Publications by authors named "Stuart J Warden"

97 Publications

Effect of fatigue loading and rest on impact strength of rat ulna.

J Biomech 2021 May 2;123:110449. Epub 2021 May 2.

Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Beckman Institute for Advanced Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA. Electronic address:

Stress 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.
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http://dx.doi.org/10.1016/j.jbiomech.2021.110449DOI Listing
May 2021

Optimal Load for Managing Low-Risk Tibial and Metatarsal Bone Stress Injuries in Runners: The Science Behind the Clinical Reasoning.

J Orthop Sports Phys Ther 2021 May 7:1-28. Epub 2021 May 7.

School of Physical Therapy and Health Sciences, University of Montana, Missoula, MT.

Background: Low-risk bone stress injuries (BSIs) of the tibia and metatarsal diaphysis account for >50% of BSIs in runners. They interrupt training and are managed using non-invasive approaches. The desire by all involved is for a speedy, but safe return to running.

Clinical Question: What is the optimal load to manage low-risk tibial and metatarsal BSIs and safely return to running?

Key Results: Optimal load can be guided by knowledge of the BSI healing process and is symptom driven. At all stages, the optimal load does not produce symptoms during, after, or the day following loading.

Clinical Application: A period of initial load reduction, via partial- or non-weightbearing, is typically needed to alleviate presenting symptoms. Analgesics or NSAIDs may be used short-term (<7 days), but only in the presence of resting and/or night pain. Healing supplements (e.g. low-intensity pulsed ultrasound and/or recombinant parathyroid hormone therapy) may be attempted to influence tissue healing. Athletes can maintain cardiopulmonary fitness via cross-training, while simultaneously addressing musculoskeletal fitness. A return-to-run program can be initiated once an athlete is pain-free with daily activities for 5 consecutive days. Progress is directed by symptom provocation and initially focuses on increasing running volume before speed. Continue optimal loading following return to running and consider including jump training and/or gait retraining to reduce subsequent BSI risk. The optimal loading approach to managing low-risk tibial and metatarsal BSIs is clinically successful, but requires further scientific validation. .
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http://dx.doi.org/10.2519/jospt.2021.9982DOI Listing
May 2021

Preventing Bone Stress Injuries in Runners with Optimal Workload.

Curr Osteoporos Rep 2021 Feb 26. Epub 2021 Feb 26.

School of Physical Therapy & Health Sciences, University of Montana, Missoula, MT, USA.

Bone stress injuries (BSIs) occur at inopportune times to invariably interrupt training. All BSIs in runners occur due to an "error" in workload wherein the interaction between the number and magnitude of bone tissue loading cycles exceeds the ability of the tissue to resist the repetitive loads. There is not a single optimal bone workload, rather a range which is influenced by the prevailing scenario. In prepubertal athletes, optimal bone workload consists of low-repetitions of fast, high-magnitude, multidirectional loads introduced a few times per day to induce bone adaptation. Premature sports specialization should be avoided so as to develop a robust skeleton that is structurally optimized to withstand multidirectional loading. In the mature skeleton, optimal workload enables gains in running performance but minimizes bone damage accumulation by sensibly progressing training, particularly training intensity. When indicated (e.g., following repeated BSIs), attempts to reduce bone loading magnitude should be considered, such as increasing running cadence. Determining the optimal bone workload for an individual athlete to prevent and manage BSIs requires consistent monitoring. In the future, it may be possible to clinically determine bone loads at the tissue level to facilitate workload progressions and prescriptions.
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http://dx.doi.org/10.1007/s11914-021-00666-yDOI Listing
February 2021

Bone Microarchitecture and Strength Adaptation to Physical Activity: A Within-Subject Controlled HRpQCT Study.

Med Sci Sports Exerc 2021 06;53(6):1179-1187

Purpose: Physical activity benefits bone mass and cortical bone size. The current study assessed the impact of chronic (≥10 yr) physical activity on trabecular microarchitectural properties and microfinite element analyses of estimated bone strength.

Methods: Female collegiate-level tennis players (n = 15; age = 20.3 ± 0.9 yr) 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 quantitative computed tomography. The distal tibia and the tibial diaphysis in both legs were also assessed, and cross-country runners (n = 15; age = 20.8 ± 1.2 yr) 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 that 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 versus 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 microfinite element estimated strength, furthering observations from short-term longitudinal studies. The data also demonstrate that tennis players exhibit crossed symmetry wherein the leg opposite the racquet arm possesses enhanced tibial properties compared with in the contralateral leg.
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http://dx.doi.org/10.1249/MSS.0000000000002571DOI Listing
June 2021

Radiographic imaging, densitometry and disease severity in Autosomal dominant osteopetrosis type 2.

Skeletal Radiol 2021 May 3;50(5):903-913. Epub 2020 Oct 3.

Indiana Center for Musculoskeletal Health, Indiana University, Indianapolis, IN, USA.

Objective: To characterize relationships between quantitative computed tomography bone mineral density measurements and other qualitative and quantitative imaging measures, as well as clinical metrics, in patients with autosomal dominant osteopetrosis type 2 (ADO2).

Materials And Methods: Clinical and radiologic parameters of 9 adults and 3 children with autosomal dominant osteopetrosis type 2 were assessed including lumbar spine quantitative computed tomography (QCT), radiographic skeletal survey (skull base thickening; Erlenmeyer flask deformity; endobone pattern; and spine density pattern (endplate sclerosis, "anvil" appearance, or diffuse sclerosis)), dual-energy x-ray absorptiometry (DXA), tibial peripheral quantitative computed tomography (pQCT) volumetric bone mineral density (vBMD), bone turnover markers, and bone marrow failure or visual impairment.

Results: The skeletal parameter most divergent from normal was lumbar spine QCT Z-score (+ 3.6 to + 38.7). Lumbar QCT Z-score correlated positively with pQCT tibial diaphysis vBMD (Pearson correlation r = 0.73, p = 0.02) and pQCT tibial metaphysis vBMD (r = 0.87, p < 0.01). A trend towards positive lumbar QCT Z-score correlation with serum P1NP/CTX ratio (r = 0.54, p = 0.10) and lumbar DXA Z-score (r = 0.55, p = 0.10) were observed. Bone marrow failure and vision impairment occurred in those with most severe quantitative and qualitative measures, while those with less severe radiographic features had the lowest QCT Z-scores.

Conclusion: Lumbar spine QCT provided the most extreme skeletal assessment in ADO2, which correlated positively with other radiologic and clinical markers of disease severity. Given the quantification of trabecular bone and greater variation from normal with wider range of values, lumbar QCT Z-scores may be useful to determine or detect impact of future treatments.
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http://dx.doi.org/10.1007/s00256-020-03625-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009803PMC
May 2021

Taking the Next Steps in Regenerative Rehabilitation: Establishment of a New Interdisciplinary Field.

Arch Phys Med Rehabil 2020 05 5;101(5):917-923. Epub 2020 Feb 5.

McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA.

The growing field of regenerative rehabilitation has great potential to improve clinical outcomes for individuals with disabilities. However, the science to elucidate the specific biological underpinnings of regenerative rehabilitation-based approaches is still in its infancy and critical questions regarding clinical translation and implementation still exist. In a recent roundtable discussion from International Consortium for Regenerative Rehabilitation stakeholders, key challenges to progress in the field were identified. The goal of this article is to summarize those discussions and to initiate a broader discussion among clinicians and scientists across the fields of regenerative medicine and rehabilitation science to ultimately progress regenerative rehabilitation from an emerging field to an established interdisciplinary one. Strategies and case studies from consortium institutions-including interdisciplinary research centers, formalized courses, degree programs, international symposia, and collaborative grants-are presented. We propose that these strategic directions have the potential to engage and train clinical practitioners and basic scientists, transform clinical practice, and, ultimately, optimize patient outcomes.
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http://dx.doi.org/10.1016/j.apmr.2020.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576442PMC
May 2020

Heterogeneous Spatial and Strength Adaptation of the Proximal Femur to Physical Activity: A Within-Subject Controlled Cross-Sectional Study.

J Bone Miner Res 2020 04 30;35(4):681-690. Epub 2019 Dec 30.

Department of Physical Therapy, School of Health and Human Sciences, Indiana University, Indianapolis, IN, USA.

Physical activity (PA) enhances proximal femur bone mass, as assessed using projectional imaging techniques. However, these techniques average data over large volumes, obscuring spatially heterogeneous adaptations. The current study used quantitative computed tomography, statistical parameter mapping, and subject-specific finite element (FE) modeling to explore spatial adaptation of the proximal femur to PA. In particular, we were interested in adaptation occurring at the superior femoral neck and improving strength under loading from a fall onto the greater trochanter. High/long jump athletes (n = 16) and baseball pitchers (n = 16) were utilized as within-subject controlled models as they preferentially load their take-off leg and leg contralateral to their throwing arm, respectively. Controls (n = 15) were included but did not show any dominant-to-nondominant (D-to-ND) leg differences. Jumping athletes showed some D-to-ND leg differences but less than pitchers. Pitchers had 5.8% (95% confidence interval [CI] 3.9%-7.6%) D-to-ND leg differences in total hip volumetric bone mineral density (vBMD), with increased vBMD in the cortical compartment of the femoral neck and trochanteric cortical and trabecular compartments. Voxel-based morphometry analyses and cortical bone mapping showed pitchers had D-to-ND leg differences within the regions of the primary compressive trabeculae, inferior femoral neck, and greater trochanter but not the superior femoral neck. FE modeling revealed pitchers had 4.1% (95% CI 1.4%-6.7%) D-to-ND leg differences in ultimate strength under single-leg stance loading but no differences in ultimate strength to a fall onto the greater trochanter. These data indicate the asymmetrical loading associated with baseball pitching induces proximal femur adaptation in regions associated with weight bearing and muscle contractile forces and increases strength under single-leg stance loading. However, there were no benefits evident at the superior femoral neck and no measurable improvement in ultimate strength to common injurious loading during aging (ie, fall onto the greater trochanter), raising questions as to how to better target these variables with PA. © 2019 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.3939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145739PMC
April 2020

Voluntary Wheel Running Has Beneficial Effects in a Rat Model of CKD-Mineral Bone Disorder (CKD-MBD).

J Am Soc Nephrol 2019 10 9;30(10):1898-1909. Epub 2019 Sep 9.

Division of Nephrology and.

Background: Reduced bone and muscle health in individuals with CKD contributes to their higher rates of morbidity and mortality.

Methods: We tested the hypothesis that voluntary wheel running would improve musculoskeletal health in a CKD rat model. Rats with spontaneous progressive cystic kidney disease (Cy/+ ) and normal littermates (NL) were given access to a voluntary running wheel or standard cage conditions for 10 weeks starting at 25 weeks of age when the rats with kidney disease had reached stage 2-3 of CKD. We then measured the effects of wheel running on serum biochemistry, tissue weight, voluntary grip strength, maximal aerobic capacity (VO), body composition and bone micro-CT and mechanics.

Results: Wheel running improved serum biochemistry with decreased creatinine, phosphorous, and parathyroid hormone in the rats with CKD. It improved muscle strength, increased time-to-fatigue (for VO), reduced cortical porosity and improved bone microarchitecture. The CKD rats with voluntary wheel access also had reduced kidney cystic weight and reduced left ventricular mass index.

Conclusions: Voluntary wheel running resulted in multiple beneficial systemic effects in rats with CKD and improved their physical function. Studies examining exercise interventions in patients with CKD are warranted.
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http://dx.doi.org/10.1681/ASN.2019040349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779348PMC
October 2019

Tester and testing procedure influence clinically determined gait speed.

Gait Posture 2019 10 28;74:83-86. Epub 2019 Aug 28.

Indiana Center for Musculoskeletal Health, Indiana University, Indianapolis, IN, United States; Division of Nephrology, Department of Medicine, School of Medicine, Indiana University, Indianapolis, IN, United States.

Background: There is a clinical need to be able to reliably detect meaningful changes (0.1 to 0.2 m/s) in usual gait speed (UGS) considering reduced gait speed is associated with morbidity and mortality.

Research Question: What is the impact of tester on UGS assessment, and the influence of test repetition (trial 1 vs. 2), timing method (manual stopwatch vs. automated timing), and starting condition (stationary vs. dynamic start) on the ability to detect changes in UGS and fast gait speed (FGS)?

Methods: UGS and FGS was assessed in 725 participants on a 8-m course with infrared timing gates positioned at 0, 2, 4 and 6 m. Testing was performed by one of 13 testers trained by a single researcher. Time to walk 4-m from a stationary start (i.e. from 0-m to 4-m) was measured manually using a stopwatch and automatically via the timing gates at 0-m and 4-m. Time taken to walk 4-m with a dynamic start was measured during the same trial by recording the time to walk between the timing gates at 2-m and 6-m (i.e. after 2-m acceleration).

Results: Testers differed for UGS measured using manual vs. automated timing (p = 0.02), with five and two testers recording slower and faster UGS using manual timing, respectively. 95% limits of agreement for trial 1 vs. 2, manual vs. automated timing, and dynamic vs. stationary start ranged from ±0.15 m/s to ±0.20 m/s, coinciding with the range for a clinically meaningful change. Limits of agreement for FGS were larger ranging from ±0.26 m/s to ±0.35 m/s.

Significance: Repeat testing of UGS should performed by the same tester or using an automated timing method to control for tester effects. Test protocol should remain constant both between and within participants as protocol deviations may result in detection of an artificial clinically meaningful change.
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http://dx.doi.org/10.1016/j.gaitpost.2019.08.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790294PMC
October 2019

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Br J Sports Med 2019 Sep 15;53(18):1131-1132. Epub 2019 Mar 15.

Rehabilitation, Aspetar Orthopaedic and Sports Medicine Hospital, Doha, Qatar.

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http://dx.doi.org/10.1136/bjsports-2018-100504DOI Listing
September 2019

Baseball and Softball Pitchers are Distinct Within-Subject Controlled Models for Exploring Proximal Femur Adaptation to Physical Activity.

Calcif Tissue Int 2019 04 21;104(4):373-381. Epub 2019 Jan 21.

Department of Physical Therapy, School of Health and Human Sciences, Indiana University, Indianapolis, IN, 46202, USA.

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. 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. BB and SB had 5.5% (95% CI 3.9-7.0%) and 6.5% (95% CI 4.8-8.2%) 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 6.4-13.0%) 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). 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.
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http://dx.doi.org/10.1007/s00223-019-00519-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6490678PMC
April 2019

Adaptation of the proximal humerus to physical activity: A within-subject controlled study in baseball players.

Bone 2019 04 8;121:107-115. Epub 2019 Jan 8.

Department of Physical Therapy, School of Health and Human Sciences, Indiana University, Indianapolis, IN, United States of America.

The 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.
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http://dx.doi.org/10.1016/j.bone.2019.01.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391178PMC
April 2019

Adiposity, Insulin Resistance, and Bone Mass in Children and Adolescents.

J Clin Endocrinol Metab 2019 03;104(3):892-899

Department of Nutrition Science, Purdue University, West Lafayette, Indiana.

Context: Insulin resistance is an adverse health outcome that accompanies obesity. Fat mass is negatively associated with the bone mass after adjustment for confounders. Insulin resistance might be an intermediary in this relationship.

Objective: To determine whether insulin resistance is an intermediary in the relationship between adiposity and bone mass in adolescents.

Design: Cross-sectional secondary analysis of baseline data from a previous randomized trial.

Setting: University research facility.

Participants: A total of 240 adolescents (68% female), aged 7 to 15 years.

Main Outcome Measures: Using dual energy x-ray absorptiometry, bone mineral content (BMC), areal bone mineral density, lean mass, and fat mass were measured. Skeletal sites of interest included the total body and lumbar spine (LS). Waist circumference was measured using an anthropometric tape measure. Insulin and glucose were measured in fasting sera, and the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Path analysis was performed to determine whether the relationship between adiposity and bone was mediated through insulin resistance.

Results: Fat mass (r = 0.467; P < 0.001) and waist circumference (r = 0.487; P < 0.001) correlated positively with HOMA-IR. Controlling for race, sex, maturation, lean mass, and height, fat mass, waist circumference, and HOMA-IR were negatively associated with LS BMC and total body areal bone mineral density (P < 0.05 for all). Additionally, path models for fat mass (95% CI, -5.893 to -0.956) and waist circumference (95% CI, -15.473 to -2.124) showed a negative relationship with LS BMC via HOMA-IR.

Conclusions: These results support an intermediary role of insulin resistance in the relationship between adiposity and LS bone mass.
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http://dx.doi.org/10.1210/jc.2018-00353DOI Listing
March 2019

Of mice and men (and women): Comment on Peacock et al., 2018.

Am J Phys Anthropol 2018 09;167(1):185-189

Department of Integrative Anatomical Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, 90033.

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http://dx.doi.org/10.1002/ajpa.23615DOI Listing
September 2018

Serum 25-Hydroxyvitamin D and Intact Parathyroid Hormone Influence Muscle Outcomes in Children and Adolescents.

J Bone Miner Res 2018 11 27;33(11):1940-1947. Epub 2018 Aug 27.

Department of Foods and Nutrition, University of Georgia, Athens, GA, USA.

Increases in 25-hydroxyvitamin D concentrations are shown to improve strength in adults; however, data in pediatric populations are scant and equivocal. In this ancillary study of a larger-scale, multi-sited, double-blind, randomized, placebo-controlled vitamin D intervention in US children and adolescents, we examined the associations between changes in vitamin D metabolites and changes in muscle mass, strength, and composition after 12 weeks of vitamin D supplementation. Healthy male and female, black and white children and adolescents between the ages of 9 and 13 years from two US states (Georgia 34°N and Indiana 40°N) were enrolled in the study and randomly assigned to receive an oral vitamin D dose of 0, 400, 1000, 2000, or 4000 IU/d for 12 weeks between the winter months of 2009 to 2011 (N = 324). Analyses of covariance, partial correlations, and regression analyses of baseline and 12-week changes (post-baseline) in vitamin D metabolites (serum 25(OH)D, 1,25(OH) D, intact parathyroid hormone [iPTH]), and outcomes of muscle mass, strength, and composition (total body fat-free soft tissue [FFST], handgrip strength, forearm and calf muscle cross-sectional area [MCSA], muscle density, and intermuscular adipose tissue [IMAT]) were assessed. Serum 25(OH)D and 1,25(OH) D, but not iPTH, increased over time, as did fat mass, FFST, forearm and calf MCSA, forearm IMAT, and handgrip strength (p < 0.05). Vitamin D metabolites were not associated with muscle strength at baseline nor after the 12-week intervention. Changes in serum 25(OH)D correlated with decreases in forearm IMAT, whereas changes in serum iPTH predicted increases in forearm and calf MCSA and IMAT (p < 0.05). Overall, increases in 25(OH)D did not influence muscle mass or strength in vitamin D-sufficient children and adolescents; however, the role of iPTH on muscle composition in this population is unknown and warrants further investigation. © 2018 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.3550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556206PMC
November 2018

Throwing enhances humeral shaft cortical bone properties in pre-pubertal baseball players: a 12-month longitudinal pilot study.

J Musculoskelet Neuronal Interact 2018 06;18(2):191-199

Department of Kinesiology and Sport, Pott College of Science, Engineering, and Education, University of Southern Indiana, Evansville, IN 47712.

Objectives: To explore throwing athletes as a prospective, within-subject controlled model for studying the response of the skeleton to exercise.

Methods: Male pre-pubertal throwing athletes (n=12; age=10.3±0.6 yrs) had distal humerus cortical volumetric bone mineral density (Ct.vBMD), cortical bone mineral content (Ct.BMC), total area (Tt.Ar), cortical area (Ct.Ar), medullary area (Me.Ar), cortical thickness (Ct.Th) and polar moment of inertia (IP) assessed within their throwing (exercised) and nonthrowing (control) arms by peripheral quantitative computed tomography at baseline and 12 months. Throwing-to-nonthrowing arm percent differences (i.e. bilateral asymmetry) were compared over time.

Results: Over 12 months, the throwing arm gained 4.3% (95% Cl=1.1% to 7.5%), 2.9% (95% Cl=0.3% to 5.4%), 3.9% (95% Cl=0.7% to 7.0%), and 8.2% (95% Cl=2.0% to 6.8%) more Ct.BMC, Ct.Ar, Tt.Ar, and I than the nonthrowing arm, respectively (all p<0.05). There was no significant effect of throwing on Ct.vBMD, Ct.Th and Me.Ar (all p=0.18-0.82).

Conclusion: Throwing induced surface-specific cortical bone adaptation at the distal humeral diaphysis that contributed to a gain in estimated strength. These longitudinal pilot data support the utility of throwing athletes as a within-subject controlled model to explore factors influencing exercise-induced bone adaptation during the critical growing years.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016504PMC
June 2018

Inhibition of CaMKK2 Enhances Fracture Healing by Stimulating Indian Hedgehog Signaling and Accelerating Endochondral Ossification.

J Bone Miner Res 2018 05 5;33(5):930-944. Epub 2018 Feb 5.

Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA.

Approximately 10% of all bone fractures do not heal, resulting in patient morbidity and healthcare costs. However, no pharmacological treatments are currently available to promote efficient bone healing. Inhibition of Ca /calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) reverses age-associated loss of trabecular and cortical bone volume and strength in mice. In the current study, we investigated the role of CaMKK2 in bone fracture healing and show that its pharmacological inhibition using STO-609 accelerates early cellular and molecular events associated with endochondral ossification, resulting in a more rapid and efficient healing of the fracture. Within 7 days postfracture, treatment with STO-609 resulted in enhanced Indian hedgehog signaling, paired-related homeobox (PRX1)-positive mesenchymal stem cell (MSC) recruitment, and chondrocyte differentiation and hypertrophy, along with elevated expression of osterix, vascular endothelial growth factor, and type 1 collagen at the fracture callus. Early deposition of primary bone by osteoblasts resulted in STO-609-treated mice possessing significantly higher callus bone volume by 14 days following fracture. Subsequent rapid maturation of the bone matrix bestowed fractured bones in STO-609-treated animals with significantly higher torsional strength and stiffness by 28 days postinjury, indicating accelerated healing of the fracture. Previous studies indicate that fixed and closed femoral fractures in the mice take 35 days to fully heal without treatment. Therefore, our data suggest that STO-609 potentiates a 20% acceleration of the bone healing process. Moreover, inhibiting CaMKK2 also imparted higher mechanical strength and stiffness at the contralateral cortical bone within 4 weeks of treatment. Taken together, the data presented here underscore the therapeutic potential of targeting CaMKK2 to promote efficacious and rapid healing of bone fractures and as a mechanism to strengthen normal bones. © 2018 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.3379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549722PMC
May 2018

Progress in the Full-Text Publication Rate of Orthopaedic and Sport Physical Therapy Abstracts Presented at the American Physical Therapy Association's Combined Sections Meeting.

J Orthop Sports Phys Ther 2018 01 7;48(1):44-49. Epub 2017 Oct 7.

Department of Physical Therapy and Center for Translational Musculoskeletal Research, School of Health and Rehabilitation Sciences, Indiana University, Indianapolis, IN.

Study Design Descriptive study. Background Professional meetings, such as the American Physical Therapy Association's (APTA's) Combined Sections Meeting (CSM), provide forums for sharing information. However, it was reported that only one-quarter of orthopaedic and sports physical therapy abstracts presented at the CSM between 2000 and 2004 went on to full-text publication. This low conversion rate raises a number of concerns regarding the full dissemination of work within the profession. Objectives The purpose of this study was to determine the full-text publication rate of work presented in abstract form at subsequent CSMs and investigate factors influencing the rate. Methods A systematic search was undertaken to locate full-text publications of orthopaedic and sports physical therapy abstracts presented at CSMs between 2005 and 2011. Eligible publications were published within 5 years following abstract presentation. The influences of year of abstract presentation, APTA section, presentation type, institution of origin, study design, and study significance were assessed. Results Over one-third (38.6%) of presented abstracts progressed to full-text publication. Odds of full-text publication increased if the abstract was presented as a platform presentation, originated from a doctorate-granting institution, reported findings of an experimental study, or reported a statistically significant finding. Conclusion The full-text publication rate for orthopaedic and sports physical therapy abstracts presented at recent CSMs has increased by over 50% compared to that reported for the preceding period. The rate is now in the range of that reported in comparable clinical disciplines, demonstrating important progress in the full dissemination of work within the profession. J Orthop Sports Phys Ther, Epub 7 Oct 2017. doi:10.2519/jospt.2018.7581.
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http://dx.doi.org/10.2519/jospt.2018.7581DOI Listing
January 2018

Become one with the force: optimising mechanotherapy through an understanding of mechanobiology.

Br J Sports Med 2017 Jul;51(13):989-990

Department of Physical Therapy and Center for Translational Musculoskeletal Research, School of Health and Rehabilitation Sciences, Indiana University, Indianapolis, Indiana, USA.

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http://dx.doi.org/10.1136/bjsports-2017-097634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546094PMC
July 2017

Improving Combination Osteoporosis Therapy in a Preclinical Model of Heightened Osteoanabolism.

Endocrinology 2017 09;158(9):2722-2740

Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202.

Combining anticatabolic agents with parathyroid hormone (PTH) to enhance bone mass has yielded mixed results in osteoporosis patients. Toward the goal of enhancing the efficacy of these regimens, we tested their utility in combination with loss of the transcription factor Nmp4 because disabling this gene amplifies PTH-induced increases in trabecular bone in mice by boosting osteoblast secretory activity. We addressed whether combining a sustained anabolic response with an anticatabolic results in superior bone acquisition compared with PTH monotherapy. Additionally, we inquired whether Nmp4 interferes with anticatabolic efficacy. Wild-type and Nmp4-/- mice were ovariectomized at 12 weeks of age, followed by therapy regimens, administered from 16 to 24 weeks, and included individually or combined PTH, alendronate (ALN), zoledronate (ZOL), and raloxifene (RAL). Anabolic therapeutic efficacy generally corresponded with PTH + RAL = PTH + ZOL > PTH + ALN = PTH > vehicle control. Loss of Nmp4 enhanced femoral trabecular bone increases under PTH + RAL and PTH + ZOL. RAL and ZOL promoted bone restoration, but unexpectedly, loss of Nmp4 boosted RAL-induced increases in femoral trabecular bone. The combination of PTH, RAL, and loss of Nmp4 significantly increased bone marrow osteoprogenitor number, but did not affect adipogenesis or osteoclastogenesis. RAL, but not ZOL, increased osteoprogenitors in both genotypes. Nmp4 status did not influence bone serum marker responses to treatments, but Nmp4-/- mice as a group showed elevated levels of the bone formation marker osteocalcin. We conclude that the heightened osteoanabolism of the Nmp4-/- skeleton enhances the effectiveness of diverse osteoporosis treatments, in part by increasing hyperanabolic osteoprogenitors. Nmp4 provides a promising target pathway for identifying barriers to pharmacologically induced bone formation.
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http://dx.doi.org/10.1210/en.2017-00355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5659666PMC
September 2017

The effect of dairy intake on bone mass and body composition in early pubertal girls and boys: a randomized controlled trial.

Am J Clin Nutr 2017 05 22;105(5):1214-1229. Epub 2017 Mar 22.

Departments of Nutrition Science and

Calcium retention increases with increasing body mass index (BMI) on recommended calcium intakes. Dairy foods are an excellent source of essential nutrients that are needed to increase bone mineral content (BMC) and potentially decrease fracture. We compared children who were overweight with children who were healthy weight for the accrual of bone mass in response to an extra 3 servings dairy/d compared with usual intake. Participants were 240 healthy boys and girls (64%), aged 8-15.9 y (mean ± SD age: 11.8 ± 1.5 y), who consumed low amounts of dairy (<800 mg Ca/d). A total of 181 subjects completed the trial-61% were black, 35% were white, and 4% were other; 50% of subjects were healthy weight [5th through 70th BMI percentiles for age (percentile)], and 50% of subjects were overweight (≥85th percentile). Participants were randomly assigned within BMI categories to receive an 18-mo dairy intervention (3 servings/d equivalent to ∼900 mg Ca/d) or control. Main outcome measures assessed every 6 mo included the total-body bone mineral content and density, cortical and trabecular bone mineral density (BMD), BMC, and bone area at the 4% tibia and anthropometric measures. No significant differences in the change of BMD, BMC, or bone area for the total-body radius, lumbar spine, and total hip were observed between subjects who received the dairy intervention (achieved consumption of 1500 mg Ca/d) and subjects who did not (achieved 1000 mg Ca/d, which represented ∼2 cups milk or other dairy as part of the diet) with the exception of a tibial BMC gain, which was greater in the group who were given dairy ( = 0.02). Body fat was not influenced by the diet assignment. Dairy food interventions generally had no effect on bone mineral acquisition or body composition either within or between weight groups. This study suggests that 2 cups milk or the dairy equivalent is adequate for normal bone gain between ages 8 and 16 y. This trial was registered at clinicaltrials.gov as NCT00635583.
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http://dx.doi.org/10.3945/ajcn.116.140418DOI Listing
May 2017

Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9 to 13 Years.

J Bone Miner Res 2017 Jul;32(7):1537-1545

Department of Foods and Nutrition, The University of Georgia, Athens, GA, USA.

IGF-I is a pivotal hormone in pediatric musculoskeletal development. Although recent data suggest that the role of IGF-I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF-I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass-dependent relationship between IGF-I and cortical bone. Children were otherwise healthy, early adolescent black and white boys and girls (ages 9 to 13 years) and were classified as having high (n = 147) or normal (n = 168) insulin resistance based on the homeostasis model assessment of insulin resistance (HOMA-IR). Cortical bone at the tibia diaphysis (66% site) and total body fat-free soft tissue mass (FFST) were measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA), respectively. IGF-I, insulin, and glucose were measured in fasting sera and HOMA-IR was calculated. Children with high HOMA-IR had greater unadjusted IGF-I (p < 0.001). HOMA-IR was a negative predictor of cortical bone mineral content, cortical bone area (Ct.Ar), and polar strength strain index (pSSI; all p ≤ 0.01) after adjusting for race, sex, age, maturation, fat mass, and FFST. IGF-I was a positive predictor of most musculoskeletal endpoints (all p < 0.05) after adjusting for race, sex, age, and maturation. However, these relationships were moderated by HOMA-IR (p  < 0.05). FFST positively correlated with most cortical bone outcomes (all p < 0.05). Path analyses demonstrated a positive relationship between IGF-I and Ct.Ar via FFST in the total cohort (β = 0.321, p < 0.001). However, this relationship was moderated in the children with high (β = 0.200, p < 0.001) versus normal (β = 0.408, p < 0.001) HOMA-IR. These data implicate insulin resistance as a potential suppressor of IGF-I-dependent cortical bone development, though prospective studies are needed. © 2017 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.3132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489353PMC
July 2017

Electroacupuncture Promotes Central Nervous System-Dependent Release of Mesenchymal Stem Cells.

Stem Cells 2017 05;35(5):1303-1315

Department of Physical Therapy, School of Health and Rehabilitation Sciences, Indianapolis, Indiana, USA.

Electroacupuncture (EA) performed in rats and humans using limb acupuncture sites, LI-4 and LI-11, and GV-14 and GV-20 (humans) and Bai-hui (rats) increased functional connectivity between the anterior hypothalamus and the amygdala and mobilized mesenchymal stem cells (MSCs) into the systemic circulation. In human subjects, the source of the MSC was found to be primarily adipose tissue, whereas in rodents the tissue sources were considered more heterogeneous. Pharmacological disinhibition of rat hypothalamus enhanced sympathetic nervous system (SNS) activation and similarly resulted in a release of MSC into the circulation. EA-mediated SNS activation was further supported by browning of white adipose tissue in rats. EA treatment of rats undergoing partial rupture of the Achilles tendon resulted in reduced mechanical hyperalgesia, increased serum interleukin-10 levels and tendon remodeling, effects blocked in propranolol-treated rodents. To distinguish the afferent role of the peripheral nervous system, phosphoinositide-interacting regulator of transient receptor potential channels (Pirt)-GCaMP3 (genetically encoded calcium sensor) mice were treated with EA acupuncture points, ST-36 and LIV-3, and GV-14 and Bai-hui and resulted in a rapid activation of primary sensory neurons. EA activated sensory ganglia and SNS centers to mediate the release of MSC that can enhance tissue repair, increase anti-inflammatory cytokine production and provide pronounced analgesic relief. Stem Cells 2017;35:1303-1315.
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http://dx.doi.org/10.1002/stem.2613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5530374PMC
May 2017

Hemangioma in the Anterior Thigh With Corresponding Periosteal Bone Reaction.

J Orthop Sports Phys Ther 2017 Mar;47(3):218

A 24-year-old female runner presented to physical therapy via direct access with an 8-month history of mid-thigh pain. At the onset of her symptoms, radiographs were negative; following physical therapy evaluation, additional imaging was requested. Lateral-view radiographs revealed cortical hypertrophy with no stress fracture. Magnetic resonance imaging revealed an enhancing mass adjacent to the anterolateral surface of the mid shaft of the femur, with associated cortical hypertrophy, consistent with a deep intramuscular hemangioma. J Orthop Sports Phys Ther 2017;47(3):218. doi:10.2519/jospt.2017.6302.
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http://dx.doi.org/10.2519/jospt.2017.6302DOI Listing
March 2017

Physical Activity for Strengthening Fracture Prone Regions of the Proximal Femur.

Curr Osteoporos Rep 2017 02;15(1):43-52

Department of Physical Therapy and Center for Translational Musculoskeletal Research, School of Health and Rehabilitation Sciences, Indiana University, 1140 W. Michigan St, Indianapolis, IN, CF-120, USA.

Purpose Of Review: Physical activity improves proximal femoral bone health; however, it remains unclear whether changes translate into a reduction in fracture risk. To enhance any fracture-protective effects of physical activity, fracture prone regions within the proximal femur need to be targeted.

Recent Findings: The proximal femur is designed to withstand forces in the weight-bearing direction, but less so forces associated with falls in a sideways direction. Sideways falls heighten femoral neck fracture risk by loading the relatively weak superolateral region of femoral neck. Recent studies exploring regional adaptation of the femoral neck to physical activity have identified heterogeneous adaptation, with adaptation principally occurring within inferomedial weight-bearing regions and little to no adaptation occurring in the superolateral femoral neck. There is a need to develop novel physical activities that better target and strengthen the superolateral femoral neck within the proximal femur. Design of these activities may be guided by subject-specific musculoskeletal modeling and finite-element modeling approaches.
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http://dx.doi.org/10.1007/s11914-017-0343-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5317179PMC
February 2017

Do Selective Serotonin Reuptake Inhibitors (SSRIs) Cause Fractures?

Curr Osteoporos Rep 2016 10;14(5):211-8

Center for Translational Musculoskeletal Research and Department of Physical Therapy, School of the Health and Rehabilitation Sciences, Indiana University, 1140 W. Michigan St., CF-120, Indianapolis, IN, USA.

Recent meta-analyses report a 70 % increase in fracture risk in selective serotonin reuptake inhibitor (SSRI) users compared to non-users; however, included studies were observational and limited in their ability to establish causality. Here, we use the Bradford Hill criteria to explore causality between SSRIs and fractures. We found a strong, consistent, and temporal relationship between SSRIs and fractures, which appears to follow a biological gradient. However, specificity and biological plausibility remain concerns. In terms of specificity, the majority of available data have limitations due to either confounding by indication or channeling bias. Self-controlled case series address some of these limitations and provide relatively strong observational evidence for a causal relationship between SSRIs and fracture. In doing so, they suggest that falls contribute to fractures in SSRI users. Whether there are also underlying changes in skeletal properties remains unresolved. Initial studies provide some evidence for skeletal effects of SSRIs; however, the pathways involved need to be established before biological plausibility can be accepted. As the link between SSRIs and fractures is based on observational data and not evidence from prospective trials, there is insufficient evidence to definitively determine a causal relationship and it appears premature to label SSRIs as a secondary cause of osteoporosis. SSRIs appear to contribute to fracture-inducing falls, and addressing any fall risk associated with SSRIs may be an efficient approach to reducing SSRI-related fractures. As fractures stemming from SSRI-induced falls are more likely in individuals with compromised bone health, it is worth considering bone density testing and intervention for those presenting with risk factors for osteoporosis.
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http://dx.doi.org/10.1007/s11914-016-0322-3DOI Listing
October 2016

Vitamin D Supplementation Does Not Impact Insulin Resistance in Black and White Children.

J Clin Endocrinol Metab 2016 04 17;101(4):1710-8. Epub 2016 Feb 17.

Departments of Foods and Nutrition (A.J.F., E.M.L., D.B.Hau., and R.D.L.) and Statistics (D.B.Hal.), The University of Georgia, Athens, Georgia 30602; Departments of Nutrition Science (C.M.W., B.R.M., K.M.H.G.) and Statistics (G.P.M.), Purdue University, West Lafayette, Indiana 47907; Department of Medicine (M.P.), Indiana University School of Medicine, Indianapolis, Indiana 46202; Department of Physical Therapy (S.J.W.), Indiana University School of Health and Rehabilitation Sciences, Indianapolis, Indiana 46202.

Context: Vitamin D supplementation trials with diabetes-related outcomes have been conducted almost exclusively in adults and provide equivocal findings.

Objective: The objective of this study was to determine the dose-response of vitamin D supplementation on fasting glucose, insulin, and a surrogate measure of insulin resistance in white and black children aged 9–13 years, who participated in the Georgia, Purdue, and Indiana University (or GAPI) trial: a 12-week multisite, randomized, triple-masked, dose-response, placebo-controlled vitamin D trial.

Design: Black and white children in the early stages of puberty (N = 323, 50% male, 51% black) were equally randomized to receive vitamin D3 (0, 400, 1000, 2000, or 4000 IU/day) for 12 weeks. Fasting serum 25-hydroxyvitamin D (25(OH)D), glucose and insulin were assessed at baseline and weeks 6 and 12. Homeostasis model assessment of insulin resistance was used as a surrogate measure of insulin resistance. Statistical analyses were conducted as intent-to-treat using a mixed effects model.

Results: Baseline serum 25(OH)D was inversely associated with insulin (r = −0.140, P = 0.017) and homeostasis model assessment of insulin resistance (r = −0.146, P = 0.012) after adjusting for race, sex, age, pubertal maturation, fat mass, and body mass index. Glucose, insulin, and insulin resistance increased (F > 5.79, P < .003) over the 12 weeks, despite vitamin D dose-dependent increases in serum 25(OH)D.

Conclusions: Despite significant baseline inverse relationships between serum 25(OH)D and measures of insulin resistance, vitamin D supplementation had no impact on fasting glucose, insulin, or a surrogate measure of insulin resistance over 12 weeks in apparently healthy children.
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http://dx.doi.org/10.1210/jc.2015-3687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880166PMC
April 2016

A Preliminary Study on the Efficacy of a Community-Based Physical Activity Intervention on Physical Function-Related Risk Factors for Falls Among Breast Cancer Survivors.

Am J Phys Med Rehabil 2016 08;95(8):561-70

From the School of Medical Rehabilitation Sciences, University of Manitoba, Winnipeg, Manitoba, Canada (CEL); School of Health and Rehabilitation Sciences, Indiana University, Indianapolis, Indiana (SJW); Winnipeg Regional Health Authority Breast Health Centre, Winnipeg, Manitoba, Canada (BS); and Department of Hematology/Oncology, CancerCare Manitoba, Winnipeg, Manitoba, Canada (YKJL).

Objective: The aim of this study was to examine the effects of a 6-week community-based physical activity (PA) intervention on physical function-related risk factors for falls among 56 breast cancer survivors (BCS) who had completed treatments.

Design: This was a single-group longitudinal study. The multimodal PA intervention included aerobic, strengthening, and balance components. Physical function outcomes based on the 4-meter walk, chair stand, one-leg stance, tandem walk, and dynamic muscular endurance tests were assessed at 6-week pre-intervention (T1), baseline (T2), and post-intervention (T3). T1 to T2 and T2 to T3 were the control and intervention periods, respectively.

Results: All outcomes, except the tandem walk test, significantly improved after the intervention period (P < 0.05), with no change detected after the control period (P > 0.05). Based on the falls risk criterion in the one-leg stance test, the proportion at risk for falls was significantly lower after the intervention period (P = 0.04), but not after the control period.

Conclusions: A community-based multimodal PA intervention for BCS may be efficacious in improving physical function-related risk factors for falls, and lowering the proportion of BCS at risk for falls based on specific physical function-related falls criteria. Further larger trials are needed to confirm these preliminary findings.
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http://dx.doi.org/10.1097/PHM.0000000000000440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4949097PMC
August 2016

Understanding Mechanobiology: Physical Therapists as a Force in Mechanotherapy and Musculoskeletal Regenerative Rehabilitation.

Phys Ther 2016 Apr 4;96(4):560-9. Epub 2015 Dec 4.

S.J. Warden, PT, PhD, FACSM, Department of Physical Therapy and Center for Translational Musculoskeletal Research, School of Health and Rehabilitation Sciences, Indiana University, 1140 W Michigan St, CF-326. Indianapolis, IN 46202 (USA).

Achieving functional restoration of diseased or injured tissues is the ultimate goal of both regenerative medicine approaches and physical therapy interventions. Proper integration and healing of the surrogate cells, tissues, or organs introduced using regenerative medicine techniques are often dependent on the co-introduction of therapeutic physical stimuli. Thus, regenerative rehabilitation represents a collaborative approach whereby rehabilitation specialists, basic scientists, physicians, and surgeons work closely to enhance tissue restoration by creating tailored rehabilitation treatments. One of the primary treatment regimens that physical therapists use to promote tissue healing is the introduction of mechanical forces, or mechanotherapies. These mechanotherapies in regenerative rehabilitation activate specific biological responses in musculoskeletal tissues to enhance the integration, healing, and restorative capacity of implanted cells, tissues, or synthetic scaffolds. To become future leaders in the field of regenerative rehabilitation, physical therapists must understand the principles of mechanobiology and how mechanotherapies augment tissue responses. This perspective article provides an overview of mechanotherapy and discusses how mechanical signals are transmitted at the tissue, cellular, and molecular levels. The synergistic effects of physical interventions and pharmacological agents also are discussed. The goals are to highlight the critical importance of mechanical signals on biological tissue healing and to emphasize the need for collaboration within the field of regenerative rehabilitation. As this field continues to emerge, physical therapists are poised to provide a critical contribution by integrating mechanotherapies with regenerative medicine to restore musculoskeletal function.
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http://dx.doi.org/10.2522/ptj.20150224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4817213PMC
April 2016

Effects of exercise and manual therapy on pain associated with hip osteoarthritis: a systematic review and meta-analysis.

Br J Sports Med 2016 Apr 26;50(8):458-63. Epub 2015 Nov 26.

School of Health and Rehabilitation Sciences, The University of Queensland, Brisbane, Queensland, Australia School of Allied Health, College of Science, Health and Engineering, La Trobe University, Bundoora, Victoria, Australia.

Aim: 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.
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http://dx.doi.org/10.1136/bjsports-2015-095255DOI Listing
April 2016