Magnetic resonance imaging based finite element modelling of the proximal femur: a short-term in vivo precision study.

Proximal femoral fractures are a serious life-threatening injury with high morbidity and mortality. Magnetic resonance (MR) imaging has potential to non-invasively assess proximal femoral bone strength in vivo through usage of finite element (FE) modelling (a technique referred to as MR-FE). To precisely assess bone strength, knowledge of measurement error associated with different MR-FE outcomes is needed. The objective of this study was to characterize the short-term in vivo precision errors of MR-FE outcomes (e.g., stress, strain, failure loads) of the proximal femur for fall and stance loading configurations using 13 participants (5 males and 8 females; median age: 27 years, range: 21-68), each scanned 3 times. MR-FE models were generated, and mean von Mises stress and strain as well as principal stress and strain were calculated for 3 regions of interest. Similarly, we calculated the failure loads to cause 5% of contiguous elements to fail according to the von Mises yield, Brittle Coulomb-Mohr, normal principal, and Hoffman stress and strain criteria. Precision (root-mean squared coefficient of variation) of the MR-FE outcomes ranged from 3.3% to 11.8% for stress and strain-based mechanical outcomes, and 5.8% to 9.0% for failure loads. These results provide evidence that MR-FE outcomes are a promising non-invasive technique for monitoring femoral strength in vivo.

Precision Errors and Monitoring Time Interval in Pediatric Muscle Imaging and Neuromuscular Performance Assessment.

OBJECTIVES: To determine precision errors and monitoring time intervals in imaged muscle properties and neuromuscular performance, and to explore growth-related factors associated with precision errors in children. METHODS: We included 35 children (mean age 10.5yrs) in the precision study cohort and 40 children (10.7yrs) in the follow-up study cohort. We assessed forearm and lower leg muscle properties (area, density) with peripheral quantitative computed tomography. We measured neuromuscular performance via maximal pushup, grip force, countermovement and standing long jump force, power, and impulse along with long jump length. We calculated precision errors (root-mean-squared coefficient of variation) from the precision cohort and monitoring time intervals using annual changes from the follow-up cohort. We explored associations between precision errors (coefficient of variation) and maturity, time interval (between repeated measures), and anthropometric changes using Spearman's rank correlation (p<0.05). RESULTS: Muscle measures exhibited precision errors of 1.3-14%. Monitoring time intervals were 1-2.6yrs, except muscle density (>43yrs). We identified only one association between precision errors and maturity (maximal pushup force: rho=-0.349; p=0.046). CONCLUSIONS: Imaging muscle properties and neuromuscular performance measures had precision errors of 1-14% and appeared suitable for follow-up on ~2yr scales (except muscle density). Maximal pushup force appeared more repeatable in mature children.

Distal radius sections offer accurate and precise estimates of forearm fracture load.

BACKGROUND: Forearm fracture risk can be estimated via factor-of-risk: the ratio of applied impact force to forearm fracture load. Simple techniques are available for estimating impact force associated with a fall; estimating forearm fracture load is more challenging. Our aim was to assess whether failure load estimates of sections of the distal radius (acquired using High-Resolution peripheral Quantitative Computed Tomography and finite element modeling) offer accurate and precise estimates of forearm fracture load. METHODS: We scanned a section of the distal radius of 19 cadaveric forearms (female, mean age 83.7, SD 8.3), and 34 women (75.0, 7.7). Sections were converted to finite element models and failure loads were acquired for different failure criteria. We assessed forearm fracture load using experimental testing simulating a fall on the outstretched hand. We used linear regression to derive relationships between ex vivo forearm fracture load and finite element derived distal radius failure load. We used derived regression coefficients to estimate forearm fracture load, and assessed explained variance and prediction error. We used root-mean-squared coefficients of variation to assess in vivo precision errors of estimated forearm fracture load. FINDINGS: Failure load estimates of sections of the distal radius, used in conjunction with derived regression coefficients, explained 89-90% of the variance in experimentally-measured forearm fracture load with prediction errors <6.8% and precision errors <5.0%. INTERPRETATION: Failure load estimates of distal radius sections can reliably estimate forearm fracture load experienced during a fall. Forearm fracture load estimates can be used to improve factor-of-risk predictions for forearm fracture.

Off-axis loads cause failure of the distal radius at lower magnitudes than axial loads: A side-to-side experimental study.

Off-axis loading associated with a fall onto the outstretched hand has been hypothesized to induce distal radius failure at lower magnitudes than axially directed loading commonly used in biomechanical models for estimating fracture risk. However, this hypothesis has not been tested with side-to-side experimental testing. The objective of this study was to compare distal radius failure loads between forearm pairs experimentally tested in an axial or off-axis loading configuration. We acquired 18 pairs of cadaveric forearms from 18 female donors (mean age (standard deviation): 84.4 (7.9) years). Each forearm pair was tested to failure using either an axial compression test (vertical orientation with 0° dorsal inclination, 3°-6° radial inclination) or an off-axis test corresponding to the hand position during a fall (15° dorsal inclination, 3°-6° radial inclination). Failure testing was performed at 3 mm/s onto the palm of the hand until fracture occurred. Of the 18 pairs, 11 sustained a distal radius fracture. We compared failure loads between the two groups using a paired t test. Results indicated that failure load under off-axis loading was 29% lower than failure load under axial compressive loading (mean difference: -0.31 kN; 95% confidence interval: -0.47 to -0.16 kN, P = .001). In conclusion, off-axis loading associated with a fall onto the outstretched hand resulted in a 29% lower failure load. Integrating an off-axis loading configuration into current biomechanical models of distal radius bone strength may prevent overestimating of failure load and may offer a clinically relevant option to estimate distal radius fracture risk and monitor therapy efficacy.

Predicting experimentally-derived failure load at the distal radius using finite element modelling based on peripheral quantitative computed tomography cross-sections (pQCT-FE): A validation study.

Dual energy X-ray absorptiometry, the current clinical criterion method for osteoporosis diagnosis, has limitations in identifying individuals with increased fracture risk, especially at the distal radius. Peripheral quantitative computed tomography (pQCT) can provide volumetric bone density data, as well as information on bone geometry, which makes it possible to establish finite element (FE) models of the distal radius from which bone strength and stiffness can be calculated. In this study, we compared experimental mechanical failure load data of the forearm with pQCT- based FE (pQCT-FE) modelling properties. Sixteen cadaveric forearm specimens were experimentally loaded until failure. Estimated stiffness and strength variables of compression, shear, bending and torsion were calculated from pQCT-FE modelling of single cross-sections of 0.2 × 0.2 × 2.4 mm of the radius pQCT image. A moderate-to-strong coefficient of determination (r2) was observed between experimental failure load and pQCT-FE variables. The highest r2 was observed for bending stiffness (r2 = 0.83). This study validates the use of pQCT-FE in the assessment of distal radius bone strength for future studies.

Investigation of white line separation under load in bovine claws with and without toe-tip necrosis.

OBJECTIVE: To compare the degree of white line separation created by increasing physiologic loads between bovine claws with and without toe-tip necrosis (TTN). SAMPLE: Cadaveric bovine hind limbs with (n = 10) and without (10) TTN. PROCEDURES: Hind limbs in which 1 or both claws had evidence of apical white line separation were considered to have TTN. Hind limbs in which neither claw had evidence of white line separation were considered controls. Each hind limb was mounted in a materials testing system with the bottom surface of the hoof angled at approximately 5° to the horizontal plane such that the apex of the claws made initial contact with the clear testing surface to simulate physiologic loading conditions. A digital camera mounted underneath the testing surface was used to obtain images of the bottom of the hoof during the application of each of 3 increasing static loads (1, 2, and 3 kN). The images were analyzed with commercial image-processing software to quantify white line separation area. RESULTS: White line separation area was significantly greater for claws with TTN than for control claws and increased as the applied load increased. White line separation was almost nonexistent in control claws and was not affected by increasing load. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that mechanical loading exacerbated TTN, but compressive loading alone, even at excessive levels, did not initiate the condition. Interventions (eg, hoof blocks) that decrease loading of affected claws may be beneficial for the treatment of TTN at its earliest stages.

Author Correction: Mechanical Metrics of the Proximal Tibia are Precise and Differentiate Osteoarthritic and Normal Knees: A Finite Element Study.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

A single-spring model predicts the majority of variance in impact force during a fall onto the outstretched hand.

The objective of this study was to validate a single-spring model in predicting measured impact forces during an outstretched arm falling scenario. Using an integrated force plate, impact forces were assessed from 10 young adults (5 males; 5 females), falling from planted knees onto outstretched arms, from a random order of drop heights: 3, 5, 7, 10, 15, 20, and 25 cm. A single-spring model incorporating body mass, drop height plus the estimated linear stiffness of the upper extremity (hand, wrist and arm) was used to predict impact force on the hand. We used an analysis of variance linearity test to test the validity of using a linear stiffness coefficient in the model. We used linear regression to assess variance (R2) in experimental impact force predicted by the single-spring model. We derived optimum linear stiffness coefficients for male, female and sex-combined. Our results indicated that the association between experimental and predicted impact forces was linear (P < 0.05). Explain variance in experimental impact force was R2 = 0.82 for sex-combined, R2 = 0.88 for males and R2 = 0.84 for females. Optimum stiffness coefficients were 7436 N/m for sex-combined, 8989 N/m for males and 4527 N/m for females. In conclusion, a linear spring coefficient used in the single-spring model proved valid for predicting impact forces from fall heights up to 25 cm. Results also suggest the use of sex-specific spring coefficients when estimating impact force using the single-spring model. This model may improve impact force to bone strength ratios (factor-of-risk) and prediction of forearm and wrist fracture.

Knee osteoarthritis patients with more subchondral cysts have altered tibial subchondral bone mineral density.

BACKGROUND: Subchondral bone cysts are a widely observed, but poorly understood, feature in patients with knee osteoarthritis (OA). Clinical quantitative computed tomography (QCT) has the potential to characterize cysts in vivo but it is unclear which specific cyst parameters (e.g., number, size) are associated with clinical signs of OA, such as disease severity or pain. The objective of this study was to use QCT-based image-processing techniques to characterize subchondral tibial cysts in patients with knee OA and to explore relationships between proximal tibial subchondral cyst parameters and subchondral bone density as well as clinical characteristics of OA (alignment, joint space narrowing (JSN), OA severity, pain) in patients with knee OA. METHODS: The preoperative knee of 42 knee arthroplasty patients was scanned using QCT. Patient characteristics were obtained, including OA severity, knee pain, JSN, and alignment. We used 3D image processing techniques to obtain cyst parameters including: cyst number, cyst number per proximal tibial volume, cyst volume per proximal tibial volume, as well as maximum and average cyst volume across the proximal tibia, as well as regional bone mineral density (BMD) excluding cysts. We used Spearman's correlation coefficients to explore associations between patient characteristics and cyst parameters. RESULTS: At both the medial and lateral compartments of the proximal tibia, greater cyst number and volume were associated with higher BMD. At the lateral region, cyst number and volume were also associated with lateral OA severity, lateral JSN, alignment and sex. Pain was not associated with any cyst parameters at any region. CONCLUSION: Cyst number and volume were associated with BMD at both the medial and lateral compartments. Lateral cyst number and volume were also associated with joint alignment, OA severity, JSN and sex. This is the first study to use clinical QCT to explore subchondral tibial cysts in patients with knee OA and provides further evidence of the relationships between subchondral cysts and clinical OA characteristics.

Moderate to vigorous physical activity and impact loading independently predict variance in bone strength at the tibia but not at the radius in children.

The objectives of this study were (i) to assess whether daily minutes of moderate to vigorous physical activity (MVPA) or vigorous physical activity (VPA) and impact counts (acceleration peaks ≥3.9g) independently predict variance in bone strength in children and youth and (ii) to estimate bone strength gain associated with increases in daily MVPA, VPA, or impact counts. We recorded 7-day activity of 49 participants (mean age 11.0 years, SD 1.7) using accelerometers and estimated radius and tibia bone strength using peripheral quantitative computed tomography. We used linear regression models adjusted for sex, body mass, and muscle area to address our objectives. Daily MVPA (mean 50 min, SD 23) and VPA (mean 17 min, SD 11) or impacts (mean 71 counts, SD 59) did not predict variance in radius strength. Daily VPA (ß = 0.24) predicted variance in tibia strength at the distal and shaft sites, and shaft strength was also predicted by MVPA (ß = 0.20) and impact counts (ß = 0.21). Our models estimated a 3%-6%, 4%, or 4%-11% gain in tibia strength after increasing daily MVPA by 10-20 min, VPA by 5 min, or impacts by 30-100 counts, respectively. In conclusion, daily minutes of MVPA or VPA and impact counts are independent predictors of tibia but not radius strength. Objective recording of activities associated with forearm bone strength and trials testing the efficacy of increasing daily MVPA, VPA, and related impacts on bone strength development in children and youth are warranted.

Cortical porosity assessment in the distal radius: A comparison of HR-pQCT measures with Synchrotron-Radiation micro-CT-based measures.

OBJECTIVE: To determine the agreement between cortical porosity derived from high resolution peripheral quantitative computed tomography (HR-pQCT) (via standard threshold, mean density and density inhomogeneity methods) and synchrotron radiation micro-CT (SR-µCT) derived porosity at the distal radius. METHODS: We scanned 10 cadaveric radii (mean donor age: 79, SD 11 years) at the standard distal region using HR-pQCT and SR-µCT at voxel sizes of 82 µm and 17.7 µm, respectively. Common cortical regions were delineated for each specimen in both imaging modalities. HR-pQCT images were analyzed for cortical porosity using the following methods: Standard threshold, mean density, and density inhomogeneity (via recommended and optimized equations). We assessed agreement in porosity measures between HR-pQCT methods and SR-µCT by reporting predicted variance from linear regression and mean bias with limits of agreement (LOA). RESULTS: The standard threshold and mean density methods predicted 85% and 89% of variance and indicated underestimation (mean bias -9.1%, LOA -15.9% to -2.2%) and overestimation (10.4%, 4.6% to 16.2%) of porosity, respectively. The density inhomogeneity method with recommended equation predicted 89% of variance and mean bias of 14.9% (-4.3 to 34.2) with systematic over-estimation of porosity in more porous specimens. The density inhomogeneity method with optimized equation predicted 91% of variance without bias (0.0%, -5.3 to 5.2). CONCLUSION: HR-pQCT imaged porosity assessed with the density inhomogeneity method with optimized equation indicated the best agreement with SR-µCT derived porosity.

Mechanical Metrics of the Proximal Tibia are Precise and Differentiate Osteoarthritic and Normal Knees: A Finite Element Study.

Our objective was to identify precise mechanical metrics of the proximal tibia which differentiated OA and normal knees. We developed subject-specific FE models for 14 participants (7 OA, 7 normal) who were imaged three times each for assessing precision (repeatability). We assessed various mechanical metrics (minimum principal and von Mises stress and strain as well as structural stiffness) across the proximal tibia for each subject. In vivo precision of these mechanical metrics was assessed using CV%RMS. We performed parametric and non-parametric statistical analyses and determined Cohen's d effect sizes to explore differences between OA and normal knees. For all FE-based mechanical metrics, average CV%RMS was less than 6%. Minimum principal stress was, on average, 75% higher in OA versus normal knees while minimum principal strain values did not differ. No difference was observed in structural stiffness. FE modeling could precisely quantify and differentiate mechanical metrics variations in normal and OA knees, in vivo. This study suggests that bone stress patterns may be important for understanding OA pathogenesis at the knee.

Unilateral strength training leads to muscle-specific sparing effects during opposite homologous limb immobilization.

Cross education (CE) occurs after unilateral training whereby performance of the untrained contralateral limb is enhanced. A few studies have shown that CE can preserve or "spare" strength and size of an opposite immobilized limb, but the specificity (i.e., trained homologous muscle and contraction type) of these effects is unknown. The purpose was to investigate specificity of CE "sparing" effects with immobilization. The nondominant forearm of 16 participants was immobilized with a cast, and participants were randomly assigned to a resistance training (eccentric wrist flexion, 3 times/week) or control group for 4 weeks. Pre- and posttesting involved wrist flexors and extensors eccentric, concentric and isometric maximal voluntary contractions (via dynamometer), muscle thickness (via ultrasound), and forearm muscle cross-sectional area (MCSA; via peripheral quantitative computed tomography). Only the training group showed strength preservation across all contractions in the wrist flexors of the immobilized limb (training: -2.4% vs. control: -21.6%; P = 0.04), and increased wrist flexors strength of the nonimmobilized limb (training: 30.8% vs. control: -7.4%; P = 0.04). Immobilized arm MCSA was preserved for the training group only (training: 1.3% vs. control: -2.3%; P = 0.01). Muscle thickness differed between groups for the immobilized (training: 2.8% vs. control: -3.2%; P = 0.01) and nonimmobilized wrist flexors (training: 7.1% vs. control: -3.7%; P = 0.02). Strength preservation was nonspecific to contraction type ( P = 0.69, [Formula: see text] = 0.03) yet specific to the trained flexors muscle. These findings suggest that eccentric training of the nonimmobilized limb can preserve size of the immobilized contralateral homologous muscle and strength across multiple contraction types. NEW & NOTEWORTHY Unilateral strength training preserves strength, muscle thickness, and muscle cross-sectional area in an opposite immobilized limb. The preservation of size and strength was confined to the trained homologous muscle group. However, strength was preserved across multiple contraction types.

Differences in Function and Fracture Risk in Postmenopausal Women With and Without a Recent Distal Radius Fracture.

A distal radius fracture (DRF) is commonly the first fracture to occur in early postmenopausal women. The reasons for sustaining a DRF may be related to fall risk, bone fragility, or both. The objective of this study was to compare functional and fracture risk status in postmenopausal women with and without a recent DRF and explore the relationships between function, grip strength, and fracture risk status. Seventy-seven women a ges 50-78 with (n = 32) and without (n = 45) a history of DRF in the past 2 years participated. Balance, timed up and go (TUG), gait velocity, balance confidence, sit to stand, grip strength, and fracture risk were assessed. There was a significant group difference after controlling for physical activity level (Pillai's Trace, p < .05) where women with DRF had poorer outcomes on sit to stand, gait velocity, TUG, and fracture risk status. Grip strength was associated with functional tests, particularly in women with DRF. Women with a recent DRF demonstrated lower functional status and higher fracture risk compared to women without. Grip strength was associated with measures of function and fracture risk, and may complement screening tools for this population.

Proximal tibial trabecular bone mineral density is related to pain in patients with osteoarthritis.

BACKGROUND: Our objective was to examine the relationships between proximal tibial trabecular (epiphyseal and metaphyseal) bone mineral density (BMD) and osteoarthritis (OA)-related pain in patients with severe knee OA. METHODS: The knee was scanned preoperatively using quantitative computed tomography (QCT) in 42 patients undergoing knee arthroplasty. OA severity was classified using radiographic Kellgren-Lawrence scoring and pain was measured using the pain subsection of the Western Ontario and McMaster Universities Arthritis Index (WOMAC). We used three-dimensional image processing techniques to assess tibial epiphyseal trabecular BMD between the epiphyseal line and 7.5 mm from the subchondral surface and tibial metaphyseal trabecular BMD 10 mm distal from the epiphyseal line. Regional analysis included the total epiphyseal and metaphyseal region, and the medial and lateral epiphyseal compartments. The association between total WOMAC pain scores and BMD measurements was assessed using hierarchical multiple regression with age, sex, and body mass index (BMI) as covariates. Statistical significance was set at p < 0.05. RESULTS: Total WOMAC pain was associated with total epiphyseal BMD adjusted for age, sex, and BMI (p = 0.013) and total metaphyseal BMD (p = 0.017). Regionally, total WOMAC pain was associated with medial epiphyseal BMD adjusted for age, sex, and BMI (p = 0.006). CONCLUSION: These findings suggest that low proximal tibial trabecular BMD may have a role in OA-related pain pathogenesis.

Accounting for spatial variation of trabecular anisotropy with subject-specific finite element modeling moderately improves predictions of local subchondral bone stiffness at the proximal tibia.

INTRODUCTION: Previously, a finite element (FE) model of the proximal tibia was developed and validated against experimentally measured local subchondral stiffness. This model indicated modest predictions of stiffness (R2=0.77, normalized root mean squared error (RMSE%)=16.6%). Trabecular bone though was modeled with isotropic material properties despite its orthotropic anisotropy. The objective of this study was to identify the anisotropic FE modeling approach which best predicted (with largest explained variance and least amount of error) local subchondral bone stiffness at the proximal tibia. METHODS: Local stiffness was measured at the subchondral surface of 13 medial/lateral tibial compartments using in situ macro indentation testing. An FE model of each specimen was generated assuming uniform anisotropy with 14 different combinations of cortical- and tibial-specific density-modulus relationships taken from the literature. Two FE models of each specimen were also generated which accounted for the spatial variation of trabecular bone anisotropy directly from clinical CT images using grey-level structure tensor and Cowin's fabric-elasticity equations. Stiffness was calculated using FE and compared to measured stiffness in terms of R2 and RMSE%. RESULTS: The uniform anisotropic FE model explained 53-74% of the measured stiffness variance, with RMSE% ranging from 12.4 to 245.3%. The models which accounted for spatial variation of trabecular bone anisotropy predicted 76-79% of the variance in stiffness with RMSE% being 11.2-11.5%. CONCLUSIONS: Of the 16 evaluated finite element models in this study, the combination of Synder and Schneider (for cortical bone) and Cowin's fabric-elasticity equations (for trabecular bone) best predicted local subchondral bone stiffness.

Effects of Ibuprofen and Resistance Training on Bone and Muscle: A Randomized Controlled Trial in Older Women.

INTRODUCTION/PURPOSE: Resistance training with ibuprofen supplementation may improve musculoskeletal health in postmenopausal women. The study purpose was to determine the efficacy of resistance training and ibuprofen supplementation on bone and muscle properties in postmenopausal women. METHODS: Participants (n = 90, 65.3 ± 4.9 yr) were randomly assigned to: supervised resistance training or stretching (placebo-exercise) with postexercise ibuprofen (400 mg) or placebo supplementation for 3 d·wk (9 months). Baseline and postintervention measurements included distal and shaft scans of the forearm and lower leg using peripheral quantitative computed tomography. Distal site outcomes included cross-sectional area, content, and density for total and trabecular bone, as well as estimated bone strength in compression. Shaft site outcomes included total bone area; cortical bone area, content, and density; estimated bone strength in torsion; and muscle area and density. RESULTS: Exercise-supplement-time interactions for total bone content at the distal radius (P = 0.009) and cortical density at the radius shaft (P = 0.038) were significant. Resistance training with ibuprofen decreased total bone content (-1.5%) at the distal radius in comparison to the resistance training (0.6%; P = 0.032) and ibuprofen alone (0.5%; P = 0.050). Change in cortical density at the radius shaft differed between the stretching with placebo and ibuprofen supplementation groups (-1.8% vs 1.1%; P = 0.050). Resistance training preserved muscle density in the lower leg more so than stretching (-3.1% vs -5.4%; P = 0.015). CONCLUSIONS: Ibuprofen consumed immediately after resistance training had a deleterious effect on bone mineral content at the distal radius, whereas resistance training or ibuprofen supplementation individually prevented bone loss. Resistance training prevented muscle density decline in the lower leg.

Optimizing finite element predictions of local subchondral bone structural stiffness using neural network-derived density-modulus relationships for proximal tibial subchondral cortical and trabecular bone.

BACKGROUND: Quantitative computed tomography based subject-specific finite element modeling has potential to clarify the role of subchondral bone alterations in knee osteoarthritis initiation, progression, and pain. However, it is unclear what density-modulus equation(s) should be applied with subchondral cortical and subchondral trabecular bone when constructing finite element models of the tibia. Using a novel approach applying neural networks, optimization, and back-calculation against in situ experimental testing results, the objective of this study was to identify subchondral-specific equations that optimized finite element predictions of local structural stiffness at the proximal tibial subchondral surface. METHODS: Thirteen proximal tibial compartments were imaged via quantitative computed tomography. Imaged bone mineral density was converted to elastic moduli using multiple density-modulus equations (93 total variations) then mapped to corresponding finite element models. For each variation, root mean squared error was calculated between finite element prediction and in situ measured stiffness at 47 indentation sites. Resulting errors were used to train an artificial neural network, which provided an unlimited number of model variations, with corresponding error, for predicting stiffness at the subchondral bone surface. Nelder-Mead optimization was used to identify optimum density-modulus equations for predicting stiffness. FINDINGS: Finite element modeling predicted 81% of experimental stiffness variance (with 10.5% error) using optimized equations for subchondral cortical and trabecular bone differentiated with a 0.5g/cm3 density. INTERPRETATION: In comparison with published density-modulus relationships, optimized equations offered improved predictions of local subchondral structural stiffness. Further research is needed with anisotropy inclusion, a smaller voxel size and de-blurring algorithms to improve predictions.

Effects of low-dose ibuprofen supplementation and resistance training on bone and muscle in postmenopausal women: A randomized controlled trial.

PURPOSE: To compare the effects of nine months of exercise training and ibuprofen supplementation (given immeditately after exercise sessions) on bone and muscle in postmenopausal women. METHODS: In a double-blind randomized trial, participants (females: n = 90, mean age 64.8, SD 4.3 years) were assigned (computer generated, double blind) to receive supervised resistance training or stretching 3 days/week, and ibuprofen (400 mg, post-exercise) or placebo (i.e. 4 groups) for 9 months. In this proof-of-concept study the sample size was halved from required 200 identified via 90% power calculation. Baseline and post-intervention testing included: Dual energy x-ray absorptiometry (DXA) for lumbar spine, femoral neck, and total body areal bone mineral density (aBMD); geometry of proximal femur; total body lean tissue and fat mass; predicted 1-repetition maximum muscle strength testing (1RM; biceps curl, hack squat). RESULTS: Exercise training or ibuprofen supplementation had no effects on aBMD of the lumbar spine, femoral neck, and total body. There was a significant exercise × supplement × time interaction for aBMD of Ward's region of the femoral neck (p = 0.015) with post hoc comparison showing a 6% decrease for stretching with placebo vs. a 3% increase for stretching with ibuprofen (p = 0.017). Resistance training increased biceps curl and hack squat strength vs. stretching (22% vs. 4% and 114% vs. 12%, respectively) (p < 0.01) and decreased percent body fat compared to stretching (2% vs. 0%) (p < 0.05). CONCLUSIONS: Ibuprofen supplementation provided some benefits to bone when taken independent of exercise training in postmenopausal women. This study provides evidence towards a novel, easily accessible stimulus for enhancing bone health [i.e. ibuprofen].

Prediction of local proximal tibial subchondral bone structural stiffness using subject-specific finite element modeling: Effect of selected density-modulus relationship.

BACKGROUND: Quantitative computed tomography based subject-specific finite element modeling has potential to clarify the role of subchondral bone alterations in knee osteoarthritis initiation, progression, and pain initiation. Calculation of bone elastic moduli from image data is a basic step when constructing finite element models. However, different relationships between elastic moduli and imaged density (known as density-modulus relationships) have been reported in the literature. The objective of this study was to apply seven different trabecular-specific and two cortical-specific density-modulus relationships from the literature to finite element models of proximal tibia subchondral bone, and identify the relationship(s) that best predicted experimentally measured local subchondral structural stiffness with highest explained variance and least error. METHODS: Thirteen proximal tibial compartments were imaged via quantitative computed tomography. Imaged bone mineral density was converted to elastic moduli using published density-modulus relationships and mapped to corresponding finite element models. Proximal tibial structural stiffness values were compared to experimentally measured stiffness values from in-situ macro-indentation testing directly on the subchondral bone surface (47 indentation points). FINDINGS: Regression lines between experimentally measured and finite element calculated stiffness had R(2) values ranging from 0.56 to 0.77. Normalized root mean squared error varied from 16.6% to 337.6%. INTERPRETATION: Of the 21 evaluated density-modulus relationships in this study, Goulet combined with Snyder and Schneider or Rho appeared most appropriate for finite element modeling of local subchondral bone structural stiffness. Though, further studies are needed to optimize density-modulus relationships and improve finite element estimates of local subchondral bone structural stiffness.