IU Indianapolis ScholarWorks :: Browsing by Subject "Musculoskeletal"

Browsing by Subject "Musculoskeletal"

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Advancing patient evidence in XLH (APEX): rationale and design of a real-world XLH global data unification program
(Frontiers Media, 2025-04-07) Brandi, Maria Luisa; Carpenter, Thomas O.; Fukumoto, Seiji; Haffner, Dieter; Imel, Erik A.; Kanematsu, Masanori; McCullough, Keith P.; Ozono, Keiichi; Medicine, School of Medicine
X-linked hypophosphatemia (XLH) is a rare, genetic, progressive, lifelong disorder caused by pathogenic variants in the phosphate-regulating endopeptidase homolog, X-linked (PHEX) gene, resulting in excess fibroblast growth factor 23 (FGF23) and consequent renal phosphate wasting. Chronic hypophosphatemia leads to deficits of the musculoskeletal system affecting bone, muscle, joint, and dental health. XLH treatments include oral phosphate and active vitamin D-which are associated with a burdensome dosing regimen, gastrointestinal disturbances, hyperparathyroidism, and nephrocalcinosis-or burosumab, a fully human anti-FGF23 antibody. Randomized clinical trials (RCTs) demonstrated burosumab to be well tolerated and efficacious in improving serum phosphate, rickets, bone turnover, and patient-reported outcomes. However, there are limited data on the natural history of XLH or real-world comparisons of the safety, effectiveness, and long-term outcomes of XLH treatments. Advancing Patient Evidence in XLH (APEX) is a global data unification project aiming to describe the burden and lifelong progression of XLH, collect real-world data on treatment effectiveness and safety, and investigate regional differences in treatment outcomes. Participants from three observational, noninterventional, retrospective and prospective, multicenter, longitudinal (10-year) studies of patients with XLH will be included: XLH Disease Monitoring Program (NCT03651505), International XLH Registry (NCT03193476), and SUNFLOWER (NCT03745521). Data collected in the Americas, Europe, Israel, Japan, and South Korea will be processed to unify identical and similar data elements. Data unification will be an iterative process with a clinical and programming review, ensuring validity and accuracy. In this observational study, unified data involving approximately 2000 pediatric and adult participants with XLH will be analyzed to address research questions in an exploratory manner. Long-term observational studies and patient registries provide opportunities to generate real-world data and address knowledge gaps in rare diseases. APEX aims to improve clinical decision-making and practice by bridging evidence gaps that cannot be addressed by RCTs or regional registries.
Development of a Musculoskeletal Ultrasound Curriculum for Internal Medicine Residents
(2025-04-25) Chaudhari, Rachna; Wilson, Reid; Chaudhari, Sonia; Ventura, Meredith
Introduction/Background: As the utilization of point of care ultrasound (POCUS) increases in internal medicine, residency programs have begun to implement aspects of training within the curriculum. Most residency programs focus on cardiac and lung, but few have strong outpatient curriculums as evidenced by literature search. Study objective/hypothesis: Our hypothesis is that by implementing a musculoskeletal (MSK) ultrasound lecture and basic skills workshop among the first-year residents at our program, knowledge of MSK POCUS in the outpatient setting will increase. Methods: This study includes internal medicine residents from Indiana University. Likert scale surveys were provided to participants to assess current knowledge, perceptions, and current utilization of diagnostic musculoskeletal ultrasound in practice. Residents then participate in a mandatory lecture session which is followed by a simulation session. A post survey utilizing a Likert scale survey will be provided to assess resident’s knowledge acquisition and utility of the session. Chi square analysis was done on pre and post survey questions. Results: 74% of PGY-1 residents had not been trained on MSK POCUS prior to residency. Prior to residency, 44% of PGY-1’s were extremely uncomfortable obtaining and interpreting MSK POCUS images, and 39% and 27% of PGY-1s were somewhat uncomfortable. Following the session, knowledge and skills improved (p<0.05). Prior to the session, 61% of respondents were uncomfortable with performing physical exam maneuvers to identify common orthopedic pathologies of the knee. After the session, 83% of respondents stated they were more comfortable (p<0.05). Conclusions: MSK POCUS can be easily incorporated into the residency curriculum. Though the power of this study was low due to low sample size, there was improvement in knowledge and skills before and after the session. In the future, this curriculum could be replicated with more residents to better assess efficacy of this pilot program.
Fat-water separation by fast metabolite cycling magnetic resonance spectroscopic imaging at 3 T: A method to generate separate quantitative distribution maps of musculoskeletal lipid components
(Wiley, 2020-09) Alhulail, Ahmad A.; Patterson, Debra A.; Xia, Pingyu; Zhou, Xiaopeng; Lin, Chen; Thomas, M. Albert; Dydak, Ulrike; Emir, Uzay E.; Radiology and Imaging Sciences, School of Medicine
Purpose: To provide a rapid, noninvasive fat-water separation technique that allows producing quantitative maps of particular lipid components. Methods: The calf muscles in 5 healthy adolescents (age 12-16 years; body mass index = 20 ± 3 kg/m2 ) were scanned by two different fat fraction measurement methods. A density-weighted concentric-ring trajectory metabolite-cycling MRSI technique was implemented to collect data with a nominal resolution of 0.25 mL within 3 minutes and 16 seconds. For comparative purposes, the standard Dixon technique was performed. The two techniques were compared using structural similarity analysis. Additionally, the difference in the distribution of each lipid over the adolescent calf muscles was assessed based on the MRSI data. Results: The proposed MRSI technique provided individual fat fraction maps for eight musculoskeletal lipid components identified by LCModel analysis (IMC/L [CH3 ], EMCL [CH3 ], IMC/L [CH2 ]n , EMC/L [CH2 ]n , IMC/L [CH2 -CH], EMC/L [CH2 -CH], IMC/L [-CH=CH-], and EMC/L [-CH=CH-]) with mean structural similarity indices of 0.19, 0.04, 0.03, 0.50, 0.45, 0.04, 0.07, and 0.12, respectively, compared with the maps generated by the used Dixon method. Further analysis of voxels with zero structural similarity demonstrated an increased sensitivity of fat fraction lipid maps from the data acquired using this MRSI technique over the standard Dixon technique. The lipid spatial distribution over calf muscles was consistent with previously published findings in adults. Conclusion: This MRSI technique can be a useful tool when individual lipid fat fraction maps are desired within a clinically acceptable time and with a nominal spatial resolution of 0.25 mL.
The Impacts of COVID-19 on Musculoskeletal Health
(Springer, 2022) Awosanya, Olatundun D.; Dadwal, Ushashi C.; Imel, Erik A.; Yu, Qigui; Kacena, Melissa A.; Orthopaedic Surgery, School of Medicine
Purpose of review: Although COVID-19 was originally characterized as a respiratory disease, recent findings have shown lingering side effects in those who have recovered, and much is still unknown about the long-term consequences of the illness. Thus, the potential of unearthing multi-system dysfunction is high, with current data revealing significant impacts on musculoskeletal health. Recent findings: Multiple animal models of COVID-19 infection have revealed significant post-infection bone loss at several different skeletal sites. While how this loss occurred is unknown, this current review discusses the primary bone loss studies, and examines the possible mechanisms of action including: direct infection of bone marrow macrophages or hematopoietic progenitors, a proinflammatory response as a result of the COVID-19 induced cytokine storm, and/or a result of hypoxia and oxidative stress. This review will further examine how therapeutics used to treat COVID-19 affect the skeletal system. Finally, this review will examine the possible consequence that delayed care and limited healthcare accessibility has on musculoskeletal-related patient outcomes. It is important to investigate the potential impact COVID-19 infection has on musculoskeletal health.
Impairment of early fracture healing by skeletal muscle trauma is restored by FK506
(Springer Nature, 2017-06-12) Hurtgen, Brady J.; Henderson, Beth E. P.; Ward, Catherine L.; Goldman, Stephen M.; Garg, Koyal; McKinley, Todd O.; Greising, Sarah M.; Wenke, Joseph C.; Corona, Benjamin T.; Orthopaedic Surgery, School of Medicine
BACKGROUND: Heightened local inflammation due to muscle trauma or disease is associated with impaired bone regeneration. METHODS: We hypothesized that FK506, an FDA approved immunomodulatory compound with neurotrophic and osteogenic effects, will rescue the early phase of fracture healing which is impaired by concomitant muscle trauma in male (~4 months old) Lewis rats. FK506 (1 mg/kg; i.p.) or saline was administered systemically for 14 days after an endogenously healing tibia osteotomy was created and fixed with an intermedullary pin, and the overlying tibialis anterior (TA) muscle was either left uninjured or incurred volumetric muscle loss injury (6 mm full thickness biopsy from middle third of the muscle). RESULTS: The salient observations of this study were that 1) concomitant TA muscle trauma impaired recovery of tibia mechanical properties 28 days post-injury, 2) FK506 administration rescued the recovery of tibia mechanical properties in the presence of concomitant TA muscle trauma but did not augment mechanical recovery of an isolated osteotomy (no muscle trauma), 3) T lymphocytes and macrophage presence within the traumatized musculature were heightened by trauma and attenuated by FK506 3 days post-injury, and 4) T lymphocyte but not macrophage presence within the fracture callus were attenuated by FK506 at 14 days post-injury. FK506 did not improve TA muscle isometric torque production CONCLUSION: Collectively, these findings support the administration of FK506 to ameliorate healing of fractures with severe muscle trauma comorbidity. The results suggest one potential mechanism of action is a reduction in local T lymphocytes within the injured musculoskeletal tissue, though other mechanisms to include direct osteogenic effects of FK506 require further investigation.
Musculoskeletal phenotypes in 3q29 deletion syndrome
(medRxiv, 2023-04-03) Pollak, Rebecca M.; Tilmon, Jacob C.; Murphy, Melissa M.; Gambello, Michael J.; Sanchez Russo, Rossana; Dormans, John P.; Mulle, Jennifer G.; Graduate Medical Education, School of Medicine
3q29 deletion syndrome (3q29del) is a rare genomic disorder caused by a 1.6 Mb deletion (hg19, chr3:195725000–197350000). 3q29del is associated with neurodevelopmental and psychiatric phenotypes, including an astonishing >40-fold increased risk for schizophrenia, but medical phenotypes are less well-described. We used the online 3q29 registry (3q29deletion.org) to recruit 57 individuals with 3q29del (56.14% male) and requested information about musculoskeletal phenotypes with a custom questionnaire. 85.96% of participants with 3q29del reported at least one musculoskeletal phenotype. Congenital anomalies were most common (70.18%), with pes planus (40.35%), pectus excavatum (22.81%), and pectus carinatum (5.26%) significantly elevated relative to the pediatric general population. 49.12% of participants reported fatigue after 30 minutes or less of activity. Bone fractures (8.77%) were significantly elevated relative to the pediatric general population, suggesting 3q29del impacts bone strength. Participants commonly report receiving medical care for musculoskeletal complaints (71.93%), indicating that these phenotypes impact quality of life for individuals with 3q29del. This is the most comprehensive description of musculoskeletal phenotypes in 3q29del to date, suggests ideas for clinical evaluation, and expands our understanding of the phenotypic spectrum of this syndrome.
Neurodegeneration Risk Factor TREM2 R47H Mutation Causes Distinct Sex- and Age- Dependent Musculoskeletal Phenotype
(2022-05) Essex, Alyson Lola; Plotkin, Lillian I.; Bonetto, Andrea; Allen, Matthew; Landreth, Gary E.
Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), a receptor expressed in myeloid cells including microglia in brain and osteoclasts in bone has been proposed as a link between brain and bone disease. Previous studies identified an AD-associated mutation (R47H) which is known to confer an increased risk for developing AD. In these studies, we used a heterozygous model of the TREM2 R47H variant (TREM2R47H/+), which does not exhibit cognitive defects, as a translational model of genetic risk factors that contribute to AD, and investigated whether alterations to TREM2 signaling could also contribute to bone and skeletal muscle loss, independently of central nervous system defects. Our study found that female TREM2R47H/+ animals experience bone loss in the femoral mid-diaphysis between 4 and 13 months of age as measured by microCT, which stalls out by 20 months of age. Female TREM2R47H/+ animals also experience significant decreases in the mechanical and material properties of the femur measured by three-point bending at 13 months of age, but not at 4 or 20 months. Interestingly, male TREM2R47H/+ animals do not demonstrate any discernable differences in bone geometry or strength until 20 months of age, where we observed slight changes in the bone volume and material properties of male TREM2R47H/+ bones. Ex vivo osteoclast differentiation assays demonstrate that only male TREM2R47H/+ osteoclasts differentiate more after 7 days with osteoclast differentiation factors compared to WT, but qPCR follow-up showed sexdependent differences in intracellular signaling. However, bone is not the only musculoskeletal tissue affected by the TREM2 R47H variant. Skeletal muscle strength measured by both in vivo plantar flexion and ex vivo contractility of the soleus is increased and body composition is altered in female TREM2R47H/+ mice compared to WT, and this is not likely due to bone-muscle crosstalk. These studies suggests that TREM2 R47H expression in the bone and skeletal muscle are likely impacting each tissue independently. These data demonstrate that AD-associated variants in TREM2 can alter bone and skeletal muscle strength in a sex-dimorphic manner independent of the presence of central neuropathology.
Osteopetrosis in the Pediatric Patient: What the Radiologist Needs to Know
(Springer, 2024) McLuckey, Morgan N.; Imel, Erik A.; Forbes-Amrhein, Monica M.; Radiology and Imaging Sciences, School of Medicine
Osteopetrosis describes several types of rare sclerosing bone dysplasias of varying clinical and radiographic severity. The classic autosomal dominant subtype emerges most often in adolescence but can present from infancy through adulthood. The autosomal recessive osteopetrosis, or "malignant infantile osteopetrosis," presents in infancy with a grimmer prognosis, though the autosomal dominant forms (often mislabeled as "benign") actually can have life-threatening consequences as well. Often osteopetrosis is detected due to skeletal findings on radiographs performed to evaluate injury or as an incidental finding during evaluation for illness. Given the varied phenotypic severity and presentations at different ages, radiologists play an integral role in the care of these patients both in diagnosis and in clinical evaluation and monitoring. A deeper understanding of the underlying genetic basis of the disease can aid in the radiologist in diagnosis and in anticipation of unique complications. An overview of current clinical management is also discussed.
The Relationship Between Body Mass Index and Pain Intensity Among Veterans with Musculoskeletal Disorders: Findings from the MSD Cohort Study
(Oxford University Press, 2020-10-01) Higgins, Diana M.; Buta, Eugenia; Heapy, Alicia A.; Driscoll, Mary A.; Kerns, Robert D.; Masheb, Robin; Becker, William C.; Hausmann, Leslie R.M.; Bair, Matthew J.; Wandner, Laura; Janke, E. Amy; Brandt, Cynthia A.; Goulet, Joseph L.; Medicine, School of Medicine
Objective: To examine the relationship between body mass index (BMI) and pain intensity among veterans with musculoskeletal disorder diagnoses (MSDs; nontraumatic joint disorder; osteoarthritis; low back, back, and neck pain). Setting: Administrative and electronic health record data from the Veterans Health Administration (VHA). Subjects: A national cohort of US military veterans with MSDs in VHA care during 2001-2012 (N = 1,759,338). Methods: These cross-sectional data were analyzed using hurdle negative binomial models of pain intensity as a function of BMI, adjusted for comorbidities and demographics. Results: The sample had a mean age of 59.4, 95% were male, 77% were white/Non-Hispanic, 79% were overweight or obese, and 42% reported no pain at index MSD diagnosis. Overall, there was a J-shaped relationship between BMI and pain (nadir = 27 kg/m2), with the severely obese (BMI ≥ 40 kg/m2) being most likely to report any pain (OR vs normal weight = 1.23, 95% confidence interval = 1.21-1.26). The association between BMI and pain varied by MSD, with a stronger relationship in the osteoarthritis group and a less pronounced relationship in the back and low back pain groups. Conclusions: There was a high prevalence of overweight/obesity among veterans with MSD. High levels of BMI (>27 kg/m2) were associated with increased odds of pain, most markedly among veterans with osteoarthritis.
Using machine learning to detect sarcopenia from electronic health records
(Sage, 2023-08-29) Luo, Xiao; Ding, Haoran; Broyles, Andrea; Warden, Stuart J.; Moorthi, Ranjani N.; Imel, Erik A.; Physical Therapy, School of Health and Human Sciences
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) were classified as meeting sarcopenia thresholds for 0 (controls), ≥1 (Sarcopenia-1), or ≥2 (Sarcopenia-2) tests. Electronic health record diagnoses, medications, and laboratory testing were extracted from the Indiana Network for Patient Care. Five machine learning models were applied to EHR data for predicting sarcopenia. Results: Of 1304 participants, 1055 were controls, 249 met Sarcopenia-1 and 76 met Sarcopenia-2. Sarcopenic participants were older, with higher fat mass, Charlson Comorbidity Index, and more chronic diseases. All models performed better for Sarcopenia-2 than Sarcopenia-1. The top performing models for Sarcopenia-1 were Logistic Regression [area under the curve (AUC) 71.59 (95% confidence interval [CI], 71.51-71.66)] and Multi-Layer Perceptron [AUC 71.48 (95%CI, 71.00-71.97)]. The top performing models for Sarcopenia-2 were Logistic Regression [AUC 91.44 (95%CI, 91.28-91.60)] and Support Vector Machine [AUC 90.81 (95%CI, 88.41-93.20)]. For the best Logistic Regression Model, important sarcopenia predictors included diabetes mellitus, digestive system complaints, signs and symptoms involving the nervous, musculoskeletal and respiratory systems, metabolic disorders, and kidney or urinary tract disorders. Opioids, corticosteroids, and antihyperlipidemic drugs were also more common among sarcopenic participants. Conclusions: Applying machine learning models, sarcopenia can be predicted from structured data in EHR, which may be developed through future studies to facilitate large-scale early detection and intervention in clinical populations.

Browsing by Subject "Musculoskeletal"

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