Within-night repeatability and long-term consistency of sleep apnea endotypes: the Multi-Ethnic Study of Atherosclerosis and Osteoporotic Fractures in Men Study.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by multiple "endotypic traits," including pharyngeal collapsibility, muscle compensation, loop gain, and arousal threshold. Here, we examined (1) within-night repeatability, (2) long-term consistency, and (3) influences of body position and sleep state, of endotypic traits estimated from in-home polysomnography in mild-to-severe OSA (apnea-hypopnea index, AHI > 5 events/h). METHODS: Within-night repeatability was assessed using Multi-Ethnic Study of Atherosclerosis (MESA): Traits derived separately from "odd" and "even" 30-min periods were correlated and regression (error vs. N windows available) provided a recommended amount of data for acceptable repeatability (Rthreshold = 0.7). Long-term consistency was assessed using the Osteoporotic Fractures in Men Study (MrOS) at two time points 6.5 ± 0.7 years apart, before and after accounting for across-year body position and sleep state differences. Within-night dependence of traits on position and state (MESA plus MrOS data) was estimated using bootstrapping. RESULTS: Within-night repeatability for traits ranged from R = 0.62-0.79 and improved to R = 0.69-0.83 when recommended amounts of data were available (20-35 7-min windows, available in 94%-98% of participants); repeatability was similar for collapsibility, loop gain, and arousal threshold (R = 0.79-0.83), but lower for compensation (R = 0.69). Long-term consistency was modest (R = 0.30-0.61) and improved (R = 0.36-0.63) after accounting for position and state differences. Position/state analysis revealed reduced loop gain in REM and reduced collapsibility in N3. CONCLUSIONS: Endotypic traits can be obtained with acceptable repeatability. Long-term consistency was modest but improved after accounting for position and state changes. These data support the use of endotypic assessments in large-scale epidemiological studies. CLINICAL TRIAL INFORMATION: The data used in the manuscript are from observational cohort studies and are not a part of the clinical trial.

Fracture prediction from FRAX for Canadian ethnic groups: a registry-based cohort study.

We identified large between-ethnicity calibration differences in the Canadian FRAX® tool which substantially overestimated the major osteoporotic fracture (MOF) risk in Asian women and Black women, and overestimated hip fracture risk in Asian women. PURPOSE: FRAX® is calibrated using population-specific fracture and mortality data. The need for FRAX to accommodate ethnic diversity within a country is uncertain. We addressed this question using the population-based Manitoba Bone Mineral Density (BMD) Program registry and self-reported ethnicity. METHODS: The study population was women aged 40 years or older with baseline FRAX assessments (Canadian and other ethnic calculators), fracture outcomes, and self-reported ethnicity (White N = 68,907 [referent], Asian N = 1910, Black N = 356). Adjusted hazard ratios (HR) with 95% confidence intervals (CI) for time to MOF and hip fracture were estimated. We examined candidate variables from DXA that might contribute to ethnic differences including skeletal size, hip axis length (HAL), trabecular bone score (TBS), and estimated body composition. RESULTS: Adjusted for baseline risk using the Canadian FRAX tool with BMD, Asian women compared with White women were at much lower risk for MOF (HR 0.46, 95% CI 0.35-0.59) and hip fracture (0.16, 95% CI 0.08-0.34). Black women were also at lower MOF risk (HR 0.58, 95% CI 0.32-1.00); there were no hip fractures. The US ethnic-specific FRAX calculators accounted for most of the between-ethnicity differences in MOF risk (86% for Asian, 92% for Black) but only partially accounted for lower hip fracture risk in Asian women (40%). The candidate variables explained only a minority of the effect of ethnicity. Gradient of risk in analyses was similar (p-interactions ethnicity*FRAX non-significant). CONCLUSIONS: We identified significant ethnic differences in performance of the Canadian FRAX tool with fracture probability overestimated among Asian and Black women. The US ethnic calculators helped to address this discrepancy for MOF risk assessment, but not for hip fracture risk among Asian women.

Racial Disparities Exist in Outcomes After Major Fragility Fractures.

BACKGROUND: Fractures associated with postmenopausal osteoporosis (PMO) are associated with pain, disability, and increased mortality. A recent, nationwide evaluation of racial difference in outcomes after fracture has not been performed. OBJECTIVE: To determine if 1-year death, debility, and destitution rates differ by race. DESIGN: Observational cohort study. SETTING: US Medicare data from 2010 to 2016. PARTICIPANTS: Non-Hispanic black and white women with PMO who have sustained a fragility fracture of interest: hip, pelvis, femur, radius, ulna, humerus, and clinical vertebral. MEASUREMENTS: Outcomes included 1-year: (1) mortality, identified by date of death in Medicare vital status information, (2) debility, identified as new placement in long-term nursing facilities, and (3) destitution, identified as becoming newly eligible for Medicaid. RESULTS: Among black and white women with PMO (n = 4,523,112), we identified 399,000 (8.8%) women who sustained a major fragility fracture. Black women had a higher prevalence of femur (9.0% vs 3.9%; P < .001) and hip (30.7% vs 28.0%; P < .001) fractures and lower prevalence of radius/ulna (14.7% vs 17.0%; P < .001) and clinical vertebral fractures (28.8% vs 33.5%; P < .001) compared with white women. We observed racial differences in the incidence of 1-year outcomes after fracture. After adjusting for age, black women had significantly higher risk of mortality 1 year after femur, hip, humerus, and radius/ulna fractures; significantly higher risk of debility 1 year after femur and hip fractures; and significantly higher risk of destitution for all fractures types. CONCLUSIONS: In a sample of Medicare data from 2010 to 2016, black women with PMO had significantly higher rates of mortality, debility, and destitution after fracture than white women. These findings are a first step toward understanding and reducing disparities in PMO management, fracture prevention, and clinical outcomes after fracture. J Am Geriatr Soc 68:1803-1810, 2020.

Transcultural adaptation and psychometric properties of the Korean version of the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO-41).

We translated and adapted transculturally the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO-41) for Korean patients. The translated Korean version of QUALEFFO-41 showed satisfactory reliability and validity. PURPOSE: The aim of this study was to translate the QUALEFFO-41 for Korean patients and then validate the Korean version of QUALEFFO-41. METHODS: Translation and transcultural adaptation of the QUALEFFO-41 was conducted according to the international recommendations. Ninety-seven patients (mean age, 73.6 years) with osteoporosis were participated in validating the Korean version of QUALEFFO-41. To test reliability, internal consistency was evaluated using Cronbach's alpha coefficient. To test validity, convergent validity was assessed using correlation with the SF-12 and EQ-5D and discriminant validity was assessed using ROC curve analysis. RESULTS: The English version of QUALEFFO-41 was translated and adapted to Korean without notable discrepancies. The Korean QUALEFFO-41 had good reliability with Cronbach's alpha ranging from 0.733 to 0.942. QUALEFFO-41 had good correlations to SF-12 and EQ-5D. Compared with subjects without history of vertebral fracture (VF), those with history of VF showed significantly worse scores according to QUALEFFO-41, but not according to SF-12 or EQ-5D. ROC curve analysis revealed that the physical function domain of QUALEFFO-41 had significant ability to discriminate between subjects with and without history of VF, while SF-12 or EQ-5D did not. CONCLUSIONS: The Korean version of QUALEFFO-41 demonstrated relevant internal consistency, convergent validity, and discriminant validity, which can be recommended to evaluate quality of life in Koreans.

Incidence and excess mortality of hip fractures in a predominantly Caucasian population in the South of Brazil.

INTRODUCTION: Osteoporosis is a very common disease, and data on its epidemiology is important for health care strategy implementation. Brazil is a developing country; its population is aging, leading to an expected increase in hip fractures and their undesirable consequences. OBJECTIVE: Assess the incidence of osteoporotic hip fractures and subsequent mortality in Southern Brazil as part of a large epidemiological study aiming to reinforce the data for FRAX Brazil. STUDY DESIGN: This study evaluated all admissions for fragility hip fractures between April 1, 2010, and March 31, 2012, in the city of Joinville, including both genders of patients 50 years old or older, which corresponded to 19.2% of the local population. Joinville was chosen because it is the third largest city in the south of Brazil, with a representative population predominantly composed of descendants of European immigrants. RESULTS: There were 213 cases of hip fractures, predominantly in Caucasians (n = 204, 96.7%) whose mean age was 77.7, ± 10.5, of which 143 (67.1%) were women (79.5 ± 9.6 years) and 70 (32.9%) were men (74 ± 11.3 years). The annual incidence of hip fractures was 268.8 for women and 153.0 for men/100,000 inhabitants. In the 60 to 64-year group, the overall incidence was 92.1/100,000, with an age-related increase of 1410.1/100,000 in the 80 to 84-year group. The mortality rate during hospitalization was 7.5%, and 25% died during the 12 months following their fractures. CONCLUSION: The incidence of hip fractures among the oldest in this predominantly Caucasian population living in Southern Brazil was similar to that of European populations from the northern hemisphere. The annual incidence of fragility hip fractures among people in their 80s was 59 times higher than that among people in their 50s. The mortality rate was 4.3 times higher in the first year after hip fracture than in the age-related local population.

Genetic risk factors identified in populations of European descent do not improve the prediction of osteoporotic fracture and bone mineral density in Chinese populations.

Aiming to investigate whether genetic risk factors (GRFs) for fracture and bone mineral density (BMD) identified from people of European descent can help improve the prediction of osteoporotic fracture (OF) risk and BMD in Chinese populations, we built assessment models for femoral neck (FN)-fracture prediction and BMD value prediction using 700 elderly Chinese Han subjects and 1,620 unrelated Chinese Han subjects, respectively. 17 fracture-associated genes and 82 FN-BMD associated genes identified in people of European descent were used to build a logistic regression model with clinical risk factors (CRFs) for FN-fracture prediction in Chinese. Meanwhile 107 BMD-associated genes from people of European descent were used to build a multiple linear regression model with CRFs for BMD prediction in Chinese. A Lasso algorithm was employed for informative SNP selection to construct the genetic risk score (GRS) with ten-fold cross-validation. The results showed that, adding fracture GRF and FN-BMD GRF to the model with CRFs, the area under the receiver operating characteristic curve (AUC) decrease from 0.653 to 0.587 and 0.588, respectively, for FN fracture prediction. 62.3% and 61.8% of the risk variation were explained by the Model with CRFs and fracture GRF and by the Model with CRFs and FN-BMD GRF, respectively, as compared to 65.5% in the Model with CRFs only. The net reclassification improvement (NRI) index in the reclassification analysis is 0.56% (P = 0.57) and 1.13% (P = 0.29), respectively. There is no significant difference either between the performance of the model with CRFs and that of the model with both CRFs and GRF for BMD prediction. We concluded that, in the current study, GRF of fracture identified in people of European descent does not contributes to improve the fracture prediction in Chinese; and GRF of BMD from people of European descent cannot help improve the accuracy of the fracture prediction in Chinese perhaps partially because GRF of BMD from people of European descent may not contribute to BMD prediction in Chinese. This study highlights the limited utility of the current genetics studies largely focused on people of European descent for disease or risk factor prediction in other ethnic groups, and calls for more and larger scale studies focused on other ethnic groups.

Hip fractures in Singapore: ethnic differences and temporal trends in the new millennium.

Despite an increase in absolute numbers, the age-standardized incidence of hip fractures in Singapore declined in the period 2000 to 2017. Among the three major ethnic groups, Chinese women had the highest fracture rates but were the only group to show a temporal decline. INTRODUCTION: A study published in 2001 predicted a 30-50% increase in Singapore hip fracture incidence rates over the ensuing 30 years. To test that prediction, we examined the incidence of hip fracture in Singapore from 2000 to 2017. METHODS: We carried out a population-based study of hip fractures among Singapore residents aged ≥ 50 years. National medical insurance claims data were used to identify admissions with a primary discharge diagnosis of hip fracture. Age-adjusted rates, based on the age distribution of the Singapore population of 2000, were analyzed separately by sex and ethnicity (Chinese, Malay, or Indian). RESULTS: Over the 18-year study period, 36,082 first hip fractures were recorded. Total hip fracture admissions increased from 1487 to 2729 fractures/year in the years 2000 to 2017. Despite this absolute increase, age-adjusted fracture rates declined, with an average annual change of - 4.3 (95% CI - 5.0, - 3.5) and - 1.1 (95% CI - 1.7, - 0.5) fractures/100,000/year for women and men respectively. Chinese women had 1.4- and 1.9-fold higher age-adjusted rates than Malay and Indian women: 264 (95% CI 260, 267) versus 185 (95% CI 176, 193) and 141 (95% CI 132, 150) fractures/100,000/year, respectively. Despite their higher fracture rates, Chinese women were the only ethnic group exhibiting a decline, most evident in those ≥ 85 years, in age-adjusted fracture rate of - 5.3 (95% CI - 6.0, - 4.5) fractures/100,000/year. CONCLUSION: Although the absolute number of fractures increased, steep drops in elderly Chinese women drove a reduction in overall age-adjusted hip fracture rates. Increases in the older population will lead to a rise in total number of hip fractures, requiring budgetary planning and new preventive strategies.

FRAX® based intervention thresholds for management of osteoporosis in Singaporean women.

Potential FRAX®-based major osteoporotic fracture (MOF) and hip fracture (HF) intervention thresholds (ITs) for postmenopausal Singaporean women were explored. Age-dependent ethnic-specific and weighted mean ITs progressively increased with increasing age. Fixed ITs were derived via discriminatory value analysis. MOF and HF ITs with highest the Youden index were chosen as optimal. INTRODUCTION: We aimed to explore FRAX®-based intervention thresholds (ITs) to potentially guide osteoporosis treatment in Singapore, a multi-ethnic nation. METHOD: One thousand and one Singaporean postmenopausal community-dwelling women belonging to Chinese, Malay and Indian ethnicities underwent clinical risk factor (CRF) and BMD assessment. FRAX® major osteoporotic fracture (MOF) and hip fracture (HF) probabilities were calculated using ethnic-specific models. We employed the translational logic adopted by NOGG (UK), whereby osteoporosis treatment is recommended to any postmenopausal woman whose fracture probability based on other CRFs is similar to or exceeds that of an age-matched woman with a fracture. Using the same logic, ethnic-specific and mean weighted age-dependent ITs were computed. Employing these age-dependent ITs as a reference, the performance of fixed (age-independent) ITs were examined using ROC curves and discriminatory analysis, with the highest Youden index (YI) (sensitivity + specificity - 1) used to identify the optimal MOF and HF ITs. RESULTS: The mean age was 58.9 (6.9) years. Seven hundred and eighty-nine (79%) women were Chinese, 136 (13.5%) Indian and 76 (7.5%) Malay. Age-dependent MOF ITs ranged from 3.1 to 33%, 2.5 to 17% and 2.5 to 16% whilst HF ITs ranged from 0.7 to 17%, 0.4 to 6% and 0.4 to 6.3% in Chinese, Malay and Indian women, respectively, between the ages of 50 and 90 years. The weighted age-dependent MOF and HF ITs ranged from 2.9% and 0.6%, respectively, at the age of 50, to 28% and 14% at 90 years of age. Fixed MOF/HF ITs of 5.5%/1%, 2.5%/1% and 2.5%/0.25% were identified as the most optimal by the highest YI in Chinese, Malay and Indian women, respectively. Fixed MOFP and HF ITs of 4% and 1%, respectively, were found to be most optimal on the weighted means analysis. CONCLUSION: The ITs for osteoporosis treatment in Singapore show marked variations across ethnicities. Weighted mean thresholds may overcome the dilemma of intervening at different thresholds for different ethnicities. Choosing fixed ITs may have to involve trade-offs between sensitivity and specificity. FRAX®-based age-dependent or the fixed intervention thresholds suggested as an alternative to be considered for use in Singapore though further studies on the societal and health economic impacts of choosing these thresholds in Singapore are needed.

Relationship of American Indian blood quantum with osteoporosis risk: a cross-sectional study of American Indian women in Oklahoma.

Information regarding the prevalence and risk of osteoporosis among American Indian (AI) women is limited. This study showed that with increasing AI blood quantum, the prevalence of osteoporosis at the hip based on BMD T-scores decreased and this appeared to be independent of other risk factors. INTRODUCTION: This study was designed to investigate the effects of AI blood quantum (BQ) on osteoporosis prevalence and risk in a cohort of AI women in Oklahoma. METHODS: Women (n = 301), aged 50 years and older, were recruited to participate in the Oklahoma American Indian Women's Osteoporosis Study. Baseline bone density, fracture history, bone biochemical markers, and potential risk factors were assessed. Participants were stratified by AI BQ into BQ1 ≤ 25%, BQ2 = 25-49%, BQ3 = 50-74%, and BQ4 = 75-100%. The effects of BQ on the prevalence and risk of osteoporosis were evaluated. RESULTS: Based on T-scores, one in approximately eight women in the study was osteoporotic at one or more sites. The prevalence of osteoporosis decreased (p < 0.05) with increasing BQ, especially at the hip, trochanteric, and intertrochanter regions. No differences in bone-specific alkaline phosphatase and C-telopeptide were observed across BQ that could account for the differences in bone density. 25-OH vitamin D decreased with increasing BQ, but mean for each BQ1-4 was > 40 ng/mL. Fracture history did not differ across BQ, and though 52% of the population consumed less than the RDA for calcium, no effect of BQ was observed. CONCLUSIONS: In this cohort of women who identified as AI, greater Indian BQ was associated with a decrease in the prevalence of osteoporosis.

Association of trabecular bone score (TBS) and prior fracture differs among minorities in NHANES 2005-2008.

The study investigates the association of trabecular bone score (TBS) and fractures among minority populations. In NHANES 2005-2008, TBS was associated with history of fractures in Caucasian subjects but demonstrated somewhat weaker associations in African American and Mexican American women. INTRODUCTION: Trabecular bone score (TBS), a textural analysis of the lumbar spine DXA image, predicts fractures well in Caucasian (CA) and Asian populations but is less well studied in African American (AA) and Mexican American (MA) subjects. It is not clear whether TBS is associated with or is predictive of fragility in these racial/ethnic groups. METHODS: We analyzed data from subjects from NHANES 2005-2008 over the age of 40 who had TBS: 1178 CA, 467 AA, and 397 MA women and 1200 CA, 502 AA, and 386 MA men. TBS was categorized into normal, ≥ 1.310, partially degraded < 1.310, and > 1.230, or degraded, ≤ 1.230. History of fracture was assessed by questionnaire. RESULTS: Among women, there was an increasing prevalence of fracture with worsening TBS category. However, when controlling for age, BMI, and low T-score, the association between TBS category and previous fracture was only significant in CA women (OR 1.49 per worsening category, 95% CI 1.20-1.85). In men, there was also an increase in the prevalence of fracture with worsening TBS category in all races/ethnicities. When controlling for age, BMI, and low T-score, the association between TBS category and previous fracture was only significant in CA men (OR 1.47 per worsening category, 95% CI 1.10-1.95), though analysis was somewhat limited by small fracture numbers. CONCLUSIONS: The association of fracture and TBS varies by race/ethnicity and gender with weaker association observed in AA and MA women. More research is needed to define the proper use of TBS for predicting fractures in minority groups.

Volumetric bone mineral density of the spine predicts mortality in African-American men with type 2 diabetes.

The study showed that in African-American men with type 2 diabetes mellitus (T2D), vertebral volumetric bone mineral density (vBMD) predicts all-cause mortality, independent of other risk factors for death. INTRODUCTION: Compared to European Americans, African Americans have lower rates of osteoporosis and higher rates of T2D. The relationships between BMD and fractures with mortality are unknown in this population. The aim of this study was to determine relationships between vertebral fractures and vertebral vBMD and mortality in African Americans with T2D. METHODS: Associations between vertebral fractures and vBMD with all-cause mortality were examined in 675 participants with T2D (391 women and 284 men) in the African American-Diabetes Heart Study (AA-DHS). Lumbar and thoracic vBMD were measured using quantitative computed tomography (QCT). Vertebral fractures were assessed on sagittal CT images. Associations of vertebral fractures and vBMD with all-cause mortality were determined in sex-stratified analyses and in the full sample. Covariates in a minimally adjusted model included age, sex, BMI, smoking, and alcohol use; the full model was adjusted for those variables plus cardiovascular disease, hypertension, coronary artery calcified plaque, hormone replacement therapy (women), African ancestry proportion, and eGFR. RESULTS: After mean 7.6 ± 1.8-year follow-up, 59 (15.1%) of women and 58 (20.4%) of men died. In men, vBMD was inversely associated with mortality in the fully adjusted model: lumbar hazard ratio (HR) per standard deviation (SD) = 0.70 (95% CI 0.52-0.95, p = 0.02) and thoracic HR per SD = 0.71 (95% CI 0.54-0.92, p = 0.01). Only trends toward association between vBMD and mortality were observed in the combined sample of men and women, as significant associations were absent in women. Vertebral fractures were not associated with mortality in either sex. CONCLUSIONS: Lower vBMD was associated with increased all-cause mortality in African-American men with T2D, independent of other risk factors for mortality including subclinical atherosclerosis.

Volumetric bone mineral density (vBMD), bone structure, and structural geometry among rural South Indian, US Caucasian, and Afro-Caribbean older men.

Peripheral quantitative computed tomography (pQCT) provides biomechanical estimates of bone strength. Rural South Indian men have reduced biomechanical indices of bone strength compared to US Caucasian and Afro-Caribbean men. This suggests an underlying higher risk of osteoporotic fractures and greater future fracture burden among the rural South Indian men. INTRODUCTION: Geographical and racial comparisons of bone mineral density (BMD) have largely focused on DXA measures of areal BMD. In contrast, peripheral quantitative computed tomography (pQCT) measures volumetric BMD (vBMD), bone structural geometry and provides estimates of biomechanical strength. To further understand potential geographical and racial differences in skeletal health, we compared pQCT measures among US Caucasian, Afro-Caribbean, and rural South Indian men. METHODS: We studied men aged ≥ 60 years enrolled in the Mobility and Independent Living among Elders Study (MILES) in rural south India (N = 245), Osteoporotic Fractures in Men Study (MrOS) in the US (N = 1148), and the Tobago Bone Health Study (N = 828). RESULTS: The BMI (kg/m2) of rural South Indian men (21.6) was significantly lower compared to the US Caucasians (28) and Afro-Caribbean men (26.9). Adjusting for age, height, body weight, and grip strength; rural South Indian men compared to US Caucasians had significantly lower trabecular vBMD [- 1.3 to - 1.5 standard deviation (SD)], cortical thickness [- 0.8 to - 1.2 SD]; significantly higher endosteal circumference [0.5 to 0.8 SD]; but similar cortical vBMD. Afro-Caribbean men compared to US Caucasians had similar trabecular vBMD but significantly higher cortical vBMD [0.9 to 1.2 SD], SSIp [0.2 to 1.4 SD], and tibial endosteal circumference [1 SD], CONCLUSIONS: In comparison to US Caucasians, rural South Indian men have reduced bone strength (lower trabecular vBMD) and Afro-Caribbean men have greater bone strength (higher cortical vBMD). These results suggest an underlying higher risk of osteoporotic fractures and greater future fracture burden among rural South Indian men.

Impact of Sexual Dimorphism on Trauma Patterns and Clinical Outcomes of Patients with a High-Risk Score of the Osteoporosis Self-Assessment Tool for Asians: A Propensity Score-Matched Analysis.

The Osteoporosis Self-assessment Tool for Asians (OSTA) is a validated index based on age and weight to predict the risk of osteoporosis in women. This cross-sectional study was designed to evaluate the impact of sexual dimorphism on the trauma patterns and the clinical outcomes of patients with high-risk OSTA scores. Trauma data of patients with high-risk OSTA scores between 1 January 2009 and 31 December 2015 were retrieved from the trauma registry system of a level I trauma center. A total of 2248 patients including 1585 women and 663 men were included in this study. In-hospital mortality was assessed as the primary outcome in the propensity score-matched analyses of the female and male patients, which were created in a 1:1 ratio under the adjustment of potential confounders, including age, co-morbidity, mechanism and injury-severity score (ISS). Female patients with a high-risk OSTA score had significantly lower mortality rates than their male counterparts. Among the propensity score-matched population, female patients had lower odds of having cerebral contusion and pneumothorax, but higher odds of presenting with radial, ulnar and femoral fractures than male patients. In addition, the female patients still had significantly lower odds of mortality (odds ratio (OR), 0.5; 95% confidence interval (CI), 0.29-0.90; p = 0.019) than the male patients. However, no significant differences were noted in the length of stay (LOS) in hospital, intensive-care unit (ICU) admission, and LOS in the ICU between the sexes. Female patients with high-risk OSTA scores showed different injury patterns and significantly lower mortality rates than their male counterparts, even after controlling for potential confounding factors.

Ethnic Variations in Serum 25(OH)D Levels and Bone Ultrasound Attenuation Measurements in Blacks and Whites.

Vitamin D deficiency is more common in Blacks, yet Blacks have lower prevalence of bone fragility fractures or osteoporosis than Whites. Broadband ultrasound attenuation (BUA) has been used to explore the association between serum 25(OH)D levels and bone quality in White and non-white populations. We investigated serum 25(OH)D status with corresponding BUA measurements assessed cross sectionally in a cohort of 232 Blacks and 260 Whites, aged 30-95 years who were part of the calibration study of the large Adventist Health Study-2 (AHS-2). At the calibration clinics, calcaneal BUA was measured and blood drawn for serum 25(OH)D assessment. In multivariable analyses, BUA was negatively associated with age (ß-coefficient = -0.38; p < 0.0001) and positively associated with body mass index (BMI) (p (trend) < 0.0001) and positively, but non-significantly, associated with serum 25(OH)D levels. Also, as expected, females had lower BUA (ß-coefficient = -5.19; p < 0.05) and Blacks had higher BUA (ß-coefficient = 4.26; p < 0.05). Gender and race modified the relationship of serum 25(OH)D on BUA with a positive association in males (p (trend) ≤ 0.05), but no significant association in females after also controlling for menopausal status and hormone therapy. After also controlling for serum 25(OH)D levels, Black males had higher BUA than White men, but such differences were not found among the females. When stratifying on race, a positive association between serum 25(OH)D levels and BUA (p (trend) ≤ 0.05) was found in Blacks, but not among Whites. Further studies are needed to understand how racial/ethnic differences in serum 25(OH)D levels influence bone health.

Total Hip Bone Area Affects Fracture Prediction With FRAX® in Canadian White Women.

Context: Areal bone mineral density (BMD) measurements are confounded by skeletal size. Hip BMD is an input to the FRAX® tool (Centre for Metabolic Bone Diseases, University of Sheffield, United Kingdom), but it is unknown whether performance is affected by hip area. Objective: To examine whether fracture prediction by FRAX® is affected by hip area. Design and Setting: Cohort study using a population-based BMD registry. Patients: A total of 58,108 white women aged ≥40 years. Main Outcome Measures: Incident major osteoporotic fracture (MOF; n = 4913) and hip fracture (n = 1369), stratified by total hip area quintile, before and after adjustment for hip axis length (HAL). Results: Smaller hip area was associated with younger age and lower FRAX® scores, whereas incident fractures were greater in those with larger hip area (P for trend < 0.001). Larger hip area quintile increased risk for MOF and hip fracture when adjusted for FRAX® score with BMD (P for trend < 0.001). Each standard deviation increase in hip area was associated with greater risk for incident MOF [adjusted hazard ratio (HR), 1.08; 95% confidence interval (CI), 1.05 to 1.11] and hip fracture (HR, 1.16; 95% CI, 1.11 to 1.21), but not after adjustment for HAL. FRAX® with BMD underestimated MOF risk in the largest hip area quintile and underestimated hip fracture risk in the three largest hip area quintiles. Conclusions: In Canadian white women, skeletal size based on hip area affects fracture risk assessment based on FRAX® score with BMD, with risk underestimated in those with larger hip areas. Including HAL in the risk assessment compensates for this confounding by skeletal size and provides for more accurate assessment of fracture risk.

Vertebral heights and ratios are not only race-specific, but also gender- and region-specific: establishment of reference values for mainland Chinese.

This study established gender-specific reference values in mainland Chinese (MC) and is important for quantitative morphometry for diagnosis and epidemiological study of osteoporotic vertebral compressive fracture. Comparisons of reference values among different racial populations are then performed to demonstrate the MC-specific characteristic. PURPOSE: Osteoporotic vertebral compressive fracture (OVCF) is a common complication of osteoporosis in the elder population. Clinical diagnosis and epidemiological study of OVCF often employ quantitative morphometry, which relies heavily on the comparison of patients' vertebral parameters to existing reference values derived from the normal population. Thus, reference values are crucial in clinical diagnosis. To our knowledge, this is the first study to establish reference values of the mainland Chinese (MC) for quantitative morphometry. METHODS: Vertebral heights including anterior (Ha), middle (Hm), posterior (Hp) heights, and predicted posterior height (pp) from T4 to L5 were obtained; and ratios of Ha/Hp, Hm/Hp and Hp/pp. were calculated from 585 MC (both female and male) for establishing reference values and subsequent comparisons with other studies. RESULTS: Vertebral heights increased progressively from T4 to L3 but then decreased in L4 and L5. Both genders showed similar ratios of vertebral dimensions, but male vertebrae were statistically larger than those of female (P < 0.01). Vertebral size of MC population was smaller than that of US and UK population, but was surprisingly larger than that of Hong Kong Chinese, although these two are commonly considered as one race. Data from different racial populations showed similar dimensional ratios in all vertebrae. CONCLUSIONS: We established gender-specific reference values for MC. Our results also indicated the necessity of establishing reference values that are not only race- and gender-specific, but also population- or region-specific for accurate quantitative morphometric assessment of OVCF.

Worldwide Fracture Prediction.

The substantial increase in the burden of non-communicable diseases in general and osteoporosis in particular, necessitates the establishment of efficient and targeted diagnosis and treatment strategies. This chapter reviews and compares different tools for osteoporosis screening and diagnosis; it also provides an overview of different treatment guidelines adopted by countries worldwide. While access to dual-energy X-ray absorptiometry to measure bone mineral density (BMD) is limited in most areas in the world, the introduction of risk calculators that combine risk factors, with or without BMD, have resulted in a paradigm shift in osteoporosis screening and management. To-date, forty eight risk assessment tools that allow risk stratification of patients are available, however only few are externally validated and tested in a population-based setting. These include Osteoporosis Self-Assessment Tool; Osteoporosis Risk Assessment Instrument; Simple Calculated Osteoporosis Risk Estimation; Canadian Association of Radiologists and Osteoporosis Canada calculator; Fracture Risk Assessment Calculator (FRAX); Garvan; and QFracture. These tools vary in the number of risk factors incorporated. We present a detailed analysis of the development, characteristics, validation, performance, advantages and limitations of these tools. The World Health Organization proposes a dual-energy X-ray absorptiometry-BMD T-score ≤ -2.5 as an operational diagnostic threshold for osteoporosis, and many countries have also adopted this cut-off as an intervention threshold in their treatment guidelines. With the introduction of the new fracture assessment calculators, many countries chose to include fracture risk as one of the major criteria to initiate osteoporosis treatment. Of the 52 national guidelines identified in 36 countries, 30 included FRAX derived risk in their intervention threshold and 22 were non-FRAX based.  No universal tool or guideline approach will address the needs of all countries worldwide.  Osteoporosis screening and management guidelines are best tailored according to the needs and resources of individual counties. While few countries have succeeded in generating valuable epidemiological data on osteoporotic fractures, to validate their risk calculators and base their guidelines, many have yet to find the resources to assess variations and secular trends in fractures, the performance of various calculators, and ultimately adopt the most convenient care pathway algorithms.

Targeted next generation sequencing of the entire vitamin D receptor gene reveals polymorphisms correlated with vitamin D deficiency among older Filipino women with and without fragility fracture.

This study aimed to discover genetic variants in the entire 101 kB vitamin D receptor (VDR) gene for vitamin D deficiency in a group of postmenopausal Filipino women using targeted next generation sequencing (TNGS) approach in a case-control study design. A total of 50 women with and without osteoporotic fracture seen at the Philippine Orthopedic Center were included. Blood samples were collected for determination of serum vitamin D, calcium, phosphorus, glucose, blood urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase and as primary source for targeted VDR gene sequencing using the Ion Torrent Personal Genome Machine. The variant calling was based on the GATK best practice workflow and annotated using Annovar tool. A total of 1496 unique variants in the whole 101-kb VDR gene were identified. Novel sequence variations not registered in the dbSNP database were found among cases and controls at a rate of 23.1% and 16.6% of total discovered variants, respectively. One disease-associated enhancer showed statistically significant association to low serum 25-hydroxy vitamin D levels (Pearson chi-square P-value=0.009). The transcription factor binding site prediction program PROMO predicted the disruption of three transcription factor binding sites in this enhancer region. These findings show the power of TNGS in identifying sequence variations in a very large gene and the surprising results obtained in this study greatly expand the catalog of known VDR sequence variants that may represent an important clue in the emergence of vitamin D deficiency. Such information will also provide the additional guidance necessary toward a personalized nutritional advice to reach sufficient vitamin D status.

Ethnic Differences in Trabecular Bone Score.

Trabecular bone score (TBS), a noninvasive textural analysis of the lumbar spine dual-energy X-ray absorptiometry (DXA) image, has been shown to predict fractures in Caucasian (CA) populations but has not been thoroughly studied in African-American (AA) populations. The aim of this study was to compare the TBS in AAs and CAs and to assess whether TBS can be used to refine fracture risk stratification in AA patients. Eight hundred twenty-five women (390 AAs, 435 CAs) referred for bone mineral density (BMD) as part of their clinical care had measurements of the TBS, the BMD of the lumbar spine, total hip, and femoral neck, and vertebral fracture assessment for detection of vertebral fractures. Unadjusted TBS was higher in CA than AA (1.275 vs 1.238, p < 0.001), but this was no longer true after adjusting for age and tissue thickness. Interestingly, differences in TBS were still highly significant in those under 60 yr of age even with adjustment for tissue thickness, but not in older subjects. There were 74 CAs and 56 AAs with vertebral fractures on vertebral fracture assessment (17% vs 14%, p = 0.30). In CA, the odds ratio (OR) for prevalent vertebral fracture per SD decrease in TBS was 2.33 (p < 0.001), whereas in AA, the OR was 1.43 (p = 0.02). In a multivariate logistic regression model that also included age, BMD T-score, and glucocorticoid use, the association between TBS and prevalent vertebral fractures was still highly significant in CAs (OR 1.54, p = 0.008) but not in AAs (OR 1.23, p = 0.21). Our results suggest that TBS may be less discriminatory in regard to fracture risk in AAs than in CAs and that TBS may need to be used differently in these 2 ethnic groups.

Ethnic Differences in Osteoporosis After Cardiac Transplantation.

Cardiac transplantation is associated with a high risk of fracture. African Americans (AAs) are believed to have a lower risk of osteoporosis than Caucasians, but it is not clear whether they are also protected from osteoporosis resulting from the use of glucocorticoids and/or organ transplantation. We examined possible ethnic differences in 33 cardiac transplant recipients (16 AAs) in a cross-sectional analysis. In addition to bone mineral density and vertebral fracture assessment, we also compared biochemical variables, trabecular bone score, total body dual-energy X-ray absorptiometry, and disability. Overall fracture rates were low in both groups, with only 6 total subjects with fractures on vertebral fracture assessment or history of fracture. While T-scores were similar between groups, Z-scores were lower in AA with the difference reaching statistical significance when controlling for important covariates. The trabecular bone score was also lower in AAs than in Caucasians even when adjusting for age and tissue thickness (1.198 ± 0.140 vs 1.312 ± 0.140, p = 0.03). While AAs are generally thought to be protected from osteoporosis, our study instead suggests that AAs may be at higher risk of bone deterioration after cardiac transplantation and may need to be managed more aggressively than suggested by current guidelines.