Stuart J Warden

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Verified

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• BPhysio (Hons), PhD, FACSM, FASBMR
• Chancellor's Professor at Indiana University Indianapolis

Significance Bones adapt to mechanical forces in youth to increase their size and strength but are more at risk for breaking later in life. Do the skeletal benefits of physical activity in youth persist with aging? Here we show at an upper extremity site that half of the benefit in bone size and one-third of the benefit in bone strength obtained fr...

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...

Purpose: Female runners have high rates of bone stress injuries (BSIs), including stress reactions and fractures. The current study explored multidirectional sports (MDS) played when younger as a potential means of building stronger bones to reduce BSI risk in these athletes. Methods: Female collegiate-level cross-country runners were recruited...

Few studies have explored hip morphology and cartilage composition in female athletes or the impact of asymmetric repetitive loading, such as occurs during softball pitching. The current cross-sectional study assessed bilateral bony hip morphology on computed tomography imaging in collegiate-level softball pitchers (‘Pitch1’, n = 25) and cross-coun...

Bone stress injuries, commonly referred to as stress reactions and stress fractures, represent overuse injuries to bone. These injuries result in physical limitations in activity and can be career-ending for high-level athletes. While bone stress injuries have received increased attention in recent years, international consensus is lacking on defin...

High resolution peripheral quantitative computed tomography (HRpQCT) offers detailed bone geometry and microarchitecture assessment, including cortical porosity, but assessing chronic kidney disease (CKD) bone images remains challenging. This proof-of-concept study merges deep learning and machine learning to 1) improve automatic segmentation, part...

Background: Patients with sarcopenia often go undetected in busy clinical practices since the muscle measurements are not easily incorporated into routine clinical practice. The current research fills the gap by utilizing unstructured clinical notes combined with structured data from electronic health records (EHR), to increase sarcopenia detection...

Endurance events are popular worldwide and have many health benefits. However, runners and Para athletes may sustain musculoskeletal injuries or experience other health consequences from endurance events. The American Medical Society for Sports Medicine (AMSSM) Runner Health Consortium aimed to generate consensus-based survey items for use in prosp...

Cross-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 isometr...

Context Autosomal dominant osteopetrosis (ADO) is a rare genetic disorder resulting from impaired osteoclastic bone resorption. Clinical manifestations frequently include fractures, osteonecrosis (particularly of the jaw or maxilla), osteomyelitis, blindness, and/or bone marrow failure. ADO usually results from heterozygous missense variants in the...

We evaluated biochemical changes in skeletal muscle of women with breast cancer initiating aromatase inhibitors (AI), including oxidation of ryanodine receptor RyR1 and loss of stabilizing protein calstabin1, and detailed measures of muscle function. Fifteen postmenopausal women with stage I–III breast cancer planning to initiate AI enrolled. Quadr...

Voltage sensitive calcium channels (VSCCs) influence bone structure and function, including anabolic responses to mechanical loading. While the pore-forming (α1) subunit of VSCCs allows Ca2+ influx, auxiliary subunits regulate the biophysical properties of the pore. The α2δ1 subunit influences gating kinetics of the α1 pore and enables mechanically...

Osteoporosis is characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility (i.e., weakness) and an increased risk for fracture. The current standard for assessing bone health and diagnosing osteoporosis is dual-energy x-ray absorptiometry (DXA), which quantifies areal bone mineral density (BMD), typically...

Epidemiological studies have reported a strong association between circulating Klotho and physical function; however, the cohorts were comprised of older adults with multiple comorbidities. Herein, we examined the relationship between Klotho and physical function in a community-based cohort of healthy adults. In this cross-sectional study, serum Kl...

As both L- and D-BAIBA are increased with exercise, we sought to determine if circulating levels would be associated with physical performance. Serum levels of L- and D-BAIBA were quantified in 120 individuals (50% female) aged 20–85 years and categorized as either a “low” (LP), “average” (AP) or “high” performing (HP). Association analysis was per...

Declining physical performance with age and disease is an important indicator of declining health. Biomarkers that identify declining physical performance would be useful in predicting treatment outcomes and identifying potential therapeutics. γ-aminobutyric acid (GABA), a muscle autocrine factor, is a potent inhibitor of muscle function and works...

Introduction Sarcopenia (low muscle mass and strength) causes dysmobility and loss of independence. Sarcopenia is often not directly coded or described in electronic health records (EHR). The objective was to improve sarcopenia detection using structured data from EHR. Methods Adults undergoing musculoskeletal testing (December 2017–March 2020) we...

Background The impact of activity-related joint loading on cartilage is not clear. Abnormal loading is considered to be a mechanical driver of osteoarthritis (OA), yet moderate amounts of physical activity and rehabilitation exercise can have positive effects on articular cartilage. Our aim was to investigate the immediate effects of joint loading...

Composite tissue injuries (CTIs) in extremities include segmental bone defects (SBDs) and volumetric muscle loss. The objective of this study was to determine if skeletal muscle autografting with minced muscle grafts (MMGs) could improve healing in a SBD and improve muscle function in a porcine CTI model that includes a SBD and adjacent volumetric...

Introduction: Running is one of the most popular recreational activities worldwide, due to its low cost and accessibility. However, little is known about the impact of running on knee joint health in runners with and without a history of knee surgery. The primary aim of this longitudinal cohort study is to compare knee joint structural features on...

Objective Bone stress injuries (BSIs) are classified in clinical practice as being at low- or high-risk for complication based on the injury location. However, this dichotomous approach has not been sufficiently validated. The purpose of this systematic review was to examine the prognostic role of injury location on return-to-sport (RTS) and treatm...

Introduction High-resolution peripheral quantitative computed tomography (HR-pQCT) is a powerful tool that has revolutionized 3D longitudinal assessment of bone microarchitecture. However, cortical porosity, a common characteristic of cortical bone loss, is still often determined by static evaluation of overall porosity at one timepoint. Therefore,...

Background The general health benefits of running are well-established, yet concern exists regarding the development and progression of osteoarthritis. Aim To systematically review the immediate (within 20 minutes) and delayed (20 minutes to 48 hours) effect of running on hip and knee cartilage, as assessed using magnetic resonance imaging (MRI)....

Purpose of Review In this review, we discuss the mechanism of action of gabapentinoids and the potential consequences of long-term treatment with these drugs on the musculoskeletal system. Recent Findings Gabapentinoids, such as gabapentin (GBP) and pregabalin (PGB) were designed as antiepileptic reagents and are now commonly used as first-line tr...

The osteopetroses are a group of rare genetic diseases caused by osteoclast dysfunction or absence. The hallmark of osteopetrosis is generalized increased bone mineral density (BMD). However, the bone is fragile and fractures are common. Autosomal recessive osteopetrosis is usually a severe disorder and often life‐threatening in childhood. We prese...

Bone stress injuries, including stress fractures, are overuse injuries that lead to substantial morbidity in active individuals. These injuries occur when excessive repetitive loads are introduced to a generally normal skeleton. Although the precise mechanisms for bone stress injuries are not completely understood, the prevailing theory is that an...

The tibia is a common site for bone stress injuries, which are believed to develop from microdamage accumulation to repetitive sub-yield strains. There is a need to understand how the tibia is loaded in vivo to understand how bone stress injuries develop and design exercises to build a more robust bone. Here, we use subject-specific, muscle-driven,...

Objective Identifying muscle weakness and probable sarcopenia using strength tests requires reference data. This study aimed to provide age- and sex-specific normative data for grip strength and common variations of the sit-to-stand (STS) test: time to complete 5 stands (5x-STS), and number of stands completed in 30 seconds (30s-STS). Predictors of...

High-resolution peripheral quantitative computed tomography (HR-pQCT) is a powerful tool to assess bone health. To determine how an individual’s or population of interest’s HR-pQCT outcomes compare to expected, reference data are required. This study provides reference data for HR-pQCT measures acquired in a population of White adults.PurposeTo pro...

Introduction 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...

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 impa...

Physical activity enhances proximal femur bone mass, but it remains unclear whether the benefits translate into an enhanced ability to resist fracture related loading. We recently used baseball pitchers as a within-subject controlled model to demonstrate physical activity induced proximal femur adaptation in regions associated with weight bearing a...

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 metata...

Purpose: 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...

FULL TEXT ARTICLE FOUND HERE: https://rdcu.be/b724e 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 : Clin...

Vor allem Läufer kennen das Problem: völlig unvermittelt bekommen sie Beschwerden, die so stark sind, dass sie nicht mehr weitermachen können. Im schlimmsten Fall leiden sie an den schmerzhaften Folgen einer Stressfraktur. Wer im Training die richtigen Reize setzt, kann das Risiko für derartige Verletzungen deutlich verringern.

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...

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) modelin...

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/+ IU) and normal littermates (NL) were...

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...

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,...

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-...

Context Insulin resistance is an adverse health outcome that accompanies obesity. Fat mass is negatively associated with bone mass while adjusting for confounders, and insulin resistance might be an intermediary in this relationship. Objective Determine whether insulin resistance is an intermediary in the relationship between adiposity and bone ma...

The pathology continuum from stress reaction to stress fracture and complete bone fracture is captured by the term bone stress injury (BSI). The mechanism responsible for BSIs remains theoretical; however, there is consensus that it involves an imbalance between load‐induced microdamage formation and its removal. In the scenario of patients taking...

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 chan...

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),...

Introduction: This study examined the relationships between egg consumption and cortical bone in children. Methods: The cross-sectional study design included 294 9-13-year-old black and white males and females. Three-day diet records determined daily egg consumption. Peripheral quantitative computed tomography measured radius and tibia cortical...

Objectives Meetings promote information sharing, but do not enable full dissemination of details. A systematic search was conducted for abstracts presented at the 2010 and 2011 Association of Applied Sport Psychology Annual Conferences to determine the full-text dissemination rate of work presented in abstract form and investigate factors influenci...

Physical activity (PA) and inactivity during adolescence have implications for short- and long-term bone health. Given the mechanical role of the skeleton, it follows that skeletal tissue can respond and adapt to its mechanical environment. The time prior to and including physical maturation during adolescence affords a “window of opportunity” to t...

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 Ca²⁺/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) reverses age-associated loss of trabecular and cortical bone volume...

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 Sections abstracts presented at the CSM between 2000 and 20...

Combining anti-catabolic agents with parathyroid hormone (PTH) to enhance bone mass has yielded mixed results in osteoporosis patients. Towards the goal of enhancing the efficacy of these regimens, we tested their utility in combination with loss of the transcription factor Nmp4 since disabling this gene amplifies PTH-induced increases in trabecula...

• Review the extent and mechanisms of bone morbidity due to osteoporosis in DMD.

Electro-acupuncture (EA) performed in rats and humans using front-limb acupuncture sites, LI-4 and LI-11, and Du-14 and Du-20 increased functional connectivity between the anterior hypothalamus and the amygdala and mobilized mesenchymal stem cells (MSC) into the systemic circulation. In human subjects, the source of the MSC was found to be primaril...

Introduction: The current study explored physical activity-induced bone adaptation at different stages of somatic maturity by comparing side-to-side differences in midshaft humerus properties between male throwing athletes and controls. Throwers present an internally controlled model, while inclusion of control subjects removes normal arm dominanc...

Background: 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. Objective: We compared children who were overweight with children who were healthy weight f...

IGF-I is a pivotal hormone in pediatric musculoskeletal development. Though 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 insuli...

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 im...

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...

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, cons...

Purpose: 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)...

Abstract: Background: Total hip arthroplasty relieves joint pain in patients with end stage osteoarthritis. However, postoperative muscle atrophy often results in suboptimal lower limb function. There is a need to improve functional recovery after total hip arthroplasty. Objectives: To assess safety and efficacy of LY2495655, a humanized monoclonal...

Context: Vitamin D supplementation trials with diabetes-related outcomes have been conducted almost exclusively in adults and provide equivocal findings. Objective: 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 to 13 years,...

An 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 m...

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, s...

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 is often dependent upon the co-introduction of therapeutic physic...

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 M...

Background: Myostatin inhibits skeletal muscle growth. The humanised monoclonal antibody LY2495655 (LY) binds and neutralises myostatin. We aimed to test whether LY increases appendicular lean body mass (aLBM) and improves physical performance in older individuals who have had recent falls and low muscle strength and power. Methods: In this proo...

Parathyroid hormone (PTH) is an osteoanabolic for treating osteoporosis but its potency wanes. Disabling the transcription factor Nmp4 in healthy, ovary-intact mice enhances bone response to PTH and BMP2 and protects from unloading-induced osteopenia. These Nmp4(-/-) mice exhibit expanded bone marrow (BM) populations of osteoprogenitors and support...