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Item Achilles tendon material properties are greater in the jump leg of jumping athletes(ISMNI, 2016-06) Bayliss, Amy J.; Weatherholt, Alyssa M.; Crandall, Trent T.; Farmer, Danielle L.; McConnell, Jethro C.; Crossley, K. M.; Warden, Stuart J.; Department of Physical Therapy, School of Health and Rehabilitation SciencesPurpose: The Achilles tendon (AT) must adapt to meet changes in demands. This study explored AT adaptation by comparing properties within the jump and non-jump legs of jumping athletes. Non-jumping control athletes were included to control limb dominance effects. Methods: AT properties were assessed in the preferred (jump) and non-preferred (lead) jumping legs of male collegiate-level long and/or high jump (jumpers; n=10) and cross-country (controls; n=10) athletes. Cross-sectional area (CSA), elongation, and force during isometric contractions were used to estimate the morphological, mechanical and material properties of the ATs bilaterally. Results: Jumpers exposed their ATs to more force and stress than controls (all p≤0.03). AT force and stress were also greater in the jump leg of both jumpers and controls than in the lead leg (all p<0.05). Jumpers had 17.8% greater AT stiffness and 24.4% greater Young’s modulus in their jump leg compared to lead leg (all p<0.05). There were no jump versus lead leg differences in AT stiffness or Young’s modulus within controls (all p>0.05). Conclusion: ATs chronically exposed to elevated mechanical loading were found to exhibit greater mechanical (stiffness) and material (Young’s modulus) properties.Item Adaptation of the proximal humerus to physical activity: a within-subject controlled study in baseball players(Elsevier, 2019-01-08) Warden, Stuart J.; Carballido-Gamio, Julio; Avin, Keith G.; Kersh, Mariana E.; Fuchs, Robyn K.; Krug, Roland; Bice, Ryan; Physical Therapy, School of Health and Human SciencesThe proximal humerus is a common, yet understudied site for osteoporotic fracture. The current study explored the impact of prolonged physical activity on proximal humerus bone health by comparing bone properties between the throwing and nonthrowing arms within professional baseball players. The proximal humerus in throwing arms had 28.1% (95% CI, 17.8 to 38.3%) greater bone mass compared to nonthrowing arms, as assessed using dual-energy x-ray absorptiometry. At the level of the surgical neck, computed tomography revealed 12.0% (95% CI, 8.2 to 15.8%) greater total cross-sectional area and 31.0% (95% CI, 17.8 to 44.2%) greater cortical thickness within throwing arms, which contributed to 56.8% (95% CI, 44.9 to 68.8%) greater polar moment of inertia (i.e., estimated ability to resist torsional forces) compared to nonthrowing arms. Within the humeral head and greater tubercle regions, throwing arms had 3.1% (95% CI, 1.1 to 5.1%) more trabecular bone, as assessed using high-resolution magnetic resonance imaging. Three-dimensional mapping of voxel- and vertex-wise differences between arms using statistical parametric mapping techniques revealed throwing arms had adaptation within much of the proximal diaphysis, especially the posterolateral cortex. The pattern of proximal diaphysis adaptation approximated the pattern of strain energy distribution within the proximal humerus during a fastball pitch derived from a musculoskeletal and finite element model in a representative player. These data demonstrate the adaptive ability of the proximal humerus to physical activity-related mechanical loads. It remains to be established how they translate to exercise prescription to improve bone health within the proximal humerus, however, they provide unique insight into the relationship between prolonged loading and skeletal adaptation at a clinically relevant osteoporotic site.Item Age-Related Changes in Proximal Humerus Bone Health in White Males(Office of the Vice Chancellor for Research, 2012-04-13) Fuchs, Robyn K.; Mantila Roosa, Sara M.; Hurd, Andrea L; Warden, Stuart J.The proximal humerus is a common site for osteoporotic fracture during aging, accounting for up to 5% of fractures to the appendicular skeleton. While falls onto an outstretched hand are usually physically responsible for proximal humerus fractures, the ability of the underlying bone to resist applied loads must also play a role. Few studies have assessed proximal humerus bone health with aging. The aim of the current study was to explore age-related bone changes at the proximal humerus in men. A cross-sectional study design was used to assess peripheral quantitative computed tomography (pQCT)-derived bone properties of the proximal humerus in a cohort of 112 white males (age range = 30-85 yrs). A tomographic slice of the non-dominant upper extremity was acquired at 80% of humeral length proximal from its distal end—a location corresponding to the surgical neck of the humerus. Images were assessed for cortical (Ct.BMC) and trabecular (Tb.BMC) BMC, total (Tt.Ar), cortical (Ct.Ar) and medullary (Me.Ar) area, periosteal (Ps.Pm) and endosteal (Es.Pm) perimeter, cortical thickness (Ct.Th), and bone strength index for compression (BSIc). BSIc was calculated as the product of Tt.Ar and the square of total volumetric BMD. Data were plotted against age and linear regression lines assessed for their slope. Slopes were subsequently converted to percent change in the bone property per year. During aging, the proximal humerus expanded with Tt.Ar and Ps.Pm increasing at rates of 0.40%/yr and 0.19%/yr, respectively. However, Me.Ar (0.62%/yr) and Es.Pm (0.34%/yr) expanded at faster rates such that there was net loss of both Ct.BMC (-0.23%/yr) and Tb.BMC (-1.08%/yr). Also, the more rapid expansion of Me.Ar relative to Tt.Ar meant that Ct.Ar (-0.15%/yr) and Ct.Th (-0.34%/yr) both decreased with age. The net result of these mass and structural changes was progressive loss of bone strength with age, as indicated by a 0.44%/yr decline in BSIc. These data provide a picture of bone changes at the proximal humerus during aging. They suggest that between age 30 and 80 yrs, approximately 54% and 11% of Tb.BMC and Ct.BMC at the proximal humerus is lost, respectively. They also suggest that compressive strength of the proximal humerus declines by 22% between age 30 and 80 years. These declines in proximal humerus bone health have implications for fracture risk at this location during aging.Item Am I big boned? Bone length scaled reference data for HRpQCT measures of the radial and tibial diaphysis in White adults(Elsevier, 2024-01-06) Warden, Stuart J.; Fuchs, Robyn K.; Liu, Ziyue; Toloday, Katelynn R.; Surowiec, Rachel; Moe, Sharon M.; Physical Therapy, School of Health and Human SciencesCross-sectional size of a long bone shaft influences its mechanical properties. We recently used high-resolution peripheral quantitative computed tomography (HRpQCT) to create reference data for size measures of the radial and tibial diaphyses. However, data did not take into account the impact of bone length. Human bone exhibits relatively isometric allometry whereby cross-sectional area increases proportionally with bone length. The consequence is that taller than average individuals will generally have larger z-scores for bone size outcomes when length is not considered. The goal of the current work was to develop a means of determining whether an individual's cross-sectional bone size is suitable for their bone length. HRpQCT scans performed at 30 % of bone length proximal from the distal end of the radius and tibia were acquired from 1034 White females (age = 18.0 to 85.3 y) and 392 White males (age = 18.4 to 83.6 y). Positive relationships were confirmed between bone length and cross-sectional areas and estimated mechanical properties. Scaling factors were calculated and used to scale HRpQCT outcomes to bone length. Centile curves were generated for both raw and bone length scaled HRpQCT data using the LMS approach. Excel-based calculators are provided to facilitate calculation of z-scores for both raw and bone length scaled HRpQCT outcomes. The raw z-scores indicate the magnitude that an individual's HRpQCT outcomes differ relative to expected sex- and age-specific values, with the scaled z-scores also considering bone length. The latter enables it to be determined whether an individual or population of interest has normal sized bones for their length, which may have implications for injury risk. In addition to providing a means of expressing HRpQCT bone size outcomes relative to bone length, the current study also provides centile curves for outcomes previously without reference data, including tissue mineral density and moments of inertia.Item Baseball and softball pitchers are distinct within-subject controlled models for exploring proximal femur adaptation to physical activity(Springer, 2019-01-21) Fuchs, Robyn K.; Thompson, William R.; Weatherholt, Alyssa M.; Warden, Stuart J.; Physical Therapy, School of Health and Human SciencesPurpose: Within-subject controlled models in individuals who preferentially load one side of the body enable efficient exploration of the skeletal benefits of physical activity. There is no established model of physical activity-induced side-to-side differences (i.e., asymmetry) at the proximal femur. Methods: Proximal femur asymmetry was assessed via dual-energy x-ray absorptiometry in male jumping athletes (JMP, n=16), male baseball pitchers (BB, n=21), female fast-pitch softball pitchers (SB, n=22), and controls (CON, n=42). The jumping leg was the dominant leg in JMP, whereas in BB, SB and CON the dominant leg was contralateral to the dominant/throwing arm. Results: BB and SB had 5.5% (95%CI, 3.9 to 7.0%) and 6.5% (95%CI, 4.8 to 8.2%) dominant-to-nondominant leg differences for total hip areal bone mineral density (aBMD), with the asymmetry being greater than both CON and JMP (p<0.05). BB and SB also possessed dominant-to-nondominant leg differences in femoral neck and trochanteric aBMD (p<0.001). SB had 9.7% (95% CI, 6.4 to 13.0%) dominant-to-nondominant leg differences in femoral neck bone mineral content, which was larger than any other group (p≤0.006). At the narrow neck, SB had large (>8%) dominant-to-nondominant leg differences in cross-sectional area, cross-sectional moment of inertia and section modulus, which were larger than any other group (p≤0.02). Conclusion: Male baseball and female softball pitchers are distinct within-subject controlled models for exploring adaptation of the proximal femur to physical activity. They exhibit adaptation in their dominant/landing leg (i.e., leg contralateral to the throwing arm), but the pattern differs with softball pitchers exhibiting greater femoral neck adaptation.Item Bone Microarchitecture and Strength Adaptation to Physical Activity: A Within-Subject Controlled, HRpQCT Study(Wolters Kluwer, 2021) Warden, Stuart J.; Wright, Christian S.; Fuchs, Robyn K.; Physical Therapy, School of Health and Rehabilitation SciencesPurpose Physical activity benefits bone mass and cortical bone size. The current study assessed the impact of chronic (≥10 years) physical activity on trabecular microarchitectural properties and micro-finite element (μFE) analyses of estimated bone strength. Methods Female collegiate-level tennis players (n=15; age=20.3±0.9 yrs) were used as a within-subject controlled model of chronic unilateral upper-extremity physical activity. Racquet-to-nonracquet arm differences at the distal radius and radial diaphysis were assessed using high-resolution peripheral computed tomography (HRpQCT). The distal tibia and tibial diaphysis in both legs were also assessed, and cross-country runners (n=15; age=20.8±1.2 yrs) included as controls. Results The distal radius of the racquet arm had 11.8% (95% confidence interval [CI], 7.9 to 15.7%) greater trabecular bone volume/tissue volume, with trabeculae that were greater in number, thickness, connectivity, and proximity to each other than in the nonracquet arm (all p<0.01). Combined with enhanced cortical bone properties, the microarchitectural advantages at the distal radius contributed a 18.7% (95% CI, 13.0 to 24.4%) racquet-to-nonracquet arm difference in predicted load before failure. At the radial diaphysis, predicted load to failure was 9.6% (95% CI, 6.7 to 12.6%) greater in the racquet vs. nonracquet arm. There were fewer and smaller side-to-side differences at the distal tibia; however, the tibial diaphysis in the leg opposite the racquet arm was larger with a thicker cortex and had 4.4% (95% CI, 1.7 to 7.1%) greater strength than the contralateral leg. Conclusion Chronically elevated physical activity enhances trabecular microarchitecture and μFE estimated strength, furthering observations from short-term longitudinal studies. The data also demonstrate tennis players exhibit crossed symmetry wherein the leg opposite the racquet arm possesses enhanced tibial properties compared to in the contralateral leg.Item Bone Morphogenetic Protein-2 Rapidly Heals Two Distinct Critical Sized Segmental Diaphyseal Bone Defects in a Porcine Model(Oxford University Press, 2023) McKinley, Todd O.; Childress, Paul; Jewell, Emily; Griffin, Kaitlyn S.; Wininger, Austin E.; Tucker, Aamir; Gremah, Adam; Savaglio, Michael K.; Warden, Stuart J.; Fuchs, Robyn K.; Natoli, Roman M.; Shively, Karl D.; Anglen, Jeffrey O.; Chu, Tien-Min Gabriel; Kacena, Melissa A.; Orthopaedic Surgery, School of MedicineIntroduction: Segmental bone defects (SBDs) are devastating injuries sustained by warfighters and are difficult to heal. Preclinical models that accurately simulate human conditions are necessary to investigate therapies to treat SBDs. We have developed two novel porcine SBD models that take advantage of similarities in bone healing and immunologic response to injury between pigs and humans. The purpose of this study was to investigate the efficacy of Bone Morphogenetic Protein-2 (BMP-2) to heal a critical sized defect (CSD) in two novel porcine SBD models. Materials and methods: Two CSDs were performed in Yucatan Minipigs including a 25.0-mm SBD treated with intramedullary nailing (IMN) and a 40.0-mm SBD treated with dual plating (ORIF). In control animals, the defect was filled with a custom spacer and a bovine collagen sponge impregnated with saline (IMN25 Cont, n = 8; ORIF40 Cont, n = 4). In experimental animals, the SBD was filled with a custom spacer and a bovine collage sponge impregnated with human recombinant BMP-2 (IMN25 BMP, n = 8; ORIF40 BMP, n = 4). Healing was quantified using monthly modified Radiographic Union Score for Tibia Fractures (mRUST) scores, postmortem CT scanning, and torsion testing. Results: BMP-2 restored bone healing in all eight IMN25 BMP specimens and three of four ORIF40 BMP specimens. None of the IMN25 Cont or ORIF40 Cont specimens healed. mRUST scores at the time of sacrifice increased from 9.2 (±2.4) in IMN25 Cont to 15.1 (±1.0) in IMN25 BMP specimens (P < .0001). mRUST scores increased from 8.2 (±1.1) in ORIF40 Cont to 14.3 (±1.0) in ORIF40 BMP specimens (P < .01). CT scans confirmed all BMP-2 specimens had healed and none of the control specimens had healed in both IMN and ORIF groups. BMP-2 restored 114% and 93% of intact torsional stiffness in IMN25 BMP and ORIF40 BMP specimens. Conclusions: We have developed two porcine CSD models, including fixation with IMN and with dual-plate fixation. Porcine models are particularly relevant for SBD research as the porcine immunologic response to injury closely mimics the human response. BMP-2 restored healing in both CSD models, and the effects were evident within the first month after injury. These findings support the use of both porcine CSD models to investigate new therapies to heal SBDs.Item Cortical and trabecular bone benefits of mechanical loading are maintained long term in mice independent of ovariectomy.(Wiley, 2014) Warden, Stuart J.; Galley, Matthew R.; Hurd, Andrea L.; Richard, Jeffrey S.; George, Lydia A.; Guildenbecher, Elizabeth A.; Barker, Rick G.; Fuchs, Robyn K.; Health Sciences, School of Health and Rehabilitation SciencesSkeletal loading enhances cortical and trabecular bone properties. How long these benefits last after loading cessation remains an unresolved, clinically relevant question. This study investigated long-term maintenance of loading-induced cortical and trabecular bone benefits in female C57BL/6 mice and the influence of a surgically induced menopause on the maintenance. Sixteen-week-old animals had their right tibia extrinsically loaded 3 days/week for 4 weeks using the mouse tibial axial compression loading model. Left tibias were not loaded and served as internal controls. Animals were subsequently detrained (restricted to cage activities) for 0, 4, 8, 26, or 52 weeks, with ovariectomy (OVX) or sham-OVX surgery being performed at 0 weeks detraining. Loading increased midshaft tibia cortical bone mass, size, and strength, and proximal tibia bone volume fraction. The cortical bone mass, area, and thickness benefits of loading were lost by 26 weeks of detraining because of heightened medullary expansion. However, loading-induced benefits on bone total area and strength were maintained at each detraining time point. Similarly, the benefits of loading on bone volume fraction persisted at all detraining time points. The long-term benefits of loading on both cortical and trabecular bone were not influenced by a surgically induced menopause because there were no interactions between loading and surgery. However, OVX had independent effects on cortical bone properties at early (4 and 8 weeks) detraining time points and trabecular bone properties at all detraining time points. These cumulative data indicate loading has long-term benefits on cortical bone size and strength (but not mass) and trabecular bone morphology, which are not influenced by a surgically induced menopause. This suggests skeletal loading associated with physical activity may provide long-term benefits by preparing the skeleton to offset both the cortical and trabecular bone changes associated with aging and menopause.Item Effect of fatigue loading and rest on impact strength of rat ulna(Elsevier, 2021-06) Yan, Chenxi; Song, Hyunggwi; Pfister, Jennifer; Andersen, Thomas L.; Warden, Stuart J.; Bhargava, Rohit; Kersh, Mariana E.; Physical Therapy, School of Health and Human SciencesStress fracture is a common injury among athletes and military personnel and is associated with fatigue-initiated damage and impact loading. The recovery of bending strength has been shown to be a function of the rest days allowed after fatigue loading in rodents and the aim of this study was to investigate if similar results would occur under impact conditions. In this study, cyclic axial compression load was applied in vivo on the right forelimbs while left forelimbs served as controls. Two rest groups were used: one day of rest and seven days of rest. Afterwards, all ulnae were scanned using micro-Computed Tomography followed by impact testing. The micro-CT scan confirmed the formation of woven bone on loaded ulnae after seven days rest. The peak impact force was 37.5% higher in the control (mean = 174.96 ± 33.25 N) specimens compared to the loaded bones (mean = 130.34 ± 22.37 N). Fourier-transformed infrared spectroscopy analyses suggested no significant change of chemical composition in the cortical region between the loaded and control ulnae, but woven bone region had lower carbonate and amide I content than contralateral controls (p < 0.05). We find that cyclic fatigue loading had a negative effect on bone’s impact response. Bones that experienced fatigue loading became less stiff, weaker, and more prone to fracture when subjected to impact. The formation of woven bone after seven days of rest did not restore the stiffness upon impact and confirm that rest time is crucial to the recovery of fatigue damage.Item Effects of exercise and manual therapy on pain associated with hip osteoarthritis: a systematic review and meta‐analysis(BMJ, 2016-04) Beumer, Lucy; Wong, Jennie; Warden, Stuart J.; Kemp, Joanne L.; Foster, Paul; Crossley, Kay M.; Department of Health Sciences, School of Health and Rehabilitation SciencesAim To explore the effects of exercise (water-based or land-based) and/or manual therapies on pain in adults with clinically and/or radiographically diagnosed hip osteoarthritis (OA). Methods A systematic review and meta-analysis was performed, with patient reported pain assessed using a visual analogue scale (VAS) or the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale. Data were grouped by follow-up time (0–3 months=short term; 4–12 months=medium term and; >12 months=long term), and standardised mean differences (SMD) with 95% CIs were used to establish intervention effect sizes. Study quality was assessed using modified PEDro scores. Results 19 trials were included. Four studies showed short-term benefits favouring water-based exercise over minimal control using the WOMAC pain subscale (SMD −0.53, 95% CI −0.96 to −0.10). Six studies supported a short-term benefit of land-based exercise compared to minimal control on VAS assessed pain (SMD −0.49, 95% CI −0.70 to −0.29). There were no medium (SMD −0.23, 95% CI −0.48 to 0.03) or long (SMD −0.22, 95% CI −0.51 to 0.06) term benefits of exercise therapy, or benefit of combining exercise therapy with manual therapy (SMD −0.38, 95% CI −0.88 to 0.13) when compared to minimal control. Conclusions Best available evidence indicates that exercise therapy (whether land-based or water-based) is more effective than minimal control in managing pain associated with hip OA in the short term. Larger high-quality RCTs are needed to establish the effectiveness of exercise and manual therapies in the medium and long term.