Fluid-structure interaction models based on patient-specific IVUS at baseline and follow-up for prediction of coronary plaque progression by morphological and biomechanical factors: A preliminary study

Plaque morphology and biomechanics are believed to be closely associated with plaque progression. In this paper, we test the hypothesis that integrating morphological and biomechanical risk factors would result in better predictive power for plaque progression prediction. A sample size of 374 intravascular ultrasound (IVUS) slices was obtained from 9 patients with IVUS follow-up data. 3D fluid-structure interaction models were constructed to obtain both structural stress/strain and fluid biomechanical conditions. Data for eight morphological and biomechanical risk factors were extracted for each slice. Plaque area increase (PAI) and wall thickness increase (WTI) were chosen as two measures for plaque progression. Progression measure and risk factors were fed to generalized linear mixed models and linear mixed-effect models to perform prediction and correlation analysis, respectively. All combinations of eight risk factors were exhausted to identify the optimal predictor(s) with highest prediction accuracy defined as sum of sensitivity and specificity. When using a single risk factor, plaque wall stress (PWS) at baseline was the best predictor for plaque progression (PAI and WTI). The optimal predictor among all possible combinations for PAI was PWS + PWSn + Lipid percent + Min cap thickness + Plaque Area (PA) + Plaque Burden (PB) (prediction accuracy = 1.5928) while Wall Thickness (WT) + Plaque Wall Strain (PWSn) + Plaque Area (PA) was the best for WTI (1.2589). This indicated that PAI was a more predictable measure than WTI. The combination including both morphological and biomechanical parameters had improved prediction accuracy, compared to predictions using only morphological features.     

Factors that differentiate acceleration ability in field sport athletes

Speed and acceleration are essential for field sport athletes. However, the mechanical factors important for field sport acceleration have not been established in the scientific literature. The purpose of this study was to determine the biomechanical and performance factors that differentiate sprint acceleration ability in field sport athletes. Twenty men completed sprint tests for biomechanical analysis and tests of power, strength, and leg stiffness. The sprint intervals analyzed were 0-5, 5-10, and 0-10 m. The subjects were split into a faster and slower group based on 0- to 10-m velocity. A 1-way analysis of variance determined variables that significantly (p ≤ 0.05) distinguished between faster and slower acceleration. All subject data were then pooled for a correlation analysis to determine factors contributing most to acceleration. The results showed that 0- to 5-m (～16% difference) and 0- to 10-m (～11% difference) contact times for the faster group were significantly lower. Times to peak vertical and horizontal force during ground contact were lower for the faster group. This was associated with the reduced support times achieved by faster accelerators and their ability to generate force quickly. Ground contact force profiles during initial acceleration are useful discriminators of sprint performance in field sport athletes. For the strength and power measures, the faster group demonstrated a 14% greater countermovement jump and 48% greater reactive strength index. Significant correlations were found between velocity (0-5, 5-10, and 0-10 m) and most strength and power measures. The novel finding of this study is that training programs directed toward improving field sport sprint acceleration should aim to reduce contact time and improve ground force efficiency. It is important that even during the short sprints required for field sports, practitioners focus on good technique with short contact times.     

Knee biomechanics of moderate OA patients measured during gait at a self-selected and fast walking speed

Osteoarthritis (OA) is a chronic disorder resulting in degenerative changes to the knee joint. Three-dimensional gait analysis provides a unique method of measuring knee dynamics during activities of daily living such as walking. The purpose of this study was to identify biomechanical features characterizing the gait of patients with mild-to-moderate knee OA and to determine if the biomechanical differences become more pronounced as the locomotor system is stressed by walking faster. Principal component analysis was used to compare the gait patterns of a moderate knee OA group (n=41) and a control group (n=43). The subjects walked at their self-selected speed as well as at 150% of that speed. The two subject groups did not differ in knee joint angles, stride length, and stride time or walking speed. Differences in the magnitude and shape of the knee joint moment waveforms were found between the two groups. The OA group had larger adduction moment magnitudes during stance and this higher magnitude was sustained for a longer portion of the gait cycle. The OA group also had a reduced flexion moment and a reduced external rotation moment during early stance. Increasing speed was associated with an increase in the magnitude of all joint moments. The fast walks did not, however, increase or bring out any biomechanical differences between the OA and control groups that did not exist at the self-selected walks.     

Age-related reduction in sagittal plane center of mass motion during obstacle crossing

Accidental falls are a leading cause of injury and death in the growing elderly population. Traumatic falls are frequent, costly, and debilitating. Control of balance during locomotion is critical for safe ambulation, but relatively little is known about the natural effect of aging on dynamic balance control. Samples of healthy young (n = 13) and elderly (n = 13) subjects were compared in the interactive measures of center of mass (COM) and center of pressure (COP) during level walking and obstacle crossing conditions. Obstacle heights were normalized to individual body height (2.5%, 5%, 10%, and 15%). Temporal-distance (T-D) variables of gait were also compared. Statistical analyses were conducted using a two-way ANOVA for subject group and obstacle height. T-D parameters were not significantly different between groups; nor were frontal plane COM and COP parameters. Significant age differences did exist for antero-posterior (A/P) motion of the COM (decreased motion in the elderly), and its relationship with the COP (reduced separation between the two variables in the elderly). Anterior COM velocities were also significantly lower in the elderly group. The results confirm the ability of healthy elderly adults to maintain dynamic balance control in the frontal plane during locomotion. Reduced A/P distances between the COM and COP indicate a conservative reduction of the mechanical load on joints of the supporting limb. This conservative strategy may be related to a reduction in muscle strength as it occurs in the natural aging process.     

Why is obesity associated with osteoarthritis? Insights from mouse models of obesity

Obesity is one of the most significant, and potentially most preventable, risk factors for the development of osteoarthritis, and numerous studies have shown a strong association between body mass index and osteoarthritis of the hip, knee, foot and hand. However, the mechanism(s) by which obesity contributes to the onset and progression of osteoarthritis are not fully understood. The strong association between body mass index, altered limb alignment, and osteoarthritis of the knee--and the protective effects of weight loss--support the classic hypothesis that the effects of obesity on the joint are due to increased biomechanical loading and associated alterations in gait. However, obesity is now considered to be a low-grade systemic inflammatory disease, and recent studies suggest that metabolic factors associated with obesity alter systemic levels of pro-inflammatory cytokines that are also associated with osteoarthritis. Thus, the ultimate influence of obesity on osteoarthritis may involve a complex interaction of genetic, metabolic, and biomechanical factors. In this respect, mouse models of obesity can provide excellent systems in which to examine causal relationships among these factors. In recent years, there have been surprisingly few reports examining the effects of obesity on osteoarthritis using mouse models. In this paper, we review studies on mice and other animal models that provide both direct and indirect evidence on the role of obesity and altered diet in the development of osteoarthritis. We also examine the use of different body mass indices for characterizing "obesity" in mice by comparing these indices to typical adiposity levels observed in obese humans. Taken together, evidence from studies using mice suggest that a complex interaction of environmental and genetic factors associated with obesity contribute to the incidence and severity of osteoarthritis. The ability to control these factors, together with the development of methods to conduct more intricate measures of local biomechanical factors, make mouse models an excellent system to study obesity and osteoarthritis.     

Electromyographic patterns of individuals suffering from lateral tennis elbow.

This study investigated the applicability of using surface electromyography (EMG) as a tool for differentiating between persons suffering from lateral tennis elbow and the healthy age-matched adults. Temporal muscle activation patterns of the tennis elbow group were evaluated to determine if they varied between subject groups and if noted variations might be interpreted as arresting or exacerbating the injury. Sixteen subjects (Healthy Controls, n = 6; Tennis Elbow, n = 10) were tested under simulated tennis playing conditions. All subjects were males (Healthy group (CON) 38.8 +/- 13.1, Injured group (INJ) 40.8 +/- 10.8 yrs). EMG response data, temporal and spatial muscle activities, of the forearm extensors (Ext), the forearm flexors (Flex) and the triceps (Tri) were recorded for each subject during a single test session using all combinations of three different velocities on three different racket head impact locations. Data were collected at a frequency of 1000 Hz. Statistical analysis was performed using a 2 x 3 x 3 (Health status x Impact velocity x Impact location) ANOVA with repeated measures. Results indicated statistically significant differences (p < 0.05) between the CON and INJ subject groups for the response variables associated with forearm extensor muscle activation. During simulated play, the INJ group employed an earlier, longer, and greater activation of Ext than the CON group, such changes may be considered detrimental to the healing process. These results support the use of surface EMG to quantify differences in muscle activation strategies employed by individuals suffering from soft tissue muscle microtrauma injuries and healthy controls.     

Comprehensive,Population-Based Sensitivity Analysis of a Two-Mass Vocal Fold Model

Previous vocal fold modeling studies have generally focused on generating detailed data regarding a narrow subset of possible model configurations. These studies can be interpreted to be the investigation of a single subject under one or more vocal conditions. In this study, a broad population-based sensitivity analysis is employed to examine the behavior of a virtual population of subjects and to identify trends between virtual individuals as opposed to investigating a single subject or model instance. Four different sensitivity analysis techniques were used in accomplishing this task. Influential relationships between model input parameters and model outputs were identified, and an exploration of the model’s parameter space was conducted. Results indicate that the behavior of the selected two-mass model is largely dominated by complex interactions, and that few input-output pairs have a consistent effect on the model. Results from the analysis can be used to increase the efficiency of optimization routines of reduced-order models used to investigate voice abnormalities. Results also demonstrate the types of challenges and difficulties to be expected when applying sensitivity analyses to more complex vocal fold models. Such challenges are discussed and recommendations are made for future studies.     

Gait and neuromuscular pattern changes are associated with differences in knee osteoarthritis severity levels

Knee osteoarthritis (OA) is a multifactoral, progressive disease process of the musculoskeletal system. Mechanical factors have been implicated in the progression of knee OA, but the role of altered joint mechanics and neuromuscular control strategies in progressive mechanisms of the disease have not been fully explored. Previous biomechanical studies of knee OA have characterized changes in joint kinematics and kinetics with the disease, but it has been difficult to determine if these biomechanical changes are involved in the development of disease, are in response to degenerative changes in the joint, or are compensatory mechanisms in response to these degenerative changes or other related factors as joint pain. The goal of this study was to explore the association between biomechanical changes and knee OA severity in an effort to understand the changing role of biomechanical factors in the progression of knee OA. A three-group cross-sectional model was used that included asymptomatic subjects, subjects clinically diagnosed with moderate knee OA and severe knee OA subjects just prior to total joint replacement surgery. Principal component analysis and discriminant analysis were used to determine the combinations of electromyography, kinematic and kinetic waveform pattern changes at the knee, hip and ankle joints during gait that optimally separated the three levels of severity. Different biomechanical mechanisms were important in discriminating between severity levels. Changes in knee and hip kinetic patterns and rectus femoris activation were important in separating the asymptomatic and moderate OA gait patterns. In contrast, changes in knee kinematics, hip and ankle kinetics and medial gastrocnemius activity were important in discriminating between the moderate and severe OA gait patterns.     

Trunk and hip muscle activity in early walkers with and without cerebral palsy – A frequency analysis

Poor control of postural muscles is a primary impairment in cerebral palsy (CP), yet core trunk and hip muscle activity has not been thoroughly investigated. Frequency analysis of electromyographic (EMG) signals provides insight about the intensity and pattern of muscle activation, correlates with functional measures in CP, and is sensitive to change after intervention. The objective of this study was to investigate differences in trunk and hip muscle activation frequency in children with CP compared to children with similar amounts of walking experience and typical development (TD). EMG data from 31 children (15 with CP, 16 with TD) were recorded from 16 trunk and hip muscles bilaterally. A time–frequency pattern was generated using the continuous wavelet transform and instantaneous mean frequency (IMNF) was calculated at each interval of the gait cycle. Functional principal component analysis (PCA) revealed that IMNF was significantly higher in the CP group throughout the gait cycle for all muscles. Additionally, stride-to-stride variability was higher in the CP group. This evidence demonstrated altered patterns of trunk and hip muscle activation in CP, including increased rates of motor unit firing, increased number of recruited motor units, and/or decreased synchrony of motor units. These altered muscle activation patterns likely contribute to muscle fatigue and decreased biomechanical efficiency in children with CP.     

A method for biomechanical analysis of bicycle pedalling

This paper reports a new method, which enables a detailed biomechanical analysis of the lower limb during bicycling. The method consists of simultaneously measuring both the normal and tangential pedal forces, the EMGs of eight leg muscles, and the crank arm and pedal angles. Data were recorded for three male subjects of similar anthropometric characteristics. Subjects rode under different pedalling conditions to explore how both pedal forces and pedalling rates affect the biomechanics of the pedalling process. By modelling the leg-bicycle as a five bar linkage and driving the linkage with the measured force and kinematic data, the joint moment histories due to pedal forces only (i.e. no motion) and motion only (i.e. no pedal forces) were generated. Total moments were produced by superimposing the two moment histories. The separate moment histories, together with the pedal forces and EMG results, enable a detailed biomechanical analysis of bicycle pedalling. Inasmuch as the results are similar for all three subjects, the analysis for one subject is discussed fully. One unique insight gained via this new method is the functional role that individual leg muscles play in the pedalling process.     

Biomechanical strategies for successful obstacle crossing with the trailing limb in older adults with medial compartment knee osteoarthritis

To investigate the biomechanical strategy adopted by older adults with medial compartment knee osteoarthritis (OA) for successful obstacle crossing with the trailing limb, and to discuss its implications for fall-prevention, 15 older adults with bilateral medial compartment knee OA and 15 healthy controls were recruited to walk and cross obstacles of heights of 10%, 20%, and 30% of their leg lengths. Kinematic and kinetic data were obtained using a three-dimensional (3D) motion analysis system and forceplates. The OA group had higher trailing toe clearance than the controls. When the trailing toe was above the obstacle, the OA group showed greater swing hip abduction, yet smaller stance hip adduction, knee flexion, and ankle eversion. They showed greater pelvic anterior tilt and toe-out angle. They also exhibited greater peak knee abductor moments during early stance and at the instant when the swing toe was above the obstacle, while a greater peak hip abductor moment was found during late stance. Smaller knee extensor, yet greater hip extensor moments, were found in the OA group throughout the stance phase. In order to achieve higher toe clearance with knee OA, particular joint kinematic and kinetic strategies have been adopted by the OA group. Weakness in the hip abductors and extensors in individuals with OA may be risk factors for tripping owing to the greater demands on these muscle groups during obstacle crossing by these individuals.     

Daily rhythms of plasma melatonin, but not plasma leptin or leptin mRNA, vary between lean, obese and type 2 diabetic men

Melatonin and leptin exhibit daily rhythms that may contribute towards changes in metabolic physiology. It remains unclear, however, whether this rhythmicity is altered in obesity or type 2 diabetes (T2DM). We tested the hypothesis that 24-hour profiles of melatonin, leptin and leptin mRNA are altered by metabolic status in laboratory conditions. Men between 45-65 years old were recruited into lean, obese-non-diabetic or obese-T2DM groups. Volunteers followed strict sleep-wake and dietary regimes for 1 week before the laboratory study. They were then maintained in controlled light-dark conditions, semi-recumbent posture and fed hourly iso-energetic drinks during wake periods. Hourly blood samples were collected for hormone analysis. Subcutaneous adipose biopsies were collected 6-hourly for gene expression analysis. Although there was no effect of subject group on the timing of dim light melatonin onset (DLMO), nocturnal plasma melatonin concentration was significantly higher in obese-non-diabetic subjects compared to weight-matched T2DM subjects (p<0.01) and lean controls (p<0.05). Two T2DM subjects failed to produce any detectable melatonin, although did exhibit plasma cortisol rhythms comparable to others in the group. Consistent with the literature, there was a significant (p<0.001) effect of subject group on absolute plasma leptin concentration and, when expressed relative to an individual's 24-hour mean, plasma leptin showed significant (p<0.001) diurnal variation. However, there was no difference in amplitude or timing of leptin rhythms between experimental groups. There was also no significant effect of time on leptin mRNA expression. Despite an overall effect (p<0.05) of experimental group, post-hoc analysis revealed no significant pair-wise effects of group on leptin mRNA expression. Altered plasma melatonin rhythms in weight-matched T2DM and non-diabetic individuals supports a possible role of melatonin in T2DM aetiology. However, neither obesity nor T2DM changed 24-hour rhythms of plasma leptin relative to cycle mean, or expression of subcutaneous adipose leptin gene expression, compared with lean subjects.     

Relationship between distance running mechanics, running economy, and performance

The relationships between biocmechanical aspects of distance running, running economy (VO2 submax), and performance were investigated. A variety of biomechanical measures for 31 subjects running at 3.6 m/s was obtained, including three-dimensional angular and translational kinematics, ground reaction forces and center of pressure patterns, mechanical power, and anthropometric measures. Physiological measures obtained included maximal and submaximal O2 consumption, muscle fiber composition, and measures of the ability to store and return elastic energy during knee bends. A subset of 16 runners was also evaluated in relation to performance in a 10-km run. Biomechanical variables were identified which showed significant differences or consistent trends between groups separated on the basis of VO2 submax, establishing the importance of biomechanical influences on running economy. It appears that no single variable or small subset of variables can explain differences in economy between individuals but rather that economy is related to a weighted sum of the influences of many variables.     

The symmetry of the medial collateral and anterior cruciate ligament properties: a biochemical study in the rat hind limb

The medial collateral (MCL) and the anterior cruciate ligament (ACL) of the rat's knee are frequently used in biomedical research and occasionally in ligament healing studies. The contralateral normal ligament serves as a control. In this study the presence of symmetry in the biomechanical properties of the MCL and the ACL was investigated. Bilateral femur-MCL-tibia and femur-ACL-tibia preparations were obtained from the hind limbs of sixty rats and were subjected to tensile testing to failure under the same loading conditions. Tensile load to failure, stiffness and energy absorption capacity were measured and the mode of failure was recorded. All biomechanical parameters were not significantly different between the two knees of the same animal, although significant individual variation was evident. The most common mechanism of failure was mid-substance tear. Symmetry seems to exist in the biomechanical properties of the MCL and the ACL in the rat knee. When ligament healing is evaluated, increased group size is necessary and the use of a normal control group may be advisable. The contralateral normal knee ligament may serve as a control when the properties of an injured ligament are evaluated and when the parameters of tensile testing failure under similar load conditions are applied.     

Influence of Noise Correction on Intra- and Inter-Subject Variability of Quantitative Metrics in Diffusion Kurtosis Imaging

Diffusion kurtosis imaging (DKI) is a promising extension of diffusion tensor imaging, giving new insights into the white matter microstructure and providing new biomarkers. Given the rapidly increasing number of studies, DKI has a potential to establish itself as a valuable tool in brain diagnostics. However, to become a routine procedure, DKI still needs to be improved in terms of robustness, reliability, and reproducibility. As it requires acquisitions at higher diffusion weightings, results are more affected by noise than in diffusion tensor imaging. The lack of standard procedures for post-processing, especially for noise correction, might become a significant obstacle for the use of DKI in clinical routine limiting its application. We considered two noise correction schemes accounting for the noise properties of multichannel phased-array coils, in order to improve the data quality at signal-to-noise ratio (SNR) typical for DKI. The SNR dependence of estimated DKI metrics such as mean kurtosis (MK), mean diffusivity (MD) and fractional anisotropy (FA) is investigated for these noise correction approaches in Monte Carlo simulations and in in vivo human studies. The intra-subject reproducibility is investigated in a single subject study by varying the SNR level and SNR spatial distribution. Then the impact of the noise correction on inter-subject variability is evaluated in a homogeneous sample of 25 healthy volunteers. Results show a strong impact of noise correction on the MK estimate, while the estimation of FA and MD was affected to a lesser extent. Both intra- and inter-subject SNR-related variability of the MK estimate is considerably reduced after correction for the noise bias, providing more accurate and reproducible measures. In this work, we have proposed a straightforward method that improves accuracy of DKI metrics. This should contribute to standardization of DKI applications in clinical studies making valuable inferences in group analysis and longitudinal studies.     

Effects of inflammatory disease on plasma oxprenolol concentrations.

When single oral doses of oxprenolol were given to three healthy subjects on three separate occasions under standardised conditions the plasma concentration-time curves for each subject were closely similar. In two of the subjects, however, a mild illness led to a dramatic, temporary increase in the peak plasma concentration and area under the plasma concentration-time curve (AUC). This effect of inflammatory disease was confirmed by comparing a group of patients with an erythrocyte sedimentation rate (ESR) of over 20 mm in the first hour with a group whose ESR was below this value. The mean peak plasma concentration and AUC were significantly higher in the group with a raised ESR. This may be related to altered concentrations of one of the acute-phase proteins. Thus it is concluded that plasma oxprenolol concentrations are raised in inflammatory disease, but further work is needed to determine the mechanism of this increase.     

Biomechanical and age-related differences in balance recovery using the tether-release method.

This paper reviews experimental studies that have used the tether-release method to examine the biomechanical and age-related differences in the stepping response used after a simulated fall. The tether-release method has been used to create a repeatable perturbation that simulates the initial unbalanced configuration of the body during a trip or slip. In this technique, the test subject is held in an initial forward or backward inclined position by means of a horizontal tether or cable. To initiate a fall, the subject is released from this position after a short time delay. This review focuses on studies that have explored various biomechanical parameters in an effort to understand what attributes allow for successful balance recovery by stepping or stumbling. Strong associations between recovery ability and biomechanical parameters such as step length, step timing, and joint torques point to the importance of neuromuscular capacities that relate to lower extremity flexibility, reaction time, and strength. Therefore, the maintenance or enhancement of these necessary attributes should be considered when developing exercise-based fall intervention programs for older adults.     

Verification of a virtual fields method to extract the mechanical properties of human optic nerve head tissues in vivo

We aimed to verify a custom virtual fields method (VFM) to estimate the patient-specific biomechanical properties of human optic nerve head (ONH) tissues, given their full-field deformations induced by intraocular pressure (IOP). To verify the accuracy of VFM, we first generated ‘artificial’ ONH displacements from predetermined (known) ONH tissue biomechanical properties using finite element analysis. Using such deformations, if we are able to match back the known biomechanical properties, it would indicate that our VFM technique is accurate. The peripapillary sclera was assumed anisotropic hyperelastic, while all other ONH tissues were considered isotropic. The simulated ONH displacements were fed into the VFM algorithm to extract back the biomechanical properties. The robustness of VFM was also tested against rigid body motions and noise added to the simulated displacements. Then, the computational speed of VFM was compared to that of a gold-standard stiffness measurement method (inverse finite element method or IFEM). Finally, as proof of principle, VFM was applied to IOP-induced ONH deformation data (obtained from one subject’s eye imaged with OCT), and the biomechanical properties of the prelamina and lamina cribrosa (LC) were extracted. From given ONH displacements, VFM successfully matched back the biomechanical properties of ONH tissues with high accuracy and efficiency. For all parameters, the percentage errors were less than 0.05%. Our method was insensitive to rigid body motions and was also able to recover the material parameters in the presence of noise. VFM was also found 125 times faster than the gold-standard IFEM. Finally, the estimated shear modulus for the prelamina and the LC of the studied subject’s eye were 33.7 and 63.5 kPa, respectively. VFM may be capable of measuring the biomechanical properties of ONH tissues with high speed and accuracy. It has potential in identifying patient-specific ONH biomechanical properties in the clinic if combined with optical coherence tomography.     

The effect of flexible magnets on hand muscle strength: a randomized, double-blind study

The purpose of this study was to determine the effect of a flexible magnet on hand grip and thumb-forefinger pinch strength. Flexible magnet use has become popular in sports medicine and rehabilitation for a number of reasons, including augmenting muscle force output. Thirty-five university students (18 men and 17 women) volunteered for this study. Each subject was tested for grip strength (grip dynamometer) and thumb-forefinger pinch strength (pinch gauge) under 3 different treatment conditions: baseline (no magnet), sham magnet (placebo), and flexible magnet (700-G intensity). The order of treatments was randomly assigned, and all data collection followed a double-blind format. For grip strength measurements, magnet placement was over the bellies of the flexor digitorum profundus and flexor digitorum superficialis, and for pinch strength measurements, it was over the bellies of the flexor pollicis brevis and opponens pollicis. Three trials for each strength measurement for each of the 3 conditions were performed. Magnets (700 G or sham) were placed on the appropriate areas of the skin 3 minutes before the first test trial, with each subsequent test trial separated by 1 minute. Comparison among the 3 treatment conditions was analyzed using a 1-way analysis of variance (ANOVA) with repeated measures. ANOVA revealed no statistically significant (p > 0.05) mean differences for strength among any of the 3 treatments (baseline, 700-G magnet, or sham magnet) for either hand grip or thumb-forefinger pinch within each sex subgroup or for the combined group. The findings indicate that flexible magnets with a field strength of 700 G do not increase muscle strength.     

Targeted Delivery of Lovastatin and Tocotrienol to Fracture Site Promotes Fracture Healing in Osteoporosis Model: Micro-Computed Tomography and Biomechanical Evaluation

Osteoporosis is becoming a major health problem that is associated with increased fracture risk. Previous studies have shown that osteoporosis could delay fracture healing. Although there are potential agents available to promote fracture healing of osteoporotic bone such as statins and tocotrienol, studies on direct delivery of these agents to the fracture site are limited. This study was designed to investigate the effects of two potential agents, lovastatin and tocotrienol using targeted drug delivery system on fracture healing of postmenopausal osteoporosis rats. The fracture healing was evaluated using micro CT and biomechanical parameters. Forty-eight Sprague-Dawley female rats were divided into 6 groups. The first group was sham-operated (SO), while the others were ovariectomized (OVx). After two months, the right tibiae of all rats were fractured at metaphysis region using pulsed ultrasound and were fixed with plates and screws. The SO and OVxC groups were given two single injections of lovastatin and tocotrienol carriers. The estrogen group (OVx+EST) was given daily oral gavages of Premarin (64.5 µg/kg). The Lovastatin treatment group (OVx+Lov) was given a single injection of 750 µg/kg lovastatin particles. The tocotrienol group (OVx+TT) was given a single injection of 60 mg/kg tocotrienol particles. The combination treatment group (OVx+Lov+TT) was given two single injections of 750 µg/kg lovastatin particles and 60 mg/kg tocotrienol particles. After 4 weeks of treatment, the fractured tibiae were dissected out for micro-CT and biomechanical assessments. The combined treatment group (OVx+Lov+TT) showed significantly higher callus volume and callus strength than the OVxC group (p<0.05). Both the OVx+Lov and OVx+TT groups showed significantly higher callus strength than the OVxC group (p<0.05), but not for callus volume. In conclusion, combined lovastatin and tocotrienol may promote better fracture healing of osteoporotic bone.