Browsing by Subject "Tibia"
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Item Internal Fixation Construct and Defect Size Affect Healing of a Translational Porcine Diaphyseal Tibial Segmental Bone Defect(Oxford University Press, 2021) McKinley, Todd O.; Natoli, Roman M.; Fischer, James P.; Rytlewski, Jeffrey D.; Scofield, David C.; Usmani, Rashad; Kuzma, Alexander; Griffin, Kaitlyn S.; Jewell, Emily; Childress, Paul; Shively, Karl D.; Chu, Tien-Min Gabriel; Anglen, Jeffrey O.; Kacena, Melissa A.; Orthopaedic Surgery, School of MedicineBackground and objective: Porcine translational models have become the gold-standard translational tool to study the effects of major injury and hemorrhagic shock because of their similarity to the human immunologic response to trauma. Segmental bone defects (SBDs) typically occur in warfighters with associated severe limb trauma. The purpose of this study was to develop a translational porcine diaphyseal SBD model in Yucatan minipigs (YMPs), which could be used in bone healing investigations that simulate injury-relevant conditions. We were specifically working toward developing a critical sized defect (CSD). Methods: We used an adaptive experimental design in which both 25.0 mm and 40.0 mm SBDs were created in the tibial mid-diaphysis in skeletally mature YMPs. Initially, eight YMPs were subjected to a 25.0 mm SBD and treated with intramedullary nailing (intramedullary nail [IMN] 25mm). Due to unanticipated wound problems, we subsequently treated four specimens with identical 25.0 mm defect with dual plating (open reduction with internal fixation [ORIF] 25mm). Finally, a third group of four YMPs with 40.0 mm defects were treated with dual plating (ORIF 40mm). Monthly radiographs were made until sacrifice. Modified Radiographic Union Score for Tibia fractures (mRUST) measurements were made by three trauma-trained orthopedic surgeons. CT scans of the tibias were used to verify the union results. Results: At 4 months post-surgery, mean mRUST scores were 11.7 (SD ± 1.8) in the ORIF 25mm YMPs vs. 8.5 (SD ± 1.4) in the IMN 25mm YMPs (P < .0001). All four ORIF 25mm YMPs were clinically healed. In contrast, none of the IMN 25mm YMPs were clinically healed and seven of eight IMN 25mm YMPs developed delayed wound breakdown. All four of the ORIF 40mm YMPs had flail nonunions with complete hardware failure by 3 months after surgery and were sacrificed early. CT scanning confirmed that none of the IMN 25mm YMPs, none of the ORIF 40mm YMPs, and two of four ORIF 25mm YMPs were healed. A third ORIF 25mm specimen was nearly healed on CT scanning. Inter-rater and intra-rater reliability interclass coefficients using the mRUST scale were 0.81 and 0.80, respectively. Conclusions: YMPs that had a 40 mm segment of bone removed from their tibia and were treated with dual plating did not heal and could be used to investigate interventions that accelerate bone healing. In contrast, a 25 mm SBD treated with dual plating demonstrated delayed but successful healing, indicating it can potentially be used to investigate bone healing adjuncts or conversely how concomitant injuries may impair bone healing. Pigs treated with IMN failed to heal and developed consistent delayed wound breakdown presumably secondary to chronic limb instability. The porcine YMP SBD model has the potential to be an effective translational tool to investigate bone healing under physiologically relevant injury conditions.Item Modifications in Bone Matrix of Estrogen-Deficient Rats Treated with Intermittent PTH(Hindawi Publishing Corporation, 2015-01-28) Pacheco-Costa, Rafael; Campos, Jenifer Freitas; Katchburian, Eduardo; de Medeiros, Valquíria Pereira; Nader, Helena Bonciani; Nonaka, Keico Okino; Plotkin, Lilian Irene; Reginato, Rejane Daniele; Department of Anatomy & Cell Biology, IU School of MedicineBone matrix dictates strength, elasticity, and stiffness to the bone. Intermittent parathyroid hormone (iPTH), a bone-forming treatment, is widely used as a therapy for osteoporosis. We investigate whether low doses of intermittent PTH (1-34) change the profile of organic components in the bone matrix after 30 days of treatment. Forty 6-month-old female Wistar rats underwent ovariectomy and after 3 months received low doses of iPTH administered for 30 days: daily at 0.3 µg/kg/day (PTH03) or 5 µg/kg/day (PTH5); or 3 times per week at 0.25 µg/kg/day (PTH025). After euthanasia, distal femora were processed for bone histomorphometry, histochemistry for collagen and glycosaminoglycans, biochemical quantification of sulfated glycosaminoglycans, and hyaluronan by ELISA and TUNEL staining. Whole tibiae were used to estimate the bone mineral density (BMD). Histomorphometric analysis showed that PTH5 increased cancellous bone volume by 6% over vehicle-treated rats. In addition, PTH5 and PTH03 increased cortical thickness by 21% and 20%, respectively. Tibial BMD increased in PTH5-treated rats and this group exhibited lower levels of chondroitin sulfate; on the other hand, hyaluronan expression was increased. Hormonal administration in the PTH5 group led to decreased collagen maturity. Further, TUNEL-positive osteocytes were decreased in the cortical compartment of PTH5 whereas administration of PTH025 increased the osteocyte death. Our findings suggest that daily injections of PTH at low doses alter the pattern of organic components from the bone matrix, favoring the increase of bone mass.Item Resonance in the mouse tibia as a predictor of frequencies and locations of loading-induced bone formation(Springer, 2014-01) Zhao, Liming; Dodge, Todd; Nemani, Arun; Yokota, Hiroki; Biomedical Engineering, School of Engineering and TechnologyTo enhance new bone formation for the treating of patients with osteopenia and osteoporosis, various mechanical loading regimens have been developed. Although a wide spectrum of loading frequencies is proposed in those regimens, a potential linkage between loading frequencies and locations of loading-induced bone formation is not well understood. In this study, we addressed a question: Does mechanical resonance play a role in frequency-dependent bone formation? If so, can the locations of enhanced bone formation be predicted through the modes of vibration? Our hypothesis is that mechanical loads applied at a frequency near the resonant frequencies enhance bone formation, specifically in areas that experience high principal strains. To test the hypothesis, we conducted axial tibia loading using low, medium, or high frequency to the mouse tibia, as well as finite element analysis. The experimental data demonstrated dependence of the maximum bone formation on location and frequency of loading. Samples loaded with the low-frequency waveform exhibited peak enhancement of bone formation in the proximal tibia, while the high-frequency waveform offered the greatest enhancement in the midshaft and distal sections. Furthermore, the observed dependence on loading frequencies was correlated to the principal strains in the first five resonance modes at 8.0-42.9 Hz. Collectively, the results suggest that resonance is a contributor to the frequencies and locations of maximum bone formation. Further investigation of the observed effects of resonance may lead to the prescribing of personalized mechanical loading treatments.Item Structural and Mechanical Improvements to Bone Are Strain Dependent with Axial Compression of the Tibia in Female C57BL/6 Mice(PLOS, 2015-06-26) Berman, Alycia G.; Clauser, Creasy A.; Wunderlin, Caitlin; Hammond, Max A.; Wallace, Joseph M.; Department of Biomedical Engineering, School of Engineering and TechnologyStrain-induced adaption of bone has been well-studied in an axial loading model of the mouse tibia. However, most outcomes of these studies are restricted to changes in bone architecture and do not explore the mechanical implications of those changes. Herein, we studied both the mechanical and morphological adaptions of bone to three strain levels using a targeted tibial loading mouse model. We hypothesized that loading would increase bone architecture and improve cortical mechanical properties in a dose-dependent fashion. The right tibiae of female C57BL/6 mice (8 week old) were compressively loaded for 2 weeks to a maximum compressive force of 8.8N, 10.6N, or 12.4N (generating periosteal strains on the anteromedial region of the mid-diaphysis of 1700 με, 2050 με, or 2400 με as determined by a strain calibration), while the left limb served as an non-loaded control. Following loading, ex vivo analyses of bone architecture and cortical mechanical integrity were assessed by micro-computed tomography and 4-point bending. Results indicated that loading improved bone architecture in a dose-dependent manner and improved mechanical outcomes at 2050 με. Loading to 2050 με resulted in a strong and compelling formation response in both cortical and cancellous regions. In addition, both structural and tissue level strength and energy dissipation were positively impacted in the diaphysis. Loading to the highest strain level also resulted in rapid and robust formation of bone in both cortical and cancellous regions. However, these improvements came at the cost of a woven bone response in half of the animals. Loading to the lowest strain level had little effect on bone architecture and failed to impact structural- or tissue-level mechanical properties. Potential systemic effects were identified for trabecular bone volume fraction, and in the pre-yield region of the force-displacement and stress-strain curves. Future studies will focus on a moderate load level which was largely beneficial in terms of cortical/cancellous structure and cortical mechanical function.Item Tibial Bone Strength is Enhanced in the Jump Leg of Collegiate-Level Jumping Athletes: A Within-Subject Controlled Cross-Sectional Study(Springer, 2016-02) Weatherholt, Alyssa M.; Warden, Stuart J.; Department of Physical Therapy, School of Health and Rehabilitation SciencesAn efficient method of studying skeletal adaptation to mechanical loading is to assess side-to-side differences (i.e., asymmetry) within individuals who unilaterally exercise one side of the body. Within-subject controlled study designs have been used to explore skeletal mechanoadaptation at upper extremity sites; however, there is no established model in the lower extremities. The current study assessed tibial diaphysis and distal tibia asymmetry in collegiate-level jumping athletes (N = 12). To account for normal crossed asymmetry, data in jumping athletes were compared to asymmetry in a cohort of athletic controls not routinely exposed to elevated unilateral lower extremity loading (N = 11). Jumpers exhibited side-to-side differences between their jump and lead legs at both the tibial diaphysis and distal tibia, with differences at the former site persisting following comparison to dominant-to-nondominant leg differences in controls. In particular, jump-to-lead leg differences for cortical area and thickness at the tibial diaphysis in jumpers were 3.6% (95% CI 0.5-6.8%) and 3.5% (95% CI 0.4-6.6%) greater than dominant-to-nondominant differences in controls, respectively (all p < 0.05). Similarly, jump-to-lead leg differences in jumpers for tibial diaphysis maximum second moment of area and polar moment of inertia were 7.2% (95% CI 1.2-13.2%) and 5.7% (95% CI 1.7-9.8%) greater than dominant-to-nondominant differences in controls, respectively (all p < 0.05). Assessment of region-specific differences of the tibial diaphysis in jumpers indicated that the jump leg had greater pericortical radii on the medial and posterior sides and greater radial cortical thickness posteromedially when compared to the lead leg. These data suggest that athletes who perform repetitive and forceful unilateral jumping may be a useful and efficient within-subject controlled model for studying lower extremity skeletal mechanoadaptation.Item Treadmill running and targeted tibial loading differentially improve bone mass in mice(Elsevier, 2019-06-01) Berman, Alycia G.; Hinton, Madicyn J.; Wallace, Joseph M.; Biomedical Engineering, School of Engineering and TechnologyTreadmill running and tibial loading are two common modalities used to assess the role of mechanical stimulation on the skeleton preclinically. The primary advantage of treadmill running is its physiological relevance. However, the applied load is complex and multiaxial, with observed results influenced by cardiovascular and musculoskeletal effects. In contrast, with tibial loading, a direct uniaxial load is applied to a single bone, providing the advantage of greater control but with less physiological relevance. Despite the importance and wide-spread use of both modalities, direct comparisons are lacking. In this study, we compared effects of targeted tibial loading, treadmill running, and their combination on cancellous and cortical architecture in a murine model. We show that tibial loading and treadmill running differentially improve bone mass, with tibial loading resulting in thicker trabeculae and increased cortical mass, and exercise resulting in greater number of trabeculae and no cortical mass-based effects. Combination of the modalities resulted in an additive response. These data suggest that tibial loading and exercise may improve mass differentially.