Strain energy in the femoral neck during exercise

Journal of Biomechanics ∎ (∎∎∎∎) ∎∎∎–∎∎∎ Contents lists available at ScienceDirect Journal of Biomechanics journal homepage: www.elsevier.com/locate/jbiomech www.JBiomech.com Strain energy in the femoral neck during exercise Saulo Martelli n, Mariana E. Kersh, Anthony G. Schache, Marcus G. Pandy Department of Mechanical Engineering, University of Melbourne, Parkville, VIC, Australia art ic l e i nf o a b s t r a c t Article history: Accepted 24 March 2014 Physical activity is recommended to mitigate the incidence of hip osteoporotic fractures by improving femoral neck strength. However, results from clinical studies are highly variable and unclear about the effects of physical activity on femoral neck strength. We ranked physical activities recommended for promoting bone health based on calculations of strain energy in the femoral neck. According to adaptive bone-remodeling theory, bone formation occurs when the strain energy (S) exceeds its homeostatic value by 75%. The potential effectiveness of activity type was assessed by normalizing strain energy by the applied external load. Tensile strain provided an indication of bone fracture. External force and joint motion data for 15 low- and high-load weight-bearing and resistance-based activities were used. Highload activities included weight-bearing activities generating a ground force above 1 body-weight and maximal resistance exercises about the hip and the knee. Calculations of femoral loads were based on musculoskeletal and finite-element models. Eight of the fifteen activities were likely to trigger bone formation, with isokinetic hip extension (ΔS ¼ 722%), one-legged long jump (ΔS ¼ 572%), and isokinetic knee flexion (ΔS ¼ 418%) inducing the highest strain energy increase. Knee flexion induced approximately ten times the normalized strain energy induced by hip adduction. Strain and strain energy were strongly correlated with the hip-joint reaction force (R2 ¼0.90–0.99; po 0.05) for all activities, though the peak load location was activity-dependent. None of the exercises was likely to cause fracture. Femoral neck mechanics is activity-dependent and maximum isokinetic hip-extension and knee-flexion exercises are possible alternative solutions to impact activities for improving femoral neck strength. & 2014 Elsevier Ltd. All rights reserved. Keywords: Osteoporosis Bone fragility Bone remodeling Hip fracture Musculoskeletal finite-element modeling Physical activity type 1. Introduction Osteoporosis is characterized by low bone density, microarchitectural deterioration of bone tissue and an increased risk of fragility fractures (Cooper and Melton, 1992). Hip fragility fractures carry the highest morbidity and mortality rates amongst the elderly, and post-menopausal women have the highest risk of fracture (Sernbo and Johnell, 1993). The prevention of hip fractures is a critical step in minimizing their burden, and physical activity is considered a key preventative solution to maintaining bone strength by promoting femoral neck bone formation (Petit et al., 2009). Bone mineral density (BMD) remains relatively constant in response to common activities of daily living that involve low loads (Nikander et al., 2010), while activities with higher loads have been suggested to promote bone formation (Kohrt et al., 1997; Rhodes et al., 2000). There is some degree of variability in n Correspondence to: Medical Device Research Institute, School of Computer Science, Engineering and Mathematics, Flinders University, Sturt Rd, Bedford Park SA 5042, Australia. E-mail addresses: saulo.martelli@flinders.edu.au, [email protected] (S. Martelli). the literature regarding what constitutes a high-load activity; for example, it has been suggested that walking and jumping are high-load tasks because they generate ground reaction forces between 1 and 3 times body weight (BW) respectively (Kohrt et al., 1997), whereas resistance exercises are considered highload when the resistance exceeds 75% of that achieved during a single maximum voluntary contraction (Rhodes et al., 2000). The reported effect of physical activity interventions on BMD is inconsistent (Bailey and Brooke-Wavell, 2010; Dornemann et al., 1997; Ebrahim et al., 1997; Kohrt et al., 1997; Lohman et al., 1995), and a comparison of these studies suggests that it is not simply attributable to differences in load magnitudes. Daily hops have been found to increase BMD by 2.8% (Bailey and Brooke-Wavell, 2010), while a more complex exercise program that included walking, jogging, and stair climbing increased BMD by 4.3% (Kohrt et al., 1997). Targeted strength exercises, typically executed using gym-based equipment, induced up to a 2% BMD increase (Lohman et al., 1995), although it is worth noting that studies investigating strength exercises are either not well described (Lohman et al., 1995) or have included only a subgroup of possible hip and/or knee strength exercises (Dornemann et al., 1997). The differing, and at times counterintuitive, response of bone to http://dx.doi.org/10.1016/j.jbiomech.2014.03.036 0021-9290/& 2014 Elsevier Ltd. All rights reserved. Please cite this article as: Martelli, S., et al., Strain energy in the femoral neck during exercise. Journal of Biomechanics (2014), http://dx. doi.org/10.1016/j.jbiomech.2014.03.036i 2 S. Martelli et al. / Journal of Biomechanics ∎ (∎∎∎∎) ∎∎∎–∎∎∎ physical activities complicates the development of exercise interventions for the prevention of hip fractures. While it has been suggested that the varying BMD response is related to the fact that alternative physical activities load the femoral neck in different ways (Martyn-St James and Carroll, 2006), a quantitative comparison and ranking of a variety of physical activities based on their effect at the femoral neck has yet to be conducted. We suggest that this ranking may provide a useful framework from which exercise interventions can be developed with the long-term aim of providing more consistent results in longitudinal studies. Computational modeling is the only viable method for estimating in vivo strain within the intact and undisturbed femoral neck. Indeed, the determination of which physical activities optimize loading of the femoral neck requires knowledge of the loads applied to the bone by muscle and joint reaction forces as well as the bone geometry and mechanical properties. Subject-specific loads have been calculated using musculoskeletal models (Correa et al., 2010; Jonkers et al., 2008; Martelli et al., 2011; Pandy and Andriacchi, 2010). Finite-element models based on computed tomography (CT) scans have been used to obtain subject-specific estimates of femoral neck strain (Keyak et al., 1993; Schileo et al., 2007), fracture load (Dall’ara et al., 2012; Schileo et al., 2008b), and mechanically-driven BMD changes (Huiskes et al., 1987; Weinans et al., 1993). Musculoskeletal and finite-element modelling approaches can be integrated to investigate the effects of different physical activities on femoral neck mechanics. The aim of this study was to calculate and rank the potential for low- and high-load physical activities that have been suggested to offset the detrimental effect of osteoporosis and to assess the risk for femoral neck fractures during such activities (Kohrt et al., 1997; Rhodes et al., 2000). Femoral neck strain energy and tensile strain were used as the two metrics for bone formation (Huiskes et al., 1987) and fracture (Schileo et al., 2008b) and were determined by combining experimental gait data with computational musculoskeletal modeling and finite-element analysis. 2. Materials and methods A lower-limb musculoskeletal model and a finite-element model of the right femur were generated from published data (Testi et al., 2010) from a single donor (female, 81 year-old, height¼ 167 cm, weight¼ 63 kg). Muscle and hip-joint reaction forces during selected activities were calculated using the musculoskeletal model, and applied to the finite-element model (Fig. 1) to obtain estimates of bone formation (strain energy) and fracture (tensile strain). 2.1. Physical activities Fifteen weight-bearing activities and resistance exercises were categorized as low- and high-load physical activities (Table 1). High-load weight-bearing activities were assumed to generate a ground reaction force above 1 BW (Kohrt et al., 1997), while resistance exercises were considered high-load when the resistance exceeded 75% of that achieved during a single maximum voluntary contraction (Rhodes et al., 2000). Weight-bearing activities were studied using joint-motion and groundreaction-force data recorded from two healthy adult female volunteers that were body-matched to the donor. The first publicly available (Testi et al., 2010, www.physiomespace.com) dataset comprised experimental data recorded for five different activities: stair ascent, stair descent, rising from and lowering into a chair, step up, and level walking (Table 1, Subject A: 25 years old, 165 cm height, and 57 kg weight). The second dataset comprised of experimental data recorded at the University of Melbourne Biomotion Laboratory for three additional tasks: onelegged maximum-distance long jump, two-legged maximum-height jump, and lifting a 10 kg weight from the ground to an upright position using both hands (Table 1, Subject B: 24 years old, 167 cm height, 62 kg weight). Ethics approval was obtained from the institutional Human Research Ethics Committee. Data reported by Pyka et al. (1994) were used to assess the effect of resistance exercises (Table 2). Data included the maximum forces exerted during concentric contractions in the sagittal and frontal planes about the hip joint and in the sagittal plane about the knee joint for a cohort of elderly men and women aged between 61- and 78-years-old. Fig. 1. Overview of the modeling pipeline. Forces acting on the femur were calculated using the donor musculoskeletal model (top right) derived from magnetic resonance images (middle left) and using input motion data collected on body-matched volunteers (top left). The finite-element model of the right femur (bottom right) was generated from computed tomography (CT) data (bottom left) obtained from the same donor and used to calculate femoral neck tensile strain and strain energy during low- and high-load activities. 2.2. Musculoskeletal model Muscle and joint reaction forces were calculated using a lower-limb musculoskeletal model based on a previous study (Martelli et al., 2011). The body was modelled as a 13-segment, 15 degree-of-freedom (DOF) articulated system, actuated by 84 muscle-tendon units. The skeletal anatomy was extracted from the donor's full-body CT scan. Inertial properties of each segment were derived from the CT images assuming homogeneous density properties for both the hard (1.42 g/cm3) and soft (1.03 g/cm3) tissues (Dumas et al., 2005). Peak isometric muscle forces were calculated using the physiological cross-sectional area of each muscle extracted from magnetic resonance images obtained from the donor and assuming a value of 1 MPa for the specific tension of muscle (Glitsch and Baumann, 1997). Values for optimum muscle-fibre length and tendon slack length reported by Delp et al. (1990) were scaled to the donor's anatomy by matching the joint angles at which each muscle exerted its maximum isometric force. All simulations were performed using an open-source musculoskeletal modeling environment called OpenSim (Delp et al., 2007). Weight-bearing activities were simulated by applying an inverse kinematics algorithm to calculate the joint positions for a representative trial of each physical activity followed by a calculation of the net joint torques. A static optimization problem was solved to decompose the net joint torques amongst the muscles by minimizing the weighted squared sum of muscle activations. Resistance exercises were simulated using the external forces reported by Pyka et al. (1994) (Table 2). The external forces were decreased by 38% to account for the lower-than-average (Ward et al., 2009) muscle volumes of the donor. For each resistance exercise, the scaled force was applied to the model in the anatomical pose and kept constant in the local frame over a physiological range of motion (Roach and Miles, 1991) while imposing a low constant joint speed ( o 7 deg/s). The resulting joint torques were consistent with those generated in age-matched subjects during muscle strength tests (Steinhilber et al., 2011; Tan et al., 1995). The same procedure described for the weight-bearing activities was used to decompose the net joint torques amongst the muscles. The hip-joint reaction forces calculated in the model were compared with measurements of hip-joint reaction forces obtained from elderly THR patients (Bergmann et al., 2001; www.orthoload.com) for level walking, stair ascent, stair descent, and rising from and lowering into a chair. 2.2.1. Finite-element model A finite-element model of the right femur was created from CT images (General Electric Co., USA, tube current: 160 mA, tube voltage: 120 kVP) of the donor (Testi et al., 2010; www.physiomespace.com). The bone geometry was segmented from the CT scan using medical image processing software (Amira©, Visage Imaging GmbH, USA). Bone tissue was modeled using 10-node tetrahedral elements. Bone Please cite this article as: Martelli, S., et al., Strain energy in the femoral neck during exercise. Journal of Biomechanics (2014), http://dx. doi.org/10.1016/j.jbiomech.2014.03.036i S. Martelli et al. / Journal of Biomechanics ∎ (∎∎∎∎) ∎∎∎–∎∎∎ 3 Table 1 Categorization of low- and high-load activities. Low-load weight-bearing activities generated a ground reaction force (GRF) r1 BW, while high-load activities generated GRF 4 1 BW. All the resistance exercises were considered high-load as the force applied during these simulations was 100% of that obtained for a single maximum voluntary contraction (MVC). Sources: (A) data recorded from a 25-year-old female volunteer (www.physiomespace.com); (B) data recorded from a 24-year-old female volunteer at the Biomotion Laboratory of the University of Melbourne, (S) simulated maximal-resistance activities. Low-load weight-bearing activities High-load weight-bearing activities High-load isokinetic contractions Activity Source GRF (BW) Activity Source GRF (BW) Activity Source %MVC Chair up/down Step up Squat Squat with weight A A A B 0.6 0.9 0.8 0.8 Stair ascent Stair descent Walking (1.3 m/s) Long jump Vertical jump A A A B B 1.2 1.3 1.3 2.6 2.0 Hip abduction Hip adduction Hip flexion Hip extension Knee extension Knee flexion S S S S S S 100% 100% 100% 100% 100% 100% Table 2 Model input data used for simulations of maximum isokinetic muscle contractions. All maximally resisted exercises were simulated at 100% of the maximum voluntary contraction level. Activity Hip abduction Hip adduction Hip flexion Hip extension Knee extension Knee flexion Pyka et al. (1994) Simulation Load (N) Loaded site Start-end angles (deg)a Load (N)b Resulting joint torque (N m) Loaded site 240 298 254 462 284 160 Distal Distal Distal Distal Distal Distal 0, 39 39, 0 20, 30 30, 20 90, 0 0, 90 149 184 158 286 176 99 61, 67, 94, 77, 60, 39, P1 P1 P1 P1 P2 P2 femur femur femur femur tibia tibia Published joint torque (N m) 83 72 98 80 72 47 1107 30c 94 7 30c 847 20c 1057 40c 53–170d 40–86d P1 ¼ intermediate point between the lateral and the medial femoral epicondyle; P2 ¼ intermediate point between the lateral and the medial tibial malleoli. a Hip abduction, flexion and knee flexion joint rotations are assumed positive. Simulation loads are obtained by scaling the published baseline loads by 0.62 (the average difference between the model muscle volumes and that from and agematched population). c Steinhilber et al. (2011), average and standard deviation. d Tan et al. (1995), min–max range. b apparent density was calculated from the CT images using the method reported by Schileo et al., 2008a, and converted into isotropic Young's modulus values using the relationship given by Morgan et al. (2003). The Young's modulus values were mapped onto the finite-element mesh using Bonemat© (Super Computing Solutions, Italy). The model was kinematically constrained at the femoral epicondyles, a condition that is statically equivalent to applying the appropriate knee-joint reaction force. The finite-element model was validated by comparing predicted cortical strains with experimental measurements obtained from the donor's femur for six different loading conditions (Testi et al., 2010, www.physiomespace.com). A load vector of 463 N (75% of the donor's body weight) was applied separately to the medial, anterior, posterior and lateral aspects of the cone spanned by the in vivo hip-joint reaction force (Bergmann et al., 2001). A fifth load direction was neutrally aligned with the diaphyseal axis, and a sixth was aligned with the average hip-joint reaction force vector measured during single-leg stance by Bergmann et al. (2001). Principal tensile and compressive strains were reported at fourteen locations in the epiphyseal femoral region. To investigate the effect of different physical activities on femoral neck loads, muscle and hip-joint reaction forces calculated from the musculoskeletal model were applied to the finite-element model (Fig. 1). Each activity was discretized into fifteen uniformly distributed time intervals ensuring that the peak hip reaction force was included. The resulting 225 linear-elastic simulations were performed in Abaqus© (Dassault Systemes, USA). For each simulation, the total strain energy and peak tensile strain in the femoral neck were correlated with muscle and hip-joint forces. The peak tensile strain was compared with a fracture threshold of 0.73% (Bayraktar et al., 2004) to provide an indication of the likelihood of femoral neck fracture. According to bone remodeling theory (Huiskes et al., 1987), bone formation occurs when the strain energy per unit of bone mass (S) exceeds a homeostatic value (Sref) by a minimum threshold (s ¼ 75%) (Kerner et al., 1999). The homeostatic value was assumed to equal the average strain energy calculated for the stance phase of walking (Martelli et al., 2011). For each physical activity, the highest percentage difference between the peak strain energy and the homeostatic value (ΔS) was calculated to identify the potential for bone formation. The relationship between the femoral loads (hip-joint force and individual muscle forces) and the resulting peak tensile strain and strain energy in the femoral neck was evaluated using linear and quadratic correlation analyses, respectively. The potential effectiveness of activity type to induce femoral neck strain energy was calculated by normalizing peak strain energy by the load magnitude. Fig. 2. Calculated hip forces (black dots) and hip force patterns (black dashed line) compared against measurements of hip contact forces expressed in body-weight (BW) obtained for instrumented total hip replacements (grey band) (Bergmann et al., 2001; www.orthoload.com). For the weight-bearing activities, the peak bone strain energy was normalized by the corresponding magnitude of the ground reaction force, while the maximalresistance exercises were normalized by the corresponding magnitude of the Please cite this article as: Martelli, S., et al., Strain energy in the femoral neck during exercise. Journal of Biomechanics (2014), http://dx. doi.org/10.1016/j.jbiomech.2014.03.036i 4 S. Martelli et al. / Journal of Biomechanics ∎ (∎∎∎∎) ∎∎∎–∎∎∎ joint torque. This method of normalization permitted physical activities that were potentially more efficacious in creating loads on the femoral neck to be readily identified. 3. Results Calculations of the hip-joint reaction force and cortical strain compared favorably with experimental data. The maximum difference between calculated and published hip-joint reaction forces was þ1.1 BW during the late stance phase of walking (Fig. 2). The calculated and measured cortical strains were significantly correlated (R2 ¼0.95, p o0.001), and the root mean square error was 12.5% (maximum error ¼35.1%) (Fig. 3). Different physical activities resulted in different peak strain energies and peak tensile strains in the femoral neck. Maximum isokinetic hip-extension, one-legged long jump, and maximum isokinetic knee-flexion resulted in the highest values of peak strain energy (0.29 J, 0.25 J, and 0.19 J, respectively) and peak tensile strain (0.51%, 0.48%, and 0.39%). The peak tensile strain was located in the proximal neck during maximum isokinetic hipextension and knee-flexion, and was in the anterior neck during one-legged maximum-distance long jump (Fig. 4). Overall, the peak strain energy ranged from 0.02 J (isokinetic hip adduction) to 0.29 J (isokinetic hip extension) (Fig. 5A), whereas peak tensile Fig. 3. Linear regression of the finite-element model predictions of principal strains compared against measured principal strains (με). All strain measurements reported by Testi et al. (2010) are shown (i.e., two strain components for 14 strain gauge locations and six loading conditions). Regression analysis results are given in the bottom right-hand corner. strain ranged from 0.10% (isokinetic hip adduction) to 0.51% (isokinetic hip extension), corresponding to 13% and 70% of the fracture threshold (Fig. 5B). The minimum threshold required to trigger bone formation was exceeded in 8 of the 15 activities (Fig. 7). Isokinetic hip extension (ΔS ¼722%), long jump (ΔS ¼572%), and isokinetic knee flexion (ΔS ¼418%) induced the highest changes in strain energy, while moderate changes were calculated for isokinetic hip flexion (ΔS ¼254%), vertical jump (ΔS¼ 184%), level walking (ΔS ¼160%), and stair descent (ΔS ¼122%). The peak tensile strain and strain energy in the femoral neck correlated with the hip reaction force during maximum isokinetic hip- Fig. 5. Ranking of activities according to peak strain energy. Peak strain energy (A) and peak tensile strain (B) calculated in the femoral neck for the studied activities. The gray bars represent activities categorized as low-load whereas the black bars represent activities categorized as high-load. The red dashed line represents the fracture threshold of 0.73% reported by Bayraktar et al. (2004). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.) Fig. 4. Tensile strain distribution in the femoral neck during isokinetic maximal hip extensions, isokinetic knee flexion and one-legged long jumps at the instant of the peak strain energy and tensile strain. Please cite this article as: Martelli, S., et al., Strain energy in the femoral neck during exercise. Journal of Biomechanics (2014), http://dx. doi.org/10.1016/j.jbiomech.2014.03.036i S. Martelli et al. / Journal of Biomechanics ∎ (∎∎∎∎) ∎∎∎–∎∎∎ 5 Fig. 6. Correlation analyses performed for the peak tensile strain and strain energy in the femoral neck and selected muscle and hip-joint reaction forces acting on the femur during isokinetic maximal hip extensions, isokinetic knee flexion and one-legged long jumps. A complete set of results can be found in the Supplementary material available on the Journal's website. extension (R2 ¼ 0.99), one-legged long jump (R2 ¼0.90), and maximum isokinetic knee-flexion (R2 ¼0.99). Correlation between the peak tensile strain and strain energy and muscle forces was variable and activity-dependent (R2 ¼ o0.1–0.99). A summary of the correlation analysis is reported in Fig. 6 (see also Supplementary material). For the weight-bearing activities, squatting with a 10 kg weight induced the highest normalized strain energy followed by the long jump (Fig. 8A). Within the group of resistance exercises, the normalized peak strain energies in the femoral neck generated during maximal hip-extensor and knee-flexor contractions were more than twice as high as the normalized peak strain energy generated during each of the other maximal-resistance exercises (Fig. 8B). 4. Discussion The aim of this study was to compare the potential for physical activities, including exercise treatments currently adopted to promote femoral neck strength, to induce bone formation and minimize the effects of osteoporosis (Bailey and Brooke-Wavell, 2010; Rhodes et al., 2000). The potential to stimulate bone formation was based on calculations of strain energy, an indicator of bone remodeling (Huiskes et al., 1987), while the potential to induce bone fracture was based on calculations of tensile strain (Dall’ara et al., 2012; Schileo et al., 2008b). The fifteen activities investigated had the potential to induce remarkably different mechanical loads in the femoral neck, though they did not always reach the minimum level required to trigger bone formation. Activities categorized as high-load were found to have the highest potential for bone formation (Fig. 7), in agreement with the findings of others (Kemmler et al., 2004; Martyn-St James and Carroll, 2006). Specifically, the one-legged long jump and maximum isokinetic hip extension and knee flexion induced the highest changes in strain energy (ΔS Z418%), whereas low to moderate changes (75% o ΔSo 418%) were associated with walking, stair descent, vertical jump, and isokinetic hip flexion. For the remaining activities, changes in strain energy were below the minimum threshold for bone formation (ΔSr 75%). Please cite this article as: Martelli, S., et al., Strain energy in the femoral neck during exercise. Journal of Biomechanics (2014), http://dx. doi.org/10.1016/j.jbiomech.2014.03.036i 6 S. Martelli et al. / Journal of Biomechanics ∎ (∎∎∎∎) ∎∎∎–∎∎∎ Fig. 7. Change in peak strain energy per unit mass (ΔS) representing the mechanical stimulus for bone formation shown for all the studied activities. The red dashed line represents the threshold (s¼ þ 75%) reported by Kerner et al. (1999) below which no bone formation is expected, assuming that the average strain energy stored in the femoral neck during the stance phase of walking is the homeostatic value. The gray bars represent activities categorized as low-load whereas the black bars represent activities categorized as high-load. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.) We observed that activities of relatively similar load were capable of producing contrasting levels and distributions of femoral neck strain and strain energy. For example, the normalized peak strain energy for squatting with a 10 kg weight was three times as high as that for a step-up task (Fig. 8), even though the peak vertical ground reaction force was roughly equivalent in these two activities (Table 1). Maximal hip-extension and kneeflexion exercises maximally loaded the proximal femoral neck in the thinnest region of the cortex (Kersh et al., 2013), whereas onelegged long jumps maximally loaded the anterior neck (Fig. 4). Therefore, when femoral neck loads are of interest, the common notion that the load associated with a given physical activity is proportional to the ground reaction force (Kohrt et al., 1997) or applied resistance during a maximum-effort exercise (Rhodes et al., 2000) needs to be reconsidered because the activity type is another important determinant of femoral neck loads. We suggest that the various hip-spanning muscle groups recruited during different activities have the ability to induce contrasting mechanical stimuli on the femoral neck through their different geometrical arrangement, some by acting directly in a nearby area (e.g., gluteus maximus), while others by influencing the hip-joint reaction force (e.g., semimembranosus). Muscles that do not span the hip may also contribute to the hip-joint reaction force, albeit to a much lesser extent, by accelerating the body's segments through dynamic coupling of the musculoskeletal system (Pandy and Andriacchi, 2010; Correa et al., 2010). None of the investigated physical activities were likely to cause femoral neck fracture. This finding supports the notion that bone fracture, in the absence of trauma, is only likely to occur when people with severely weak bones undertake tasks that result in abnormal loading conditions (Viceconti et al., 2012). Our results are qualitatively consistent with clinical studies showing that changes in BMD depend on the type of loading intervention (Hamilton et al., 2010). Specifically, clinical investigations involving jumping and maximally-resisted muscle contractions have reported a BMD increase in the femoral neck (Bailey and Brooke-Wavell, 2010; Rhodes et al., 2000). A high mechanical stimulus for bone formation was found in the present study for similar tasks. Common weight-bearing activities showed a Fig. 8. Peak strain energy (J) normalized by either the ground reaction force magnitude (BW) for weight-bearing activities (A) or the net joint torque (N m) for resistance activities (B). Both the ground reaction force magnitude and the net joint torque were calculated at the time of peak strain energy. The gray bars represent activities categorized as low-load whereas the black bars represent activities categorized as high-load. small to moderate likelihood of promoting bone formation, in agreement with previous clinical reports (Guadalupe-Grau et al., 2009; Kemmler et al., 2004; Martyn-St James and Carroll, 2008). For example, several researchers have investigated the potential for walking to promote bone formation and some have reported no change in BMD (Guadalupe-Grau et al., 2009), whereas others have found a moderate BMD increase (Martyn-St James and Carroll, 2008). Our results are in agreement with the work of Martyn-St James and Carroll (2008) One limitation of this study was that musculoskeletal loading calculated using motion data recorded from a young volunteer may be quantitatively different from that present in older adults and future studies would benefit from investigating these tasks in an elderly population. However, the calculated hip-joint reaction force was consistent with published measurements (Bergmann et Please cite this article as: Martelli, S., et al., Strain energy in the femoral neck during exercise. Journal of Biomechanics (2014), http://dx. doi.org/10.1016/j.jbiomech.2014.03.036i S. Martelli et al. / Journal of Biomechanics ∎ (∎∎∎∎) ∎∎∎–∎∎∎ al., 2001) obtained from older subjects during four weight-bearing activities (Fig. 2) with the only exception being during the late stance phase of walking. This discrepancy likely originates from the higher ground reaction force (1.3 BW; Table 1) recorded from the young volunteer compared to that measured by Bergmann et al. (2001) in elderly patients (o1.08 BW). We do not know whether and how the calculations of the hip-joint forces are representative of impact activities in older adults because direct measurements of the hip contact force are not yet available under such conditions. Nonetheless, we suggest that the normalization of strain energy by the external loads (i.e., ground reaction forces and joint torques) (Fig. 8) partially accounts for the variation in bone mechanics that may arise when the same activities are performed with different load magnitudes. Second, the study was based on a single anatomical dataset and a representative trial for each activity. The variability of femoral neck loads caused by different anatomies and capabilities of performing a given activity remain unexplored. Third, we calculated the maximal strain energy in the femoral neck while other factors such as the loading rate, exercise duration and the number of daily repetitions known to influence bone response were not considered (Bailey and Brooke-Wavell, 2010). However, the use of strain energy alone has been shown to describe the general femoral bone response to mechanical loads in the elderly (Kerner et al., 1999). Finally, muscle forces calculated using optimization theory may underestimate antagonist muscle contractions (Yeadon et al., 2010). Higher levels of antagonist muscle contraction may lead to increased strains in the femoral neck region (Viceconti et al., 2012). Despite the aforementioned limitations, the present findings provide the first quantitative comparison relating indicators of bone formation and fracture to specific physical activities using computational methods. Different activity types of similar load magnitude resulted in a highly different potential to generate strain energy in the femoral neck. The highest mechanical stimulus for bone formation and fracture were associated with maximal isokinetic hip extension, onelegged long jump, and maximal isokinetic knee flexion. In summary, the findings of this study show that activities involving maximum hip-extension and knee-flexion contractions are possible alternatives to high-impact activities (e.g., one-legged long jump) for promoting femoral neck bone formation. These results may help to inform the design of more targeted exercise regimens for improving bone strength in the proximal femora of older adults. Further research is necessary to elucidate the separate effects of the different muscles on femoral neck strain and strain energy. Conflict of interest statement None of the authors have a conflict of interest in relation to this study. Acknowledgements The authors would like to thank Sheridan Laing for her contribution to the experiments. This study was supported by the Australian Research Council (Discovery Project Grant DP1095366) and an Innovation Fellowship provided by the Victorian State Government to M.G.P and an Early Career Research project from the University of Melbourne awarded to S.M. Appendix A. Supporting information Supplementary data associated with this article can be found in the online version at http://dx.doi.org/10.1016/j.jbiomech.2014.03.036. 7 References Bailey, C., Brooke-Wavell, K., 2010. Optimum frequency of exercise for bone health: randomised controlled trial of a high-impact unilateral intervention. Bone 46, 1043–1049. Bayraktar, H.H., Morgan, E.F., Niebur, G.L., Morris, G.E., Wong, E.K., Keaveny, T.M., 2004. Comparison of the elastic and yield properties of human femoral trabecular and cortical bone tissue. J. Biomech. 37, 27–35. Bergmann, G., Deuretzbacher, G., Heller, M., Graichen, F., Rohlmann, A., Strauss, J., Duda, G.N., 2001. Hip contact forces and gait patterns from routine activities. J. Biomech. 34, 859–871. Cooper, C., Melton, L.J., 1992. Epidemiology of osteoporosis. Trends Endocrinol. Metab. 3, 224–229. Correa, T.A., Crossley, K.M., Kim, H.J., Pandy, M.G., 2010. Contributions of individual muscles to hip joint contact force in normal walking. J. Biomech. 43, 1618–1622. Dall’ara, E., Luisier, B., Schmidt, R., Kainberger, F., Zysset, P., Pahr, D., 2012. A nonlinear QCT-based finite element model validation study for the human femur tested in two configurations in vitro. Bone 52, 27–38. Delp, S.L., Anderson, F.C., Arnold, A.S., Loan, P., Habib, A., John, C.T., Guendelman, E., Thelen, D.G., 2007. OpenSim: open-source software to create and analyze dynamic simulations of movement. IEEE Trans. Biomed. Eng. 54, 1940–1950. Delp, S.L., Loan, J.P., Hoy, M.G., Zajac, F.E., Topp, E.L., Rosen, J.M., 1990. An interactive graphics-based model of the lower extremity to study orthopaedic surgical procedures. IEEE Trans. Biomed. Eng. 37, 757–767. Dornemann, T.M., McMurray, R.G., Renner, J.B., Anderson, J.J., 1997. Effects of highintensity resistance exercise on bone mineral density and muscle strength of 40–50-year-old women. J. Sports Med. Phys. Fitness 37, 246–251. Dumas, R., Aissaoui, R., Mitton, D., Skalli, W., de Guise, J. a, 2005. Personalized body segment parameters from biplanar low-dose radiography. IEEE Trans. Biomed. Eng. 52, 1756–1763. Ebrahim, S., Thompson, P.W., Baskaran, V., Evans, K., 1997. Randomized placebocontrolled trial of brisk walking in the prevention of postmenopausal osteoporosis. Age Ageing 26, 253–260. Glitsch, U., Baumann, W., 1997. The three-dimensional determination of internal loads in the lower extremity. J. Biomech. 30, 1123–1131. Guadalupe-Grau, A., Fuentes, T., Guerra, B., Calbet, J. a L., 2009. Exercise and bone mass in adults. Sports Med 39, 439–468. Hamilton, C.J., Swan, V.J.D., Jamal, S. a, 2010. The effects of exercise and physical activity participation on bone mass and geometry in postmenopausal women: a systematic review of pQCT studies. Osteoporos Int. 21, 11–23. Huiskes, R., Weinans, H., Grootenboer, H.J., Dalstra, M., Fudala, B., Slooff, T.J., 1987. Adaptive bone-remodelling theory applied to prosthetic-design analysis. J. Biomech. 20, 1135–1150. Jonkers, I., Lenaerts, G., Mulier, M., Van der Perre, G., Jaecques, S., 2008. Relation between subject-specific hip joint loading, stress distribution in the proximal femur and bone mineral density changes after total hip replacement. J. Biomech. 41, 3405–3413. Kemmler, W., Lauber, D., Weineck, J., Hensen, J., Kalender, W., Engelke, K., 2004. Benefits of 2 years of intense exercise on bone density, physical fitness, and blood lipids in early postmenopausal osteopenic women. Arch. Intern. Med. 164, 1084–1091. Kerner, J., Huiskes, R., van Lenthe, G.H., Weinans, H., van Rietbergen, B., Engh, C.A., Amis, A.A., 1999. Correlation between pre-operative periprosthetic bone density and post-operative bone loss in THA can be explained by strainadaptive remodelling. J. Biomech. 32, 695–703. Kersh, M.E., Pandy, M.G., Bui, Q.M., Jones, A.C., Arns, C.H., Knackstedt, M. a, Seeman, E., Zebaze, R.M., 2013. The heterogeneity in femoral neck structure and strength. J. Bone Miner. Res. 28, 1022–1028. Keyak, J.H., Fourkas, M.G., Meagher, J.M., Skinner, H.B., 1993. Validation of an automated method of three-dimensional finite element modelling of bone. J. Biomech. Eng. 15, 505–509. Kohrt, W.M., Ehsani, A.A., Birge, S.J., 1997. Effects of exercise involving predominantly either joint-reaction or ground-reaction forces on bone mineral density in older women. J. Bone Miner. Res. 12, 1253–1261. Lohman, T., Going, S., Pamenter, R., Hall, M., Boyden, T., Houtkooper, L., Ritenbaugh, C., Bare, L., Hill, A., Aickin, M., 1995. Effects of resistance training on regional and total bone mineral density in premenopausal women: a randomized prospective study. J. Bone Miner. Res.: Off. J. Am. Soc. Bone Miner. Res 10, 1015–1024. Martelli, S., Taddei, F., Cappello, A., van Sint Jan, S., Leardini, A., Viceconti, M., 2011. Effect of sub-optimal neuromotor control on the hip joint load during level walking. J. Biomech. 44, 1716–1721. Martyn-St James, M., Carroll, S., 2006. Progressive high-intensity resistance training and bone mineral density changes among premenopausal women: evidence of discordant site-specific skeletal effects. Sports Med 36, 683–704. Martyn-St James, M., Carroll, S., 2008. Meta-analysis of walking for preservation of bone mineral density in postmenopausal women. Bone 43, 521–531. Morgan, E.F., Bayraktar, H.H., Keaveny, T.M., 2003. Trabecular bone modulus– density relationships depend on anatomic site. J. Biomech. 36, 897–904. Nikander, R., Sievänen, H., Heinonen, A., Daly, R.M., Uusi-Rasi, K., Kannus, P., 2010. Targeted exercise against osteoporosis: a systematic review and meta-analysis for optimising bone strength throughout life. BMC Med 8, 47. Pandy, M.G., Andriacchi, T.P., 2010. Muscle and joint function in human locomotion. Annu. Rev. Biomed. Eng. 12, 401–433. Please cite this article as: Martelli, S., et al., Strain energy in the femoral neck during exercise. Journal of Biomechanics (2014), http://dx. doi.org/10.1016/j.jbiomech.2014.03.036i 8 S. Martelli et al. / Journal of Biomechanics ∎ (∎∎∎∎) ∎∎∎–∎∎∎ Petit, M.A., Hughes, J.M., Warpeha, J.M., 2009. Exercise Prescription for People with Osteoporosis. In: Sixth ed. ACSM's Resource Manual for Guidelines for Exercise Testing and Prescription. pp. 1–16. Pyka, G., Lindenberger, E., Charette, S., Marcus, R., 1994. Muscle strength and fiber adaptations to a year-long resistance training program in elderly men and women. J. Gerontol. 49, M22–M27. Rhodes, E.C., Martin, A.D., Taunton, J.E., Donnelly, M., Warren, J., Elliot, J., 2000. Effects of one year of resistance training on the relation between muscular strength and bone density in elderly women. Br. J. Sports Med. 34, 18–22. Roach, K.E., Miles, T.P., 1991. Normal hip and knee active range of motion: the relationship to age. Phys. Ther. 71, 656–665. Schileo, E., Dall’ara, E., Taddei, F., Malandrino, A., Schotkamp, T., Baleani, M., Viceconti, M., 2008a. An accurate estimation of bone density improves the accuracy of subject-specific finite element models. J. Biomech. 41, 2483–2491. Schileo, E., Taddei, F., Cristofolini, L., Viceconti, M., 2008b. Subject-specific finite element models implementing a maximum principal strain criterion are able to estimate failure risk and fracture location on human femurs tested in vitro. J. Biomech. 41, 356–367. Schileo, E., Taddei, F., Malandrino, A., Cristofolini, L., Viceconti, M., 2007. Subjectspecific finite element models can accurately predict strain levels in long bones. J. Biomech. 40, 2982–2989. Sernbo, I., Johnell, O., 1993. Consequences of a hip fracture: a prospective study over 1 year. Osteoporos Int. 3, 148–153. Steinhilber, B., Haupt, G., Boeer, J., Grau, S., Krauss, I., 2011. Reproducibility of concentric isokinetic and isometric strength measurements at the hip in patients with hip osteoarthritis: a preliminary study. Isokinet. Exerc. Sci. 19, 39–46. Tan, J., Balci, N., Sepici, V., Gener, F.A., 1995. Isokinetic and isometric strength in osteoarthrosis of the knee. Am. J. Phys. Med. Rehabil. 74, 364–369. Testi, D., Quadrani, P., Viceconti, M., 2010. PhysiomeSpace: digital library service for biomedical data. Philos. Trans. R. Soc. London, Ser. A 368, 2853–2861. Viceconti, M., Taddei, F., Cristofolini, L., Martelli, S., Falcinelli, C., Schileo, E., 2012. Are spontaneous fractures possible? An example of clinical application for personalised, multiscale neuro-musculo-skeletal modelling. J. Biomech. 45, 421–426. Ward, S.R., Eng, C.M., Smallwood, L.H., Lieber, R.L., 2009. Are current measurements of lower extremity muscle architecture accurate? Clin. Orthop. Relat. Res 467, 1074–1082. Weinans, H., Huiskes, R., van Rietbergen, B., Sumner, D.R., Turner, T.M., Galante, J.O., 1993. Adaptive bone remodeling around bonded noncemented total hip arthroplasty: a comparison between animal experiments and computer simulation. J. Orthop. Res. 11, 500–513. Yeadon, M.R., King, M.A., Forrester, S.E., Caldwell, G.E., Pain, M.T.G., 2010. The need for muscle co-contraction prior to a landing. J. Biomech. 43, 364–369. Please cite this article as: Martelli, S., et al., Strain energy in the femoral neck during exercise. Journal of Biomechanics (2014), http://dx. doi.org/10.1016/j.jbiomech.2014.03.036i