participants were enrolled: 169 elected to begin DMPA-IM; 26 chose nonhormonal methods and 194 were abstinent. The baseline characteristics indicated significant disparities between DMPA-IM users and nonusers: compared with the nonusers, DMPA-IM users had more advanced chronologic and gynecologic ages, were more likely to have smoked, been pregnant and included more blacks. These factors would likely influence bone accretion rates independent of DMPA-IM exposure. Comparison of participant BMDs with standard reference data revealed that the study cohorts did not match reference populations closely enough to make a direct between-cohort comparative analysis feasible. CONCLUSIONS: The baseline differences in cohort characteristics preclude a meaningful comparison of mean BMD changes over time between DMPA-IM users and nonusers cohorts, and comparisons of changes in Z-scores between cohorts were also not appropriate. Therefore, within-participant BMD decreases from baseline were established as safety thresholds, and the proportion of individuals crossing those thresholds on a persistent or progressive basis was identified as the revised primary end point.

Comparisons of body size, composition, and whole body bone mass between North American and South African children.

UNLABELLED: We compared whole body BMC of 811 black, white, and mixed ancestral origin children from Detroit, MI; Johannesburg, South Africa; and Cape Town, South Africa. Our findings support the role of genetic and environmental influences in the determination of bone mass in prepubertal children. INTRODUCTION: Higher bone mass and lower fracture rates have been shown in black compared with white children and adults in North America. MATERIALS AND METHODS: We compared whole body BMC (WBBMC), whole body fat mass (WBFM), and whole body fat free soft tissue (WBFFST) data between three ethnic groups of children from Detroit, MI (n = 181 white, USW; n = 230 black, USB), Johannesburg, South Africa (n = 73 white, SAW; n = 263 black, SAB), and Cape Town, South Africa (n = 64 mixed ancestral origin, SAM). RESULTS: SAB and SAW groups were slightly older than USW and USB groups (9.5 +/- 0.3 versus 9.3 +/- 0.1 yr); however, USB and USW boys were significantly taller, were heavier, and had a higher BMI than SAM and SAB boys. USB girls were significantly taller than SAB girls and heavier than SAB and SAM girls. In South Africa and the United States, black children had a significantly higher WBBMC than white children, after adjusting for selected best predictors. After adjusting for age, weight, and height, WBBMC was significantly higher in the SAB and SAW boys than in USW and USB and in the SAM group compared with the USW and USB groups. WBFFST and WBFM made significant contributions to a best linear model for log(WBBMC), together with age, height, and ethnicity. The best model accounted for 79% of the WBBMC variance. When included separately in the model, the model containing WBFFST accounted for 76%, and the model containing WBFM accounted for 70%, of the variance in WBBMC. CONCLUSIONS: WBBMC is lower in children of European ancestry compared with African ancestry, irrespective of geographical location; however, South African children have significantly higher WBBMC compared with USB and USW groups, thereby acknowledging the possible contribution of environmental factors. Reasons for the significantly higher WBBMC in the children of mixed ancestral origin compared with the other groups need to be studied further.

Is BMD testing appropriate for all menopausal women?

The United States Preventive Services Task Force has provided an evidence-based guideline indicating that bone mineral density (BMD) testing is appropriate for all women aged 65 or older. This does not preclude BMD testing in younger postmenopausal women but places the onus on the treating physician to justify the procedure to the patient and often the patient's insurance carrier. There are very few circumstances in which BMD testing is appropriate for healthy premenopausal women, but BMD testing in younger postmenopausal women is often appropriate: when there is a family history of osteoporosis with fracture, a personal history of fracture as an adult, and a medical, surgical or therapeutic history that might be associated with accelerated bone loss or increased risk of fracture. Medical conditions include intestinal diseases associated with malabsorption, such as non-tropical sprue, or primary hyperparathyroidism. Women who have neurologic conditions that increase the risk of falling should also be tested. There are data to suggest that patients with hemoglobinopathy are at increased risk for osteoporosis. Surgical conditions include the increasingly performed surgery for obesity and other surgery resulting in bowel resection (e.g., for inflammatory bowel disease). The major medication-related concern is corticosteroid therapy, but chronic or over-treatment with thyroxine, and chronic heparin therapy, should also be considered risk factors for osteoporosis. When performing a BMD test for the first time, it is essential to remember that 50% of women at menopause will have a negative T-score, but this does not imply that the patient has indeed lost any bone from her peak bone mass.

Comparison of cross-sectional geometry of the proximal femur in white and black women from Detroit and Johannesburg.

UNLABELLED: There are known black-white differences in bone density measured by DXA but less is known about bone architecture. We compared cross-sectional geometric properties of the proximal femur in U.S. black (n = 86) and white (n = 151) and South African black (n = 60) and white (n = 48) postmenopausal women. Results are consistent with greater bone strength in the black groups in both countries. INTRODUCTION: There are well-known ethnic differences in bone density, but little is known about ethnic differences in bone architecture between U.S. and South African blacks and whites. MATERIALS AND METHODS: We compared bone density and cross-sectional geometric properties of the proximal femur in 237 U.S. black (n = 86) and white (n = 151) and 108 South African black (n = 60) and white (n = 48) postmenopausal women. The proximal femur (neck, intertrochanteric region, and proximal shaft regions of interest) was measured with DXA and further analyzed with a hip structural analysis program. For each region, BMD, cross-sectional area, outer diameter, section modulus, endosteal diameter, average cortical thickness, and the buckling ratio were estimated. RESULTS AND CONCLUSIONS: In the femoral neck, in both countries, the blacks had narrower endosteal diameters (mean difference, 2.6% and 5.1% in U.S. and South African women, respectively), thicker cortices (9.3% and 11.0%), and a lower buckling ratio (11.6% and 15.2%) despite a similar outer diameter. In the intertrochanteric region, the whites had a greater outer diameter (2.2% and 3.0% in U.S. and South African women, respectively), lower cross-sectional area (4.8% and 7.2%), and a higher buckling ratio (7.6% and 3.6%). There are fewer differences in the shaft. Compared with South African whites, U.S. whites had wider (mean difference 2.9%) femoral necks and a greater section modulus (6.4%) in the shaft. U.S. whites also had greater cross-sectional area in both the neck and shaft (5.2% and 4.6%, respectively). The U.S. blacks had significantly greater outer diameters, cross-sectional areas, endosteal diameters, and section moduli in the neck region compared with South African blacks. Our observations are consistent with greater bone strength in the black groups in both countries, and they also suggest that there are fewer differences between the same ethnic groups in the two countries than there are between different ethnic groups within a country.

Trabecular and integral bone density in adults with sickle cell disease.

Sickle cell disease (SCD) is a hereditary disorder of hemoglobin synthesis that can affect the skeletal system owing to accelerated hematopoiesis and/or bone infarction. Additionally, several studies have suggested that a low bone mass is associated with SCD, partly because of adverse effects on growth and development. The few previous studies of bone mineral density (BMD) in these patients have utilized dual-photon or dual-energy x-ray absorptiometric (DXA) techniques, which may have limited value in this population because it cannot correct for differences in bone size. We undertook a study of BMD in the forearm of patients with sickle cell disease using peripheral quantitative computed tomography (QCT), which provides a measure of volumetric bone density for the trabecular bone component as well as cortical and trabecular bone together. We studied 32 African-American SCD patients with no known history of bone infarction in the wrist, and compared them with data from healthy African-American volunteers. We found a 13% lower integral (cortical and trabecular) BMD in the SCD patients (p=0.001), but no difference in trabecular BMD (p=0.40 for males, 0.32 for females). We hypothesize that the maintenance of trabecular BMD in the wrist may be related to the persistence of metabolically active red marrow in this region in adults with SCD.

Radiographic measurements, bone mineral density, and the Singh Index in the proximal femur of white and black postmenopausal women.

BACKGROUND: Radiographic measurements, bone mineral density (BMD), and the Singh Index were examined to assess ethnic differences in the architecture and trabecular patterns in the proximal femur. METHODS: We measured height (cm), weight (kg), and the following radiographic variables in 326 white and black postmenopausal women participating in the Women's Health Initiative at the Clinical Center in Detroit, MI: neck breadth, inferior neck cortical thickness, head diameter, subtrochanteric breadth, and subtrochanteric medial and lateral cortical thicknesses. Bone densitometry was performed by dual-energy x-ray absorptiometry (Hologic QDR 1000 plus; Hologic Inc, Bedford, MA) at 5 regional sites in the proximal femur. The Singh Index was read by its originator. RESULTS AND CONCLUSIONS: There was no significant ethnic difference in mean age, height, or body mass index, but weight and BMD was higher in the black group at all regional sites. The inferior neck cortical thickness was significantly greater in the black group. The Singh Index was found to be grade VI (normal) in 87%, grade V in 9%, and grades II-IV in 4% of all subjects. Multiple regression models explained 35% to 60% of the variance in the regional BMDs; the Singh Index, weight, and subtrochanteric cortical thicknesses were significant contributors to all regional hip BMD models. Although there were ethnic differences in BMD, there were no ethnic differences in the distribution of the Singh Index scores.

Genetic determinants of bone mass do not relate with breast cancer risk in US white and African-American women.

INTRODUCTION: The association between high bone mass and increased breast cancer risk has been established. Identification of polymorphisms and the resultant variant receptors suggests the possibility of differential effects on hormone responsive genes when complexed with the hormones. Both estrogen receptor-alpha (ER) and vitamin D receptor (VDR) polymorphisms have been associated with bone density. Thus, we examined these polymorphisms for association with increased breast cancer risk among US African-American and white women. METHODS: A case-control study was conducted to measure ER and VDR polymorphisms and radial bone mineral density (BMD) in African-American and white women, and to examine the association between polymorphisms, bone density and breast cancer risk. Genotypes and bone density were obtained from 412 women (220 cases and 192 controls, with equal distribution between the two ethnic groups). RESULTS: We found no evidence for an association between either the ER or VDR genotypes and breast cancer risk. Also, there was no difference in the risk of breast cancer by genotypes after adjusting for ethnicity. The addition of age, sex and ethnicity-specific BMD (Z-scores) did not significantly change the odds ratio for breast cancer. CONCLUSIONS: Our data suggest that the polymorphisms investigated had no effect on risk of breast cancer in this population. Thus, we found no evidence to support our hypothesis that breast cancer cases and controls would have a different distribution of ER and VDR genotypes. Furthermore, the polymorphisms were not associated with differences in bone mass and its relationship with breast cancer risk.

Sex and ethnic differences in bone architecture.

Technologic developments and applications such as dual energy x-ray absorptiometry, magnetic resonance imaging, and computed tomography have enabled researchers to assess bone quantity (ie, bone mineral density) and bone quality (ie, bone architecture), which are two important and independent contributions to bone strength. Recent studies on sex differences in bone architecture indicate that a number of biomechanical variables lead to increased bone strength in males compared with females. Ethnic differences in bone architecture are less clear-cut, indicating a need to identify and test the social and biologic variables that race and ethnicity represent. New methods using magnetic resonance imaging technology may become important in creating efficient and reliable in vivo methods of assessing features of bone architecture that are relevant to fracture risk and contribute to the elucidation of sex and ethnic differences in osteoporosis.