Investigation of index finger triggering force using a cadaver experiment: Effects of trigger grip span, contact location, and internal tendon force.

A cadaver study was conducted to investigate the effects of triggering conditions (trigger grip span, contact location, and internal tendon force) on index finger triggering force and the force efficiency of involved tendons. Eight right human cadaveric hands were employed, and a motion simulator was built to secure and control the specimens. Index finger triggering forces were investigated as a function of different internal tendon forces (flexor digitorum profundus + flexor digitorum superficialis = 40, 70, and 100 N), trigger grip spans (40, 50, and 60 mm), and contact locations between the index finger and a trigger. Triggering forces significantly increased when internal tendon forces increased from 40 to 100 N. Also, trigger grip spans and contact locations had significant effects on triggering forces; maximum triggering forces were found at a 50 mm span and the most proximal contact location. The results revealed that only 10-30% of internal tendon forces were converted to their external triggering forces.

Femoral fixation strength following soft-tissue posterolateral corner reconstruction using fibular-based technique: Biomechanical analysis of four techniques in normal and low-density synthetic bone.

BACKGROUND: Optimal femoral fixation of soft-tissue grafts has been described for anterior cruciate ligament reconstruction. Posterolateral corner reconstruction differs from ACL reconstruction in two ways: (a) soft-tissue fixation into the femur requires two tails and (b) the line of force is different. Our purpose was to determine the optimal femoral fixation of soft-tissue grafts during posterolateral corner reconstructions. We hypothesized that interference screw fixation is the strongest technique in normal-density lateral femoral condyle, whereas, cortically-based fixation techniques are stronger methods in low-density lateral femoral condyle. METHODS: We evaluated elongation during cyclic loading, yield load, peak load-to-failure, and stiffness of four soft-tissue graft femoral fixation methods during posterolateral corner reconstruction. Our model included bovine flexor tendons and contoured synthetic bones. Grafts were secured to the lateral epicondyle in normal- or low-density bone models using spiked washer, button, interference screw, or button and interference screw. Five specimens for each were tested in each bone density. Analysis of variance using Tukey-Kramer adjustment for multiple hypothesis testing was used. Six cadaver bones whose density was analyzed using computerized tomography scan quantitation were tested using interference screw fixation. RESULTS: No method produced significantly stronger yield load or peak load-to-failure in normal-density bone. In low-density bone, cortically-based methods produced significantly higher yield load or peak load-to-failure. Yield load or peak load-to-failure was significantly higher in normal-density bone when using spiked washer or interference screw fixation. CONCLUSION: No femoral fixation method tested produced superior yield load or peak load-to-failure. Spiked washer and interference screw fixation are inferior fixation methods in low-density bone. CLINICAL RELEVANCE: For fibular-based posterolateral corner reconstructions, all fixation methods tested are acceptable in high-density bone, while cortical fixation methods should be considered in low-density bone.

Midtarsal joint locking: new perspectives on an old paradigm.

We investigated the existence of a midtarsal joint locking mechanism using cadaveric simulations of normal gait. Previous descriptions of this phenomenon led us to hypothesize that non-coupled rotations of the calcaneocuboid and talonavicular (i.e., midtarsal) joints and cubonavicular and talocalcaneal joints occur at heel strike and during weight acceptance, after which joint rotations cease with all bone-to-bone orientations remaining constant during the latter portions of stance phase. Three-dimensional kinematics of the talus, calcaneus, cuboid, and navicular were recorded along with muscle and ground reaction forces. Finite helical axis parameters and joint angles of directly articulating bones were subsequently derived and examined. During weight acceptance, the midtarsal joints everted with obvious changes in the relative orientation of their helical axes. The relative non-parallel orientation of these axes then remained constant until late in stance when these joints inverted and dorsiflexed toward their original pre-stance orientation. The cubonavicular and talocalcaneal joints demonstrated complimentary behavior. Contrary to our hypothesis, the midtarsal joints remained compliant during foot flat and even more so during push-off, despite divergent joint axes. Joint rotations were present after weight acceptance, thereby challenging the concept that midtarsal joint locking produces a rigid lever during push-off. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:110-115, 2014.

Segmental motion of forefoot and hindfoot as a diagnostic tool.

Segmental motions derived from non-invasive motion analysis are being used to investigate the intrinsic functional behavior of the foot and ankle in health and disease. The goal of this research was to examine the ability of a generic segmented model of the foot to capture and differentiate changes in internal skeletal kinematics due to neuromuscular disease and/or trauma. A robotic apparatus that reproduces the kinematics and kinetics of gait in cadaver lower extremities was employed to produce motion under normal and aberrant neuromuscular activation patterns of tibialis posterior and/or tibialis anterior. Stance phase simulations were conducted on 10 donor limbs while recording three-dimensional kinematic trajectories of (1) skin-mounted markers used clinically to construct segmented foot models, and (2) bone-mounted marker clusters to capture actual internal bone motion as the gold standard for comparison. The models constructed from external marker data were able to differentiate the kinematic behaviors elicited by different neuromuscular conditions in a manner similar to that using the bone-derived data. Measurable differences between internal and externally measured kinematics were small, variable and random across the three axes of rotation and neuromuscular conditions, with a tendency toward more differences noted during early and late stance. Albeit slightly different, three-dimensional motion profiles of the hindfoot and forefoot segments correlated well with internal skeletal motion under all neuromuscular conditions, thereby confirming the utility of measuring segmental motions as a valid means of clinical assessment.

Experimental evidence supporting isometric functioning of the extrinsic toe flexors during gait.

BACKGROUND: The extrinsic toe flexors, flexor hallucis longus and flexor digitorum longus, play an important role in stabilizing the longitudinal arch and supporting high forefoot loads during the stance phase of gait. It was hypothesized that these muscles function isometrically during stance, a strategy thought to provide efficient energy transfer across adjoining body segments, but one for which there is little direct experimental evidence in vivo or in situ. METHODS: Eight lower extremity cadavers were loaded into a robotic apparatus that simulates the kinematics and extrinsic muscle activity of the foot and distal tibia during the stance phase of gait. Instantaneous tendon excursions and forces of the extrinsic toe flexors, as well as plantar pressure distributions during stance, were measured under two muscle control strategies: (1) force feedback control, where tendon forces were matched to forces predicted from normal electromyographic patterns and (2) isometric displacement control, where the representative myotendinous junction was held in a constant location. RESULTS: Tendon excursions of the flexor hallucis longus (7.18 (1.75)mm) and flexor digitorum longus (6.32 (1.74)mm) under force feedback control were small relative to optimal muscle fiber length (13.6% and 14.2%, respectively). Instantaneous tendon forces and plantar pressure variables were not different (P=0.112-0.912) between the two different muscle control strategies for either muscle. INTERPRETATION: These findings suggest that the extrinsic toe flexors function isometrically during the stance phase of gait in vivo.

Partial sleep deprivation and energy balance in adults: an emerging issue for consideration by dietetics practitioners.

During the past 30 years, rates of partial sleep deprivation and obesity have increased in the United States. Evidence linking partial sleep deprivation, defined as sleeping <6 hours per night, to energy imbalance is relevant to weight gain prevention and weight loss promotion. With a majority of Americans overweight or obese, weight loss is a recommended strategy for reducing comorbid conditions. Our purpose was to review the literature regarding the role of partial sleep deprivation on energy balance and weight regulation. An inverse relationship between obesity and sleep duration has been demonstrated in cross-sectional and prospective studies. Several intervention studies have tested mechanisms by which partial sleep deprivation affects energy balance. Reduced sleep may disrupt appetitive hormone regulation, specifically increasing ghrelin and decreasing leptin and, thereby, influence energy intake. Increased wakefulness also may promote food intake episodes and energy imbalance. Energy expenditure may not be greatly affected by partial sleep deprivation, although additional and more accurate methods of measurements may be necessary to detect subtle changes in energy expenditure. Body weight loss achieved by reduced energy intake and/or increased energy expenditure combined with partial sleep deprivation may contribute to undesirable body composition change with proportionately more fat-free soft tissue mass lost compared with fat mass. Evaluating sleep patterns and recommending regular, sufficient sleep for individuals striving to manage weight may be prudent.

Mechanical characteristics of a novel posterior-step prosthesis for biconcave glenoid defects.

BACKGROUND: Posterior glenoid defects increase the risk of glenoid component loosening after total shoulder arthroplasty (TSA). The goal of this work was to evaluate the mechanical performance of a novel posterior-step glenoid prosthesis, designed to compensate for biconcave (type B2) glenoid defects. Two prototypes ("Poly-step" and "Ti-step") were constructed by attaching polyethylene or titanium step-blocks onto standard (STD) glenoid prostheses. We hypothesized that the mechanical performance of the experimental prostheses in the presence of a B2 defect would be similar to that of an STD prosthesis in the absence of a defect. METHODS: Fifteen normal shoulder specimens were consistently loaded under simulated muscle activity while peri-glenoid bone strains were measured. In 5 specimens, arthroplasty was performed with an STD glenoid prosthesis. In the remaining 10 specimens, a 20° B2 glenoid defect was created before arthroplasty was performed with the Poly-step or Ti-step prosthesis. RESULTS: Load-induced peri-glenoid strains after TSA with either the STD or Poly-step prosthesis did not show statistical differences as compared with the native joints (P > .05). A posterior defect decreased superior glenoid strain as compared with the intact specimens (P < .05). The change in strains after Poly-step prosthesis implantation in the presence of a biconcave glenoid defect was not different than the change induced by STD prosthesis implantation in the absence of a defect. In contrast, strains after Ti-step prosthesis implantation were statistically different from those induced by the STD and Poly-step prostheses (P < .05). CONCLUSIONS: The Poly-step prosthesis may be a viable option for treating posterior glenoid defects.

Enhanced osteoclastic resorption and responsiveness to mechanical load in gap junction deficient bone.

Emerging evidence suggests that connexin mediated gap junctional intercellular communication contributes to many aspects of bone biology including bone development, maintenance of bone homeostasis and responsiveness of bone cells to diverse extracellular signals. Deletion of connexin 43, the predominant gap junction protein in bone, is embryonic lethal making it challenging to examine the role of connexin 43 in bone in vivo. However, transgenic murine models in which only osteocytes and osteoblasts are deficient in connexin 43, and which are fully viable, have recently been developed. Unfortunately, the bone phenotype of different connexin 43 deficient models has been variable. To address this issue, we used an osteocalcin driven Cre-lox system to create osteoblast and osteocyte specific connexin 43 deficient mice. These mice displayed bone loss as a result of increased bone resorption and osteoclastogenesis. The mechanism underlying this increased osteoclastogenesis included increases in the osteocytic, but not osteoblastic, RANKL/OPG ratio. Previous in vitro studies suggest that connexin 43 deficient bone cells are less responsive to biomechanical signals. Interestingly, and in contrast to in vitro studies, we found that connexin 43 deficient mice displayed an enhanced anabolic response to mechanical load. Our results suggest that transient inhibition of connexin 43 expression and gap junctional intercellular communication may prove a potentially powerful means of enhancing the anabolic response of bone to mechanical loading.

A biomechanical study of posterior glenoid bone loss and humeral head translation.

BACKGROUND: Results of shoulder arthroplasty have been reported to be inferior with posterior glenoid wear and accompanying subluxation of the humeral head. The purpose of this study was to examine the effect of posterior glenoid wear on posterior subluxation of the humeral head. MATERIAL AND METHODS: A custom loading device was used to simulate physiologic loading conditions in 8 cadaver shoulders with the humerus positioned at neutral, forward flexion, and extension. Three-dimensional motion analysis recorded humeral head translation with respect to the scapula at each humerus position after removing posterior glenoid bone in 5° increments. The magnitude of humeral head translation was analyzed with 2-way ANOVA to determine the effects of arm position and glenoid condition. RESULTS: Glenoid condition and arm position in the transverse plane significantly influenced head translation (P < .0001). With the humerus at neutral, posterior translation became significant after 20° of posterior bone removal (P < .05). However, with the humerus in forward flexion, posterior translation became significant at only 5° of posterior bone removal (P < .001). No significant differences in translation were detected for posterior defects up to 25° with the arm in extension. CONCLUSION: Posterior humeral head translation increased significantly with 5° of posterior glenoid bone loss, which equates to approximately 2.5° of glenoid retroversion. Awareness that humeral head translation may be seen with small amounts of retroversion should be recognized during preoperative planning for shoulder arthroplasty and when counseling the patient with regard to expected outcomes.

Localization of osteoblast inflammatory cytokines MCP-1 and VEGF to the matrix of the trabecula of the femur, a target area for metastatic breast cancer cell colonization.

Bone likely provides a hospitable environment for cancer cells as suggested by their preferential localization to the skeleton. Previous work has shown that osteoblast-derived cytokines increased in the presence of metastatic breast cancer cells. Thus, we hypothesized that osteoblast-derived cytokines, in particular IL-6, MCP-1, and VEGF, would be localized to the bone metaphyses, an area to which breast cancer cells preferentially traffic. Human metastatic MDA-MB-231 breast cancer cells were inoculated into the left ventricle of the heart of athymic mice. Three to four weeks later, tumor localization within isolated femurs was examined using muCT and MRI. In addition, IL-6, MCP-1, and VEGF localization were assayed via immunohistochemistry. We found that MDA-MB-231 cells colonized trabecular bone, the area in which murine MCP-1 and VEGF were visualized in the bone matrix. In contrast, IL-6 was expressed by murine cells throughout the bone marrow. MDA-MB-231 cells produced VEGF, whose expression was not only associated with the breast cancer cells, but also increased with tumor growth. This is the first study to localize MCP-1, VEGF, and IL-6 in bone compartments via immunohistochemistry. These data suggest that metastatic cancer cells may co-opt bone cells into creating a niche facilitating cancer cell colonization.

Biomimetic bone mechanotransduction modeling in neonatal rat femur organ cultures: structural verification of proof of concept.

The goal of this work was to develop and validate a whole bone organ culture model to be utilized in biomimetic mechanotransduction research. Femurs harvested from 2-day-old neonatal rat pups were maintained in culture for 1 week post-harvest and assessed for growth and viability. For stimulation studies, femurs were physiologically stimulated for 350 cycles 24 h post-harvest then maintained in culture for 1 week at which time structural tests were conducted. Comparing 1 and 8 days in culture, bones grew significantly in size over the 7-day culture period. In addition, histology supported adequate diffusion and organ viability at 2 weeks in culture. For stimulation studies, 350 cycles of physiologic loading 24 h post-harvest resulted in increased bone strength over the 7-day culture period. In this work, structural proof of concept was established for the use of whole bone organ cultures as mechanotransduction models. Specifically, this work established that these cultures grow and remain viable in culture, are adequately nourished via diffusion and are capable of responding to a brief bout of mechanical stimulation with an increase in strength.

Changes in postural sway as a consequence of wearing a military backpack.

Military personnel are often required to carry all of their personal supplies and equipment for long distances during both training and combat situations, creating many biomechanical and postural challenges for these individuals. In addition to other problems such as generalized fatigue and the development of stress fractures, significant external loads may also affect a soldier's postural sway. The purpose of this study was to assess changes in postural sway as a consequence of wearing a military backpack in females. Forty-three female subjects between the ages of 18 and 25 volunteered to participate. There were two conditions: unloaded and while wearing an 18.1 kg military backpack. Each subject stood with two feet on a force platform for 30s under both conditions while center of pressure (COP) data were collected. COP path length increased 64%, medial-lateral excursion increased 131%, anterior-posterior excursion increased 54%, and COP area increased 229% with addition of the backpack (p<0.0001 for all of these measures). These data show that wearing 18.1 kg of external weight in a military backpack increases the postural sway of females, which may in turn increase the likelihood of falls and injury.

Bone, muscle, and physical activity: structural equation modeling of relationships and genetic influence with age.

Correlations among bone strength, muscle mass, and physical activity suggest that these traits may be modulated by each other and/or by common genetic and/or environmental mechanisms. This study used structural equation modeling (SEM) to explore the extent to which select genetic loci manifest their pleiotropic effects through functional adaptations commonly referred to as Wolff's law. Quantitative trait locus (QTL) analysis was used to identify regions of chromosomes that simultaneously influenced skeletal mechanics, muscle mass, and/or activity-related behaviors in young and aged B6xD2 second-generation (F(2)) mice of both sexes. SEM was used to further study relationships among select QTLs, bone mechanics, muscle mass, and measures of activity. The SEM approach provided the means to numerically decouple the musculoskeletal effects of mechanical loading from the effects of other physiological processes involved in locomotion and physical activity. It was found that muscle mass was a better predictor of bone mechanics in young females, whereas mechanical loading was a better predictor of bone mechanics in older females. An activity-induced loading factor positively predicted the mechanical behavior of hindlimb bones in older males; contrarily, load-free locomotion (i.e., the remaining effects after removing the effects of loading) negatively predicted bone performance. QTLs on chromosomes 4, 7, and 9 seem to exert some of their influence on bone through actions consistent with Wolff's Law. Further exploration of these and other mechanisms through which genes function will aid in development of individualized interventions able to exploit the numerous complex pathways contributing to skeletal health.

Reliability and validity of a novel muscle contusion device.

CONTEXT: Many models have been employed to replicate skeletal muscle injury associated with trauma; however, most are restricted to 1 level of severity. OBJECTIVE: To create and validate an injury-producing device that could generate multiple levels of injury severity. DESIGN: Validation study. PATIENTS OR OTHER PARTICIPANTS: Twenty-six male Wistar rats, 3 to 4 months old. INTERVENTION(S): A contusion device was developed and its ability to deliver consistent impacts was validated alone and in the presence of an experimental animal. A free-falling mass (267 g) was adjusted to the desired height (40, 50, 60, or 70 cm) and then dropped. MAIN OUTCOME MEASURE(S): Peak load, peak displacement, impulse, energy, and velocity peak were measured. Injury severity was determined using magnetic resonance imaging. RESULTS: Outcome measures observed from the device alone were different by height (F(18,136) = 21.807, P < .001, 1-beta = 1.0). Outcomes using the experimental animals were also dependent on height (F(14,102) = 68.679, P < .001, 1-beta = 1.0). Linear regression analyses indicated that height accounted for 17% to 89% of the variance. CONCLUSIONS: Mild to moderate and moderate to severe injuries can be replicated with this device, which will be useful in evaluating clinical treatments on acute muscle injury.

Magnetic resonance imaging of acute injury in rats and the effects of buprenorphine on limb volume.

The purposes of this study were to determine 1) whether magnetic resonance imaging (MRI)-based T2 mapping and measurements of limb volume can differentiate injured and uninjured tissue after blunt trauma to rat hindlimbs and 2) whether administration of buprenorphine influences these assessments. Male Wistar rats (age, 3 to 4 mo) underwent blunt contusion injury to the posterior aspect of the hindlimb; MRI was conducted at 6, 12, 24, 48, 72, and 96 h after injury. The imaging results showed that administration of buprenorphine had no effect on the T2 value {area under the receiver operating characteristic [ROC] curve: with drug, 0.869 [95% confidence interval (CI), 0.78 to 0.96]; without drug, 0.809 [95% CI, 0.72 to 0.90]} but did influence limb volume [area under the ROC curve; without drug, 0.954 (95% CI, 0.92 to 0.99); with drug, 0.713 (95% CI, 0.61 to 0.82)]. When using MRI to determine the extent of injury or to track injury over time, calculated limb volumes may lose sensitivity to detect injury, due to the intrinsic increase in volume from morphine-derived drugs. During administration of morphine derivatives, T2 maps may provide more accurate assessments of muscle tissue injury both initially after injury and over time.

An objective evaluation of a segmented foot model.

Segmented foot and ankle models divide the foot into multiple segments in order to obtain more meaningful information about its functional behavior in health and disease. The goal of this research was to objectively evaluate the fidelity of a generalized three-segment foot and ankle model defined using externally mounted markers. An established apparatus that reproduces the kinematics and kinetics of gait in cadaver lower extremities was used to independently examine the validity of the rigid body assumption and the magnitude of soft tissue artifact induced by skin-mounted markers. Stance phase simulations were conducted on ten donated limbs while recording the three-dimensional kinematic trajectories of skin-mounted and then bone-mounted marker constructs. Segment kinematics were compared to underlying bone kinematics to examine the rigid body assumption. Virtual markers were calculated from the bone mounted marker set and then compared to the skin-mounted markers to examine soft tissue artifact. The shank and hindfoot segments behaved as rigid bodies. The forefoot segment violated the rigid body assumption, as evidenced by significant differences between motions of the first metatarsal and the forefoot segment, and relative motion between the first and fifth metatarsals. Motion vectors of the external skin markers relative to their virtual counterparts were no more than 3mm in each direction, and 3-7 mm overall. Artifactual marker motion had mild affects on inter-segmental kinematics. Despite errors, the segmented model appeared to perform reasonably well overall. The data presented here enable more informed interpretations of clinical findings using the segmented model approach.

Contribution of the flexor hallucis longus to loading of the first metatarsal and first metatarsophalangeal joint.

BACKGROUND: A recent clinical study suggested that restrictive tenosynovitis of the flexor hallucis longus (FHL) may play an important causative role in hallux rigidus. The goals of this research were to assess normal function of the FHL and the effect of restricted FHL gliding on the loading of the hallux metatarsophalangeal joint (MTPJ). We hypothesized that proximal displacement of the FHL would increase the forces carried by the FHL tendon, causing increased loading of the first metatarsal and MTPJ. MATERIALS AND METHODS: Dynamic simulations of the stance phase of walking were created by loading 5 non-embalmed, non-paired cadaver lower extremities (2 male, 3 female; mean age, 69; range, 56 to 75) in the Robotic Dynamic Activity Simulator (RDAS). The RDAS recreates lower leg motion and muscle activity based on kinematic and electromyographic data of healthy subjects. FHL tendon forces and excursions were measured for the entire stance phase of gait. Bone strains in the mid-shaft of the first metatarsal were recorded and used to derive the in situ forces and moments imposed on the metatarsal and the hallux MTPJ. RESULTS: Under force-feedback control, FHL excursion averaged 6.57 (+/-3.13) mm during gait. When the FHL was held 2-, 4-, and 6-mm proximal to the mid-point of normal excursion to simulate progressive stenosis, the forces in the FHL tendon, first metatarsal and first MTP joint were progressively, and significantly, increased (p < 0.05). CONCLUSION: These findings support the hypothesis that progressive fibrosis at the FHL myotendinous junction can cause increased loading of the hallux MTPJ, thereby leading to hallux rigidus.

Genes in context: probing the genetics of fracture resistance.

Fracture resistance is a complex trait dictated by bone volume, shape, internal architecture, and material performance of the calcified tissue itself, all of which may be influenced by a large number of different genetic and environmental processes. Quantitative Trait Loci analyses provide a sobering picture of this system and illustrate the importance of considering genes in context.

Effects of strontium on bone strength, density, volume, and microarchitecture in laying hens.

UNLABELLED: Strontium has been reported to have beneficial effects on bone. Treatment of laying hens, which are susceptible to osteoporosis and bone fracture, with strontium increased DXA measurements of BMD and BMC and microCT measurements of bone volume and microarchitecture and improved the mechanical performance of whole bone, but had no effect on the estimated material properties of the bone tissue. INTRODUCTION: Strontium (Sr) has been reported to dissociate bone remodeling and have positive influences on bone formation. We supplemented the diet of laying hens, which are susceptible to osteoporosis and bone fracture, with Sr to study the capacity of the element to improve bone mechanical integrity and resistance to fracture. MATERIALS AND METHODS: Increasing dosages of Sr (0, 3000, 4500, and 6000 ppm) were fed to 196 13-week-old pullets for 11 months. BMD and BMC, as measured by conventional and DXA methods, microarchitectural parameters derived from microCT, and structural and material properties as determined by three-point bending test, were studied. Calcium (Ca), phosphorus (P), and Sr levels in plasma and bone, as well as egg output, shell quality, and composition, were assessed. RESULTS: Sr concentrations in plasma and bone increased in a dose-dependent manner without affecting Ca and P. Treatment with Sr increased BMD and BMC as measured by DXA, increased cortical and medullary bone volume, trabecular thickness, number, and surface, and improved whole bone ultimate load, but had no effect on the estimated material properties of diaphyseal bone. Sr also increased the ash content of eggshells and did not affect egg output and shell quality. CONCLUSIONS: Sr supplementation induced large positive effects on bone density, volume, and microarchitecture as measured by radiographic methods. Sr treatment also improved the structural strength of diaphyseal bone but had no effect on the estimated material properties of the bone tissue.

QTL analysis of trabecular bone in BXD F2 and RI mice.

UNLABELLED: A sample of 693 mice was used to identify regions of the mouse genome associated with trabecular bone architecture as measured using microCT. QTLs for bone in the proximal tibial metaphysis were identified on several chromosomes indicating regions containing genes that regulate properties of trabecular bone. INTRODUCTION: Age-related osteoporosis is a condition of major concern because of the morbidity and mortality associated with osteoporotic fractures in humans. Osteoporosis is characterized by reduced bone density, strength, and altered trabecular architecture, all of which are quantitative traits resulting from the actions of many genes working in concert with each other and the environment over the lifespan. microCT gives accurate measures of trabecular bone architecture providing phenotypic data related to bone volume and trabecular morphology. The primary objective of this research was to identify chromosomal regions called quantitative trait loci (QTLs) that contain genes influencing trabecular architecture as measured by microCT. MATERIALS AND METHODS: The study used crosses between C57BL/6J (B6) and DBA/2J (D2) as progenitor strains of a second filial (F2) generation (n = 141 males and 148 females) and 23 BXD recombinant inbred (RI) strains (n approximately 9 of each sex per strain). The proximal tibial metaphyses of the 200-day-old mice were analyzed by microCT to assess phenotypic traits characterizing trabecular bone, including bone volume fraction, trabecular connectivity, and quantitative measures of trabecular orientation and anisotropy. Heritabilities were calculated and QTLs were identified using composite interval mapping. RESULTS: A number of phenotypes were found to be highly heritable. Heritability values for measured phenotypes using RI strains ranged from 0.15 for degree of anisotropy in females to 0.51 for connectivity density in females and total volume in males. Significant and confirmed QTLs, with LOD scores 4.3 in the F2 cohort and 1.5 in the corresponding RI cohort were found on chromosomes 1 (43 cM), 5 (44 cM), 6 (20 cM), and 8 (49 cM). Other QTLs with LOD scores ranging from 2.8 to 6.9 in the F2 analyses were found on chromosomes 1, 5, 6, 8, 9, and 12. QTLs were identified using data sets comprised of both male and female quantitative traits, suggesting similar genetic action in both sexes, whereas others seemed to be associated exclusively with one sex or the other, suggesting the possibility of sex-dependent effects. CONCLUSIONS: Identification of the genes underlying these QTLs may lead to improvements in recognizing individuals most at risk for developing osteoporosis and in the design of new therapeutic interventions.