Difference in femoral head and neck material properties between osteoarthritis and osteoporosis

Difference in femoral head and neck material properties between osteoarthritis and osteoporosis

Available online at www.sciencedirect.com Clinical Biomechanics 23 (2008) S39–S47 www.elsevier.com/locate/clinbiomech Difference in femoral head and ...

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Available online at www.sciencedirect.com

Clinical Biomechanics 23 (2008) S39–S47 www.elsevier.com/locate/clinbiomech

Difference in femoral head and neck material properties between osteoarthritis and osteoporosis Shih-Sheng Sun a, Hsiao-Li Ma b, Chien-Lin Liu b,c, Chang-Hung Huang d,f, Cheng-Kung Cheng d,e, Hung-Wen Wei d,* a

Department of Orthopedics and Traumatology, Lotung St. Mary’s Hospital, I-Lan, Taiwan Department of Orthopedics and Traumatology, Veterans General Hospital, Taipei, Taiwan c Faculty of Medicine, National Yang Ming University, Taipei, Taiwan d Joint Prosthesis Technology Research Center, National Yang Ming University, No. 155, Section 2, Li-Nung Street, Beitou, Taipei 11221, Taiwan e Institute of Biomedical Engineering, National Yang Ming University, Taipei, Taiwan f Biomechanics Research Laboratory, Department of Biomedical Research, Mackay Memorial Hospital, Taipei, Taiwan b

Received 4 August 2007; accepted 21 November 2007

Abstract Background. Osteoarthritis and osteoporosis are the two most common musculoskeletal diseases found in the aged population. It is of interest to measure and study the material properties of the femoral head and neck of these two groups, and hopefully to offer explanation of the observed phenomenon that most patients suffer from one of the two disorders, not both. Methods. Seven osteoarthritic and seven osteoporotic femoral heads were used for this study. The principal compressive region of the femoral heads were cut to determine the Young’s modulus and yielding stress by a material testing machine. Comparisons between these two groups were conducted by using material properties and the properties normalized by individual patient physical parameters, including body weight, body height and femoral head diameter, respectively. The finite element model of femoral neck cuboid in OA and OP were obtained based on the micro-CT-scan cross-section. The intrinsic material properties were calculated from the solid FE models. Findings. The results showed significant differences in density, modulus and strength between the osteoarthritic and osteoporotic femoral heads as measured, with the former having 2–3 times the values of the latter. Femoral head diameter has stronger influence in mechanical properties than patient’s body weight and body height. Regarding to bone volume (BV), bone surface (BS), bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and true trabecular elastic modulus, the intrinsic material properties of femoral neck with OA were higher than OP. Interpretation. It is still unknown why patients do not suffer from both osteoporosis and osteoarthritis at the same time. Many studies aimed to investigate the mechanical property of two groups. However, individual difference of the femoral head and neck is too difficult to obtain a reasonable comparison between these two groups. This study investigated the two groups more quantitatively and further estimated the factors which influence mechanical properties from a biomechanical point of view. Ó 2007 Published by Elsevier Ltd. Keywords: Femoral head; Femoral neck; Osteoarthritis; Osteoporosis; Principal compressive region; Bone mineral density

1. Introduction Osteoarthritis (OA) and osteoporosis (OP) are the two most common musculoskeletal disorders in the elder popu*

Corresponding author. E-mail address: [email protected] (H.-W. Wei).

0268-0033/$ - see front matter Ó 2007 Published by Elsevier Ltd. doi:10.1016/j.clinbiomech.2007.11.018

lation. Studies have reported that these two disorders do not coexist (Dequeker, 1985; Foss and Byers, 1972; Healey et al., 1985; Verstraeten et al., 1991). There are reports showing that OA protects against or retards the development of OP, but the biological reason for this is not clear. Both OA and OP are age-related disorders. OA is considered as a disorder of cartilage failure with secondary bone

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changes, such as marginal osteophytes and subchondral sclerosis, while OP is considered as a disorder characterized by a reduced amount of bone mass, leading to diminished physical strength of the bone and increased susceptibility to fracture, particularly, neck fracture. There are more and more evidences showing that primary OA might initially be a bone disease rather than a cartilage disease. OA cases have a stiffer bone mass (Carlsson et al., 1979; Moore et al., 1994; Roh et al., 1974). Osteoarthritis has been defined as organ failure of a joint due to mechanical factors, causing loss of articular cartilage and inducing subchondral bone sclerosis. Mechanical wear is believed to contribute to the progression of the disease. Loss of superficial zone in normal cartilage may result in rapid wear of intermediate and deep zones caused by stress concentration. Burr and Schaffler (1997) reviewed evidence for the role of subchondral bone and calcified cartilage in the initiation and progression of osteoarthritis and concluded that thickening and stiffening of the subchondral plate or calcified cartilage are not required to initiate cartilage fibrillation, but appear to be necessary for progression. There is evidence that suggests that the initiation and progression of osteoarthritis involves a disruption of the normal mechanical equilibrium between bone and cartilage. However, it is uncertain whether osteoarthritis is initiated in the cartilage layer, bone layer or both layers simultaneously. Normal bones under physical stimulation undergo a functional adaptation response that changes the bony structure. On the other hand, the bony internal microstructure may change with the aging process and thus affect the bone’s biomechanical characteristics, leading to the onset of diseases such as OP or OA. Nevitt et al. (1995) studied OA in hips of Caucasian women and found that their overall bone mineral density including the femur and the spine was higher than that of those who did not suffer from OA, and people who did not suffer from femoral neck fracture were found to have a higher chance of developing OA in the hip later on. Other related studies (Byers et al., 1970; Dretakis et al., 1998) reported that there was no sign of wear on the cartilage overlying the femoral heads of patients who had femoral neck fracture. Pogrund et al. (1982) studied hip X-rays of 641 randomly chosen patients and found that 16.1% suffered from OP, 4.1% OA, and only 0.5% both OA and OP. These reports all supported the observation that cases of patients suffering from OA and OP simultaneously were very rare. A few research works were found to measure bone properties of femoral heads through biomechanical methods. Li and Aspden, 1997a used ultrasound system to perform mechanical analysis of normal, osteoarthritic, and osteoporotic femoral heads by taking the bone samples from the superior, inferior, anterior, posterior, medial, lateral and central regions of the femoral head. Brown, 1981 performed mechanical analysis on 9 cases of femoral head osteonecrosis. They took 5 mm3 cubic testing samples from three locations of the femoral head: (1) well within the main infarct, (2) at the fibrotic/sclerotic margin of the

infarct, and (3) immediately subjacent to the fibrotic/sclerotic margin. Due to the anisotropy and inhomogeneity of human bone tissues, femoral head mechanical properties evaluated by other researchers were significantly influenced by the location and direction of sample extraction. It is evident that bone quality and structure is important in determining the risk of fracture in OP. The microstructure and material property of trabecular bone are essential to dominate bone strength and stiffness. Jordan et al. (2003) provided the evidence that the increase in the percentage of cancellous area, trabecular thickness, and apparent density that occurred in the cases of OA. Li and Aspden, 1997b concluded that the increased apparent density of the OA trabecular bone resulted in a greater stiffness, yield strength and energy absorbed to yield than OP bone. Differences of mechanical and tissue properties between OA and OP bone can be identified in the researches described above. However, how the intrinsic material properties and histomorphometric structure of OA and OP affect apparent strength is rarely known. Trabecular bone was also reported to have energy absorption capability (Dequeker et al., 1995). It is reasonable to assume that properties of the principal compressive region in the femoral head and femoral neck directly affect the cartilage wear, indicating either OA or OP. The purpose of this study was to compare the material properties in the principal compressive region of femoral heads, respectively from OA and OP patients. In the other hand, a threedimensional finite element model of a trabecular cuboid sectioned from femoral neck was used to derive the intrinsic material properties in both cases because few FE studies into OA and OP have focused on the femoral neck. 2. Methods 2.1. Mechanical testing of femoral head The femoral heads used for this study were divided into two groups: seven samples with primary OA and seven samples with OP. These samples were all retrieved from patients who underwent total hip arthroplasty. In radiograph, the patients with severe hip osteoarthritis were diagnosed as joint space narrowing (joint space is less than 1.5 mm), subchondral sclerosis, or osteophytes occurring. The patients with femoral neck fracture were regarded as OP group. Diseases such as osteonecrosis, rheumatoid arthritis, infection and developmental dysplasia of hips were excluded from the study. Patient’s data for each femoral head sample include age, sex, body height, weight, and femoral head diameter as shown in Table 1. Dual-energy X-ray absorptiometry (HOLOGIC QDR-1500, Bedford, USA) was used to determine the BMD for each femoral head prior to the biomechanical testing. The samples were then frozen and stored at 10 °C, and was defrosted 24 h before the biomechanical testing. A linear precision saw (Isomet 5000, Buehler Ltd., IL, USA) was used to cut two 1 cm3 cubes from the principal compressive region in

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Table 1 Details of the two groups of femoral heads Group

Numbers of femoral head

Gender F/M

Age (years)

Body height (cm)

Body weight (kg)

Femoral head diameter (mm)

OA

7

3=

4

79 ± 8.6 (62–89)

163.1 ± 6.1 (156–175)

67.8 ± 8.6 (58–79)

50.3 ± 2.5 (47–52)

OP

7

5/2

75 ± 7.5 (55–85)

159.4 ± 5.8 (152–168)

63.3 ± 9.4 (48–78)

46.1 ± 2.0 (44–49)

P = 0.44

P = 0.26

P = 0.36

P < 0.05

Values shown are mean ± SD. Numbers in parentheses are the range.

Fig. 1. The illustration of the sample and testing: (a) a schematic diagram of the site in the femoral head where cubic samples of cancellous bone were removed; (b) 1-cm-sided cubic testing samples were taken for testing.

each femoral head. The two cubic samples, as designated I and II, are illustrated in Fig. 1. The material testing machine (Bionix 858; MTS system comp., MN, USA) was used for the compression test. All samples were loaded in the superior–inferior direction which coincides with the principal stress direction. The strain rate, 0.04 mm/s (Brown, 1981), was used. The stress–strain curve was obtained at the end of each test and was used to calculate the compressive Young’s modulus and the yielding stress. The slope of the straight segment of the stress–strain curve is taken as the modulus (E) and the largest value on the curve is taken as the yielding stress (ry) as shown in Fig. 2. For comparison between

the OA and OP groups, average Young’s modulus and yielding stress of seven samples for each group were calculated. Note that human bones are viscoelastic and non-isotropic with the compressive strain extending up to 70%, where true strain is needed for large-deformation analysis. However, for our discussion of the yielding stress which occurs within 5%, engineering strain as shown and reported was used. Linear regression between the BMD and the modulus E was conducted. The values of the materials properties, BMD, E and ry as obtained from the tests were also normalized by the individual body height, body weight and femoral head diameter, respectively, for further correlation search. Student’s t test was used for the statistical analysis and the level of significance was set at P = 0.05. 2.2. Finite element analysis of femoral neck trabecular cuboid

Fig. 2. Example of compressive stress–strain curves. The slope of the straight segment of the stress–strain curve is the Young’s modulus and the maximum value of the curve is the yielding stress.

A 10  10  40 mm cuboid was obtained out of femoral neck along the neck axis in both OA and OP sample. To model the cuboid samples, the micro-CT-scan (Institute of Nuclear Energy Research (INER), Taiwan) cross-section of each sample was obtained to establish the geometric configuration. The finite element models were obtained based on the configuration by ANSYS 8.0 (ANSYS, Inc., PA, USA) (Fig. 3). The element type of SOLID 45 was used and material properties were assumed as homogeneous, isotropic and linear behavior. ECUBIC was defined

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Fig. 3. The 10  10  40 mm finite element model obtained out of femoral neck: the model of OA.

as true apparent modulus and obtained by the BMD measurement (Wirtz et al., 2000). The trabecular bone of two models was given an initial elastic modulus of 1000 MPa and Poisson’s ratio of 0.3. The top and bottom surface of cubic bone model were fixed in X and Y axis. A compressive simulation with the strain of 1% in Z axis was performed to obtain simulated apparent modulus (EFEM). The intrinsic material properties of tissue volume (TV), bone volume (BV), bone surface (BS), and bone volume fraction (BV/TV) were calculated from the solid models generated by micro-CT-scan. Trabecular thickness (Tb.Th = 2/(BS/BV)), trabecular number (Tb.N = (BV/TV)/ Tb.Th), and trabecular spacing (Tb.Sp = (1/Tb.N)-Tb.Th) were also determined in either OA or OP cubic model (Linde and Hvid, 1989).

Table 2 List of values of BMD (g/cm2) and modulus E (MPa) of the seven OA femoral heads and the seven OP femoral heads as well as their averages and standard deviations for each group No.

OA femoral heads

OP femoral heads

BMD

E

BMD

E

1 2 3 4 5 6 7 Average SD

1.04 0.98 1.14 0.93 1.18 1.25 0.92 1.06 0.13

858 738 1109 642 709 954 789 829 160

0.69 0.41 0.54 0.53 0.57 0.45 0.73 0.56 0.12

534 544 258 385 220 284 316 363 131

Ratio (OA/OP)

1.9

2.3

The ratios of these average values of OA over OP are also shown.

3. Results 3.1. Mechanical testing of femoral head In data analysis, values of material properties as well as their normalized values by individual patient’s physical parameters including height, weight and femoral head diameter, respectively, were studied in order to seek correlation of the properties between these two patient groups. The average BMDs of the OA and OP groups were, respectively 1.06 ± 0.13 and 0.56 ± 0.12 g/cm2 (Table 2). It is seen that BMD of the OA group is significantly higher than that of the OP group (P < 0.05). BMD of OA and OP group are ranged from 0.92 to 1.25 and from 0.41 to 0.73 g/ cm2, respectively. Values of the modulus, E, of the seven cubic samples I and II of the OA group were 791 ± 170 MPa and 866 ± 260 MPa, respectively, but, there was

no significant difference between samples I and II (P > 0.05). For the OA group, there was also no significant difference seen in ry values between the cubic samples I and II, which were 17.2 ± 3.9 MPa and 17.2 ± 4.8 MPa, respectively. Similarly, for the OP group, both E and ry values did not show significant difference between the sampling locations I and II (P > 0.05). (E values: 339 ± 178 MPa and 388 ± 136 MPa; ry values: 5.3 ± 2.3 MPa and 6.2 ± 2.4 MPa, respectively for samples I and II). Fig. 4 shows the bar graphs of the aforementioned average values and standard deviations for cases, ‘‘OA I”, ‘‘OA II”, ‘‘OP I”, ‘‘OP II”, ‘‘OA ave”, and ‘‘OP ave”, where I and II denote the cubic samples from I and II locations as shown in Fig. 1. It can be seen that the mechanical properties between I and II locations, i.e., the upper and lower bone sampling positions, were not significantly different within

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Fig. 4. The mechanical properties from regions I and II of the OA and OP femoral heads as defined in Fig. 1(a): (a) the Young’ modulus (MPa); (b) the yielding stress (MPa). *Statistically significantly different between the OA group and the OP group (P < 0.05).

either the OA or the OP group, but were significant different when comparison was made between the OA and OP groups, of which the average E values were 829 ± 215 MPa and 363 ± 154 MPa, respectively and the ry values were 17.2 ± 4.2 MPa and 5.7 ± 2.3 MPa. These data affirm the known observation that the OA group is significantly stiffer and stronger than its OP counterpart (P < 0.05) with direct mechanical measurement, similar results were found in BMD measurements for the two group. BMD was regressed with the modulus E. The result is shown in Fig. 5a. The OA samples (square dots) are seen of higher BMD and higher Young’s modulus than the OP samples (rhombus dots) as expected. Each data point, either OA or OP, is an average of the two cubic samples, I and II. The correlation coefficient, R2 = 0.72, assesses the prediction of using BMD for the modulus E. Similar regression analyses, as shown in Fig. 5b and c were carried out between BMD and yielding stress and between modulus and the yielding stress with the resulting R2 values, respectively, 0.64, and 0.56. The ratios of OA over OP in material properties, BMD, E and ry were, respectively 1.9, 2.28 and 3.01 as also shown in Fig. 6. By normalizing all material properties with respect to individual body height, their aforementioned ratios decreased, respectively to 1.85, 2.23 and 2.93. By normalization with respect to individual body weight, the resulting ratios were, respectively 1.76, 2.12 and 2.77,

Fig. 5. Plots of linear regression using all data of both OA and OP groups: (a) Young’s modulus versus BMD, (b) yielding stress versus BMD, (c) yielding stress versus Young’s modulus.

and, normalization with respect to the femoral head diameter resulted in ratios 1.73, 2.08 and 2.77, respectively. Normalization of the materials properties with respect to the femoral head diameter results in the smallest difference in materials properties between OA and OP among the physical parameters investigated. Note that the OA patients had significantly larger femoral head than the OP patients (Table 1). This quantitative observation was a new finding, not previously reported in the clinical literature surveyed. 3.2. Finite element analysis of femoral neck trabecular cuboid Table 3 shows the intrinsic material properties calculated from three-dimensional solid models. Regarding to bone volume (BV), bone surface (BS), bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N), the intrinsic material properties of OA were higher than OP. And trabecular spacing (Tb.Sp)

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Fig. 6. OA/OP ratios as well as ratios with BMD, E, and ry values normalized by physical parameters of the individual patient. The femoral head diameter shows the strongest influence in reducing OA/OP ratios. Table 3 The intrinsic material properties of OA and OP cuboid model TV (mm3) BV (mm3) BS (mm2) BV/TV Tb.Th (mm) Tb.N (mm 1) Tb.Sp (mm) Elastic modulus (GPa)

OA

OP

0.062500 0.047016 6.566875 0.752 0.0143 52.59 0.0047 17.17

0.062500 0.020906 3.386250 0.335 0.0123 27.24 0.0244 10.19

was higher in OP model than OA. In finite element analysis, the simulated apparent modulus (EFEM) of OA and OP cuboid model were obtained with an initial elastic modulus of trabecular bone (1000 MPa) under the strain rate of 1%. Because linear and elastic properties were assumed, the true trabecular elastic modulus was calculated by the ratio of ECUBIC/EFEM and shown in Table 3. The true trabecular elastic modulus was higher in OA model. The von-Mises stress distribution in both models under the strain rate is shown in Fig. 7. 4. Discussion OA and OP are the two main musculoskeletal diseases in the aged population. Bone mass in osteoarthritic patients is higher than that in normal subjects. The cartilage wear is frequently observed in these patients. This observation is generally not present in osteoporotic patients, of whom cartilage wear is not evident and bone mass is low with a higher risk of femoral neck fractures. At present, the physiological mechanisms responsible for the cause of either

OA or OP disorders are not clear. The larger femoral head size of OA patients as found in this report is a biomechanically sensible outcome because the higher strength and energy absorption of the denser OA femoral head adapt the femoral head for activities of higher loadings, which stimulate bone growth but at the same time aggravate cartilage wear. Li and Aspden, 1997c analyzed cylindrical samples (diameter: 9 mm, average height: 7.7 ± 1.6 mm) taken from the femoral heads in various directions of osteoarthritic, osteoporotic and normal subjects as previously mentioned. Li and Aspden also found BMD and bone strength of OP femoral heads were significantly less than those of OA femoral heads. Additionally, they found that bone strength was highest at the superior section of the femoral heads, and was lowest at the inferior sections. Our study showed a 130% increase in the modulus when the OA group was compared with the OP group, in contrast to the 40% increase reported by Li and Aspden. Also, our results showed that the OA group had a 200% increase in the yielding stress over the OP group, while a 72% increase in Li and Aspden’s results. Difference in sample extraction from the femoral head was considered the primary reason for the aforementioned difference in the percentage increase of the OA group between our results and those of Li and Aspden. In this study, the testing samples were adopted from principal compressive region instead of whole femoral head of OA and OP patients. The Wolff’s law says that the arrangement of trabecular bone in the femoral head is dependent on the direction of the force sustained, thus the mechanical properties of bone samples are dependent on the location in the femoral head as well as the direction tested. Under hip joint reaction force, the material

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Fig. 7. von-Mises stress distribution in (a) OA and (b) OP model under the strain rate of 1%. The simulated apparent modulus (EFEM) was calculated by assuming the initial trabecular bone elastic modulus of 1000 MPa.

properties along the principal compressive region of femoral heads would adapt to the load directly. Significantly different measurement of mechanical properties can be expected due to difference in the design of experiment. Note that our sample yielded higher modulus and strength since they were cut from the principal compressive region of the femoral head and tested along the principal compressive direction as shown in Fig. 1 in contrast to those from the superior, inferior, anterior, posterior, medial, lateral and central regions done by Li and Aspden. This explains for the difference discussed above, where possible different severity of OP and OA disorders between these two studies is also noted.

There are few studies that estimate which individual factor influencing bone mechanical property. In the current study, we had performed normalization analysis to individual factors. When the mechanical properties were normalized by the physical parameters, we found that femoral head diameter was significant in influencing (reducing) the OA over OP ratios of material properties when compared with the factors of body weight and body height. It suggested that the large difference of materials properties between the OA and OP had a certain level of correlation with the size of the femoral head. This is echoed by the observation that OA patients have a statistically significant larger femoral head than the OP patients as shown in

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Table 1. This clinical observation was not seen reported from our literature survey and we believe it serves as a clue to the different activities of cellular bone growth factors yet to be revealed for these two patient groups. In this study, the whole femoral head structure properties were not determined and normalized to head diameter. The reason is that principal compressive region would sustain more primary reaction force than any other regions of femoral head. In contrast to the whole femoral head structure, the sample cut from the region is more meaningful to represent the mechanical properties normalized to physical parameters. Our results showed that BMD, E and ry values of the OA group are 2–3 times more than those of the OP group. As the femoral head becomes stiffer, it comes with two effects: first the bone including the head and the neck has less energy absorption, second the contact area between the head and the acetabulum may be more localized, i.e., less conformity and higher stress at the head/acetabulum contact point. These all contribute to higher wear in the cartilage for the OA femoral head. However, for the OP femoral head, though it has more energy absorption and more uniform stress in the contact, the chance of femoral neck fracture is elevated because of the decreased bone strength. Similar findings were reported that higher BMD was observed in older patients with OA (Naganathan et al., 2002). It should be noted that femoral head samples are difficult to obtain, especially from normal people. The sample collection is still an ongoing effort for further extended research work. The values of apparent elastic modulus obtained by the volumetric BMD help derive intrinsic material properties via finite element simulation (Wirtz et al., 2000). In this study, volumetric BMD of cuboid samples was estimated from the DXA scan (depth of cubiod bone is 10 mm) and not a true volumetric measurement. The strength of DXA is that it measures the amount of mineralization in bone and surrounding tissues. Its major limitation is that it does not provide a true volumetric bone density. DXA provides an ‘‘areal BMD”, expressed as gm/cm2, since the bone mineral content is divided by the projected (two-dimensional) area to calculate a ‘‘BMD”. As such, it fails to account for the depth of the bones, and individuals with bigger bones will have higher BMD values by DXA, despite having the same volumetric BMDs as individuals with smaller bones. In the methods of this study, nevertheless, each 10  10  40 mm cuboid was scanned by DXA. The artifact caused from different depth of the sample could be diminished. It was demonstrated that the femoral neck in patients with OA had increased cancellous bone area, connectivity and trabecular thickness which may all protect the neck against fracture (Jordan et al., 2003). The neck is important in transmitting the compressive stress between the femoral head and the shaft of the femur. In our previous study, it was demonstrated that stiffening the femoral neck has a slight effect on the progression of cartilage degeneration (Wei et al., 2005). The femoral neck is cantilevered when

under loads, resulting in substantial bending in the neck. The results showed there is a significant increase of the largest maximum tensile stress at the bone/cartilage interface as the modulus of the femoral neck doubled. They corroborated the explanation that the aetiology of OA is related to the changes in the mechanical properties of the femoral neck. In the finite element model of this study, most intrinsic material property indices of femoral neck are higher in OA, including bone volume (BV), bone surface (BS), bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and elastic modulus. The results provided some evidence that OAassociated changes in femoral neck increase the ability to withstand stress and provide protection against intracapsular hip fracture. 5. Conclusion The study provided a meaningful mechanical method to compare material properties between OA and OP femoral head and neck and found significant difference between the two groups. It was also found that femoral head diameter has stronger influence in mechanical properties than patient’s body weight and body height. The results indicated a significantly higher bone strength and BMD for OA samples. Based on the FE analysis, the increased amount of bone volume, trabecular thickness, trabecular number, and elastic modulus in OA patient offers an explanation of why OA patients rarely fracture femoral neck. References Brown, T.D., 1981. Mechanical characteristics of bone in femoral capital aseptic necrosis. Clin. Orthop. 156, 240–247. Burr, D.B., Schaffler, M.B., 1997. The involvement of subchondral mineralized tissues in osteoarthrosis: quantitative microscopic evidence. Microsc. Res. Tech. 37, 343–357. Byers, P.D., Contepenni, C.A., Farkas, T.A., 1970. A post mortem study of the hip joint. Ann. Rheum. 29, 15–31. Carlsson, A., Nillson, B.E., Westlin, N.E., 1979. Bone mass in primary coxarthrosis. Acta Orthop. Scand. 5, 187–189. Dequeker, J., 1985. The relationship between osteoporosis and osteoarthritis. Clin. Rheum. Dis. 11, 271–295. Dequeker, J., Mokassa, L., Aerssens, J., 1995. Bone density and osteoarthritis. J. Rheum. 22 (1, (Suppl. 43)), 98–100. Dretakis, E.K., Steriopoulos, K.A., Kontakis, G.M., 1998. Cervical hip fractures do not occur in arthrotic joints. Acta Orthop. Scand. 69, 384– 386. Foss, M.V.L., Byers, P.D., 1972. Bone density, Osteoarthritis of the hip, and fracture of the upper end of the femur. Ann. Rheum. Dis. 31, 259– 264. Healey, J.H., Vigorita, V.H., Lane, J.M., 1985. The coexistence and characteristics of osteoarthritis and osteoporosis. J. Bone Joint Surg. [Am] 67, 586–592. Jordan, G.R., Loveridge, N., Bell, K.L., Power, J., Dickson, G.R., Vedi, S., Rushton, N., Clarke, M.T., Reeve, J., 2003. Increased femoral neck cancellous bone and connectivity in coxarthrosis (hip osteoarthritis). Bone 32, 86–95. Li, B., Aspden, R.M., 1997a. Composition and mechanical properties of cancellous bone from the femoral head of patients with osteoporosis or osteoarthritis. J. Bone Mater. Res. 12, 641–651.

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