Regional Variations in Trabecular Morphological Features of Femoral Head of Patients with Proximal Femoral Fractures

Journal of Bionic Engineering 12 (2015) 294–303

Regional Variations in Trabecular Morphological Features of Femoral Head of Patients with Proximal Femoral Fractures Linwei Lv1,2, Guangwei Meng1, He Gong1, Dong Zhu3, Jiazi Gao1, Meisheng Zhao4 1. School of Mechanical Science and Engineering, Jilin University, Changchun 130022, China 2. School of Mechanical Engineering, Tianjin University of Technology, Tianjin 300384, China 3. Department of Orthopedic Surgery, the First Clinical Hospital of Jilin University, Changchun 130021, China 4. Department of Cataract, Eye Hospital of the Second Clinical Hospital of Jilin University, Changchun 130000, China

Abstract The regional microstructural variations in femoral head from proximal femoral fracture patients were investigated. Micro-CT scanning was performed on seven femoral heads from proximal femoral fracture patients. Each femoral head was divided into three regions according to the trabecular orientation from the fovea of femoral head to the femoral neck. Eight three-dimensional trabecular cube models were reconstructed from each region. A total of 154 trabecular cubic models were reconstructed because the corresponding areas for 14 cubic models were damaged during the surgeries. Eight trabecular morphological parameters were measured and analyzed, namely, trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), specific bone surface (BS/BV), bone volume fraction (BV/TV), structural model index (SMI), degree of anisotropy (DA), trabecular pattern factor (Tb.Pf), and trabecular number (Tb.N). Bivariate correlation analyses were performed for all morphological parameters. One-way ANOVA tests were performed to analyze the differences of each parameter among three regions. Post-hoc multiple comparisons (Student-Newman-Keuls method) were performed to analyze the morphological difference between two regions. Trabecular bone of proximal femoral fracture patients significantly degenerated in all regions of femoral heads. BV/TV was statistically correlated with Tb.Th, Tb.Sp, BS/BV, Tb.Pf, and Tb.N (p < 0.05). Statistical differences in morphological parameters were observed between regions (p < 0.05). The trabecular strength in the middle regions was significantly higher than that in other regions because of the relationships between morphological parameters and mechanical parameters. Trabeculae in the medial region were more uniform and stable along each direction than those in the lateral region. Most trabeculae in the lateral region only grew along the weight-bearing direction, and those along the other directions degenerated significantly. This study provides detailed trabecular morphological information on fractured femoral heads, as well as references for the prevention of high fracture risk in the elderly. Keywords: femoral head, trabeculae, proximal femur fracture, morphological parameter, micro-CT Copyright © 2015, Jilin University. Published by Elsevier Limited and Science Press. All rights reserved. doi: 10.1016/S1672-6529(14)60122-0

1 Introduction In many countries, the frequency of hip fracture increases with adult development and aging[1]. A survey estimated that the hip fracture rate in Asia will rise to 37% in 2025 and 45% in 2050[2]. The general clinical manifestation of fracture risk is usually caused by osteoporosis[3]. The World Health Organization defines osteoporosis as Bone Mineral Density (BMD) of more than 2.5 standard deviations below the mean of a young healthy reference population of the same gender. HowCorresponding author: Meisheng Zhao E-mail: [email protected]

ever, BMD is only a moderate predictor of fracture risk[4], and may only account for 30% of reduction in fracture risk following therapy[5–8]. Some fracture patients have normal BMD[9,10]. Microstructural features of trabeculae are also another important factor contributing to mechanical properties[6,11]. A previous study on fractured femoral heads, which were from patients with a particular form of coxarthrosis and those that underwent fragility fractures, showed that Young’s modulus and ultimate stress are positively correlated with bone volume fraction (BV/TV, Bone Volume divided by Tissue

Lv et al.: Regional Variations in Trabecular Morphological Features of Femoral Head of Patients with Proximal Femoral Fractures

Volume) and trabecular number (Tb.N), and negatively correlated with trabecular separation (Tb.Sp)[12]. BV and TV were defined as trabecular bone volume and cancellous bone tissue volume, respectively. The subjects comprised males and females, including 11 proximal fractured patients (mean age 81 years old) and 20 coxarthrosis patients (mean age 81 years old)[12]. Using a combination of BMD and microstructural measurements, 94% of the overall strength of trabecular bone was explained in comparison with 64% if BMD was used alone[13]. Bone quality can be measured using Dual-energy X-ray Absorptiometry (DXA), Quantitative Computed Tomography (QCT), or quantitative ultrasound[14]. DXA cannot account for three-dimensional (3D) bone morphology. Evaluation of in vivo BMD and 3D bone morphology in QCT is more useful than areal density assessment by DXA. However, QCT can only measure the macro areas, such as femoral head, femoral neck, or greater trochanter, because of low resolution. The nature of fracture involves the accumulation of trabecular micro-damage[15–17]. Thus, trabecular morphology at the tissue level can directly reflect the state of bone quality. The micro-CT images of trabecular bone at the tissue level can be easily obtained and reconstructed into 3D models nondestructively without any sample preparation[12,18, 19]. The voxel size of general micro-CT devices is about tens of microns. The pores and trabecular structures of cancellous bone can be distinguished clearly[20]. Morphological parameters of trabecular bone can be measured and analyzed accurately on the reconstructed models with this level of precision[21–23]. Some studies on the analysis of trabecular morphological parameters of proximal femur have been published. Previous studies analyzed the correlations and regional differences of trabecular morphological parameters of proximal femur[24,25]. These studies observed significant differences in BV/TV, trabecular thickness (Tb.Th), Tb.Sp, Tb.N, and Degree of Anisotropy (DA) between superior and inferior necks, as well as between superior and inferior great trochanter[24]. The donors in these investigations were Asian male cadavers (mean age 61.8 years old) without macroscopic pathological changes in musculoskeletal disease. Studies on the effect of age on trabecular morphological parameters showed that the reduction in BV/TV is significantly associated with the decrease in structural model index

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(SMI), decrease in Tb.Th, and increase in Tb.Sp at most sites of proximal femur (femoral head, femoral neck, and femoral trochanter) with aging[25]. Samples for these studies were from human cadavers with ages ranging from 52 years old to 99 years old without any musculoskeletal disorders. Femoral neck fracture has been extensively studied, but femoral head fracture is also a common disease[26–29]. However, most studies on femoral heads mainly focused on trabecular microstructural features as a whole. The trabecular bone bearing the weight and daily gait load directly maintains high density, and that bearing the load indirectly degenerates, which results in regional inhomogeneity of BMD[30–33]. The features that trabeculae grow along the main load directions result in the anisotropy of trabecular microstructures. Micro-CT images showed that trabeculae grew along approximately two cantilever structures from shaft to femoral head, which indicated that they work together to resist the principal compressive loads and cantilever-bending moments[30,34]. This phenomenon reveals the regional inhomogeneity of Tb.N and anisotropy of trabecular orientation. The strength and stability of bone at macroscopic level are affected by the microstructural features of trabecular bone. Thus, the fracture risk can be affected. However, few studies on the regional differences of trabecular morphological parameters exist. The mechanism underlying aging fragility fracture can be elucidated by investigating trabecular microstructures of elderly patients and those of healthy elderly individuals. The objective of this study was to refine regional morphological differences of femoral heads of patients with proximal femoral fractures. Trabecular morphological parameters of femoral heads were measured regionally on 3D bone models reconstructed from micro-CT images. Trabecular microstructure of fracture patients degenerated severely to cause fractures. These microstructures were significantly different from those of healthy individuals. According to the effect of trabecular morphologies on the strength, we attempted to analyze trabecular morphological features and correlations between trabecular morphological parameters of femoral heads from elderly proximal femoral fracture patients, which would help clarify the mechanism of femoral head fracture and improve prevention and treatment strategies in clinics.

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Fig. 1 A piece of micro-CT image from the middle region of femoral head.

Fig. 2 Regional division method.

2 Materials and methods 2.1 Sample preparation The study was approved by the ethics committee of the First Hospital of Jilin University (No. 2012-064). Seven femoral heads were obtained from 72- to 88-year-old patients with proximal femoral fracture for hip arthroplasty. Written consent was obtained from each participant of this study. The femoral heads were cryopreserved after surgery. Specimens were stored in air-evacuated polyethylene bags at −20 ˚C until scanning. The surrounding muscles and ligaments were removed before scanning.

2.2 Micro-CT imaging and measurements All specimens were subjected to micro-CT scanning (Skyscan 1076, micro-CT system, Belgium). Approximately 900 images were obtained for one sample with a nominal isotropic resolution of 38 μm (field of view 1024 × 1024, source voltage 79 kV, source current 125 μA, and exposure time 100 ms). A piece of micro-CT image from the middle region of femoral head is shown in Fig. 1. Since the micro-CT was a kind of quantitative CT and the grey value was linearly related with BMD, the average BMD of seven femoral heads was calculated as 1.41±0.45 g·cm−3. They were all kept in the normal level. A femoral head was divided into three regions according to the growth characteristics of trabeculae, that is, medial, middle, and lateral regions from the fovea of the femoral head to the femoral neck. Trabeculae bearing tension load were separated from those bearing compression load in the medial and lateral regions, whereas trabeculae in the middle region bore tension and compression loads simultaneously, which showed the cross growth phenomenon. Eight 125 mm3 cubic trabecular bone blocks were reconstructed from each region. Regional division and bone block positions are shown in Fig. 2. All femoral head centers were destroyed during the surgeries. The areas for fourteen blocks from two regions of two femoral heads, respectively, were damaged. Thus, 154 bone blocks were generated from all seven femoral heads. Eight morphological parameters of trabeculae were measured, namely, Tb.Th, Tb.Sp, specific bone surface (BS/BV, trabecular bone surface area divided by bone tissue volume), BV/TV, SMI, DA, trabecular pattern factor (Tb.Pf), and Tb.N. BS and BV were defined as the area of trabecular bone and the volume of cancellous bone, respectively. All parameters were measured by the built-in program of the micro-CT system. Explanations of morphological parameters are shown in Table 1. 2.3 Statistics The mean and standard deviations of all parameters were calculated for each region. One-way ANOVA was used to analyze the differences of morphological parameters among the three regions of the femoral head. In case of differences among regions, post-hoc multiple comparisons (Student-Newman-Keuls method) were performed to analyze the differences of morphological parameters between two regions.

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Table 1 All tested morphological parameters of trabecular bone Term

Unit

Explanation

Tb.Th

mm

Average trabecular thickness

Tb.Sp

mm

Trabecular separation: Average spaces between trabeculae

−1

BS/BV mm BV/TV

1.25

Specific bone surface

%

Bone volume proportion: Percentage of trabecular volume

SMI

–

Structural model index

DA

–

Degree of anisotropy

Tb.Pf

mm−1

Tb.N

−1

mm

1.00 0.75 0.50

Trabecular pattern factor: Connectivity of bone pattern

0.25

Numbers of trabeculae encountered per millimeter 0.00

Medial

0.4

0.3

2.0

0.2

1.5

0.1

1.0

0.0

Medial

Middle Groups (a)

Lateral

Middle Groups (a)

Lateral

0.5

0.0 0.3

Medial

Middle Groups (b)

Lateral

Fig. 4 Statistical charts of mean and regional differences for the parameters between regions. The regions with the same marker (*) mean that there are significant differences between regions.

0.2

3 Results 0.1

0.0

Medial

Middle Groups (b)

Lateral

Fig. 3 Statistical charts of mean and regional differences for the parameters with no regional differences.

Bivariate correlation tests (Pearson correlation method) were performed to determine the relationships between every two morphological parameters. All statistical analyses were processed in SPSS 17 (IBM Inc., USA), with a significance level of p < 0.050.

Figs. 3–5 show the basic descriptive statistics of the directly assessed morphological parameters (i.e., Tb.Th, Tb.Sp, and Tb.N) and calculated parameters (i.e., BS/BV, SMI, DA, BV/TV, and Tb.Pf) in each region. BV/TV and Tb.Th, which are important factors affecting bone strength, were quite similar among the three regions with no statistical differences. The diagram is shown in Fig. 3. Significant differences were observed in the other morphological parameters, namely, Tb.Sp, BS/BV, SMI, DA, Tb.Pf, and Tb.N among the three regions. One-way ANOVA revealed significant morphological differences in Tb.Sp, BS/BV, SMI, DA, Tb.Pf, and Tb.N (p < 0.05). Significant differences in SMI and DA were found between any two regions of femoral

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298 20

4 2

15 0 10 −2 5

0

−4 −6 Medial

Middle Groups

Medial

Lateral

1.0

Middle Groups

Lateral

1.2 1.0

0.8

0.8

0.6

0.6 0.4 0.4 0.2 0.0

0.2 Medial

Middle Groups

Lateral

0.0

Medial

Middle Groups

Lateral

Fig. 5 Statistical charts of mean and regional differences for the parameters between regions. The regions with the same marker (* or #) mean that there are significant differences between regions.

head, which is shown in Fig. 4. The difference in BS/BV between medial and lateral regions was close to the significance level (p = 0.057). Tb.Pf in the medial region was the minimum, and was significantly different from those in the middle and lateral regions (p = 0.000). No statistical difference was found in Tb.Pf between the middle and lateral regions. Trabecular structure in the middle region where the two beams of trabecular bone cross was compact because of two intersected cantilever beam structures. Thus, we observed statistical differences in Tb.Sp between the middle and medial regions, as well as between the middle and lateral regions. By contrast, Tb.N showed the opposite trend. The statistical charts of BS/BV, Tb.Pf, Tb.Sp and Tb.N are shown in Fig. 5. The basic descriptions and one-way ANOVA tests of all morphological parameters showed that the lateral region of femoral head had more homogeneous Tb.Th, less BS/BV, and lower Tb.Sp than the medial region. The medial region had more plate-like trabeculae (SMI),

less DA, and better connectivity (Tb.Pf) than the lateral region. These results indicate that trabecular bones in the lateral region were stronger than those in the medial region, whereas trabeculae in the medial region were more uniform along different directions. SMI results indicate that the femoral head was mainly composed of plate-like trabeculae even though the samples were severely osteoporotic. Bivariate correlation tests between every two parameters revealed various significant correlations between trabecular morphological parameters (Table 2). Five parameters, namely, Tb.Th, Tb.Sp, BS/BV, Tb.Pf, and Tb.N were statistically correlated with BV/TV. Among these parameters, Tb.Th and Tb.N had positive correlations with BV/TV, whereas Tb.Sp, BS/BV, and Tb.Pf had negative correlations with BV/TV. The parameter most relevant to BV/TV was BS/BV, and the coefficient was −0.839 (p < 0.05). BS/BV was also a morphological parameter that was correlated with most of the other parameters. Tb.N was significantly

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Table 2 Correlations between every two morphological parameters Tb.Th Tb.Sp BS/BV

Tb.Th

Tb.Sp

BS/BV

SMI

DA

Tb.Pf

Tb.N

1

−.088

−.286**

−.058

.115

−.081

−.006

.208**

1

.429**

−.200*

−.127

.051

−.420**

−.647**

1

.110

−.078

.249**

−.195*

−.839**

1

.241**

.878**

.408**

−.122

1

.278**

−.009

.108

1

−.010

−.318**

1

.215**

SMI DA Tb.Pf Tb.N BV/TV

BV/TV

1

* Correlation is significant at the level of 0.05; ** Correlation is significant at the level of 0.01.

correlated with Tb.Sp and SMI. Only SMI was statistically correlated with DA. The most correlated parameters were Tb.Pf and SMI, with a correlation coefficient of 0.878 (p < 0.05).

4 Discussion The femur from a patient with proximal fragility fracture represents the most degenerative microstructural features of trabecular bone. The 3D trabecular morphological parameters measured from high-resolution micro-CT images indicate various regional differences in the femoral head. According to Wolff’s law, trabecular microarchitecture is adapted to its local mechanical environment[22]. The complex trabecular morphologies of femoral heads are optimized to accommodate its daily loads during gait cycles. Bone mass and trabecular orientation are influenced by the magnitude and direction of principal stress[35]. Quantitative analyses of trabecular morphological parameters can reflect the trabecular degenerative tendency of fractured elderly individuals, so the site that is more susceptible to fracture can be inferred. In this study, the results demonstrate the regional trabecular microstructures of femoral heads from fractured patients according to the relationships among trabecular morphological parameters. The regions susceptible to fracture were characterized by thinner trabeculae, larger porosity, and more rod-like, disconnected structures. The rate of bone remodeling cannot compensate for the rate of micro-damage because of serious degeneration. With time, fractures form eventually[16,29]. All samples collected in this study were femoral heads from proximal fracture patients, whose femoral necks were completely destroyed. Most subjects suffered from femoral neck fractures, but the aging patients’ femoral

heads with significant trabecular degeneration were still at high fracture risk[29]. Thus, the investigation on microstructural features of femoral heads not only helps elucidate the mechanism of fracture, but also provides references to the microstructures of medial neck[28,29]. The lack of samples was a limitation of this study. Similar to the limitations of radiation dose for micro-CT and the size of shipping space, the in vivo microstructure of proximal trabecular bone could not be obtained by micro-CT scanning. To measure and analyze the 3D morphological features of the individuals with high fracture risk, only the femoral heads replaced from total hip arthroplasty were collected. In addition, the subjects should be aging patients who suffered from non-impact proximal fractures. However, samples that met the above requirements were scarce. Nevertheless, exploring the mechanism of proximal fracture of aging individuals was logical. The changes in bone in the senile fracture patients included low bone density, bone mass loss, and microstructural degeneration. Bone mass loss and low bone density enhanced trabecular fragility and fracture risk. Microstructure of trabecular bone was also an important factor contributing to fracture risk. Trabecular morphology of proximal fractured femurs significantly degenerated compared with healthy people in the same age group[24,26,36]. BV/TV was the trabecular morphological parameter, as well as a parameter of bone mass. BV/TV was among the most widely used parameters for bone strength prediction[10,18,28]. The mean BV/TV measured in the current study was 0.212, which was 28.8% less than that in healthy individuals[36] and 34.87% less than that in healthy Asians with an average age of 61.8 years old[24]. Considering the obtained BV/TV, the bone mass of individuals with high fracture risk degenerated

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(a)

(b)

(c)

Fig. 6 Typical trabecular bone blocks in three regions. (a) The lateral region; (b) the middle region; (c) the medial region. Trabeculae in the lateral region were mostly composed of plate-like structures and mainly grew along the loading direction. The distribution of trabeculae in medial region was more uniform along each direction in comparison with lateral region. Trabeculae in the middle region were disordered because of the crossing structures of trabeculae.

significantly. The decrease in BV/TV not only indicates the loss of bone mass, but also reveals the degeneration of trabecular microstructures. Based on the parameters significantly correlated with BV/TV, the reduction in BV/TV resulted in thinner trabeculae, larger separation and porosity, and bad connectivity. One-way ANOVA post hoc tests showed that BV/TV in the three regions were similar, and no statistical difference was observed among regions. Although BV/TV is more suitable for evaluating the differences of bone mass among femoral head, femoral neck, and greater trochanter[22], in this study, BV/TV was not suitable for evaluating the differences within femoral head. Thus, the regional morphological variations in femoral head trabecular bone could not be reflected by BV/TV. Furthermore, BV/TV, as a calculated parameter, was affected by most morphological parameters according to the correlation tests. Therefore, the analyses of regional morphological variations in trabecular bone still need to refer to other morphological parameters. Significant differences were found in other trabecular morphological parameters except BV/TV. SMI represented the differences between rod-like trabeculae and plate-like trabeculae. A large number of plate-like structures led to well-connected stable trabecular network. The osteoclastic resorption cavities were initiated from the plate-like trabeculae, leading to focal perforation of plate-like trabeculae, followed by progressive enlargement of the perforation with conversion from plates to rods. Thus, small changes caused by perforations may lead to loss of bone stability without a significant loss in bone volume. Tb.pf (trabecular pattern factor) was a measure of how well the trabecular net-

work is connected[37]. Lower Tb.Pf indicates better connected trabecular lattices with most concave structures, whereas higher Tb.Pf means a more disconnected trabecular structure with most convex structures[37]. The trabecular bone characterized by low SMI and Tb.Pf indicates more stable microstructures. The connectivity and stability in the medial region were better than those in the lateral and middle regions, and the middle region showed the worst connectivity and stability. This finding was caused by the presence of cross-section microstructures of two trabecular beams. Fig. 6 shows a crossed, more rod-like, and poor connective structure in the middle region, whereas the trabecular bone in the medial region showed more plate-like structures and better connectivity. Trabecular bones in the lateral region were mainly composed of rod-like structures between plate-like structures along the coronary axis. Thus, SMI and Tb.Pf in the lateral region were relatively high because of unstable structures along the coronary direction. Rod-like structures were more susceptible to large deformations, such as bending and rotation of trabeculae, than plate-like structures. This result explains why the trabecular bone in lateral region had high fracture risk. However, no significant difference was found in bone mass among regions. Thus, SMI and Tb.Pf were more sensitive to age-related changes in trabecular structure. Such structural information could not be directly determined by BMD or bone mass. DA index were computed using a marching-cubes algorithm, which was defined as the length of longest vector divided by that of shortest vector. DA could reflect the trabecular orientation. The bone remodeling processes along the trabecular orientation maintained strong trabeculae to bear the weight according to the principle of bone functional adaption. Fig. 4 shows that DA increased significantly from the medial region to the lateral region. DA increased significantly with aging in the area of femoral head and femoral neck[24]. The mean DA was 0.45 in healthy individuals (40 years old to 90 years old), which was significantly lower than our measured value of 1.43. Therefore, the anisotropy of trabecular bone in fractured patients was higher than that in healthy individuals. DA in the medial region was better than that in the lateral region. Thus, DA is a predominant factor in determining the microstructural properties of cancellous bone. The porosity of trabecular bone was described by

Lv et al.: Regional Variations in Trabecular Morphological Features of Femoral Head of Patients with Proximal Femoral Fractures

BV/TV. The pore volume fractions in different regions were similar because no significant difference was found in BV/TV between regions. Tb.N and Tb.Sp were significantly relevant parameters to BV/TV with coefficients of 0.215 and −0.647 (p < 0.01). Decrease in bone mass resulted in thinning trabeculae and significantly increased porosity, which was also confirmed in the literature[38,39]. Thus, the morphology of the pore cannot be determined by BV/TV alone. The increase in Tb.Sp and decrease in Tb.N revealed that trabeculae were further separated from each other. In this study, Tb.Sp was 50% higher than that in healthy individuals. However, no significant differences were found in Tb.Th[36]. Given that Tb.Sp is significantly and negatively correlated with apparent Young’s modulus and ultimate stress, the strength of trabecular bone from fracture patients decreased significantly[12]. Thus, two conclusions could be inferred from the relationships between porosity and mechanical properties. First, the whole strength of fractured femoral head degenerated significantly. Second, the trabecular strength in the middle region was the highest. The trabecular stability of the lateral region was worse than that of the medial region, which indicates that the lateral region was at higher risk of fracture. In this study, analysis of trabecular morphological parameters showed that femoral head trabecular bone from proximal femoral fractured patients degenerated severely. BV/TV was affected by most morphological parameters, and only reflected the degree of osteoporosis of whole femoral head with no regional differences. Tb.Sp was the minimum and Tb.N was the maximum in the middle region because of the cross-section of trabecular bone structure. Thus, the strength of the middle region was higher than those of the medial and lateral regions according to the relationships between mechanical parameters and Tb.N and Tb.Sp. Given that the medial region of femoral head was in close contact with the acetabulum, the forces exerted on the trabeculae were more uniform along all directions. Therefore, the trabecular materials were homogeneous and the microstructures were stable. The trabecular strength along the trabecular orientation in the lateral region was higher than those in other directions because of thicker trabeculae and lower porosity. However, trabecular bone in the lateral region along other directions degenerated severely without the protection of the acetabulum, so

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impact could easily cause fractures. Micro-CT measurement offers a novel technique to refine the regional variations in femoral head trabeculae. Analyses of regional morphological variations explained the fragility of the fracture mechanism of femoral head in the elderly.

Acknowledgment This work is supported by the National Natural Science foundation of China (Nos. 11322223, 11432016, 81471753), and the 973 Program (No. 2012CB821202).

References [1]

Kanis J A, Oden A, McCloskey E V, Johansson H, Wahl D A, Cooper C. A systematic review of hip fracture incidence and probability of fracture worldwide. Osteoporosis International, 2012, 23, 2239–2256.

[2]

Gullberg B, Johnell O, Kanis J A. World-wide projections for hip fracture. Osteoporosis International, 1997, 7, 407–413.

[3]

Kanis J A. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: Synopsis of a WHO Report. Osteoporosis International, 1994, 4, 368–381.

[4]

Pasco J A, Seeman E, Henry M J, Merriman E N, Nicholson G C, Kotowicz M A. The population burden of fractures originates in women with osteopenia, not osteoporosis. Osteoporosis International, 2006, 17, 1404–1409.

[5]

Aaron J E, Shore P A, Shore R C, Beneton M, Kanis J A. Trabecular architecture in women and men of similar bone mass

with

and

without

vertebral

fracture:

II.

Three-dimensional histology. Bone, 2000, 27, 277–282. [6]

Bouxsein M L. Mechanisms of osteoporosis therapy: A bone strength perspective. Clinical Cornerstone, 2003, S2, S13–S21.

[7]

Hochberg M C, Greespan S, Wasnich R D, Miller P, Thompson D E, Ross P D. Changes in bone density and turnover explain the reductions in incidence of nonvertebral fractures that occur during treatment with antiresorptive agents. Journal of Clinical Endocrinology Metabolism, 2002, 87, 1586–1592.

[8]

Cummings S R, Karpf D B, Harris F, Genant H K, Ensrud K, LaCroix AZ, Black DM. Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs. American Journal of Medicine. 2002, 112, 281–289.

[9]

Goulet R W, Goldstein S A, Ciarelli M J, Kuhn J L, Brown M B, Feldkamp L A. The relationship between the structural and orthogonal compressive properties of trabecular bone.

302

Journal of Bionic Engineering (2015) Vol.12 No.2

Journal of Biomechanics, 1994, 27, 375–389. [10] Ulrich D, Rietbergen B V, Laib A, Ruegsegger P. The ability of three-dimensional structural indices to reflect mechanical aspects of trabecular bone. Bone, 1999, 25, 55–60. [11] Seeman E. Pathogenesis of bone fragility in women and men. Lancet, 2002, 359, 1841–1850.

mechanics of vertebral cancellous bone of Chinese males. The Aging Male, 2012, 15, 233–239. [22] Turunen M J, Prantner V, Jurvelin J S, Kroger H, Isaksson H. Composition and microarchitecture of human trabecular bone change with age and differ between anatomical locations. Bone, 2013, 54, 118–125.

[12] Vale A C, Pereira M F C, Mauricio A, Amarai P, Rosa L G,

[23] Isaksson H, Toyras J, Hakulinen M, Aula A S, Tamminen I,

Lopes A, Rodrigues A, Caetano-Lopes J, Viadal B, Monteiro

Julkunen P, Kroger H, Jurvelin J S. Structural parameters of

J, Fonseca J E, Canhao H, Fatima M. Micro-computed to-

normal and osteoporotic human trabecular bone are affected

mography and compressive characterization of trabecular

differently by microCT image resolution. Osteoporosis In-

bone. Colloids and surfaces A: Physicochemical and Engineering Aspects, 2013, 438, 199–205.

ternational, 2011, 22, 167–177. [24] Cui W Q, Won Y Y, Baek M H, Lee D H, Chung Y S, Hur J

[13] Hilderband T, Liab A, Muller R, Dequeker J, Ruegsegger P.

H, Ma Y Z. Age-and region-dependent changes in

Direct three-dimensional morphometric analysis of human

three-dimensional microstructural properties of proximal

cancellous bone: Microstructural data from spine, femur,

femoral trabeculae. Osteoporosis International, 2008, 19,

iliac crest, and calcaneus. Journal of Bone and Mineral Re-

1579–1587.

search, 1999, 14, 1167–1174. [14] Kanis J A. Diagnosis of osteoporosis and assessment of fracture risk. Lancet, 2002, 359, 1929–1936. [15] Wu Z H, Laneve A J, Niebur G L. In vivo microdamage is an indicator of susceptibility to initiation and propagation of microdamage in human femoral trabecular bone. Bone, 2013, 55, 208–215. [16] Nagaraja S, Couse T L, Gulderg R E. Trabecular bone microdamage and microstructural stresses under uniaxial

[25] Lochmuller E M, Matsuura M, Bauer J, Hitzl W, Link T M, Muller R, Eckstein F. Site-specific deterioration of trabecular bone architecture in men and women with advancing age. Journal of Bone and Mineral Research, 2008, 23, 1964–1973. [26] Li B, Aspden R M. Composition and mechanical properties of cancellous bone from the femoral head of patients with osteoporosis or osteoarthritis. Journal of Bone and Mineral Research, 1997, 12, 641–651.

compression. Journal of Biomechanics, 2005, 38, 707–716.

[27] Ohman C, Baleani M, Perilli E, Dall’Ara E, Tassani S, Ba-

[17] Arlot M E, Burt-Pichat B, Roux J P, Vashishth D, Bouxsein

ruffaldi F, Viceconti M. Mechanical testing of cancellous

M L, Delmas P D. Microarchitecture influences micro-

bone from the femoral head: Experimental errors due to

damage accumulation in human vertebral trabecular bone.

off-axis measurement. Journal of Biomechanics, 2007, 40,

Journal of Bone and Mineral Research, 2008, 23,

2426–2433.

1613–1618. [18] Zhang Z M, Li Z C, Jiang L S, Jiang S D, Dai L Y. Micro-CT

[28] Tanck E, Bakker A D, Kregting S, Cornelissen B, Klein-Nulend J, Van Rietbergen B. Predictive value of

and mechanical evaluation of subchondral trabecular bone

femoral head heterogeneity for fracture risk. Bone, 2009, 44,

structure between postmenopausal women with osteoarthri-

590–595.

tis and osteoporosis. Osteoporosis International, 2010, 21, 1383–1390. [19] Gonzalez-Garcia R, Monje F. Is micro-computed tomography reliable to determine the microstructure of the maxillary alveolar bone. Clinical Oral Implants Research, 2013, 24, 730–737. [20] Djuric M, Zagorac S, Milovanovic P, Djonic D, Nikolic S, Hahn M, Zivkovic V, Bumbasirevic M, Amling M, Marshall

[29] Mori S, Harruff R, Ambrosius W, Burr D B. Trabecular bone volume and microdamage accumulation in the femoral heads of women with and without femoral neck fractures. Bone, 1997, 21, 521–526. [30] Singh M, Nagrath A R, Maini P S. Changes in trabecular pattern of the upper end of the femur as an index of osteoporosis. Journal of Bone and Joint Surgery (Am.), 1970, 52, 457–467.

R P. Enhanced trabecular micro-architecture of the femoral

[31] Stauter M, Rapillard L, Lenthe G H V, Zysset P, Muller R.

neck in hip osteoarthritis vs. healthy controls: A mi-

Importance of individual rods and plates in the assessment of

cro-computer tomography study in postmenopausal women.

bone quality and their contribution to bone stiffness. Journal

International Orthopaedics, 2013, 37, 21–26.

of Bone and Mineral Research, 2006, 21, 586–595.

[21] Liu G M, Xu C J, Kong N, Zhu X M, Zhang X Y, Yao Y.

[32] Skedros J G, Baucom S L. Mathematical analysis of trabe-

Age-related differences in microstructure, density and bio-

cular ‘trajectories’ in apparent trajectorial structures: The

Lv et al.: Regional Variations in Trabecular Morphological Features of Femoral Head of Patients with Proximal Femoral Fractures unfortunate historical emphasis in the human proximal fe-

303

[36] Nazarian A, Muller J, Zurakowski D, Muller R, Snyder B D.

mur. Journal of Theoretical Biology, 2007, 244, 15–45.

Densitometric, morphometric and mechanical distributions

[33] Liu X S, Sajda P, Saha P K, Wehrli F W, Bevill G, Keaveny T

in the human proximal femur. Journal of Biomechanics.

M, Guo X E. Complete volumetric decomposition of indi-

2007, 40, 2573–2579.

vidual trabecular plates and rods and its morphological

[37] Hahn M, Vogel M, Pompesius-Kempa M, Delling G. Tra-

correlations with anisotropic elastic moduli in human tra-

becular bone pattern factor–A new parameter for simple

becular bone. Journal of Bone and Mineral Research, 2008,

quantification of bone microarchitecture. Bone, 1992, 13,

23, 223–235. [34] Brown S J, Pollintine P, Powell D E, Davie M W, Sharp C A.

327–330. [38] Parkinson I H, Fazzalari N L. Interrelationships between

Regional differences in mechanical and material properties

structural parameters of cancellous bone reveal accelerated

of femoral head cancellous bone in health and osteoarthritis.

structural change at low bone volume. Joint of Bone and

Calcified Tissue International, 2002, 71, 227–234.

Mineral Research, 2003, 18, 2200–2205.

[35] Carter D R, Fyhrie D P, Whalen R T. Trabecular bone den-

[39] Stauber M, Rapillard L, van Lenthe G H, Zysset P, Muller R.

sity and loading history: Regulation of connective tissue

Importance of individual rods and plates in the assessment of

biology by mechanical energy. Journal of Biomechanics.

bone quality and their contribution to bone stiffness. Joint of

1987, 20, 785–787.

Bone and Mineral Research, 2006, 21, 586–595.