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Most balance assessment studies using inertial measurement units (IMUs) in smartphones use a body strap and assume the alignment of the smartphone with the anatomical axes. To replace the need for a body strap, we have used an anatomical alignment method that employs a calibration maneuver and Principal Component Analysis (PCA) so that the smartphone can be held by the user in a comfortable position. The objectives of this study were to determine if correlations existed between angular velocity scores derived from a handheld smartphone with PCA functional alignment vs. a smartphone placed in a strap with assumed alignment, and to analyze acceleration score differences across balance poses of increasing difficulty. The handheld and body strap smartphones exhibited moderately to strongly correlated angular velocity scores in the calibration maneuver (r = 0.487-0.983, p < 0.001). Additionally, the handheld smartphone with PCA functional calibration successfully detected significant variance between pose type scores for anteroposterior, mediolateral, and superoinferior acceleration data ( p < 0.001).

Balance assessment, or posturography, tracks and prevents health complications for a variety of groups with balance impairment, including the elderly population and patients with traumatic brain injury. Wearables can revolutionize state-of-the-art posturography methods, which have recently shifted focus to clinical validation of strictly positioned inertial measurement units (IMUs) as replacements for force-plate systems. Yet, modern anatomical calibration (i.e., sensor-to-segment alignment) methods have not been utilized in inertial-based posturography studies. Functional calibration methods can replace the need for strict placement of inertial measurement units, which may be tedious or confusing for certain users. In this study, balance-related metrics from a smartwatch IMU were tested against a strictly placed IMU after using a functional calibration method. The smartwatch and strictly placed IMUs were strongly correlated in clinically relevant posturography scores (r = 0.861-0.970, p < 0.001). Additionally, the smartwatch was able to detect significant variance ( p < 0.001) between pose-type scores from the mediolateral (ML) acceleration data and anterior-posterior (AP) rotation data. With this calibration method, a large problem with inertial-based posturography has been addressed, and wearable, "at-home" balance-assessment technology is within possibility.

This study's objectives were to: (1) assess whether dual energy X-ray absorptiometry (DXA)-mass inverse dynamics (ID) alters predictions of youth pitching arm kinetics and (2) investigate correlations between kinetics and body composition. Eighteen 10- to 11-year-olds pitched 10 fastballs. DXA scans were conducted to obtain participant-specific upper arm, forearm, and hand masses. Pitching arm segment masses and kinetics calculated with scaled and DXA masses were compared with paired t-tests and correlations were investigated with linear regression. Hand (p < 0.001) and upper arm (p < 0.001) DXA masses were greater, while forearm (p < 0.001) DXA masses were lesser, than their scaled masses. Shoulder compressive force (p < 0.001), internal rotation torque (p < 0.001), and horizontal adduction torque (p = 0.002) increased when using DXA masses. Shoulder compressive force correlated with body mass (p < 0.001) and body mass index (BMI; p = 0.002) and elbow varus torque correlated with body mass (p < 0.05). The main conclusions were that (1) using participant-specific mass ratios leads to different predictions of injury-related pitching arm kinetics and, thus, may improve our understanding of injury risk factors; and (2) pitching arm kinetics were correlated with body composition measures and a relatively high total body mass and/or BMI may increase shoulder and/or elbow injury risk.

Many baseball pitching studies have used inverse dynamics to assess throwing arm kinetics as high and repetitive kinetics are thought to be linked to pitching injuries. However, prior studies have not used participant-specific body segment inertial parameters (BSIPs), which are thought to improve analysis of high-acceleration motions and overweight participants. This study's objectives were to (1) calculate participant-specific BSIPs using dual energy X-ray absorptiometry (DXA) measures, (2) compare inverse dynamic calculations of kinetics determined by DXA-calculated BSIPs (full DXA-driven inverse dynamics) against kinetics using the standard inverse dynamics approach with scaled BSIPs (scaled inverse dynamics), and (3) examine associations between full DXA-driven kinetics and overweight indices: body mass index (BMI) and segment mass index (SMI). Eighteen participants (10-11 years old) threw 10 fastballs that were recorded for motion analysis. DXA scans were used to calculate participant-specific BSIPs (mass, center of mass, radii of gyration) for each pitching arm segment (upper arm, forearm, hand), BMI, and SMI. The hypotheses were addressed with t-tests and linear regression analyses. The major results were that (1) DXA-calculated BSIPs differed from scaled BSIPs for each pitching arm segment; (2) calculations for shoulder, but not elbow, kinetics differed between the full DXA-driven and scaled inverse dynamics analyses; and (3) full DXA-driven inverse dynamics calculations for shoulder kinetics were more often associated with SMI than BMI. Results suggest that using participant-specific BSIPs and pitching arm, SMIs may improve evidence-based injury prevention guidelines for youth pitchers., (Copyright © 2022 by ASME.)

Principal component analysis (PCA) has been used as a post-hoc method for reducing knee crosstalk errors during gait analysis. PCA minimizes correlations between flexion-extension (FE), abduction-adduction (AA), and internal-external rotation (IE) angles. However, previous studies have not considered PCA for exercises involving knee flexion angles that are greater than those typically experienced during gait. Thus, the goal of this study was to investigate using PCA to correct for crosstalk during one exercise (i.e., cycling) that involves relatively high flexion angles. Fifteen participants were tested in gait and cycling using a motion analysis system. Uncorrected FE, AA and IE angles were compared to those calculated with PCA performed on (1) all angles (FE-AA-IE PCA correction) and (2) only FE-AA angles (FE-AA PCA correction). Significant differences existed between uncorrected and FE-AA-IE PCA corrected AA and IE angles for both exercises, between uncorrected and FE-AA PCA corrected AA angles for both exercises, and between FE-AA-IE and FE-AA PCA corrected IE angles for cycling. Correlations existed before PCA correction and were eliminated following PCA correction with the exception that FE-IE correlations remained following FE-AA PCA correction. Since the two PCA analyses differed only in their IE angle predictions for the high flexion exercise (cycling), IE angle results were compared to previous studies. Using FE-AA PCA correction may be the preferred protocol for cycling as it appeared to retain physiological IE angle correlations at high flexion angles. However, there exists a critical need for studies aimed at obtaining more accurate IE angles in such exercises., (Copyright © 2021 by ASME.)

Transtibial amputees may experience decreased quality of life due to increased risk of knee joint osteoarthritis (OA). No prior studies have compared knee joint biomechanics for the same group of transtibial amputees in gait, cycling, and elliptical training. Thus, the goal of this study was to identify preferred exercises for transtibial amputees in the context of reducing risk of knee OA. The hypotheses were: 1) knee biomechanics would differ due to participant status (amputee, control), exercise, and leg type (intact, residual) and 2) gait kinematic parameters would differ due to participant status and leg type. Ten unilateral transtibial amputee and ten control participants performed exercises while kinematic and kinetic data were collected. Two-factor repeated measures analysis of variance with post-hoc Tukey tests and non-parametric equivalents were performed to determine significance. Maximum knee compressive force, extension torque, and abduction torque were lowest in cycling and highest in gait regardless of participant type. Amputee maximum knee extension torque was higher in the intact vs. residual knee in gait. Amputee maximum knee flexion angle was higher in the residual vs. intact knee in gait and elliptical. Gait midstance knee flexion angle timing was asymmetrical for amputees and knee angle was lower in the amputee residual vs. control non-dominant knees. The results suggest that cycling, and likely other non-weight bearing exercises, may be preferred exercises for amputees due to significant reductions in biomechanical asymmetries and joint loads., Competing Interests: A. Matt Robinson declares an author commercial affiliation to Hanger Clinic. Mr. Robinson is a licensed Hanger Clinic prosthetist and contributed to study design and implementation. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Pitching while fatigued and body composition may increase the injury risk in youth and adult pitchers. However, the relationships between game pitch count, biomechanics, and body composition have not been reported for a study group restricted to 9- to 10-year-old athletes., Hypothesis: During a simulated game with 9- to 10-year-old athletes, (1) participants will experience biomechanical signs of fatigue, and (2) shoulder and elbow kinetics will correlate with body mass index (BMI)., Study Design: Descriptive laboratory study., Methods: Thirteen 9- to 10-year-old youth baseball players pitched a simulated game (75 pitches). Range of motion and muscular output tests were conducted before and after the simulated game to quantify fatigue. Kinematic parameters at foot contact, maximum external rotation, and maximum internal rotation velocity (MIRV), as well as maximum shoulder and elbow kinetics between foot contact and MIRV were compared at pitches 1-5, 34-38, and 71-75. Multivariate analyses of variance were used to test the first hypothesis, and linear regressions were used to test the second hypothesis., Results: MIRV increased from pitches 1-5 to 71-75 ( P = .007), and head flexion at MIRV decreased from pitches 1-5 to 34-38 ( P = .022). Maximum shoulder horizontal adduction, external rotation, and internal rotation torques increased from pitches 34-38 to 71-75 ( P = .031, .023, and .021, respectively). Shoulder compression force increased from pitches 1-5 to 71-75 ( P = .011). Correlations of joint torque/force with BMI were found at every pitch period: for example, shoulder internal rotation ( R 2 = 0.93, P < .001) and elbow varus ( R 2 = 0.57, P = .003) torques at pitches 1-5., Conclusion: Several results differed from those of previous studies with adult pitchers: (1) pitch speed remained steady, (2) shoulder MIRV increased, and (3) shoulder kinetics increased during a simulated game. The strong correlations between joint kinetics and BMI reinforce previous findings that select body composition measures may be correlated with pitching arm joint kinetics for youth baseball pitchers., Clinical Relevance: The results improve our understanding of pitching biomechanics for 9- to 10-year-old baseball pitchers and may be used in future studies to improve evidence-based injury prevention guidelines., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This work was supported by an undergraduate education grant from the W.M. Keck Foundation and Donald E. Bently Center for Engineering Innovation.

A continuum mixture model with distinct collagen (COL) and glycosaminoglycan elastic constituents was developed for the solid matrix of immature bovine articular cartilage. A continuous COL fiber volume fraction distribution function and a true COL fiber elastic modulus ([Formula: see text] were used. Quantitative polarized light microscopy (qPLM) methods were developed to account for the relatively high cell density of immature articular cartilage and used with a novel algorithm that constructs a 3D distribution function from 2D qPLM data. For specimens untreated and cultured in vitro, most model parameters were specified from qPLM analysis and biochemical assay results; consequently, [Formula: see text] was predicted using an optimization to measured mechanical properties in uniaxial tension and unconfined compression. Analysis of qPLM data revealed a highly anisotropic fiber distribution, with principal fiber orientation parallel to the surface layer. For untreated samples, predicted [Formula: see text] values were 175 and 422 MPa for superficial (S) and middle (M) zone layers, respectively. TGF-[Formula: see text]1 treatment was predicted to increase and decrease [Formula: see text] values for the S and M layers to 281 and 309 MPa, respectively. IGF-1 treatment was predicted to decrease [Formula: see text] values for the S and M layers to 22 and 26 MPa, respectively. A novel finding was that distinct native depth-dependent fiber modulus properties were modulated to nearly homogeneous values by TGF-[Formula: see text]1 and IGF-1 treatments, with modulated values strongly dependent on treatment.

In vitro cultures with insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1) have previously been shown to differentially modulate the growth of immature bovine articular cartilage. IGF-1 stimulates expansive growth yet decreases compressive moduli and increases compressive Poisson's ratios, whereas TGF-β1 maintains tissue size, increases compressive moduli, and decreases compressive Poisson's ratios. The current study's hypothesis was that sequential application of IGF-1 and TGF-β1 during in vitro culture produces geometric and compressive mechanical properties that lie between extreme values produced when using either growth factor alone. Immature bovine articular cartilage specimens were harvested and either untreated (D0, i.e., day zero) or cultured in vitro for either 6 days with IGF-1 (D6 IGF), 12 days with IGF-1 (D12 IGF), or 6 days with IGF-1 followed by 6 days with TGF-β1 (D12 SEQ, i.e., sequential). Following treatment, all specimens were tested for geometric, biochemical, and compressive mechanical properties. Relative to D0, D12 SEQ treatment enhanced volumetric growth, but to a lower value than that for D12 IGF. Furthermore, D12 SEQ treatment maintained compressive moduli and Poisson's ratios at values higher and lower, respectively, than those for D12 IGF. Considering the previously described effects of 12 days of treatment with TGF-β1 alone, D12 SEQ induced both growth and mechanical property changes between those produced with either IGF-1 or TGF-β1 alone. The results suggest that it may be possible to vary the durations of select growth factors, including IGF-1 and TGF-β1, to more precisely modulate the geometric, biochemical, and mechanical properties of immature cartilage graft tissue in clinical repair strategies.

Objective: The purpose of this study was to evaluate the effect of Cox-2 administration on direct (primary) fracture healing., Methods: A transverse tibial osteotomy was created in adult male rabbits and rigidly fixed in compression using a 2.7-mm dynamic compression plate. Animals were randomized to receive either rofecoxib (12.5 mg orally per day) or placebo. Animals were killed at 4 weeks and fracture healing assessed by mechanical testing., Results: There were no significant differences between the control and Cox-2 treated animals in terms of mechanical strength at 4 weeks. There was a high complication rate of peri-implant fractures during the daily medication administration., Conclusion: The immediate administration of a Cox-2 specific inhibitor did not impair primary (direct) bone healing at the dose administered in this rabbit tibial osteotomy model.

Mechanisms of articular cartilage growth and maturation have been elucidated by studying composition-function dynamics during in vivo development and in vitro culture with stimuli such as insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta 1 (TGF-beta1). This study tested the hypothesis that IGF-1 and TGF-beta1 regulate immature cartilage compressive moduli and Poisson's ratios in a manner consistent with known effects on tensile properties. Bovine calf articular cartilage from superficial-articular (S) and middle-growth (M) regions were analyzed fresh or following culture in medium with IGF-1 or TGF-beta1. Mechanical properties in confined (CC) and unconfined (UCC) compression, cartilage matrix composition, and explant size were assessed. Culture with IGF-1 resulted in softening in CC and UCC, increased Poisson's ratios, substantially increased tissue volume, and accumulation of glycosaminoglycan (GAG) and collagen (COL). Culture with TGF-beta1 promoted maturational changes in the S layer, including stiffening in CC and UCC and increased concentrations of GAG, COL, and pyridinoline crosslinks (PYR), but little growth. Culture of M layer explants with TGF-beta1 was nearly homeostatic. Across treatment groups, compressive moduli in CC and UCC were positively related to GAG, COL, and PYR concentrations, while Poisson's ratios were negatively related to concentrations of these matrix components. Thus, IGF-1 and TGF-beta1 differentially regulate the compressive mechanical properties and size of immature articular cartilage in vitro. Prescribing tissue growth, maturation, or homeostasis by controlling the in vitro biochemical environment with such growth factors may have applications in cartilage repair and tissue engineering.

Bisphosphonates (BPs) slow bone loss by reducing initiation of new basic multicellular units (BMUs). Whether or not BPs simply prevent osteoclasts from initiating new BMUs that resorb bone or also reduce the amount of bone they resorb at the BMU level is not clear. The goal of this study was to determine the effects of BPs on three morphological parameters of individual BMUs, resorption depth (Rs.De), area (Rs.Ar), and width (Rs.Wi). After 1 year of treatment with vehicle (VEH), alendronate (ALN; 0.10, 0.20, or 1.00 mg/kg/day), or risedronate (RIS; 0.05, 0.10, or 0.50 mg/kg/day), resorption cavity morphology was assessed in vertebral trabecular bone of beagle dogs by histology. Animals treated with ALN or RIS at the doses representing those used to treat postmenopausal osteoporosis (0.20 and 0.10 mg/kg/day, respectively) had significantly lower Rs.Ar (-27%) and Rs.Wi (-17%), with no difference in Rs.De, compared to VEH-treated controls. Low doses of ALN and RIS did not affect any parameters, whereas higher doses resulted in similar changes to those of the clinical dose. There were no significant differences in the resorption cavity measures between RIS and ALN at any of the dose equivalents. These results highlight the importance of examining parameters beyond erosion depth for assessment of resorption parameters. Furthermore, these results suggest that in addition to the well-known effects of BPs on reducing the number of active BMUs, these drugs also reduce the activity of osteoclasts at the individual BMU level at doses at and above those used clinically for the treatment of postmenopausal osteoporosis.

Stress fractures are overuse injuries of bone that affect elite athletes and military recruits. One response of cortical bone to stress fracture is to lay down periosteal callus. The objectives of this study were to determine if material properties are different among bones with different stages of stress fracture callus, at both a callus site and at a distal site. Cortical specimens were mechanically tested to determine their stress-strain response. Material property differences were examined using nonparametric and regression analyses. At the callus site, material properties were low during the earliest stages of callus, higher with increasing callus maturity, but dropped at the late stage of callus. At the distal site, the material properties were low during early stages of callus and approached, or returned to, those of bones without callus during the late stages of callus. The effects of stress fracture and bone callus are not limited to the focal site of stress fracture., ((c) 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

The compliance technique has been used to monitor crack length during fracture and fatigue testing of materials. Difficulties arise when this technique is applied to anisotropic biological materials such as bone. In this tutorial, two different methods of analyzing compliance calibration data are described: the standard ASTM method and a new approach developed by the authors specifically for anisotropic materials. An example is given showing how data from equine cortical bone can be analyzed. In this example, calibration tests were conducted on thirty-six three point bend specimens machined from the mid-diaphysis of six pairs of equine third metacarpal bones. Cracks were propagated in three orientations with respect to the long axis of the bone: transverse, longitudinal, and radial. Specimen compliance was determined for a crack range of 0.30 to 0.65 times the specimen width from load vs. crack opening displacement data. The results demonstrate that the ASTM method is not applicable to anisotropic biomaterials such as bone. Rather, it is necessary to develop separate compliance calibration equations for each crack propagation orientation investigated.

Bisphosphonates suppress bone remodeling activity, increase bone volume, and significantly reduce fracture risk in individuals with osteoporosis and other metabolic bone diseases. The objectives of the current study were to develop a mathematical model that simulates control and 1 year experimental results following bisphosphonate treatment (alendronate or risedronate) in the canine fourth lumbar vertebral body, validate the model by comparing simulation predictions to 3 year experimental results, and then use the model to predict potential long term effects of bisphosphonates on remodeling and microdamage accumulation. To investigate the effects of bisphosphonates on bone volume and microdamage, a mechanistic biological model was modified from previous versions to simulate remodeling in a representative volume of vertebral trabecular bone in dogs treated with various doses of alendronate or risedronate, including doses equivalent to those used for treatment of post-menopausal osteoporosis in humans. Bisphosphonates were assumed to affect remodeling by suppressing basic multicellular unit activation and reducing resorption area. Model simulation results for trabecular bone volume fraction, microdamage, and activation frequency following 1 year of bisphosphonate treatment are consistent with experimental measurements. The model predicts that trabecular bone volume initially increases rapidly with 1 year of bisphosphonate treatment, and continues to slowly rise between 1 and 3 years of treatment. The model also predicts that microdamage initially increases rapidly, 0.5-1.5-fold for alendronate or risedronate during the first year of treatment, and reaches its maximum value by 2.5 years before trending downward for all dosages. The model developed in this study suggests that increasing bone volume fraction with long term bisphosphonate treatment may sufficiently reduce strain and damage formation rate so that microdamage does not accumulate above that which is initiated in the first two years of treatment.

Volume effects are a fundamental determinant of structural failure. A material exhibits a volume effect if its failure properties are dependent on the specimen volume. Many brittle ceramics exhibit volume effects due to loading a structure in the presence of "critical" flaws. The number of flaws, their locations, and the effect of stress field within the stressed volume play a role in determining the structure's failure properties. Since real materials are imperfect, structures composed of large volumes of material have higher probabilities of containing a flaw than do small volumes. Consequently, large material volumes tend to fail at lower stresses compared to smaller volumes when tested under similar conditions. Volume effects documented in brittle ceramic and composite structures have been proposed to affect the mechanical properties of bone. We hypothesized that for cortical bone material, (1) small volumes have greater yield strengths than large volumes and (2) that compared to microstructural features, specimen volume was able to account for comparable amounts of variability in yield strength. In this investigation, waisted rectangular, equine third metacarpal diaphyseal specimens (n=24) with nominal cross sections of 3 x 4 mm and gage lengths of either 10.5, 21, or 42 mm, were tested monotonically in tension to determine the effect of specimen volume on their yield strength. Yield strength was greatest in the smallest volume group compared to the largest volume group. Within each group of specimens the logarithm of yield strength was positively correlated with the cumulative failure probability, indicating that the data follow the two-parameter Weibull distribution. Additionally, log yield strength was negatively correlated with log volume, supporting the hypothesis that small stressed volumes of cortical bone possess greater yield strength than similarly tested large stressed volumes.

Objective: To assess improvements in fixation stability when a hinged unilateral external fixator is used to supplement compromised internal fixation for distal humerus fractures., Methods: Removing a 1-cm section of the distal humerus in cadaveric whole-arm specimens created a comminuted distal humerus fracture model (AO type 13-A3). Fixation was then performed using different constructs representing optimal, compromised, or supplemented internal fixation. Internal fixation consisted of either 2 reconstruction plates with 1, 2, or 3 (optimal) distal attachment screws, or crossing medial and lateral cortical screws. A hinged external fixator was applied in combination with compromised internal fixation. The stability of the different constructs was then evaluated using 3-point bending stiffness and distal fragment displacement measurements during flexion and extension testing., Results: Addition of the external fixator increased the stiffness of all constructs. Stiffness of the compromised reconstruction plate constructs with supplemented fixation was similar to or significantly greater than that of optimal internal fixation. Addition of the fixator to the reconstruction plates with 1 screw or the crossing screws produced displacements of the distal fragment that were similar to those of the compromised constructs alone. However, medial/lateral and anterior/posterior displacements of the distal fragment during flexion and extension of the elbow for supplemented fixation were found to be greater than those for optimal internal fixation., Conclusions: The use of a hinged external fixator for supplemental fixation of distal humerus fractures may be effective in cases where internal fixation is severely compromised, although displacements may increase above optimal fixation.

Evidence suggests that osteocyte apoptosis is involved in the adaptive response of bone, although the specific role of osteocytes in the signaling mechanism is unknown. Here, we examined and correlated regional variability in indices of remodeling, modeling, osteocyte apoptosis, and osteocyte density in rabbit tibia midshafts. Histomorphometric analysis indicated that remodeling parameters (BMU activation frequency, osteon density, forming osteon density, and resorption cavity density) were lower in the cranial region compared to other quadrants. In addition, pericortical subregions displayed less remodeling relative to intracortical and endocortical ones. Modeling indices also demonstrated regional variability in that periosteal surfaces exhibited a greater extent of bone forming surface than endosteal ones across all anatomic quadrants. In contrast, endosteal surfaces demonstrated significantly greater surface mineral apposition rates compared to periosteal surfaces in caudal, medial, and lateral but not cranial quadrants. Using TUNEL analysis to detect osteocytes undergoing apoptosis, the density of apoptotic osteocytes was found to be lower in cranial quadrants relative to medial ones. In addition, the densities of osteocyte lacunae, empty lacunae, and total osteocytes were higher in lateral fields relative to caudal quadrants. There was a strong, statistically significant linear correlation between the remodeling indices and apoptotic osteocyte density, supporting the theory that osteocytes undergoing apoptosis produce signals that attract or direct bone remodeling. In contrast, the modeling parameters did not exhibit a correlation with apoptotic osteocytes, although there was a strong correlation between the modeling indices and the density of empty osteocyte lacunae, corroborating previous studies that have found that osteocytes inhibit bone formation. It was found that osteocyte density and osteocyte lacunar density did not significantly correlate with modeling or remodeling parameters, suggesting that cell viability should be examined in studies correlating bone turnover parameters with the functional role of osteocytes in bone adaptation.

Materials, including bone, often fail due to loading in the presence of critical flaws. The relative amount, location, and interaction of these flaws within a stressed volume of material play a role in determining the failure properties of the structure. As materials are generally imperfect, larger volumes of material have higher probabilities of containing a flaw of critical size than do smaller volumes. Thus, larger volumes tend to fail at fewer cycles compared with smaller volumes when fatigue loaded to similar stress levels. A material is said to exhibit a volume effect if its failure properties are dependent on the specimen volume. Volume effects are well documented in brittle ceramics and composites and have been proposed for bone. We hypothesized that (1) smaller volumes of cortical bone have longer fatigue lives than similarly loaded larger volumes and (2) that compared with microstructural features, specimen volume was able to explain comparable amounts of variability in fatigue life. In this investigation, waisted rectangular specimens (n=18) with nominal cross-sections of 3x4 mm and gage lengths of 10.5, 21, or 42 mm, were isolated from the mid-diaphysis of the dorsal region of equine third metacarpal bones. These specimens were subjected to uniaxial load controlled fatigue tests, with an initial strain range of 4000 microstrain. The group having the smallest volume exhibited a trend of greater log fatigue life than the larger volume groups. Each volume group exhibited a significant positive correlation between the logarithm of fatigue life and the cumulative failure probability, indicating that the data follow the two-parameter Weibull distribution. Additionally, log fatigue life was negatively correlated with log volume, supporting the hypothesis that smaller stressed volumes of cortical bone possess longer fatigue lives than similarly tested larger stressed volumes.

Mathematical models of small animals that predict in vivo forces acting on the lower extremities are critical for studies of musculoskeletal biomechanics and diseases. Rabbits are advantageous in this regard because they remodel their cortical bone similar to humans. Here, we enhance a recent mathematical model of the rabbit knee joint to include the loading behavior of individual muscles, ligaments, and joint contact at the knee and ankle during the stance phase of hopping. Geometric data from the hindlimbs of three adult New Zealand white rabbits, combined with previously reported intersegmental forces and moments, were used as inputs to the model. Muscle, ligament, and joint contact forces were computed using optimization techniques assuming that muscle endurance is maximized and ligament strain energy resists tibial shear force along an inclined plateau. Peak forces developed by the quadriceps and gastrocnemius muscle groups and by compressive knee contact were within the range of theoretical and in vivo predictions. Although a minimal force was carried by the anterior cruciate and medial collateral ligaments, force patterns in the posterior cruciate ligament were consistent with in vivo tibial displacement patterns during hopping in rabbits. Overall, our predictions compare favorably with theoretical estimates and in vivo measurements in rabbits, and enhance previous models by providing individual muscle, ligament, and joint contact information to predict in vivo forces acting on the lower extremities in rabbits.

The purpose of this study was to evaluate the effect of low molecular weight heparin (LMWH) on fracture healing in a standard stabilized rat femur fracture model. A closed, mid-diaphyseal transverse fracture was created in the right femur of Long-Evans rats after insertion of a 0.8-mm K-wire into the medullary canal. Animals were randomized to receive either LMWH (70 units/kg dalteparin) or an injection of normal saline daily for 2 weeks. Animals were sacrificed at 2, 3, and 6 weeks. Fracture healing was assessed by radiographs, histology, and mechanical testing. There were no significant differences between the control and LMWH groups in the percentage of animals with radiographic bridging callus at each time point. Histologic appearance of fracture healing was similar between the control and LMWH groups. There were no significant differences in the normalized mechanical properties of the control and LMWH groups at 2 and 3 weeks. At 6 weeks, the percent torque of the LMWH group was significantly greater than the control group ( p = 0.0072), however, there was no significant difference in the stiffness and energy absorption. Dalteparin, at the dosage used in this study, did not impair fracture healing in this standard stabilized rat femur fracture model., (Copyright 2006 Orthopaedic Research Society)

We hypothesized that recently formed, incompletely mineralized, and thus, relatively deformable osteons in the equine third metacarpus enhance in vitro load-controlled fatigue life in two ways. Macroscopically, there is a compliance effect, because reduced tissue elastic modulus diminishes the stress required to reach a given strain. Microscopically, there is a cement line effect, in which new osteons and their cement lines more effectively serve as barriers to crack propagation. We studied 18 4 x 10 x 100 mm beams from the medial, lateral, and dorsal cortices of metacarpal bones from 6 thoroughbred racehorses. Following load-controlled fatigue testing to fracture in 4 point bending, a transverse, 100 microm thick, basic fuchsin-stained cross-section was taken from the load-bearing region. The number and diameter of all intact (and thus recently formed/compliant) secondary osteons in a 3.8 x 3.8 mm region in the center of the section were determined. The associated area fraction and cement line length of intact osteons were calculated, and the relationships between these variables, elastic modulus (E), and the logarithm of fatigue life (logN(F)) were analyzed. As expected, logN(F) was negatively correlated with E, which was in turn negatively correlated with intact osteon area fraction and density. (LogN(F))/E increased in proportion to intact osteon density and nonlinearly with cement line density (mm/mm(2)). These results support the hypothesis that remodeling extends load-controlled fatigue life both through the creation of osteonal barriers to microdamage propagation and modulus reduction.

The purpose of this study was to evaluate the influence of age on the effectiveness of rhBMP-7 treatment in a fracture with severe periosteal damage that is known to result in non-union formation. Closed stabilized femur fractures were produced in 3-month-old and 18-month-old rats. The fracture site was exposed and 2 mm of the periosteum cauterized circumferentially to impair normal fracture healing. The cauterized fracture site was immediately treated with either 100 microg rhBMP-7 (BMP-7 group), or with 25 microL of vehicle alone (control group). Fracture healing was evaluated with radiographs taken at 3 and 6 weeks. Animals were sacrificed at 3 and 6 weeks and specimens subjected to biomechanical and histological evaluation. In both age groups, none of the control animals healed throughout the 6 weeks experimental duration. All of the rhBMP-7-treated 3-month-old animals were radiographically healed at 3 weeks. In comparison, only 56% (9/16) of the rhBMP-7-treated 18-month-old animals were radiographically healed at 3 weeks. At 6 weeks, however, all of the 18-month-old rhBMP-7-treated animals had healed. Histology revealed slower healing in the 18-month-old animals. Treatment with rhBMP-7 significantly increased all of the biomechanical properties in both age groups. In the 3-month-old animals the mechanical strength approached that of the intact femur at 3 weeks, while in the 18-month-old animals this did not occur until 6 weeks. In conclusion, rhBMP-7 can effectively stimulate fracture repair in both young (3-month-old) and old (18-month-old) rats. However, the effect of rhBMP-7 on the rate of fracture healing is greater in young rats compared to old rats.

Using a computational model of bone adaptation, we investigated the long-term ability of bisphosphonates to minimize proximal bone loss that is associated with stress shielding in the tibia after long-stemmed total knee arthroplasty (TKA). When invoking bisphosphonate effects, the remodeling activity was suppressed, and the resorption size was reduced. Compared with the untreated simulation, bisphosphonate slowed the rate of bone loss after TKA (42% reduction in bone loss at 1 year). Activating the drug 3 months before the surgery reversed bone loss associated with the reduction in such activities as walking, but it did not provide any substantial benefit in the long-term. Late bisphosphonate treatment did not reverse the bone loss that occurred 3.5 years after TKA, although it preserved 3% of bone normally lost without treatment.

Severe periosteal and soft tissue disruption at the time of fracture may result in the formation of an atrophic nonunion. We have developed a reproducible atrophic nonunion in an animal model. The purpose of this study was to evaluate whether the immediate application of recombinant human BMP-7 to the fracture site could rescue the healing process in this nonunion model. A total of 56 three month old Fisher 344 rats were utilized. A 1.25 mm diameter K-wire was inserted into the femur in a retrograde fashion, and a mid-diaphyseal closed transverse fracture was created using a standard three point bending device. To create a nonunion, the fracture site was exposed and 2 mm of the periosteum was cauterized on each side of the fracture. The fracture site was immediately treated with either the application of rhBMP-7 50 microg in 25 microl of rat tail tendon collagen buffer (BMP-7 group), or with 25 microl of rat tail tendon collagen buffer only (Control group). Fracture healing was evaluated with serial radiographs every two weeks for an eight weeks period. Specimens at four and eight weeks were subjected to biomechanical and histological evaluation. None of the Control group healed throughout the eight weeks experimental duration. At four weeks 63% of the BMP-7 group had healed, and all had healed by six weeks. This investigation showed pronounced differences between the BMP-7 group and the Control group both histologically and biomechanically. In conclusion, we have demonstrated that the immediate application of BMP-7 may rescue the fracture healing process and prevent the development of nonunion following severe periosteal disruption.

Fatigue of cortical bone produces microcracks; it has been hypothesized that these cracks are analogous to those occurring in engineered composite materials and constitute a similar mechanism for fatigue resistance. However, the numbers of these linear microcracks increase substantially with age, suggesting that they contribute to increased fracture incidence among the elderly. To test these opposing hypotheses, we fatigued 20 beams of femoral cortical bone from elderly men and women in load-controlled four point bending having initial strain ranges of 3000 or 5000 microstrain. Loading was stopped at fracture or 10(6) cycles, whichever occurred first, and microcrack density and length were measured in the loaded region and in a control region that was not loaded. We studied the dependence of fatigue life and induced microdamage on initial microdamage, cortical region, subject gender and age, and several other variables. When the effect of modulus variability was controlled, longer fatigue life was associated with higher rather than lower initial crack density, particularly in the medial cortex. The increase in crack density following fatigue loading was greater in specimens from older individuals and those initially having longer microcracks. Crack density increased as much in specimens fatigued short of the failure point as in those that fractured, and microcracks were, on average, shorter in specimens with greater numbers of resorption spaces, a measure of remodeling rate.

Bisphosphonates increase bone mass and reduce fracture risk, but their anti-resorptive action may lead to increases in fatigue microdamage. To investigate how bisphosphonate effects influence changes in bone volume and microdamage in the long term, a strain-adaptive model of bone remodeling and microdamage balance was developed for a continuum-level volume of postmenopausal trabecular bone by invoking Frost's mechanostat hypothesis. Both disuse and fatigue microdamage were assumed to stimulate the activation frequency of basic multicellular units (BMUs) such that bone remodeling served to remove excess bone mass and microdamage. Bisphosphonate effects were simulated as follows: low, intermediate, high, or complete suppression of BMU activation frequency either without a change in resorption by the BMU or with an independent decrease in resorption while the bone formation process was unaffected (i.e., formation initially exceeded resorption). Of the bisphosphonate effects, a reduction in resorption relative to formation dictated the long-term gain in bone volume while the potency of activation frequency suppression controlled the rate of gain. A plateau in the bone mass gain that typically occurs in clinical studies of bisphosphonate treatment was predicted by the model because the resultant reduction in strain forced bone formation by the BMU to decrease over time until it matched the reduction in BMU resorption. A greater suppression of activation frequency proportionally increased microdamage, but the accumulation was limited over the long term as long as remodeling was incompletely suppressed. The results of the model suggest creating bisphosphonates that provide minimal suppression of remodeling and a large decrease in BMU resorption because this would minimize damage accumulation and increase bone mass, respectively.

The ability of an interlocking screw fixation technique to minimize bone loss related to stress shielding in the tibia was investigated and compared to the abilities of cement and press-fit fixation. Full bony ingrowth has been associated with greater stress shielding than partial ingrowth; therefore, the effect of intimate bonding of the stem to bone on subsequent bone loss was also studied. A damage- and disuse-based remodeling theory was coupled with a two-dimensional finite element model of the tibia to predict changes in bone remodeling following long stemmed total knee arthroplasty (TKA) for four different fixation techniques (cement, press-fit, interlock with bony ingrowth, and interlock without bony ingrowth). Remodeling changes commenced with the model state variables--bone area fraction, mechanical stimulus, damage, and remodeling activity--at steady-state values predicted by the intact tibia simulation. After TKA and irrespective of fixation technique, the model predicted elevated remodeling due to disuse, in which more bone was removed than replenished. In regions below the tibial tray and along the cortices, the interlocking stem with full bony ingrowth and the cemented stem caused the least amount of bone loss. An interlocking stem with a smooth, matted finish did not reduce the bone loss associated with interlocking fixation.

Although most fractures heal, some fail to heal and become nonunions. Many animal models have been developed to study problems of fracture healing. The majority of nonunion models have involved segmental bone defects, but this may not adequately represent the biologic condition in which nonunions clinically develop. The objective of the present study is to develop a nonunion model that better simulates the clinical situation in which there is soft tissue damage including periosteal disruption and to compare this model to a standard closed fracture model utilizing identical fracture stabilization, providing a similar mechanical environment. A total of 96 three month old Long Evans rats were utilized. A 1.25 mm diameter K-wire was inserted into the femur in a retrograde fashion, and a mid-diaphyseal closed transverse fracture was created using a standard three-point bending device. To create a nonunion, 48 of the rats received additional surgery to the fractured femur. The fracture site was exposed and 2 mm of the periosteum was cauterized on each side of the fracture. Fracture healing was evaluated with serial radiographs every two weeks. Animals were maintained for intervals of two, four, six or eight weeks after surgery. Specimens from each time interval were subjected to biomechanical and histological evaluation. None of the cauterized fractures healed throughout the eight weeks experimental duration. The radiographical appearance of nonunion models was atrophic. This investigation showed pronounced differences between the experimental nonunions and standard closed fractures both histologically and biomechanically. In conclusion, we have developed a reproducible atrophic nonunion model in the rat femur that simulates the clinical condition in which there is periosteal disruption but no bone defect.

An important concept in bone mechanics is that osteons influence mechanical properties in several ways, including contributing to toughness and fatigue strength by debonding from the interstitial matrix so as to "bridge" developing cracks. Observations of "pulled out" osteons on fracture surfaces are thought to be indicative of such behavior. We tested the hypothesis that osteon pullout varies with mode of loading (fatigue vs. monotonic), cortical region, elastic modulus, and fatigue life. Mid-diaphseal beams from the dorsal, medial, and lateral regions of the equine third metacarpal bone were fractured in four point bending by monotonic loading to failure under deflection control, with or without 10(5) cycles of previous fatigue loading producing 5000 microstrain (15-20% of the expected failure strain) on the first cycle; or sinusoidal fatigue loading to failure, under load or deflection control, with the initial cycle producing 10,000 microstrain (30-40% of the expected failure strain). Using scanning electron microscopy, percent fracture surface area exhibiting osteon pullout (%OP.Ar) was measured. Monotonically loaded specimens and the compression side of fatigue fracture surfaces exhibited no osteon pullout. In load-controlled fatigue, pullout was present on the tension side of fracture surfaces, was regionally dependent (occurring to a greater amount dorsally), and was correlated negatively with elastic modulus and positively with fatigue life. Regional variation in %OP.Ar was also significant for the pooled (load and deflection controlled) fatigue specimens. %OP.Ar was nearly significantly greater in deflection controlled fatigue specimens than in load-controlled specimens (p=0.059). The data suggest that tensile fatigue loading of cortical bone eventually introduces damage that results in osteonal debonding and pullout, which is also associated with increased fatigue life via mechanisms that are not yet clear.

Revision total knee replacements or primary total knee replacements with large amounts of bone loss frequently require long-stemmed prostheses to stabilize the components. The hypothesis of the current study was that long-stemmed prostheses can be fixed with interlocking screws, provide a successful outcome, avoid extensive stress-shielding, and allow easy revision in the future. Ten patients with a minimum 2-year followup were studied. Outcomes were studied preoperatively and postoperatively using the Short Form-12 questionnaires, physical examinations, and radiographs. Complications were recorded. Ability to do activities of daily living, strenuous work, and sedentary work were recorded on a 10-point analog scale. Results indicated that 80% of stems well-fixed as shown on serial radiographs, functional outcome scores postoperatively improved significantly from preoperatively, pain was improved significantly, and positive bone remodeling without stress-shielding was seen in 80% of patients, but 20% had significant stress-shielding in the metaphysis. Complications included two periprosthetic fractures for which the patients did not require revision surgery, and one infection. Long-stemmed total knee components with interlocking fixation seem to be a reasonable alternative when large bone defects exist in the femur or tibia.

Bone is a dynamic tissue which, through the process of bone remodeling in the mature skeleton, renews itself during normal function and adapts to mechanical loads. It is, therefore, important to understand the effect of remodeling on the mechanical function of bone, as well as the effect of the inherent time lag in the remodeling process. In this study, we develop a constitutive model for bone remodeling which includes a number of relevant mechanical and biological processes and use this model to address differences in the remodeling behavior as a volume element of bone is placed in disuse or overload. The remodeling parameters exhibited damped oscillatory behavior as the element was placed in disuse, with the amplitude of the oscillations increasing as the severity of disuse increased. In overload situations, the remodeling parameters exhibited critically sensitive behavior for loads beyond a threshold value. These results bear some correspondence to experimental findings, suggesting that the model may be useful when examining the importance of transient responses for bone in disuse, and for investigating the role fatigue damage removal plays in preventing or causing stress fractures. In addition, the constitutive algorithm is currently being employed in finite element simulations of bone adaptation to predict important features of the internal structure of the normal femur, as well as to study bone diseases and their treatment.

Activation frequency is often used as a measure of basic multicellular unit (BMU) activity in cancellous bone. However, activation frequency expresses the rate of BMU appearance in a histologic slide and not the rate of origination, which is a more physiologic indicator of remodeling activity and is necessary for the development of BMU-level bone remodeling simulations. Using identical assumptions to those for calculating the activation frequency, it is shown that the origination frequency in cancellous bone is equal to the activation frequency divided by the total distance traveled by the BMU and its width.