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A trabecular plate-like phenotype is overrepresented in Chinese-American versus Caucasian women

Walker, M D; Shi, S; Russo, J J; Liu, X S; Zhou, B; Zhang, C; Liu, G; McMahon, D J; Bilezikian, J P; Guo, X E
UNLABELLED:This study used extreme phenotype selection to define two trabecular bone phenotypes in a cohort of Chinese-American and Caucasian women. A trabecular plate-predominant phenotype is more common in Chinese-Americans while the rod-predominant phenotype is more typical of Caucasians. The robustness of these phenotypic associations with respect to lifestyle factors suggests that this trait may have a genetic basis and that these phenotypes can be utilized in future genetic studies. INTRODUCTION/BACKGROUND:Compared to Caucasians, Chinese-Americans have more plate-like trabecular bone when measured by individual trabecula segmentation (ITS). These findings suggest a phenotypic difference between the races, which may be amenable to genetic analysis. We sought to identify a single ITS plate trait to pursue in genetic studies by conducting an extreme phenotype selection strategy to numerically define two distinct phenotypes-plate-like and rod-like-and determine whether the selected phenotypic associations were independent of lifestyle factors in order to conduct future genetic studies. METHODS:A previously described cohort of 146 Chinese-American and Caucasian women with high-resolution peripheral quantitative computed tomography imaging and ITS analyses were studied with logistic regression and receiver operator characteristic analyses. RESULTS:The tibial plate-to-rod (TPR) ratio was the best ITS discriminator of race. Using extreme phenotypic selection, two TPR ratio phenotypes were defined numerically: plate-like as a TPR ratio value in the highest quartile (≥1.336) and rod-like as a TPR ratio value in the lowest quartile (≤0.621). Women with a plate-like phenotype were 25.7 times more likely (95 % CI 7.3-90.1) to be Chinese-American than women with rod-like morphology. After controlling for constitutional and lifestyle covariates, women in the highest vs. lowest TPR ratio quartile were 85.0 times more likely (95 % CI 12.7-568.0) to be Chinese-American. CONCLUSION/CONCLUSIONS:Using extreme phenotype selection, we defined a plate- and rod-like trabecular bone phenotype for the TPR ratio trait. The former phenotype is more common in Chinese-American women, while the latter is more typical of Caucasian women. The robustness of these phenotypic associations after controlling for differences in constitution and lifestyle suggest that the TPR ratio may have a genetic basis and that the extreme phenotypes defined in this analysis can be utilized for future studies.
PMID: 25069706
ISSN: 1433-2965
CID: 5213352

Lower cortical porosity and higher tissue mineral density in Chinese American versus white women

Boutroy, Stephanie; Walker, Marcella D; Liu, X Sherry; McMahon, Donald J; Liu, George; Guo, X Edward; Bilezikian, John P
Asian women have lower rates of hip and forearm fractures compared to other racial groups despite lower areal bone mineral density (aBMD). We have demonstrated microarchitectural differences, including greater cortical thickness (Ct.Th) and cortical volumetric BMD (Ct.BMD), in Chinese American versus white women. Yet it is not known whether greater Ct.BMD in Chinese American women is a result of greater tissue mineral density (TMD) or reduced cortical porosity (Ct.Po). Using an advanced segmentation algorithm based on high-resolution peripheral quantitative computed tomography (HR-pQCT) images, we tested the hypothesis that Chinese American women have better cortical skeletal integrity owing to lower Ct.Po and higher Ct.TMD compared with white women. A total of 78 Chinese American women (49 premenopausal and 29 postmenopausal) and 114 white women (46 premenopausal and 68 postmenopausal) were studied. Premenopausal Chinese American versus white women had greater Ct.Th, Ct.BMD, and Ct.TMD at both the radius and tibia, and decreased Ct.Po (p < 0.05). A similar pattern was observed between postmenopausal Chinese American and white women. As expected, postmenopausal versus premenopausal women had lower Ct.BMD at the radius and tibia in both races (p < 0.001). Ct.Po largely increased between premenopausal and postmenopausal women, whereas Ct.TMD decreased by 3% to 8% (p < 0.001) in both races. Age-related differences in Ct.Po and Ct.TMD did not differ by race. In summary, both reduced Ct.Po and greater Ct.TMD explain higher Ct.BMD in Chinese American versus white women. Thicker and preserved cortical bone structure in Chinese American women may contribute to greater resistance to fracture compared to white women.
PMID: 23913668
ISSN: 1523-4681
CID: 5213322

Circulating sclerostin levels and markers of bone turnover in Chinese-American and white women

Costa, Aline G; Walker, Marcella D; Zhang, Chiyuan A; Cremers, Serge; Dworakowski, Elzbieta; McMahon, Donald J; Liu, George; Bilezikian, John P
CONTEXT/BACKGROUND:Chinese-American women have bone microarchitectural features that confer greater bone stiffness compared to white women, but the physiology underlying these findings has not been investigated. OBJECTIVE:The purpose of the study was to assess racial differences in serum sclerostin and bone turnover markers (BTMs), and to explore their associations with each other, volumetric bone mineral density (BMD), and bone microarchitecture in Chinese-American and white women. DESIGN AND SETTING/METHODS:We conducted a cross-sectional study at a university hospital. PARTICIPANTS/METHODS:We studied 138 women. RESULTS:Serum osteocalcin was 19-28% lower in pre- and postmenopausal Chinese-American vs white women, respectively (both P < .01). C-Terminal telopeptide of type I collagen (CTX) level was 18-22% lower in pre- and postmenopausal Chinese-American vs white women (both P < .05). Pre- vs postmenopausal differences in osteocalcin and CTX were greater in white vs Chinese-American women. Sclerostin levels were similar in both races, but BTMs were differentially associated with sclerostin by race and menopausal status. BTMs were not correlated with sclerostin in Chinese-Americans. CTX and bone-specific alkaline phosphatase were positively associated with sclerostin (r = 0.353, r = 0.458; both P < .05) in white premenopausal women. In contrast, in postmenopausal white women, the associations of sclerostin with amino-terminal propeptide of type I procollagen, isoform 5b of tartrate-resistant acid phosphatase, and CTX were negative (all P < .05). Adjusting for covariates, sclerostin was positively associated with areal BMD in both races. CONCLUSIONS:Lower BTMs in Chinese-American women and greater age-related differences in BTMs among white women provide a physiological framework to account for racial differences in BMD, microarchitecture, and fracture.
PMCID:3849675
PMID: 24037879
ISSN: 1945-7197
CID: 5213332

Trabecular bone score is associated with volumetric bone density and microarchitecture as assessed by central QCT and HRpQCT in Chinese American and white women

Silva, Barbara C; Walker, Marcella D; Abraham, Alice; Boutroy, Stephanie; Zhang, Chiyuan; McMahon, Donald J; Liu, George; Hans, Didier; Bilezikian, John P
Although high-resolution peripheral quantitative computed tomography (HRpQCT) and central quantitative computed tomography (QCT) studies have shown bone structural differences between Chinese American (CH) and white (WH) women, these techniques are not readily available in the clinical setting. The trabecular bone score (TBS) estimates trabecular microarchitecture from dual-energy X-ray absorptiometry spine images. We assessed TBS in CH and WH women and investigated whether TBS is associated with QCT and HRpQCT indices. Areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry, lumbar spine (LS) TBS, QCT of the LS and hip, and HRpQCT of the radius and tibia were performed in 71 pre- (37 WH and 34 CH) and 44 postmenopausal (21 WH and 23 CH) women. TBS did not differ by race in either pre- or postmenopausal women. In the entire cohort, TBS positively correlated with LS trabecular volumetric bone mineral density (vBMD) (r = 0.664), femoral neck integral (r = 0.651), trabecular (r = 0.641) and cortical vBMD (r = 0.346), and cortical thickness (C/I; r = 0.540) by QCT (p < 0.001 for all). TBS also correlated with integral (r = 0.643), trabecular (r = 0.574) and cortical vBMD (r = 0.491), and C/I (r = 0.541) at the total hip (p < 0.001 for all). The combination of TBS and LS aBMD predicted more of the variance in QCT measures than aBMD alone. TBS was associated with all HRpQCT indices (r = 0.20-0.52) except radial cortical thickness and tibial trabecular thickness. Significant associations between TBS and measures of HRpQCT and QCT in WH and CH pre- and postmenopausal women demonstrated here suggest that TBS may be a useful adjunct to aBMD for assessing bone quality.
PMCID:3818347
PMID: 24080513
ISSN: 1094-6950
CID: 5213342

Premenopausal and postmenopausal differences in bone microstructure and mechanical competence in Chinese-American and white women

Walker, Marcella D; Liu, X Sherry; Zhou, Bin; Agarwal, Shivani; Liu, George; McMahon, Donald J; Bilezikian, John P; Guo, X Edward
Compared to white women, premenopausal Chinese-American women have more plate-like trabecular (Tb) bone. It is unclear whether these findings are relevant to postmenopausal women and if there are racial differences in the deterioration of bone microarchitecture with aging. We applied individual trabecula segmentation and finite element analysis to high-resolution peripheral quantitative computed tomography images in premenopausal and postmenopausal Chinese-American and white women to quantify within-race age-related differences in Tb plate-versus-rod microarchitecture and bone stiffness. Race-menopause status interactions were assessed. Comparisons between races within menopause status were adjusted for age, height and weight. Comparisons between premenopausal and postmenopausal women were adjusted for height and weight. Adjusted analyses at the radius indicated that premenopausal Chinese-Americans had a higher plate bone volume fraction (pBV/TV), Tb plate-to-rod ratio (P-R ratio), and greater plate-plate junction densities (P-P Junc.D) versus white women (all p < 0.01), resulting in 27% higher Tb stiffness (p < 0.05). Greater cortical thickness and density (Ct.Th and Dcort) and more Tb plates led to 19% greater whole bone stiffness (p < 0.05). Postmenopausal Chinese-Americans had similar pBV/TV and P-P Junc.D, yet a higher P-R ratio versus white women. Postmenopausal Chinese-American versus white women had greater Ct.Th, Dcort, and relatively intact Tb plates, resulting in similar Tb stiffness but 12% greater whole bone stiffness (p < 0.05). In both races, Ct.Th and Dcort were lower in postmenopausal versus premenopausal women and there were no differences between races. Tb plate parameters were also lower in postmenopausal versus premenopausal women, but age-related differences in pBV/TV, P-R ratio, and P-P Junc D were greater (p < 0.05) in Chinese-Americans versus white women. There are advantages in cortical and Tb bone in premenopausal Chinese-American women. Within-race cross-sectional differences between premenopausal and postmenopausal women suggest greater loss of plate-like Tb bone with aging in Chinese-Americans, though thicker cortices and more plate-like Tb bone persists.
PMCID:3644543
PMID: 23299863
ISSN: 1523-4681
CID: 5213312

Volumetric bone mineral density at the spine and hip in Chinese American and White women

Walker, M D; Saeed, I; McMahon, D J; Udesky, J; Liu, G; Lang, T; Bilezikian, J P
UNLABELLED:This study evaluated racial differences in bone size and volumetric density at the spine and hip in pre- and postmenopausal Chinese American and White women. Compared with White women, Chinese American women have greater cortical volumetric bone density (vBMD) at the hip, congruent with the results at the peripheral skeleton. INTRODUCTION/BACKGROUND:Chinese American women have lower rates of fracture than White women despite lower areal bone density. At the forearm and tibia, however, Chinese American women have higher cortical vBMD as well as greater trabecular and cortical thickness, but smaller bone area as measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) compared with White women. Since HR-pQCT data are obtained at peripheral sites, it is unclear whether these differences are relevant to the clinically important lumbar spine and hip. This study assesses racial differences in bone size and vBMD at the spine and hip in Chinese American and White women. METHODS:QCT of the spine and hip was measured to assess racial differences in bone size, structure, and vBMD in pre- (n = 83) and postmenopausal (n = 50) Chinese American and White women. Data were adjusted for weight, height, physical activity, total calcium intake, parathyroid hormone, and 25-hydroxyvitamin D levels. RESULTS:Among premenopausal women, lumbar spine trabecular vBMD was 5.8% greater in Chinese American versus White women (p = 0.01). At the hip, cortical vBMD was 3% greater at the femoral neck (p = 0.05) and 3.6% greater at the total hip (p = 0.01) in premenopausal Chinese American compared with White women. Among postmenopausal women, there was no difference in lumbar spine trabecular vBMD. Cortical vBMD was 4% greater at the total hip (p = 0.02) and tended to be greater at the femoral neck (p = 0.058) in Chinese American versus White women. CONCLUSIONS:Consistent with earlier findings in the peripheral skeleton, cortical vBMD is greater at the hip in Chinese American versus White women.
PMCID:3552556
PMID: 22147209
ISSN: 1433-2965
CID: 5213302

Better skeletal microstructure confers greater mechanical advantages in Chinese-American women versus white women

Liu, X Sherry; Walker, Marcella D; McMahon, Donald J; Udesky, Julia; Liu, George; Bilezikian, John P; Guo, X Edward
Despite lower areal bone mineral density (aBMD), Chinese-American women have fewer fractures than white women. We hypothesized that better skeletal microstructure in Chinese-American women in part could account for this paradox. Individual trabecula segmentation (ITS), a novel image-analysis technique, and micro-finite-element analysis (µFEA) were applied to high-resolution peripheral quantitative computed tomography (HR-pQCT) images to determine bone microarchitecture and strength in premenopausal Chinese-American and white women. Chinese-American women had 95% and 80% higher plate bone volume fraction at the distal radius and tibia, respectively, as well as 20% and 18% higher plate number density compared with white women (p < .001). With similar rodlike characteristics, the plate-to-rod ratio was twice as high in the Chinese-American than in white trabecular bone (p < .001). Plate-rod junction density, a parameter indicating trabecular network connections, was 37% and 29% greater at the distal radius and tibia, respectively, in Chinese-American women (p < .002). Moreover, the orientation of the trabecular bone network was more axially aligned in Chinese-American women because axial bone volume fraction was 51% and 32% higher at the distal radius and tibia, respectively, than in white women (p < .001). These striking differences in trabecular bone microstructure translated into 55% to 68% (distal radius, p < .001) and 29% to 43% (distal tibia, p < .01) greater trabecular bone strength, as assessed by Young's moduli, in the Chinese-American versus the white group. The observation that Chinese-American women have a major microstructural advantage over white women may help to explain why their risk of fracture is lower despite their lower BMD.
PMCID:3551974
PMID: 21351150
ISSN: 1523-4681
CID: 5213292

Differences in bone microarchitecture between postmenopausal Chinese-American and white women

Walker, Marcella D; Liu, X Sherry; Stein, Emily; Zhou, Bin; Bezati, Ervis; McMahon, Donald J; Udesky, Julia; Liu, George; Shane, Elizabeth; Guo, X Edward; Bilezikian, John P
Chinese-American women have lower rates of hip and forearm fracture than white women despite lower areal bone density (aBMD) by dual X-ray absorptiometry (DXA). We recently reported higher trabecular (D(trab) ) and cortical (D(comp) ) bone density as well as greater trabecular (Tb.Th) and cortical thickness (C.Th) but smaller bone area (CSA), as measured by high-resolution peripheral quantitative computed tomography (HR-pQCT), in premenopausal Chinese-American compared with white women. These findings may help to account for the lower fracture rate among Chinese-American women but were limited to measurements in premenopausal women. This study was designed to extend these investigations to postmenopausal Chinese-American (n = 29) and white (n = 68) women. Radius CSA was 10% smaller in the Chinese-American versus the white group (p = .008), whereas their C.Th and D(comp) values were 18% and 6% greater (p < .001 for both). Tibial HR-pQCT results for cortical bone were similar to the radius, but Tb.Th was 11% greater in Chinese-American versus white women (p = .007). Tibial trabecular number and spacing were 17% lower and 20% greater, respectively, in Chinese-American women (p < .0001 for both). There were no differences in trabecular or whole-bone stiffness estimated by microstructural finite-element analysis, but Chinese-American women had a greater percentage of load carried by the cortical bone compartment at the distal radius and tibia. There was no difference in load distribution at the proximal radius or tibia. Whole-bone finite-element analysis may indicate that the thicker, more dense cortical bone and thicker trabeculae in postmenopausal Chinese-American women compensate for fewer trabeculae and smaller bone size.
PMID: 21305606
ISSN: 1523-4681
CID: 5213282

Application of high-resolution skeletal imaging to measurements of volumetric BMD and skeletal microarchitecture in Chinese-American and white women: explanation of a paradox

Walker, Marcella D; McMahon, Donald J; Udesky, Julia; Liu, George; Bilezikian, John P
Asian women have lower rates of hip and forearm fractures despite lower areal BMD (aBMD) by DXA compared with white women and other racial groups. We hypothesized that the lower fracture rates may be explained by more favorable measurements of volumetric BMD (vBMD) and microarchitectural properties, despite lower areal BMD. To address this hypothesis, we used high-resolution pQCT (HRpQCT), a new method that can provide this information noninvasively. We studied 63 premenopausal Chinese-American (n = 31) and white (n = 32) women with DXA and HRpQCT. aBMD by DXA did not differ between groups for the lumbar spine (1.017 +/- 0.108 versus 1.028 +/- 0.152 g/cm(2); p = 0.7), total hip (0.910 +/- 0.093 versus 0.932 +/- 0.134 g/cm(2); p = 0.5), femoral neck (0.788 +/- 0.083 versus 0.809 +/- 0.129 g/cm(2); p = 0.4), or one-third radius (0.691 +/- 0.052 versus 0.708 +/- 0.047 g/cm(2); p = 0.2). HRpQCT at the radius indicated greater trabecular (168 +/- 41 versus 137 +/- 33 mg HA/cm(3); p = <0.01) and cortical (963 +/- 46 versus 915 +/- 42 mg HA/cm(3); p < 0.0001) density; trabecular bone to tissue volume (0.140 +/- 0.034 versus 0.114 +/- 0.028; p = <0.01); trabecular (0.075 +/- 0.013 versus 0.062 +/- 0.009 mm; p < 0.0001) and cortical thickness (0.98 +/- 0.16 versus 0.80 +/- 0.14 mm; p < 0.0001); and lower total bone area (197 +/- 34 versus 232 +/- 33 mm(2); p = <0.001) in the Chinese versus white women and no difference in trabecular number, spacing, or inhomogeneity before adjustment for covariates. Similar results were observed at the weight-bearing tibia. At the radius, adjustment for covariates did not change the direction or significance of differences except for bone, which became similar between the groups. However, at the tibia, adjustment for covariates attenuated differences in cortical BMD and bone area and accentuated differences in trabecular microarchitecture such that Chinese women additionally had higher trabecular number and lower trabecular spacing, as well as inhomogeneity after adjustment. Using the high-resolution technology, the results provide a mechanistic explanation for why Chinese women have fewer hip and forearm fractures than white women.
PMID: 20001598
ISSN: 1523-4681
CID: 5213272

Determinants of bone mineral density in Chinese-American women

Walker, M D; Babbar, R; Opotowsky, A; McMahon, D J; Liu, G; Bilezikian, J P
Summary: Few data are available regarding bone mineral density (BMD) and its determinants among Chinese Americans. We identified determinants of BMD among 359 Chinese-American women in order to identify risk factors for low BMD in this burgeoning population. BMD in Chinese-American women is influenced by a number of factors, including immigration. INTRODUCTION: Osteoporosis and low BMD are common among Chinese women, including Chinese Americans, who are a growing population at risk for osteoporosis in the US. Few data are available regarding BMD and its determinants among Chinese-American women. METHODS: In this study, we examined predictors of BMD in 359 ambulatory Chinese-American women, ages 20-90, using stepwise multiple regression analysis. Variables in the model included age, weight, height, menarche age, years since menopause, immigration age, years in US, percentage of life in US, number of pregnancies, oral contraceptive use, family history of osteoporosis, family history of hip fracture, daily calcium intake, exercise, time outdoors, alcohol consumption and tobacco use. RESULTS: Among premenopausal women, weight was the strongest predictor of BMD, accounting for 10.5% of the variance at the lumbar spine (LS), 15.2% at the total hip (TH) and 16.6% at the femoral neck (FN). Time outdoors was also a positive predictor of BMD (1.4% at LS, 2.8% at TH and 1.6% at FN), while family history of osteoporosis (1.4% at TH) and age (3.7% at FN) were negative predictors. Among postmenopausal women, greater BMD at the LS and TH was associated with greater weight and earlier immigration age. Weight accounted for 16.4% of the variance at the LS and 19.8% at the TH; immigration age accounted for 3.1% of the variance at the LS and 4.1% at the TH. At the FN, years since menopause and weight were predictors of BMD, accounting for 14.4% and 8.7% of the variance, respectively. While older age at immigration had a negative effect on BMD, years in and proportion of life in the United States were not significant predictors of BMD. CONCLUSIONS: Bone mineral density in Chinese-American women is influenced by a number of biological and lifestyle factors, including immigration. The results of this study provide new insights into risk factors for low bone density as they relate to environmental determinants in the growing population of Chinese-American women.
PMID: 17120181
ISSN: 0937-941x
CID: 1071312