Aging Clin Exp Res DOI 10.1007/s40520-015-0406-4
ORIGINAL ARTICLE
Proximal femur geometry assessed by hip structural analysis in hip fracture in women Giovanni Iolascon1 • Antimo Moretti1 • Giovanni Cannaviello1 • Giuseppina Resmini2 Francesca Gimigliano3
•
Received: 13 May 2015 / Accepted: 1 July 2015 Ó Springer International Publishing Switzerland 2015
Abstract Introduction In the pathogenesis of hip fracture, proximal femur geometry plays a key role as well as decreased bone density. The hip structural analysis (HSA) processes dual energy X-ray absorptiometry (DXA) images containing information on the geometry closely related to the strength of the proximal femur. The objective of this study was to investigate bone mineral density (BMD) and mechanical properties of the proximal femur in a group of women with a previous contralateral hip fragility fracture compared to women without history of hip fracture. Materials and methods In a population of postmenopausal women, we evaluated bone density by DXA and bone geometry using the HSA parameters (femoral strength index, cross-sectional moment of inertia, crosssectional area, section modulus, and buckling ratio) including hip axis length (HAL) and neck shaft angle. Results Of a total of 62 postmenopausal women, twentysix with a history of hip fracture had a mean femoral neck BMD significantly lower in comparison with 36 women in the control group (0.703 versus 0.768 g/cm2, p = 0.0347). There was a statistically significant difference between groups also for HAL (106.75 mm in fracture group versus 100.93 mm in control group, p = 0.0015).
& Giovanni Iolascon [email protected] 1
Department of Medical and Surgical Specialties and Dentistry, Second University of Naples, Naples, Italy
2
Centre for the Study of Osteoporosis and Metabolic Bone Disease, Section of Orthopaedic and Traumatology, Treviglio-Caravaggio Hospital, Bergamo, Italy
3
Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Naples, Italy
Discussion and conclusions Our results demonstrated that all the geometrical parameters resulted worst into the group of patients with history of hip fracture, even though only the HAL was significantly lower in control subjects. In our opinion HSA is useful to characterize the risk of hip fracture in postmenopausal women, providing additional data on the spatial distribution of bone mass strongly related to bone strength. Keywords Osteoporosis Hip fracture Advanced hip assessment Hip structural analysis Hip geometry
Introduction Osteoporosis is one of the most significant health problems, affecting 200 million of people worldwide [1]. Hip fracture is considered the most serious osteoporotic fracture causing a huge impact on patient morbidity, functional capacity, and mortality. It is linked to high medical costs comparable to that of strokes and higher than that of acute myocardial infarction (AMI), both in terms of hospitalizations and health care expenditures [2]. The main determinant of hip fractures is falling. Falls and its circumstances have been well characterized in a recent Italian study [3]. In Italy, there were 93,169 femoral neck fractures in 2009 (21,345 men and 71,824 women) with an incidence of 77.8 per 10,000 (42.4 in men and 103.5 in women) [4]. The risk of hip fractures increases ten-fold every 20 years of age, its 1-year mortality amounts to 20 % and a permanent loss in function has been reported in 50 % of cases [5–7]. Considering this huge burden for individual and social health system, it is required to establish fracture risk more accurately as possible. Currently, the gold standard for the
123
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estimation of the risk of hip fracture is the dual energy X-ray absorptiometry (DXA) measurement of the proximal femur bone mineral density (BMD), since bone mass highly correlates with bone strength, accounting for 80–90 % of the variance in ultimate compressive strength of both compact and trabecular bone [8]. However, hip bone strength also depends on the spatial distribution of bone mass that characterizes the structural geometric properties (diameter, area, length, and angle of the femoral neck). Age-related bone loss in the proximal femur is partially compensated with redistribution of bone mass and enlargement of the diameter of the femoral neck by concurrent periosteal apposition that anyway does not inhibit the overall worsening of material and structural properties of bone tissue. Recent technological advances of DXA devices are able to provide data for the measurement of both BMD and bone geometry parameters including femoral size, shape, and strength. Using two-dimensional DXA-derived images of the hip, the advanced hip assessment (AHA) software package allows to perform the hip structural analysis (HSA) that measures bone geometric properties of cross sections in cut planes traversing the bone at that location [9]. This study aimed to compare the proximal femur density and geometry, assessed by DXA exam, in two groups of postmenopausal women with or without history of hip fracture in the contralateral limb.
Materials and methods Study population In this retrospective case–control study, we analyzed data of consecutive postmenopausal women aged 50 years or older, obtained by DXA of the proximal femur, using the GE Healthcare Lunar iDXA. DXA images were purchased from patients referred to our outpatient rehabilitation service, in a 6-month period. We divided population into two groups: women that sustained a previous hip fracture in the contralateral limb, and women without history of hip fragility fracture. All scans were rated by a single operator with a specific expertise in the management of osteoporosis, according to the manufacturer’s recommended protocol. Structural parameters Areal BMD (aBMD) of the femoral neck was usually measured in non-dominant leg by DXA scan. For women who previously sustained a hip fracture, BMD was measured at the contralateral limb. Structural parameters were
123
determined using the manufacturer’s AHA software package, that automatically provides bone mass distribution variables, derived by information contained within DXA absorption curves, and several bone geometry parameters from the same scan image. The AHA software defines the distribution of mineral mass in a line of pixels across the bone axis to measure hip geometric properties. This software allows to perform the HSA evaluating the following parameters: (1) cross-sectional moment of inertia (CSMI, in mm4), also called second moment of area, that is used to measure the distribution of material around the neck axis necessary to calculate resistance to bending. Mechanical stress within a cross-section subjected to bending is inversely related to the CSMI and varies with the distance from the neutral axis [9]. In most bones, cross sections are not axially symmetric and the CSMI for bending is higher in some directions than in others; (2) cross-sectional area (CSA, in mm2), the sum surface area of bone in a cross-sectional slice, after excluding all the spaces occupied by marrow and other soft tissues within pores. It is also described as the minimum CSMI section within the neck region of interest (ROI); (3) neck shaft angle (NSA), the angle between femoral neck and femoral shaft; (4) section modulus (Z), a strength parameter that derives from CSMI, that is equal to the CSMI divided by what is called the centroidal distance, from centroidal axis to the edge of the section; (5) hip axis length (HAL, in mm), calculated as the distance from the tip of the greater trochanter to the internal pelvic rim; (6) femoral strength index (FSI), the ratio of estimated compressive yield strength of the femoral neck to the expected compressive stress of a fall on the greater trochanter adjusted for the patient’s age, height and weight. The greater the FSI, the lower the hip fracture risk from a fall on the greater trochanter; (7) buckling ratio (BR), the ratio of the outer radius to the cortical thickness, that represents a mean for estimating stability of the cortex in thin-walled regions subjected to bending. Statistical analysis Data management and analyses were conducted according to a pre-specified statistical analytical plan. Descriptive summary statistics included means and standard deviations (SD) for continuous variables. We performed the Shapiro– Wilk normality test for all the continuous outcomes data. If data followed a normal distribution the Student’s t test was used to compare data across groups; if not the two-sample Wilcoxon rank-sum (Mann–Whitney) test was used when appropriate. All statistical tests were carried out on a two-sided significance level of 0.05, using STATA 11.0.
Aging Clin Exp Res
Results Sixty-two postmenopausal women aged 50 years or older were evaluated. Twenty-six of them sustained a previous hip fracture in the contralateral limb, and 36 women had no history of hip fragility fracture. Table 1 reports the demographic, densitometric and HSA characteristics of the whole sample and of the two groups. There was no statistically significant difference between groups according to age and body composition, but mean femoral neck (FN) BMD was significantly lower in the group of women who sustained a previous contralateral hip fracture compared to the control group (respectively, 0.703 and 0.768, p = 0.0347). Some indexes of femoral strength were better in this group compared to the hip fracture group, but not reaching a statistically significance. On the other hand, we found a statistically significant difference of the mean HAL between the two groups (p = 0.0015) with higher values in women who experienced a fracture in the contralateral hip. Moreover, in this group, proximal femur was in a more valgus position if compared to the control group (129.62 and 127.25, respectively), but the difference was not statistically significant (p = 0.1368).
Discussion In this study, we compared the mechanical properties of the proximal femur that can be assessed through the elaboration of DXA-derived images in two groups of postmenopausal women, with or without history of hip fracture.
Our results confirmed that the strength of the proximal femur in women who sustained a contralateral hip fracture was lower if compared with the control group. Women with a previous hip fracture had a lower bending strength, expressed as section modulus, and a higher bone instability, expressed as BR. However, the differences between groups reached a statistically significant difference only for two parameters: FN BMD that was higher in control group, and HAL that was higher in the hip fracture group. Currently, DXA is the gold standard for the evaluation of mineral density of the bone because of its reproducibility, large normative data, non-invasive technology and little time required for the procedure [10]. If the role of low BMD, measured by DXA exam, as risk factor for fragility fractures has been well established [11], the impact of geometrical parameters on hip fracture risk is still controversial. Several studies have been performed with the aim to investigate the role of hip geometry on the risk of hip fracture. Some cross-sectional studies have shown the modest association between low CSMI, Z, HAL and FSI and hip fractures, independent of BMD [12, 13]. Several prospective studies, such as the Rotterdam cohort study, showed that the predictive capability for hip fracture of BMD was better than the geometric parameters resulting from the HSA [14]. On the other hand, in the large population-based Study of Osteoporotic Fractures (SOF), Kaptoge et al. [15], analyzing data from 7474 women, suggested that the geometric parameters derived from HSA provided a better hip fracture risk prediction than that obtained by hip aBMD. The Manitoba Study
Table 1 Demographic characteristics, densitometric and HSA parameters Variables
Population (n = 62)
Hip fracture group (n = 26)
Control group (n = 36)
p value
Age (years)
74.94 ± 7.81
76.46 ± 6.26
73.83 ± 8.68
0.1933*
BMI (kg/m2)
27.90 ± 5.41
26.40 ± 3.88
28.99 ± 6.11
0.0624*
FN BMD (g/cm2)
0.741 ± 0.121
0.703 ± 0.100
0.768 ± 0.129
0.0347**
FN T score (SD)
-1.99 ± 1.01
-2.31 ± 0.83
-1.76 ± 1.08
0.0327**
FN Z score (SD)
-0.33 ± 0.78
-0.51 ± 0.73
-0.20 ± 0.80
0.1203*
CSMI (mm4)
9629.27 ± 2423.31
9597.73 ± 3058.52
9652.06 ± 1884.59
0.1992**
CSA (mm2)
118.26 ± 19.81
116.08 ± 20.15
119.83 ± 19.69
0.4658*
Z (mm3)
520.49 ± 104.42
512.41 ± 123.52
526.33 ± 89.56
0.1799**
HAL (mm)
103.37 ± 7.34
106.75 ± 7.41
100.93 ± 6.33
0.0015*
10.26 ± 4.85
10.41 ± 5.75
10.14 ± 4.15
0.8529**
128.24 ± 5.36 1.41 ± 0.41
129.62 ± 6.31 1.37 ± 0.35
127.25 ± 4.39 1.44 ± 0.44
0.1368** 0.6722**
BR NSA (h) FSI
Continuous variables are expressed as mean ± standard deviation (SD) BMI body mass index, FN BMD femoral neck bone mineral density, CSMI cross-sectional moment of inertia, CSA cross-sectional area, Z section modulus, HAL hip axis length, BR buckling ratio, NSA neck shaft angle, h degrees, FSI femoral strength index * Student’s t test ** Two-sample Wilcoxon rank-sum (Mann–Whitney) test
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reported hip DXA measurements of 30,953 women aged C50 years with 270 incident hip fractures during 3.7 years of observation [16]. Of all parameters of hip bone geometry, only HAL and FSI seemed to give a small but significant contribute to hip fracture prediction independently of age and BMD measurement. It was hypothesized that the progressive enlargement of the cortical bone in the femoral neck occurring with aging might lower the FN BMD value regardless of bone loss, making reason for additional information provided by the analysis of the geometric parameters rather than the single measurement of BMD [15]. BR, a mechanical parameter used in engineering, was introduced in the bone fragility assessment by Beck et al. [8], as an index of cortical instability, representing the ratio of the outer radius to cortical thickness. Rivadeneira et al. [14] performed a large cohort prospective study to investigate the predictive value of HSA parameters for hip fracture risk demonstrating that BR had a higher correlation with FN BMD (-0.90) compared with Z (0.70). However, the authors specified that a 3D measurement of BR should be performed in order to enhance its predictive value for fracture risk. HAL was one of the first geometric indexes, independent from FN BMD measurement, proposed as an indicator of proximal femur fracture risk for women [17], but its importance is still controversial because some authors did not consider it as an independent risk factor [17, 18]. In a recent study, Leslie et al. [19] investigated the hip fracture predictive value of geometrical parameters of the proximal femur demonstrating that HAL was a risk factor independent from the BMD and the fracture risk assessment tool (FRAXÒ). FSI, that assesses the ability of a hip to withstand a fall on the greater trochanter, was introduced by Yoshikawa et al. [20] in 1994. This concept uses structural variables of the proximal femur, including CSMI and CSA, adjusted for height and weight, to estimate the femoral neck strength. Our study found that FSI was lower in patients with previous hip fracture, but the difference between fracture group (1.37) and control group (1.44) was not statistically significant. This finding might be due to the small sample size of our population. In another study, Faulkner et al. [12] included the FSI in an analysis model along with the HAL and the FN BMD T score demonstrating an independent relationship between these structural parameters of proximal femur and hip fracture risk. The NSA, also called angle of inclination, is the angle opened medialward between the femoral neck and the femoral shaft axes. Its growth pattern and its changes during aging were well characterized in a recent study [21].
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Women with a higher NSA have an increased risk to undergo a hip fracture, and the detection in early postmenopause of a more valgus NSA together with a low FN BMD could identify women with a high probability of incident hip fracture [22]. These findings are in line with the results of a previous cross-sectional study [23] on demonstrating that higher NSA was an independent risk factor for proximal femur fractures (OR 3.48 for women). On the other hand, a lower NSA (‘‘coxa vara’’) was associated with a higher risk of atypical femoral fractures in patients receiving long-term bisphosphonates therapy [24]. In our study, the patients who experienced a previous hip fragility fractures showed not only a reduction of BMD, but also a worsening of HSA parameters compared to the control group. In particular, the HAL was significantly longer in the fracture group, while the difference between groups in other HSA parameters (CSMI, CSA, NSA and Z) not reached statistically significance. These results could be due to the small sample of our population. Moreover, another limitation of our study is that individuals, pooled from outpatient service for management of osteoporosis, represented a non-random sample of women aged 50 or over. The retrospective design of our study did not allow to define the timing of bone loss in women with history of hip fracture, that might be occurred before or after the fracture event. Furthermore, hip fractures were not categorized according to fracture type (cervical or trochanteric). Therefore, the results of this study should be evaluated with some caution and further studies with a prospective design are needed to confirm these findings.
Conclusions BMD is indicative of the amount of mineral present in bone while geometric and structural parameters describe bone quality. DXA is able to measure both quantitative and qualitative factors that play a pivotal role in the pathogenesis of hip fracture with a single examination. The population of this study represents a typical sample of patients with high functional demand that refers to a rehabilitation service. In these patients, it is important to perform a comprehensive bone strength assessment to determine the risk of new fragility fractures on the same limb or on the contralateral one. In conclusion, the instrumental characterization of the hip fracture risk using DXA images must provide not only the bone mass assessment as BMD, but also parameters of geometry of the proximal femur through the HSA. Specifically, the HAL seems to be more closely related than other HSA parameters to the hip fracture risk.
Aging Clin Exp Res Compliance with ethical standards Conflict of interest On behalf of all authors, the corresponding author states that there is no conflict of interest. No funding was received in support of this study. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from all individual participants included in the study.
References 1. Lin JT, Lane JM (2004) Osteoporosis: a review. Clin Orthop Relat Res 425:126–134 2. Piscitelli P, Iolascon G, Argentiero A et al (2012) Incidence and costs of hip fractures vs strokes and acute myocardial infarction in Italy: comparative analysis based on national hospitalization records. Clin Interv Aging 7:575–583 3. Iolascon G, Gravina P, Luciano F et al (2013) Characteristics and circumstances of falls in hip fractures. Aging Clin Exp Res. 25 Suppl 1:S133–S135 4. Piscitelli P, Feola M, Rao C et al (2014) Ten years of hip fractures in Italy: For the first time a decreasing trend in elderly women. World J Orthop 5(3):386–391 5. Kanis JA, Ode´n A, McCloskey EV et al (2012) A systematic review of hip fracture incidence and probability of fracture worldwide. Osteoporos Int 23(9):2239–2256 6. Center JR, Nguyen TV, Schneider D et al (1999) Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet 353(9156):878–882 7. Leibson CL, Tosteson AN, Gabriel SE et al (2002) Mortality, disability, and nursing home use for persons with and without hip fracture: a population-based study. J Am Geriatr Soc 50(10):1644–1650 8. Beck TJ, Ruff CB, Warden KE et al (1990) Predicting femoral neck strength from bone mineral data. A structural approach. Invest Radiol. 25(1):6–18 9. Beck TJ (2007) Extending DXA beyond bone mineral density: understanding hip structure analysis. Curr Osteoporos Rep. 5(2):49–55 10. Blake GM, Fogelman I (2007) The role of DXA bone density scans in the diagnosis and treatment of osteoporosis. Postgrad Med J 83:509–517
11. Johnell O, Kanis JA, Oden A et al (2005) Predictive value of BMD for hip and other fractures. J Bone Miner Res 20(7):1185–1194 (Erratum in: J Bone Miner Res. 2007 May;22(5):774) 12. Faulkner KG, Wacker WK, Barden HS et al (2006) Femur strength index predicts hip fracture independent of bone density and hip axis length. Osteoporos Int 17(4):593–599 13. Ahlborg HG, Nguyen ND, Nguyen TV et al (2005) Contribution of hip strength indices to hip fracture risk in elderly men and women. J Bone Miner Res 20(10):1820–1827 14. Rivadeneira F, Zillikens MC, De Laet CE et al (2007) Femoral neck BMD is a strong predictor of hip fracture susceptibility in elderly men and women because it detects cortical bone instability: the Rotterdam Study. J Bone Miner Res 22(11):1781–1790 15. Kaptoge S, Beck TJ, Reeve J et al (2008) Prediction of incident hip fracture risk by femur geometry variables measured by hip structural analysis in the study of osteoporotic fractures. J Bone Miner Res 23(12):1892–1904 16. Leslie WD, Pahlavan PS, Tsang JF (2009) Prediction of hip and other osteoporotic fractures from hip geometry in a large clinical cohort. Osteoporos Int 20(10):1767–1774 17. Gao G, Zhang ZL, Zhang H et al (2008) Hip axis length changes in 10,554 males and females and the association with femoral neck fracture. J Clin Densitom. 11:360–366 18. Yu N, Liu YJ, Pei Y et al (2010) Evaluation of compressive strength index of the femoral neck in Caucasians and Chinese. Calcif Tissue Int 87:324–332 19. Leslie WD, Lix LM, Morin SN et al (2015) Hip axis length is a FRAX- and bone density-independent risk factor for hip fracture in women. J Clin Endocrinol Metab 100(5):2063–2070 20. Yoshikawa T, Turner CH, Peacock M et al (1994) Geometric structure of the femoral neck measured using dual-energy x-ray absorptiometry. J Bone Miner Res 9(7):1053–1064 (Erratum in: J Bone Miner Res 1995 Mar;10(3):510) 21. Wang Q, Chen D, Cheng SM et al (2015) Growth and aging of proximal femoral bone: a study with women spanning three generations. J Bone Miner Res 30(3):528–534 22. Gnudi S, Sitta E, Pignotti E (2012) Prediction of incident hip fracture by femoral neck bone mineral density and neck-shaft angle: a 5-year longitudinal study in post-menopausal females. Br J Radiol 85(1016):e467–e473 23. Alonso CG, Curiel MD, Carranza FH et al (2000) Femoral bone mineral density, neck-shaft angle and mean femoral neck width as predictors of hip fracture in men and women. Multicenter Project for Research in Osteoporosis. Osteoporos Int 11(8):714–720 24. Taormina DP, Marcano AI, Karia R et al (2014) Symptomatic atypical femoral fractures are related to underlying hip geometry. Bone 63:1–6
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ORIGINAL ARTICLE
Proximal femur geometry assessed by hip structural analysis in hip fracture in women Giovanni Iolascon1 • Antimo Moretti1 • Giovanni Cannaviello1 • Giuseppina Resmini2 Francesca Gimigliano3
•
Received: 13 May 2015 / Accepted: 1 July 2015 Ó Springer International Publishing Switzerland 2015
Abstract Introduction In the pathogenesis of hip fracture, proximal femur geometry plays a key role as well as decreased bone density. The hip structural analysis (HSA) processes dual energy X-ray absorptiometry (DXA) images containing information on the geometry closely related to the strength of the proximal femur. The objective of this study was to investigate bone mineral density (BMD) and mechanical properties of the proximal femur in a group of women with a previous contralateral hip fragility fracture compared to women without history of hip fracture. Materials and methods In a population of postmenopausal women, we evaluated bone density by DXA and bone geometry using the HSA parameters (femoral strength index, cross-sectional moment of inertia, crosssectional area, section modulus, and buckling ratio) including hip axis length (HAL) and neck shaft angle. Results Of a total of 62 postmenopausal women, twentysix with a history of hip fracture had a mean femoral neck BMD significantly lower in comparison with 36 women in the control group (0.703 versus 0.768 g/cm2, p = 0.0347). There was a statistically significant difference between groups also for HAL (106.75 mm in fracture group versus 100.93 mm in control group, p = 0.0015).
& Giovanni Iolascon [email protected] 1
Department of Medical and Surgical Specialties and Dentistry, Second University of Naples, Naples, Italy
2
Centre for the Study of Osteoporosis and Metabolic Bone Disease, Section of Orthopaedic and Traumatology, Treviglio-Caravaggio Hospital, Bergamo, Italy
3
Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Naples, Italy
Discussion and conclusions Our results demonstrated that all the geometrical parameters resulted worst into the group of patients with history of hip fracture, even though only the HAL was significantly lower in control subjects. In our opinion HSA is useful to characterize the risk of hip fracture in postmenopausal women, providing additional data on the spatial distribution of bone mass strongly related to bone strength. Keywords Osteoporosis Hip fracture Advanced hip assessment Hip structural analysis Hip geometry
Introduction Osteoporosis is one of the most significant health problems, affecting 200 million of people worldwide [1]. Hip fracture is considered the most serious osteoporotic fracture causing a huge impact on patient morbidity, functional capacity, and mortality. It is linked to high medical costs comparable to that of strokes and higher than that of acute myocardial infarction (AMI), both in terms of hospitalizations and health care expenditures [2]. The main determinant of hip fractures is falling. Falls and its circumstances have been well characterized in a recent Italian study [3]. In Italy, there were 93,169 femoral neck fractures in 2009 (21,345 men and 71,824 women) with an incidence of 77.8 per 10,000 (42.4 in men and 103.5 in women) [4]. The risk of hip fractures increases ten-fold every 20 years of age, its 1-year mortality amounts to 20 % and a permanent loss in function has been reported in 50 % of cases [5–7]. Considering this huge burden for individual and social health system, it is required to establish fracture risk more accurately as possible. Currently, the gold standard for the
123
Aging Clin Exp Res
estimation of the risk of hip fracture is the dual energy X-ray absorptiometry (DXA) measurement of the proximal femur bone mineral density (BMD), since bone mass highly correlates with bone strength, accounting for 80–90 % of the variance in ultimate compressive strength of both compact and trabecular bone [8]. However, hip bone strength also depends on the spatial distribution of bone mass that characterizes the structural geometric properties (diameter, area, length, and angle of the femoral neck). Age-related bone loss in the proximal femur is partially compensated with redistribution of bone mass and enlargement of the diameter of the femoral neck by concurrent periosteal apposition that anyway does not inhibit the overall worsening of material and structural properties of bone tissue. Recent technological advances of DXA devices are able to provide data for the measurement of both BMD and bone geometry parameters including femoral size, shape, and strength. Using two-dimensional DXA-derived images of the hip, the advanced hip assessment (AHA) software package allows to perform the hip structural analysis (HSA) that measures bone geometric properties of cross sections in cut planes traversing the bone at that location [9]. This study aimed to compare the proximal femur density and geometry, assessed by DXA exam, in two groups of postmenopausal women with or without history of hip fracture in the contralateral limb.
Materials and methods Study population In this retrospective case–control study, we analyzed data of consecutive postmenopausal women aged 50 years or older, obtained by DXA of the proximal femur, using the GE Healthcare Lunar iDXA. DXA images were purchased from patients referred to our outpatient rehabilitation service, in a 6-month period. We divided population into two groups: women that sustained a previous hip fracture in the contralateral limb, and women without history of hip fragility fracture. All scans were rated by a single operator with a specific expertise in the management of osteoporosis, according to the manufacturer’s recommended protocol. Structural parameters Areal BMD (aBMD) of the femoral neck was usually measured in non-dominant leg by DXA scan. For women who previously sustained a hip fracture, BMD was measured at the contralateral limb. Structural parameters were
123
determined using the manufacturer’s AHA software package, that automatically provides bone mass distribution variables, derived by information contained within DXA absorption curves, and several bone geometry parameters from the same scan image. The AHA software defines the distribution of mineral mass in a line of pixels across the bone axis to measure hip geometric properties. This software allows to perform the HSA evaluating the following parameters: (1) cross-sectional moment of inertia (CSMI, in mm4), also called second moment of area, that is used to measure the distribution of material around the neck axis necessary to calculate resistance to bending. Mechanical stress within a cross-section subjected to bending is inversely related to the CSMI and varies with the distance from the neutral axis [9]. In most bones, cross sections are not axially symmetric and the CSMI for bending is higher in some directions than in others; (2) cross-sectional area (CSA, in mm2), the sum surface area of bone in a cross-sectional slice, after excluding all the spaces occupied by marrow and other soft tissues within pores. It is also described as the minimum CSMI section within the neck region of interest (ROI); (3) neck shaft angle (NSA), the angle between femoral neck and femoral shaft; (4) section modulus (Z), a strength parameter that derives from CSMI, that is equal to the CSMI divided by what is called the centroidal distance, from centroidal axis to the edge of the section; (5) hip axis length (HAL, in mm), calculated as the distance from the tip of the greater trochanter to the internal pelvic rim; (6) femoral strength index (FSI), the ratio of estimated compressive yield strength of the femoral neck to the expected compressive stress of a fall on the greater trochanter adjusted for the patient’s age, height and weight. The greater the FSI, the lower the hip fracture risk from a fall on the greater trochanter; (7) buckling ratio (BR), the ratio of the outer radius to the cortical thickness, that represents a mean for estimating stability of the cortex in thin-walled regions subjected to bending. Statistical analysis Data management and analyses were conducted according to a pre-specified statistical analytical plan. Descriptive summary statistics included means and standard deviations (SD) for continuous variables. We performed the Shapiro– Wilk normality test for all the continuous outcomes data. If data followed a normal distribution the Student’s t test was used to compare data across groups; if not the two-sample Wilcoxon rank-sum (Mann–Whitney) test was used when appropriate. All statistical tests were carried out on a two-sided significance level of 0.05, using STATA 11.0.
Aging Clin Exp Res
Results Sixty-two postmenopausal women aged 50 years or older were evaluated. Twenty-six of them sustained a previous hip fracture in the contralateral limb, and 36 women had no history of hip fragility fracture. Table 1 reports the demographic, densitometric and HSA characteristics of the whole sample and of the two groups. There was no statistically significant difference between groups according to age and body composition, but mean femoral neck (FN) BMD was significantly lower in the group of women who sustained a previous contralateral hip fracture compared to the control group (respectively, 0.703 and 0.768, p = 0.0347). Some indexes of femoral strength were better in this group compared to the hip fracture group, but not reaching a statistically significance. On the other hand, we found a statistically significant difference of the mean HAL between the two groups (p = 0.0015) with higher values in women who experienced a fracture in the contralateral hip. Moreover, in this group, proximal femur was in a more valgus position if compared to the control group (129.62 and 127.25, respectively), but the difference was not statistically significant (p = 0.1368).
Discussion In this study, we compared the mechanical properties of the proximal femur that can be assessed through the elaboration of DXA-derived images in two groups of postmenopausal women, with or without history of hip fracture.
Our results confirmed that the strength of the proximal femur in women who sustained a contralateral hip fracture was lower if compared with the control group. Women with a previous hip fracture had a lower bending strength, expressed as section modulus, and a higher bone instability, expressed as BR. However, the differences between groups reached a statistically significant difference only for two parameters: FN BMD that was higher in control group, and HAL that was higher in the hip fracture group. Currently, DXA is the gold standard for the evaluation of mineral density of the bone because of its reproducibility, large normative data, non-invasive technology and little time required for the procedure [10]. If the role of low BMD, measured by DXA exam, as risk factor for fragility fractures has been well established [11], the impact of geometrical parameters on hip fracture risk is still controversial. Several studies have been performed with the aim to investigate the role of hip geometry on the risk of hip fracture. Some cross-sectional studies have shown the modest association between low CSMI, Z, HAL and FSI and hip fractures, independent of BMD [12, 13]. Several prospective studies, such as the Rotterdam cohort study, showed that the predictive capability for hip fracture of BMD was better than the geometric parameters resulting from the HSA [14]. On the other hand, in the large population-based Study of Osteoporotic Fractures (SOF), Kaptoge et al. [15], analyzing data from 7474 women, suggested that the geometric parameters derived from HSA provided a better hip fracture risk prediction than that obtained by hip aBMD. The Manitoba Study
Table 1 Demographic characteristics, densitometric and HSA parameters Variables
Population (n = 62)
Hip fracture group (n = 26)
Control group (n = 36)
p value
Age (years)
74.94 ± 7.81
76.46 ± 6.26
73.83 ± 8.68
0.1933*
BMI (kg/m2)
27.90 ± 5.41
26.40 ± 3.88
28.99 ± 6.11
0.0624*
FN BMD (g/cm2)
0.741 ± 0.121
0.703 ± 0.100
0.768 ± 0.129
0.0347**
FN T score (SD)
-1.99 ± 1.01
-2.31 ± 0.83
-1.76 ± 1.08
0.0327**
FN Z score (SD)
-0.33 ± 0.78
-0.51 ± 0.73
-0.20 ± 0.80
0.1203*
CSMI (mm4)
9629.27 ± 2423.31
9597.73 ± 3058.52
9652.06 ± 1884.59
0.1992**
CSA (mm2)
118.26 ± 19.81
116.08 ± 20.15
119.83 ± 19.69
0.4658*
Z (mm3)
520.49 ± 104.42
512.41 ± 123.52
526.33 ± 89.56
0.1799**
HAL (mm)
103.37 ± 7.34
106.75 ± 7.41
100.93 ± 6.33
0.0015*
10.26 ± 4.85
10.41 ± 5.75
10.14 ± 4.15
0.8529**
128.24 ± 5.36 1.41 ± 0.41
129.62 ± 6.31 1.37 ± 0.35
127.25 ± 4.39 1.44 ± 0.44
0.1368** 0.6722**
BR NSA (h) FSI
Continuous variables are expressed as mean ± standard deviation (SD) BMI body mass index, FN BMD femoral neck bone mineral density, CSMI cross-sectional moment of inertia, CSA cross-sectional area, Z section modulus, HAL hip axis length, BR buckling ratio, NSA neck shaft angle, h degrees, FSI femoral strength index * Student’s t test ** Two-sample Wilcoxon rank-sum (Mann–Whitney) test
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reported hip DXA measurements of 30,953 women aged C50 years with 270 incident hip fractures during 3.7 years of observation [16]. Of all parameters of hip bone geometry, only HAL and FSI seemed to give a small but significant contribute to hip fracture prediction independently of age and BMD measurement. It was hypothesized that the progressive enlargement of the cortical bone in the femoral neck occurring with aging might lower the FN BMD value regardless of bone loss, making reason for additional information provided by the analysis of the geometric parameters rather than the single measurement of BMD [15]. BR, a mechanical parameter used in engineering, was introduced in the bone fragility assessment by Beck et al. [8], as an index of cortical instability, representing the ratio of the outer radius to cortical thickness. Rivadeneira et al. [14] performed a large cohort prospective study to investigate the predictive value of HSA parameters for hip fracture risk demonstrating that BR had a higher correlation with FN BMD (-0.90) compared with Z (0.70). However, the authors specified that a 3D measurement of BR should be performed in order to enhance its predictive value for fracture risk. HAL was one of the first geometric indexes, independent from FN BMD measurement, proposed as an indicator of proximal femur fracture risk for women [17], but its importance is still controversial because some authors did not consider it as an independent risk factor [17, 18]. In a recent study, Leslie et al. [19] investigated the hip fracture predictive value of geometrical parameters of the proximal femur demonstrating that HAL was a risk factor independent from the BMD and the fracture risk assessment tool (FRAXÒ). FSI, that assesses the ability of a hip to withstand a fall on the greater trochanter, was introduced by Yoshikawa et al. [20] in 1994. This concept uses structural variables of the proximal femur, including CSMI and CSA, adjusted for height and weight, to estimate the femoral neck strength. Our study found that FSI was lower in patients with previous hip fracture, but the difference between fracture group (1.37) and control group (1.44) was not statistically significant. This finding might be due to the small sample size of our population. In another study, Faulkner et al. [12] included the FSI in an analysis model along with the HAL and the FN BMD T score demonstrating an independent relationship between these structural parameters of proximal femur and hip fracture risk. The NSA, also called angle of inclination, is the angle opened medialward between the femoral neck and the femoral shaft axes. Its growth pattern and its changes during aging were well characterized in a recent study [21].
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Women with a higher NSA have an increased risk to undergo a hip fracture, and the detection in early postmenopause of a more valgus NSA together with a low FN BMD could identify women with a high probability of incident hip fracture [22]. These findings are in line with the results of a previous cross-sectional study [23] on demonstrating that higher NSA was an independent risk factor for proximal femur fractures (OR 3.48 for women). On the other hand, a lower NSA (‘‘coxa vara’’) was associated with a higher risk of atypical femoral fractures in patients receiving long-term bisphosphonates therapy [24]. In our study, the patients who experienced a previous hip fragility fractures showed not only a reduction of BMD, but also a worsening of HSA parameters compared to the control group. In particular, the HAL was significantly longer in the fracture group, while the difference between groups in other HSA parameters (CSMI, CSA, NSA and Z) not reached statistically significance. These results could be due to the small sample of our population. Moreover, another limitation of our study is that individuals, pooled from outpatient service for management of osteoporosis, represented a non-random sample of women aged 50 or over. The retrospective design of our study did not allow to define the timing of bone loss in women with history of hip fracture, that might be occurred before or after the fracture event. Furthermore, hip fractures were not categorized according to fracture type (cervical or trochanteric). Therefore, the results of this study should be evaluated with some caution and further studies with a prospective design are needed to confirm these findings.
Conclusions BMD is indicative of the amount of mineral present in bone while geometric and structural parameters describe bone quality. DXA is able to measure both quantitative and qualitative factors that play a pivotal role in the pathogenesis of hip fracture with a single examination. The population of this study represents a typical sample of patients with high functional demand that refers to a rehabilitation service. In these patients, it is important to perform a comprehensive bone strength assessment to determine the risk of new fragility fractures on the same limb or on the contralateral one. In conclusion, the instrumental characterization of the hip fracture risk using DXA images must provide not only the bone mass assessment as BMD, but also parameters of geometry of the proximal femur through the HSA. Specifically, the HAL seems to be more closely related than other HSA parameters to the hip fracture risk.
Aging Clin Exp Res Compliance with ethical standards Conflict of interest On behalf of all authors, the corresponding author states that there is no conflict of interest. No funding was received in support of this study. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from all individual participants included in the study.
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