J Bone Miner Metab (2011) 29:449–457 DOI 10.1007/s00774-010-0240-x
ORIGINAL ARTICLE
Inter-sex differences in structural properties of aging femora: implications on differential bone fragility: a cadaver study Danijela Djonic • Petar Milovanovic • Slobodan Nikolic Miomira Ivovic • Jelena Marinkovic • Thomas Beck • Marija Djuric
•
Received: 5 February 2010 / Accepted: 7 October 2010 / Published online: 4 December 2010 Ó The Japanese Society for Bone and Mineral Research and Springer 2010
Abstract In this paper we examined age-related and sexspecific deterioration in bone strength of the proximal femur reflected in mechanical properties from dual energy X-ray absorptiometry (DXA)-based hip structural analysis (HSA) on a cadaveric sample from the Balkans. Cadaveric studies permit more precise measurement of HSA parameters and allow further analyses by micromorphometric methods. DXA and HSA analysis was performed on a total of 138 cadaveric proximal femora (63 female, 75 male, age range 20–101 years) from Belgrade. HSA parameters are reported for three standard regions of the proximal femur (narrow neck, intertrochanteric, and shaft). Major agerelated findings include an increase in the radius of gyration (first reported in this study), a decline in the cross-sectional area (CSA), a shift in the centroid towards the medial D. Djonic P. Milovanovic M. Djuric (&) Laboratory for Anthropology, Institute of Anatomy, School of Medicine, University of Belgrade, 4/2 Dr Subotica, 11000 Belgrade, Serbia e-mail:
[email protected] S. Nikolic Institute for Forensic Medicine, School of Medicine, University of Belgrade, 31a Deligradska, 11000 Belgrade, Serbia M. Ivovic Institute for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, 13 Dr Subotica, 11000 Belgrade, Serbia J. Marinkovic Institute for Medical Statistics and Informatics, School of Medicine, University of Belgrade, 15 Dr Subotica, 11000 Belgrade, Serbia T. Beck Johns Hopkins University School of Medicine, Baltimore, MD, USA
cortex, higher buckling ratios and lower section moduli. Whereas age appears to affect mostly the neck region in men, weakening is also evident in the intertrochanteric region in women, particularly after the age of 80. Aging femoral neck declines in bending strength and increases in buckling susceptibility. The reduced bone mass tends to be distributed farther from the centroidal axis (increase in radius of gyration with decline in CSA). Bone mass is preferentially lost from the lateral part of the cross-section shifting the centroid towards the medial cortex which may increase fragility of the lateral part during fall impact. Results of this study contribute to the epidemiologic data on gender differences and age trends in aging male and female femora. Keywords Aging Bone strength HSA Proximal femur Bone fragility
Introduction Age-related hip fracture is a growing problem worldwide that attracts intense scientific attention. Particular emphasis has been on determining the factors associated with an increased fracture risk [1–5]. In mechanical terms, bone susceptibility or resistance to fracture depends on bone strength. Areal bone mineral density (BMD) is widely accepted and clinically used as a ‘‘surrogate’’ for bone strength [1, 3, 6–8]; however, age-related decrease of BMD fails to sufficiently explain the high increase of hip fracture risk with aging [9–11]. Therefore, the role of BMD as an exclusive fracture risk predictor cannot fully satisfy and, while a useful correlate, is not actually a component of bone strength [4, 5, 12, 13]. Hip structural analysis (HSA) [14] provides limited capability to determine geometric
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components of bone strength of the femur from dual energy X-ray absorptiometry (DXA) images by the use of specially designed software. The wealth of HSA data from a number of patients in large clinical studies makes this method particularly useful in investigating the features of bone aging and hip fracture risk [15, 16]. This method was applied in various populations such as American [15, 17], American black [18], Australian [19], Japanese [20], Chinese [21] and European [16, 22]; however, so far the Balkan region has practically been devoid of HSA studies. Furthermore, HSA analysis has not been reported on cadaveric femora. One potential advantage of a cadaveric study is the precise measurement of the bone parameters as bones are devoid of soft tissues and the positioning of the specimens should be more accurate than with patients. Moreover, cadaveric specimens can be further examined by micromorphometric methods, which allow us to draw a parallel between age-related changes in the macroscopic geometry measured by HSA and those in the fine internal architecture assessed by ex vivo research tools, such as micro-computerized tomography (micro-CT). In this paper we estimated sex-specific age trends in bone structure at the proximal femur as reflected in densitometric and HSA-derived mechanical parameters on a cadaveric sample from the Balkans, in order to provide insight into bone aging in this under-studied population. We also discuss possible implications of observed gender and age differences with respect to hip fracture susceptibility in senescence.
the sample was granted by the Ethics Committee of the School of Medicine, University of Belgrade. As shown in Table 1, cadaver donors ranged in age from 20 to 101 years, and included 63 females (average age 56 years, SD 20 years) and 75 males (mean age 56 years, SD 20 years). Based on clinical and autopsy reports, the main causes of death included cardiac arrest, stroke, motor vehicle accidents or other sudden, traumatic injuries. Only individuals lacking macroscopic and radiographic bone pathologic changes or history of musculoskeletal diseases were included in the study. To improve our ability to evaluate age trends in this limited sample, the sample was further divided into four biologically and clinically relevant age categories: I (less than 39 years), II (40–59 years), III (60–79 years) and IV (over 80 years). There were no significant differences in gender across these age categories (Chi square, P [ 0.05). DXA measurements In vitro DXA scans of the femora were obtained by using a Hologic QDR 1000/W (Hologic, Waltham, MA) bone densitometer, with the femoral specimens placed in an antero-posterior position and submerged in a water bath to simulate soft tissue [23]. The scans were automatically evaluated by DXA software providing values of bone mineral content (BMC; g), bone area (BA; cm2), and areal bone mineral density (BMD; g/cm2) in the standard femoral neck region. Hip structural analysis
Materials and methods Bone specimens The study sample comprised 138 proximal femora collected at the Forensic Department, School of Medicine, University of Belgrade. Ethics approval for collection of
We used HSA software developed by Beck and colleagues [14] to calculate structural indices from the DXA scans. Three regions of interest corresponding to 5-mmthick cross-sectional slabs of bone were assessed in this analysis: narrow neck (NN, n) located at the narrowest diameter of the neck; the intertrochanteric (IT, it) at the
Table 1 Characteristics of the study population Age category
Females N
Age (years) mean (SD)
Males 2
Height (cm) mean (SD)
Weight (kg) mean (SD)
BMI (kg/m ) N mean (SD)
Age (years) mean (SD)
Height (cm) mean (SD)
Weight (kg) mean (SD)
BMI (kg/m2) mean (SD)
I (less than 39 years)
17 30 (6)
165.8 (9.9)
63.1 (16.2)
23.0 (5.8)
18 30 (6)
177.7 (8.8)
85.0 (19.7)
26.9 (5.8)
II
17 50 (5)
168.2 (7.8)
74.4 (12.8)
26.2 (3.6)
23 50 (6)
175.7 (10.4)
80.5 (16.1)
26.0 (4.6)
III 21 69 (5) (60–79 years)
162.4 (9.0)
66.9 (20.4)
25.0 (5.7)
23 68 (5)
175.6 (9.0)
81.1 (19.5)
26.0 (4.6)
IV (over 80 years)
8 87 (7)
154.9 (10.9)
53.1 (11.6)
22.0 (3.0)
11 85 (5)
176.7 (7.9)
77.7 (9.8)
24.9 (3.0)
63 56 (20)
163.9 (9.9)
66.1 (17.4)
24.4 (5.1)
75 56 (20)
176.3 (9.1)
81.4 (17.2)
26.1 (4.7)
(40–59 years)
Total
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level of the section of neck and shaft axes; and the shaft (S, fs) located 1.5 times minimum neck diameter distal to the intersection of the neck and shaft axes. The following structural parameters were calculated for each region of interest: cross-sectional area (CSA, cm2), outer or periosteal diameter (PD, cm), estimated endocortical diameter (ED, cm), section modulus (Z, cm3), cross-sectional moment of inertia (CSMI, cm4), estimated cortical thickness (CTh, cm), estimated buckling ratio (BR, dimensionless), radius of gyration (G, cm), and relative position of the centroid (CentPos, dimensionless). The last two parameters describe distribution of bone within crosssections. Radius of gyration is derived as the square root of CSMI/CSA and provides an index of the average distance of the bone material from the center of mass; it was not reported in previous HSA studies. The centroid position reflects the distance of the centroid from the medial cortical margin, divided by the total outer diameter. Based on experience with the method, BR and centroid position are not meaningful at the femur shaft region and are not reported here. The HSA program and the parameters it generates have been described in detail elsewhere [15]. Statistical analysis The Kolmogorov–Smirnov test was used to verify the normality of the data distribution. Student’s t test was applied to assess differences between men and women for each investigated parameter. One-way analysis of variance was used to evaluate the significance of the differences in the mean values of observed densitometric and HSA properties between the four age categories, separately in males and females. In post-hoc multiple comparison procedures, Bonferroni adjustment was used, which set the significance level to 0.05/number of comparisons. Given that the dimensions of the femur as well as the cross-sectional properties depend, at least partially, on bone size, all obtained data were adjusted for standardized body height and weight in order to avoid the influence of these parameters on the results [17, 24]. Analysis of covariance was performed controlling for height and weight to assess whether differences in the means of densitometric and structural properties between the four age categories trend differently in each sex. For multiple comparisons, a Bonferroni correction was used. The relationships of HSA and densitometric parameters with the age of the individual were assessed by linear regression analysis. All analyses were conducted using SPSS statistical software (version 12.0) and the results were considered statistically significant at the 0.05 level.
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Results In our sample, the femoral neck areal BMD and BMC significantly differed between the sexes, even after adjusting for body height and weight (Table 2). Areal BMD and BMC in the femoral neck showed negative correlation with age in both sexes (P \ 0.05) while the neck region area displayed a modest tendency to increase that did not reach significance (Table 3). CSA, section modulus, estimated CTh, and PD were significantly different between males and females (Table 2). The degree of sex difference varied with age with the largest differences between the sexes in the oldest age category (data not shown). Table 3 displays the apparent variation in HSA parameters as a linear function of age. In both sexes, section modulus significantly decreased with age only in the neck region. PD trended upward (at all regions) but none of the trends reached significance in this sample. CTh significantly declined as a function of age at the narrow neck. We demonstrated that the radius of gyration increased significantly with age in both sexes and in all regions, indicating that bone mass is more peripherally distributed in older cross-sections. The relative position of the centroid in the narrow neck region shifted medially with age in both sexes and at the intertrochanteric region in females. These effects, together with the declining CSA, indicate that as age progresses in both sexes, bone is preferentially lost from the lateral part of the cross-section, thus shifting the centroid towards the medial cortex. In male femora the BR significantly increased with age only in the neck region (Table 3) particularly after the age of 60 (Table 4), while in women the BR increased significantly with age at both the neck (particularly after the age of 60, Tables 3, 4) and intertrochanteric regions (Table 3). After the age of 60, the decline in several parameters became statistically significant in the neck region of males (CSA, Z, CTh, BR; P \ 0.05) (Table 4), whereas in females CTh appeared to decrease significantly in the oldest age category, i.e., after the age of 80 (P \ 0.05) (Table 4). In females, the intertrochanteric region was also affected by aging (CSA and CTh declined particularly after the age of 80, Table 4).
Discussion As in other studies [15, 17, 25, 26], areal BMD significantly differed between the sexes in the femoral neck region in our sample. After adjusting for body height and weight, the percent of differences increased, which contrasts to other studies [27, 28]. Hence, our results suggest that the sex-related differences are not entirely a
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Table 2 Intersexual differences in conventional densitometric and HSA parameters Unadjusted
Adjusted for height and weight
Males (Mean ± SD)
Females (Mean ± SD)
% Difference M versus F
P
Males (Mean ± SE)
Females (Mean ± SE)
% Difference M versus F
P
0.011
BMCn (g)
4.18 ± 1.06
3.39 ± 0.97
18.90
0.000
4.18 ± 0.11
3.33 ± 0.11
20.33
BMDn (g/cm2)
0.79 ± 1.16
0.68 ± 0.15
13.92
0.000
0.79 ± 0.02
0.66 ± 0.02
16.45
0.002
BAn (cm2) CSAn (cm2)
5.28 ± 0.09 3.22 ± 0.62
4.96 ± 0.09 2.54 ± 0.56
6.06 21.12
0.024 0.000
5.19 ± 0.11 3.22 ± 0.06
5.14 ± 0.12 2.50 ± 0.06
0.09 22.36
0.791 0.000
CSAit (cm2)
6.63 ± 1.28
4.93 ± 1.02
25.64
0.000
6.72 ± 0.15
4.85 ± 0.12
27.83
0.000
2
CSAfs (cm )
5.02 ± 0.75
3.85 ± 0.74
23.31
0.000
5.04 ± 0.08
3.76 ± 0.09
25.40
0.000
Zn (cm3)
1.93 ± 0.41
1.32 ± 0.35
31.61
0.000
1.94 ± 0.04
1.30 ± 0.04
32.99
0.000
Zit (cm3)
6.81 ± 1.69
4.54 ± 1.19
33.33
0.000
6.99 ± 0.19
4.52 ± 0.12
35.34
0.000
Zfs (cm3)
3.02 ± 0.58
2.11 ± 0.50
30.13
0.000
3.05 ± 0.07
2.14 ± 0.05
29.84
0.000
CTh.n (cm)
0.18 ± 0.04
0.16 ± 0.03
11.11
0.001
0.18 ± 0.004
0.15 ± 0.004
16.67
0.017
CTh.it (cm)
0.53 ± 0.35
0.48 ± 0.43
9.43
0.509
0.55 ± 0.35
0.50 ± 0.43
9.09
0.682
CTh.fs (cm) BRn
0.62 ± 0.15
0.53 ± 0.17
14.52
0.006
0.70 ± 0.15
0.55 ± 0.17
21.43
0.000
11.48 ± 3.05
12.03 ± 3.46
-4.79
0.328
11.63 ± 0.31
12.66 ± 0.37
-8.86
0.082
BRit
7.68 ± 2.04
8.02 ± 2.71
-4.43
0.425
7.71 ± 0.26
8.21 ± 0.39
-6.48
0.959
PDn (cm)
3.61 ± 0.28
3.19 ± 0.43
11.63
0.000
3.63 ± 0.03
3.23 ± 0.06
11.02
0.001
PDit (cm)
6.49 ± 0.80
5.67 ± 0.97
12.63
0.000
6.60 ± 0.80
5.80 ± 0.97
12.12
0.000
PDfs (cm)
3.25 ± 0.34
2.84 ± 0.50
12.61
0.000
3.40 ± 0.34
2.94 ± 0.50
13.53
0.000
nCentPos itCentPos
0.53 ± 0.03 0.57 ± 0.06
0.51 ± 0.04 0.56 ± 0.04
3.77 1.75
0.000 0.258
0.53 ± 0.00 0.56 ± 0.01
0.50 ± 0.00 0.56 ± 0.01
5.66 0.00
0.001 0.960
Gn (cm)
1.09 ± 0.09
0.96 ± 0.09
11.93
0.000
1.06 ± 0.01
0.99 ± 0.01
6.60
0.000
Git (cm)
1.93 ± 0.22
1.72 ± 0.17
10.88
0.000
1.89 ± 0.03
1.76 ± 0.03
6.88
0.003
Gfs (cm)
1.00 ± 0.10
0.90 ± 0.11
10.00
0.000
0.99 ± 0.02
0.91 ± 0.02
8.08
0.001
BMC bone mineral content, BMD areal bone mineral density, BA bone area at the femoral neck region, CSA cross-sectional area, Z section modulus, CTh estimated cortical thickness, BR buckling ratio, PD periosteal diameter, CentPos position of the centroid, G radius of gyration, n femoral narrow neck region, it intertrochanteric region, fs femoral shaft region
consequence of body size. In both sexes BMC and BMD declined with age. The decrease in BMC as one of the reasons for the decrease in areal BMD of the neck region of males is clearly supported by our micro-CT analysis of trabecular bone from the same cadaveric femora [29]. Namely, our micro-CT study demonstrated that the lateral neck of male specimens was the most prominent region for trabecular bone deterioration and decline of bone volume fraction (highly significant age-related decline in bone volume fraction, with the highest difference between the youngest and the oldest specimens––nearly 60%) [29]. The section modulus appeared to decline significantly with aging only in the neck region in both sexes, although some authors reported no change [15, 20, 25]. Longitudinal studies in men and women [22, 30], as well as cross-sectional studies [31–33], generally show positive trends in the femur outer diameter and, although trends at all regions were positive with age, none reached significance in our sample. Since the section modulus reflects bone section strength [34], the decreased femoral neck section modulus
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with advanced age leads to lower resistance to bending. In contrast to the neck, the intertrochanteric and shaft regions were stable with aging (unchanged section modulus), as also shown in studies on living subjects [15]. Predicting strength with the section modulus assumes that bone cross-sections remain relatively intact until failure begins, but this may not be the case with excessively thin cortices when subjected to high compressive loads: this is what happens to the osteoporotic femur in a fall impacting the greater trochanter [35]. Under these conditions, failure may occur by local buckling of the cortical shell which requires specialized analytical methods to predict [36]. Given the limited information present in a DXA scan, buckling susceptibility can only be crudely estimated using the BR. Despite its crude nature the BR is elevated in hip fractures of both genders [30, 37, 38]. According to Yates et al. [17], a significant increase of the BR at a given region may suggest increased risk for fracture at that site. In that context, a high BR in the neck of males is compatible with reported data that there are more
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Table 3 Correlation coefficient on age and DXA/HSA parameters Narrow neck
Intertrochanteric
Shaft
BMC Males
-0.430*
–
–
Females
-0.373*
–
–
Males
-0.464*
–
–
Females
-0.502*
–
–
Males
0.066
–
–
Females
0.028
–
–
BMD
BA
CSA Males Females
-0.371* -0.376*
-0.142 -0.299*
-0.154 -0.279*
Males
-0.292*
-0.079
-0.155
Females
-0.281*
-0.198
-0.007
Males
0.520*
0.240
–
Females
0.604*
0.303*
–
Z
BR
CTh Males
-0.454*
-0.085
Females
-0.459*
0.149
-0.204 -0.324*
Males
0.200
0.204
0.117
Females
0.147
0.075
0.139
Males
0.322*
0.282*
0.272*
Females CentPos
0.297*
0.215*
0.308*
Males
0.371*
0.031
–
Females
0.405*
0.409*
–
PD
G
BMC bone mineral content, BMD areal bone mineral density, BA bone area, CSA cross-sectional area, Z section modulus, BR estimated buckling ratio, CTh estimated cortical thickness, PD periosteal diameter, G radius of gyration, CentPos position of the centroid * P \ 0.05
cervical than trochanteric fractures in elderly males [39], while a low BR of the femoral shaft is consistent with the rarity of a low trauma fracture at that site. Our study suggests that women between 60 and 79 have a greater risk for cervical fractures, while after the age of 80 [given that both the neck BR and intertrochanteric BR exceed the ‘‘critical’’ value (data not shown)] both cervical and trochanteric fractures are likely to occur. This is in agreement with epidemiologic data which report increased proportions of trochanteric fractures with aging in females [39, 40]. Moreover, at the intertrochanteric region of aging females almost all HSA parameters showed significant agerelated deterioration in contrast to males (Table 3). The
findings of micro-CT (performed on the same cadaveric sample after DXA/HSA imaging) support the significance of the intertrochanteric region as a ‘‘weak spot’’ of aging female femora [29]. In our study, females had significantly lower neck region area (BAn) and PD than males. Given that bending strength (in terms of the section modulus) is more dependent on the periosteal than endosteal diameter, females show lower resistance to bending. Furthermore, a significantly lower CSA and section modulus make female femora less able to resist compressive and bending forces. Namely, the section modulus in each region of females is about 30% lower than in males; while the CSA of females is 20–25% lower than in males. Given that the difference in BMD was only 10–13% in the same region, our results indicate that HSA-derived structural parameters display more inter-sex differences than BMD obtained by classical DXA. The significance of the CSA and section modulus as discriminatory parameters between the sexes is in agreement with studies on living subjects [15, 17, 22, 24]. The radius of gyration describes the way in which the total CSA is distributed around the centroidal axis and was not reported in previous HSA studies. A higher radius of gyration (for equivalent CSA) reflects increased CSMI which increases resistance to bending. Given that in our study the radius of gyration increased significantly with aging in both sexes, while the CSA tended to decrease, it may reflect a ‘‘compensatory mechanism’’ to preserve bone bending strength in the presence of net bone loss by distributing the available bone mass farther from the centroidal axis. Such kind of bone behavior as a ‘‘compensatory mechanism’’ was suggested previously (see ref. [15]). The relative position of the centroid in the narrow neck region decreased significantly with age indicating that the bone mass proportions are shifted inferiorly towards the medial neck cortex. This is consistent with the results of our micro-CT study on the same cadaveric specimens [29] which revealed preferential trabecular bone loss in the male lateral neck with aging. These observations included decreases in trabecular bone volume fraction and connectivity density, as well as an increased proportion of ‘‘weaker’’ rod-like trabeculae (higher structure-model index, SMI) and higher trabecular separation in the lateral neck [29]. In contrast, the medial neck kept relatively ‘‘good’’ status with aging, with unchanged volume fraction (r = -0.2, P [ 0.05), the thickest trabeculae and the highest trabecular number [29]. Cortical thinning in the lateral neck of both sexes reported by Mayhew et al. [41] also contributes to the observed centroid shift. This particular deterioration is a likely adaptation to the low loading stimulus in the lateral neck region in normal
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454 Table 4 ANOVA, post-hoc comparisons for HSA parameters between age categories
J Bone Miner Metab (2011) 29:449–457 HSA parametera
CSAn CSAit
Age categories: I (less than 39 years), II (40–59 years), III (60–79 years) and IV (over 80 years) NS––P [ 0.05 CSA cross-sectional area, Z section modulus, CTh estimated cortical thickness, BR buckling ratio, n femoral narrow neck region, it intertrochanteric region, fs femoral shaft region a
Only HSA parameters displaying differences between some of the age categories are shown in the table
CSAfs
Males Age categories which differ significantly
P
I vs. III
0.003
None
None
NS
NS
Age categories which differ significantly
P
I vs. IV
0.006
II vs. IV
0.014
I vs. IV
0.016
II vs. IV
0.015
III vs. IV
0.022
I vs. IV
0.007
II vs. IV III vs. IV
0.002 0.005 NS
Zn
I vs. III
0.012
None
CTh.n
I vs. III
0.001
I vs. IV
0.000
I vs. IV
0.004
II vs. IV
0.006
III vs. IV
0.034 0.035
CTh.it
None
NS
III vs. IV
BRn
I vs. III
0.000
I vs. III
0.007
I vs. IV
0.000
I vs. IV
0.000
II vs. III
0.009
II vs. IV
0.000
II vs. IV
0.011
III vs. IV
0.002
ambulation as apposed to the very high compressive loads borne by the medial neck [41–44]. The significance of an eccentric position of the centroid for stresses at the superior and inferior surfaces of the neck and its possible influence on the risk of failure was discussed by Fox and Keaveny [45]. The observed centroid shift with preferential bone loss at the lateral neck (both cortical and trabecular bone) should increase vulnerability of this femoral subregion during fall impact, which explains why it is considered as a fracture-initiating site. This study had a number of limitations, one of which was its cross-sectional nature, i.e., it examined subject femora at various ages at death and did not follow the aging process in the same individuals; however, obtained results are quite compatible with the few available longitudinal studies [22, 46]. Our relatively small sample size is a consequence of analyzing cadaveric material. Although lean body mass is more important for evaluating customary muscle loads [47], it was not available in this study. As in other studies lacking body composition [22, 24, 48] statistical adjustment employed body height and weight. This may have influenced the magnitudes of gender differences since males tend to be leaner than females. In addition, the restraints of DXA technology can influence HSA parameters given that it is not yet able to detect minor differences in PD. Moreover, HSA analysis makes some approximations necessary for applying mechanical principles to the biological reality of proximal femur [14, 15]. However, it is clear that bone fragility is evident in the bone geometry even if crudely measured by current DXA methods [30].
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Females
Inter-population similarities and variability: comparisons with age trends in other White populations Overall the trends in geometry were similar to those observed in the US NHANES III study as illustrated with the plotted means for age categories in Fig. 1. In the narrow neck region, the age-dependent linear decrease in CTh in our study (both sexes, age range 20–101 years) is compatible with the results of other studies in European populations: the MINOS study (French population, males, age [40 years––[49, 50]) and the EPIC study (UK population, both sexes, age range 67–79 years––[22]). The PD in Belgrade cadavers showed a tendency to increase. This is consistent with the NHANES data and suggests that age trends would be significant in a larger sample. Similarly, in the majority of European studies there was an increase in PD with age (the EPIC study [22]; the EPOS multicentric study, both sexes, age 50–80 years [48]; the MINOS study [50]). In a cross-sectional study in the UK [51], aging was associated with increasing sub-PDs in all three HSA regions. PD decreased slightly with age in a sample from Spain [52] (sample age not available), and was unchanged between the age of 52–54 to the age of 61–63 years in women from Finland [53]. The section modulus in our study decreased with age, which is similar to a study from Spain where it showed a strong decrease with age (both sexes, age range not available [52]), and to a study of Finish women where it decreased from the age of 52–54 to the age of 61–63 years
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Fig. 1 HSA data: comparisons between Belgrade cadaver sample and US White non-Hispanic population (NHANES III study) show similar age trends (NHW US White non-Hispanic population, CSA cross-sectional area)
[53]; however, the section modulus was stable with age in the MINOS study [50], in the EPIC study [51], and in a UK male study [22]; it even increased with age in women (age 67–79 years) in a UK study[22]. CSA in the narrow neck declined with age in our study, while variable results were obtained in other studies: no change with age (in range 67–79 years [51]), increase (UK study, both sexes, age 67–79 years––[22]), and decrease (Spain––[52]; Finland, women aged 52–54 compared to age 61–63 years––[53]). BR increased in our study as in other studies [22, 50, 53], while in a Spanish population study it was stable [52]. Similar to our study, medial shift of the centroid in the femoral neck was demonstrated in a longitudinal study in the UK (age 65–74 years) [54], while other studies reported no shift with age [52]. In the intertrochanteric region, CSA, section modulus and estimated CTh decreased, while sub-periosteal width and BR increased [22]. In the shaft region, only the BR showed a significant increase in men (age 67–79 years) from the UK [22], while CTh and PD were stable. In women, CTh decreased, while sub-periosteal width and BR increased [22].
From the data presented above, variability within European samples is apparent; however, the variability in the results does not necessarily mean real differences, since the available studies differ in sample age and sex distribution as well as some differences in methodology and size adjustments which make serious comparisons difficult. However, despite some differences, the majority of findings are similar across the studies on European populations and consistent with the present study. It can be speculated about possible cohort effects in our population. As suggested by Crabtree et al. [48] caution is necessary in the interpretation of age trends in cross-sectional studies because of possible differences between age cohorts. For example, the privation and substandard nutrition experienced by some individuals from our study during critical periods of bone growth before skeletal maturity (e.g., older age groups during the Second World War, or younger individuals during the economic and political crises during 1990s) might have influenced femoral neck geometry of the particular cohort thus blurring the real age effects. However, the Second World War doubtlessly left traces in other European populations and such effects have not been studied. In particular the first
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age category in our study was in the process of skeletal growth and maturation during the severe political and economic crisis in the last decade of the twentieth century. It may be interesting to follow such groups to determine if severe privation influences their femur geometry in old age when compared to other European populations who grew up in better economic conditions. In summary, the results of this study reveal that agerelated trends in the proximal femur geometry show gender and subregion differences. After the age of 60 in both sexes, the femoral neck shows decreased bending strength and an increase in buckling susceptibility (decreased section modulus and increased BR). Age patterns in our sample appeared to be most evident in the neck region in men, whereas in women changes were also evident in the intertrochanteric region, particularly after the age of 80. These data obtained by HSA analysis are consistent with (and can be supported and explained by) the results obtained on the same cadaveric specimens by a research tool (micro-CT), and may be helpful in interpreting epidemiologic studies on the relative prevalence of cervical versus trochanteric fractures in aging males and females [39, 40, 55, 56]. Acknowledgments This study was supported by a grant from the Ministry of Science of the Republic of Serbia, subproject name: ‘‘Age-Related Microarchitectural and Mechanical Bone Properties: Implications for Increased Fragility’’ within the project: ‘‘Functional, Functionalized and Advanced Nano Materials’’.
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