Male–female differences in the association between incident hip fracture and proximal femoral strength: A finite element analysis study

Abstract

Hip fracture risk is usually evaluated using dual energy X-ray absorptiometry (DXA) or quantitative computed tomography (QCT) which provide surrogate measures for proximal femoral strength. However, proximal femoral strength can best be estimated explicitly by combining QCT with finite element (FE) analysis. To evaluate this technique for predicting hip fracture in older men and women, we performed a nested age- and sex-matched case–control study in the Age Gene/Environment Susceptibility (AGES) Reykjavik cohort. Baseline (pre-fracture) QCT scans of 5500 subjects were obtained. During 4–7 years follow-up, 51 men and 77 women sustained hip fractures. Ninety-seven men and 152 women were randomly selected as age- and sex-matched controls. FE-strength of the left hip of each subject for stance (F_Stance) and posterolateral fall (F_Fall) loading, and total femur areal bone mineral density (aBMD) were computed from the QCT data. F_Stance and F_Fall in incident hip fracture subjects were 13%–25% less than in control subjects (p ≤ 0.006) after controlling for demographic parameters. The difference between FE strengths of fracture and control subjects was disproportionately greater in men (stance, 22%; fall, 25%) than in women (stance, 13%; fall, 18%) (p ≤ 0.033), considering that F_Stance and F_Fall in fracture subjects were greater in men than in women (p < 0.001). For men, F_Stance was associated with hip fracture after accounting for aBMD (p = 0.013). These data indicate that F_Stance provides information about fracture risk that is beyond that provided by aBMD (p = 0.013). These findings support further exploration of possible sex differences in the predictors of hip fracture and of sex-specific strategies for using FE analysis to manage osteoporosis.

Introduction

Hip fracture is one of the most serious consequences of osteoporosis, leading to significant reductions in mobility, independence, and quality of life, and in some cases, increased mortality [1], [2]. In the United States alone, over 2 million osteoporotic fractures occurred in 2005 at a cost of $17 billion, with hip fracture accounting for 14% of the total incident fractures, and 72% of the total cost [2]. Because of the rapid increase in the mean age of the population of the United States and other industrialized countries, the incidence of hip fracture is expected to rise significantly. This underscores the importance of developing and validating techniques to estimate hip fracture risk, to better understand the etiology of hip fracture, and to evaluate the effects of risk-reducing interventions.

The risk of hip fracture fundamentally depends on two factors: (1) the proximal femoral structural strength, defined as the minimum force on the femoral head that would be required to break the proximal femur, is also called the hip bone strength or the hip fracture load; and (2) the probability of encountering a situation in which the force applied to the proximal femur exceeds the proximal femoral structural strength. The strength of the proximal femur depends strongly on the three-dimensional (3-D) geometry of the bone and the 3-D distribution of the material properties within the bone (e.g. elastic modulus and yield strength at each point) as well as the direction and location of the applied force. For example, the proximal femur can withstand the great forces on the hip during ambulation and other routine activities. However, if a force of the same magnitude were applied to the proximal femur during a fall onto the greater trochanter, this force would far exceed the hip bone strength and a fracture would occur. For falls, the probability of encountering an applied force that exceeds the hip bone strength and results in a fracture is related to multiple factors, among them the probability of falling in any given direction, the height from which the fall occurred, the ability to use the arm to break the fall, the compliance of the surface upon which the subject might fall, and the soft tissue thickness over the greater trochanter.

Hip fracture risk is often evaluated using non-invasive imaging techniques such as dual energy X-ray absorptiometry (DXA) and volumetric quantitative computed tomography (QCT), providing surrogate measures of bone strength. Both DXA and volumetric QCT measure bone mineral content and bone mineral density (BMD) in specific anatomic regions of the hip, such as the femoral neck or trochanter. However, DXA provides a single, combined measure of cortical and trabecular areal BMD (aBMD), whereas volumetric QCT provides separate 3-D measures for cortical and trabecular bone. Although these technologies are commonly used to evaluate hip fracture risk [3], DXA and QCT-derived BMD explain only 56%–72% and 47%–87% of the variance in proximal femoral strength, respectively [4], [5]. Thus, we may be able to improve the assessment of hip fracture risk by implementing more robust techniques for evaluating proximal femoral strength.

Previous literature has demonstrated that proximal femoral strength can best be estimated by combining QCT imaging, which provides the bone geometry and density at each point in the bone, with a structural engineering technique called finite element (FE) analysis [4], [6], [7]. In essence, this numerical technique subdivides a structure into many smaller parts (finite elements) which, together, explicitly represent the complex material heterogeneity and 3-D bone geometry as a mathematical model. Force or displacement is then mathematically applied to represent a specific loading condition (e.g. single-limb stance or a particular type of fall onto the greater trochanter). When the model is analyzed, stress and strain throughout the structure are computed and used in conjunction with material failure criteria to estimate the strength of the proximal femur under the particular loading condition. The strength of the proximal femur as measured on cadaveric femora under single-limb stance loading is more strongly predicted by QCT-based patient-specific FE modeling (r² = 0.77 to 0.96 [4], [6], [7]) than by aBMD from DXA [4]. Studies of cadaveric femora under loading from a fall onto the greater trochanter have shown similar trends [8], [9], [10], [11].

Although FE models can strongly predict actual, measured hip bone strength, there is limited experience in using this technique to predict hip fracture in vivo. In a recent prospective study of hip fracture in a large multicenter cohort of older men, Orwoll et al. showed that FE-computed hip bone strength for loading due to a sideways fall onto the lateral aspect of the greater trochanter and, to a lesser extent, estimated fall impact force divided by lateral fall hip bone strength were strongly associated with incident fracture [12]. However, this study only included men and it only evaluated hip strength for a sideways fall. Thus, in the present study, we have evaluated FE-computed hip bone strength for loading similar to that during single-limb stance (F_Stance) and a fall onto the posterolateral aspect of the greater trochanter (F_Fall) in older male and female hip fracture and control subjects. The objectives were (1) to determine if F_Stance and F_Fall are associated with hip fracture, (2) to determine if these associations differ for men and women, and (3) to determine if F_Stance and F_Fall continue to be associated with hip fracture after accounting for aBMD computed from the same QCT images.