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Keywords:

  • bone microarchitecture;
  • Chinese;
  • white;
  • women;
  • pQCT

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. REFERENCES

To identify the racial differences in macro- and microstructure of the distal radius and tibia that may account for the lower fracture rates in Asians than whites, we studied 61 healthy premenopausal Chinese and 111 white women 18–45 yr of age using high-resolution pQCT (HR-pQCT). The Chinese were shorter and leaner. Distal radius total cross-sectional area (CSA) was 14.3% smaller in Chinese because of an 18.0% smaller trabecular area (p < 0.001). Cortical thickness was 8.8% greater in the Chinese, but cortical area was no different. Total volumetric BMD (vBMD) was 10.3% higher in the Chinese because of the 8.8% higher cortical thickness and 2.8% greater cortical density (all p < 0.01). Trabecular vBMD and bone volume/tissue volume (BV/TV) did not differ by race because trabeculae were 7.0% fewer but 10.8% thicker in Chinese than whites (both p < 0.01). Similar results were found at the distal tibia. Lower fracture risk in Chinese women may be partly caused by thicker cortices and trabeculae in a smaller bone-more bone within the bone than in whites.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. REFERENCES

The incidence of hip fractures is generally lower in Asians than whites, especially in northern China.(1–4) There is also evidence to suggest that distal forearm fracture is less frequent in Asians than whites.(5–8) The structural basis responsible for the lower incidence of hip and distal forearm fractures in Asian than white is unknown because methods for quantifying bone structure in vivo have not been available until recently. Bone densitometry is unable to distinguish cortical and trabecular bone compartments or to accurately measure bone size.(9,10)

We have reported that areal BMD (aBMD) at the femoral neck (FN) was lower in Chinese than white women, but no racial difference in estimated vBMD was detected.(11) Using hip structure analysis derived from DXA images, we reported that the estimated FN cortical thickness was greater in the smaller bone in Chinese women compared with white counterparts.(11)

Given that the assumptions in deriving morphology from projectional techniques and the recent availability of high-resolution pQCT (HR-pQCT) with a voxel size 82 μm, we studied racial differences in the 3D structure at the distal radius and tibia in vivo to test the hypothesis that smaller bones are assembled with a higher vBMD than larger bones, a feature that may offset the vulnerability of a narrower bone to bending.(12–14)

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. REFERENCES

Subjects

One hundred seventy-two premenopausal women (61 Chinese and 111 whites) 18–45 yr of age were recruited from the local community in northeast Melbourne, Australia. The Chinese subjects were of Chinese ancestry with parents or grandparents from China. About 95% of the Chinese participants were born in China, and 80% were from southern China. All subjects were citizens or residents of Australia, with a mean stay of 12 yr in Australia (range, 0.1–27 yr). A questionnaire was used to define ethnic origins, history of illness, medications, reproductive history, and lifestyle factors (e.g., smoking, alcohol intake). Alcohol intake was measured by the standard glasses of beer, wine, and spirits per week. Details of methods of recruitment of Chinese and white participants are published.(11,15,16) The white subjects were recruited from the community by posted flyers or word of mouth as part of ongoing research in the department. All participants were in good health, without fractures or illness or drug therapies known to affect bone. All subjects gave written informed consent. The study was approved by the Austin Health Ethics Committee.

Measurements of bone microarchitecture and density

Bone macro- and microarchitecture and vBMD were measured at the distal radius and distal tibia using 3D HR-pQCT (Xtreme CT; Scanco Medical, Bassersdorf, Switzerland). This system uses a 2D detector array in combination with a 0.08-mm point-focus X-ray tube. This enables the simultaneous acquisition of a stack of parallel CT slices with a resolution (voxel size) of 82 μm. The following settings were used: effective energy of 60 kVp, X-ray tube current of 0.9 mA, and matrix size of 1536 × 1536. During measurement, the nondominant arm or leg of the patient was immobilized in an anatomically formed carbon fiber shell. The reference line was manually placed at the middle point of the endplate of the radius and tibia on the scout view. As a default, the first CT slice started at a certain distance from the reference line (i.e., 9.5 mm at radius, 22.5 mm at tibia, respectively).(17) One hundred ten slices were obtained at each skeletal site over a 9.02-mm distance. The effective dose was <3 μSv per measurement, with a measurement time of 2.8 min.(18)

Analyses use a threshold-based algorithm to separate the volume of interest into the cortical and trabecular regions.(19) Attenuation data are converted to equivalent hydroxyapatite (HA) densities. The vBMD (mgHA/cm3) in the trabecular region (vBMDtrab), cortical region (vBMDcort), and the combined total vBMD (vBMDtot) were computed as the average mineral density within the trabecular, cortical, and entire volume of interest, respectively. Trabecular bone volume/tissue volume (BV/TV, %) was determined by dividing the apparent trabecular BMD by 1200 mgHA/cm3, which represents fully mineralized bone [i.e., BV/TV (%) = 100 × (vBMDtrab/1200)]. Trabecular number (TbN) was defined as the mean inverse distance between the ridges (the center points of trabeculae). The method was described in detail by Laib et al.(19) Briefly, the 3D ridges were extracted from the original 3D grayscale images. The distances of the ridges were directly assessed by the newly developed methods derived from distance transformation.(20) This is not affected by the structure of trabeculae whether it is plate- or rodlike. Trabecular thickness (TbTh, mm) and separation (TbSp, mm) were calculated from BV/TV and TbN using histomorphometry methods [i.e., TbTh = (BV/TV)/TbN and TbSp = (1 − BV/TV)/TbN].(21) Cortical thickness (CTh) was calculated by dividing the mean cortical volume by the outer bone surface. The CV ranged from 0.6% to 0.9% for density measurements and 1.4% to 7.4% for structural parameters.(22)

Statistical analysis

All statistical analyses were performed on SPSS software (version 16.0). Bone areas were body size dependent, so differences between groups were assessed using analysis of covariance (ANCOVA) adjusting for height and weight. χ2 test and two-sample Student's t-tests were used to compare traits between races. The results were expressed as mean ± SE, with significance set at the 5% level (two tailed).

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. REFERENCES

As shown in Table 1, the mean age of the Chinese women was similar to their white counterparts. Relative to white women, Chinese women were 5.4 cm shorter and 11.9 kg lighter. No Chinese women smoked, whereas 19.8% of white women currently smoked. No racial difference in alcohol intake was found.

Table Table 1.. Age, Height, Weight, Total CSA, CortA and TrabA, vBMDtot and vBMDcort, CTh, vBMDtrab, BV/TV, TbN, TbTh, and TbSp at the Distal Radius and Distal Tibia in Chinese and White Women
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At the distal radius, total CSA was 14.3% smaller in the Chinese than whites because trabecular area was 18.0% smaller (both p < 0.001); cortical bone area did not differ by race (Fig. 1; Table 1). Total vBMD (cortical plus trabecular) was 10.3% higher in the Chinese because cortical thickness was 8.8% greater and cortical density was 2.8% greater in the Chinese (all p < 0.01; Fig. 2). Trabecular vBMD and BV/TV did not differ by race, but the Chinese had 7.0% fewer and 10.8% thicker trabeculae (both p < 0.01; Figs. 3 and 4). Several of these racial differences attenuated after height and weight adjustment (Table 1).

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Figure Figure 1. Total, trabecular, and cortical bone CSAs in Chinese (filled dots, solid line) and white (open dots, dashed line) women as a function of age at distal radius (left) and distal tibia (right).

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Figure Figure 2. Total vBMD, cortical thickness, and cortical vBMD in Chinese (filled dots, solid line) and white (open dots, dashed line) women as a function of age at distal radius (left) and distal tibia (right).

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Figure Figure 3. Trabecular BV/TV, number, and thickness in Chinese (filled dots, solid line) and white (open dots, dashed line) women as a function of age at distal radius (left) and distal tibia (right).

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Figure Figure 4. Representative 2D images of trabeculae (A) and 3D images (B) of distal radius from a white woman (left) and a Chinese woman (right).

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At the distal tibia, total CSA and trabecular area were 10.8% and 13.0% lower in the Chinese before but not after height and weight adjustment. Cortical area did not differ by race before and after height and weight adjustment (Fig. 1; Table 1). Total vBMD was 4.0% higher in the Chinese than whites (p = 0.16, NS). Cortical thickness and cortical density was 6.4% and 3.1% greater in the Chinese (p < 0.05 and p < 0.001, respectively; Fig. 2). Trabecular BV/TV did not differ by race because trabeculae were fewer (15.6%), more separated (19.6%), and thicker (11.7%) in the Chinese (all p < 0.001; Fig. 3).

When Chinese and white nonsmokers and non-alcohol drinkers were compared, the results of racial differences in bone traits were the same. No trait differences were found in white smokers and nonsmokers.

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. REFERENCES

We reported that Chinese women had a smaller bone at the distal radius and tibia, containing a similar cortical area that conferred thicker cortices (derived by dividing cortical area by periosteal perimeter), whereas a smaller medullary area contained fewer but thicker trabeculae than white women. Racial differences in total CSA of the tibia, but not the radius, disappeared after adjustment for height and weight.

These structural differences are likely to originate in the peripubertal period because there are few racial differences in bone size and microarchitecture present before puberty.(23,24) Bachrach et al.(25) reported that peak bone mineral accretion tended to occur earlier in Asians than whites. There is also evidence to suggest that the age of onset of puberty, the timing of peak height velocity, and the age at menarche occur earlier in Chinese than white girls.(26–32) Given the effect of estrogen in inhibiting periosteal apposition and promoting epiphyseal closure, the earlier exposure to estrogen may partly account for the narrower and shorter appendicular bones in Chinese than white women.

The racial differences in estrogen and bone turnover markers in Chinese and white children are not well defined. Circulating levels of estrogen, bone formation, and resorption markers are lower in Chinese than white women.(33–35) Less resorptive excavation of the marrow or more endocortical bone formation is likely to produce a smaller marrow cavity containing fewer but thicker trabeculae and a thicker cortex. Thus, higher total vBMD could be the result of less resorptive excavation of the marrow and/or more endocortical apposition during growth in the Chinese than whites. The fewer trabecular number suggests that the number of trabeculae per unit area of the growth plate is less, whereas the greater thickness of trabeculae produces higher connectivity in Chinese. Consequently, there is less trabecular surface producing a lower surface/volume ratio in the Chinese than whites. Because remodeling is surface dependent, the lower remodeling rate is likely a consequence of these geometric features in Chinese women. Remodeling is lower in blacks than whites for the same reason.(36,37)

The structural basis underlying the lower incidence of hip and distal forearm fractures in Chinese than whites is uncertain. Studies addressing the structural basis underlying the racial differences in hip fracture risk in Asians and whites have reported a shorter hip axis length or femoral neck axis length.(38,39) We reported a relatively thicker cortex (estimated by DXA) within a smaller FN conferred a lower risk of focal buckling in Chinese women.(11) Because periosteal and endosteal diameter increased similarly in the Chinese and whites across age, the racial differences in bone structure (i.e., a relatively thicker cortex within a smaller FN in old age in Chinese women) is likely to be largely established during growth.(11,15) Asian women have shorter stature than white women primarily because of their shorter leg length; trunk length is similar.(40,41) Whether the shorter leg length is associated with a lower risk of falls and a lower impact in a fall is uncertain, but if so, this may contribute to the reduced risk of fracture in Asian women.(42,43)

The cortices at the distal radius and tibia of premenopausal Chinese women were thicker in absolute terms as well as relative to bone size than in whites. This also conferred a lower risk of focal buckling at the radius and tibia in Chinese, a feature that may contribute to racial differences in distal forearm fracture rates. This resembles racial differences in bone structure reported by Han et al.(36,37) Blacks had thicker iliac crest cortices, thicker trabeculae, and a lower trabecular surface area. The diminution across age was similar by race in blacks and whites, suggesting the racial differences in old age were likely established during growth.

A limitation of this study was that racial differences in bone length may affect the measurement site. Chinese had an ∼1-cm shorter radius and 2-cm shorter tibia (unpublished data). Because the first CT slice is fixed to 0.95 cm (2.25 cm) proximal to the reference line for the distal radius and tibia, the region of interest (ROI) was 0.4% and 0.8% nearer the midshaft of the radius and tibia, respectively, in the Chinese than whites. Thus, smaller area and thicker cortices could be partly attributed to the more proximal ROI. We cannot exclude this possibility. However, when the ROI was chosen based on 4% of radius length instead of a fixed distance in Chinese (n = 17) and white (n = 18) postpubertal girls, the results were similar to the adults reported here. Chinese postpubertal girls had a smaller total CSA (−7.8%, p = 0.1), with higher total vBMD (12.0%, p = 0.056), thicker cortices (23.0%, p < 0.05), similar trabecular BV/TV, but 10.4% fewer and 7.4% thicker trabeculae than whites at the distal radius (p < 0.05 and p = 0.1, respectively).

In conclusion, there are macro- and microarchitectural differences at the distal radius and tibia that produce thicker cortices and fewer but thicker trabeculae within a smaller bone in Chinese premenopausal women. The resulting higher vBMD in Chinese women in young adulthood may partly account for the lower risk of fractures in Chinese than whites.

Acknowledgements

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. REFERENCES

This study was supported by the Australian National Health and Medical Research Council Biomedical Postgraduate Scholarship (ID 400419, X.W.) and by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO)-Amgen Osteoporosis Fellowship Award (Q.W.).

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. REFERENCES