Publications

2023

Coulombe, Jennifer C, Fjola Johannesdottir, Katelyn A Burkhart, Henriette Brummer, Brett T Allaire, and Mary L Bouxsein. (2023) 2023. “Changes in Vertebral Bone Density and Paraspinal Muscle Morphology Following Spaceflight and 1 Year Readaptation on Earth.”. JBMR Plus 7 (12): e10810. https://doi.org/10.1002/jbm4.10810.

Astronauts have an increased risk of back pain and disc herniation upon returning to Earth. Thus, it is imperative to understand the effects of spaceflight and readaptation to gravity on the musculoskeletal tissues of the spine. Here we investigated whether  6 months of spaceflight led to regional differences in bone loss within the vertebral body. Additionally, we evaluated the relationships between vertebral bone density and paraspinal muscle morphology before flight, after flight, and after readaptation on Earth. We measured vertebral trabecular bone mineral density (Tb.BMD), paraspinal muscle cross-sectional area (CSA), and muscle density in 17 astronauts using computed tomography (CT) images of the lumbar spine obtained before flight (before flight, n = 17), after flight (spaceflight, n = 17), and  12 months of readaptation to gravitational loading on Earth (follow-up, n = 15). Spaceflight-induced declines in Tb.BMD were greater in the superior region of the vertebral body (-6.7%) than the inferior (-3.1%, p = 0.052 versus superior region) and transverse regions (-4.3%, p = 0.057 versus superior region). After a year of readaptation to Earth's gravity, Tb.BMD in the transverse region remained significantly below preflight levels (-4.66%, p = 0.0094). Paraspinal muscle CSA and muscle density declined -1.0% (p = 0.005) and -0.83% (p = 0.001) per month of spaceflight, respectively. Ultimately, bone loss in the superior vertebral body, along with fatty infiltration of paraspinal muscles and incomplete recovery even after a year of readaptation on Earth, may contribute to spinal pathology in long-duration astronauts. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Liu, Ching-Ti, Timothy Tsai, Brett T Allaire, Mary L Bouxsein, Marian T Hannan, Thomas G Travison, and Douglas P Kiel. (2023) 2023. “Accumulation in Visceral Adipose Tissue Over 6 Years Is Associated With Lower Paraspinal Muscle Density.”. The Journal of Clinical Endocrinology and Metabolism 108 (6): 1348-54. https://doi.org/10.1210/clinem/dgac744.

CONTEXT: Visceral adipose tissue (VAT) has been recognized to be a metabolically active fat depot that may have paracrine effects on surrounding tissues, including muscle. Since many adults accumulate VAT as they age, the effect of changes in VAT on muscle is of interest.

OBJECTIVE: We determined the association between 6-year changes in VAT and paraspinal muscle density, an indicator of fatty infiltration.

METHODS: This study included 1145 participants from the Framingham Study third-generation cohort who had both quantitative computed tomography scans of the spine at baseline and 6-year's follow-up, on whom muscle density was measured along with VAT. We implemented multiple regression to determine the association of muscle density at follow-up as primary outcome measure with changes in VAT (follow-up minus baseline divided by 100), adjusting for VAT at baseline, age, sex, height, menopausal status, presence of diabetes, and physical activity. Analyses were performed in men and women separately.

RESULTS: After adjustment for covariates, individuals with the greatest accumulation of VAT over 6 years had significantly lower paraspinal density at the follow-up with an estimated 0.302 (95% CI, -0.380 to -0.224) and 0.476 (95% CI: -0.598 to -0.354) lower muscle density (HU) per 100-cm3 increase in VAT (both P values < .001) in men and women, respectively.

CONCLUSION: These results highlight that age-related accumulation of VAT in men and women is associated with lower muscle density. VAT may represent a modifiable risk factor for poor musculoskeletal outcomes with aging.

Saunders, Rylee K, Kathleen M Kilroe, Taïsha Joseph V, Signe Caksa, Mary L Bouxsein, Madhusmita Misra, and Deborah M Mitchell. (2023) 2023. “Total Calcium Intake Is Associated With Trabecular Bone Density in Adolescent Girls With Type 1 Diabetes.”. JBMR Plus 7 (11): e10813. https://doi.org/10.1002/jbm4.10813.

Type 1 diabetes (T1D) confers an increased risk of fracture and is associated with lower bone mineral density (BMD) and altered microarchitecture compared with controls. Adequate calcium (Ca) intake promotes bone mineralization, thereby increasing BMD. The objective of this analysis was to evaluate the associations of total daily Ca intake with bone outcomes among youth with T1D. This was a cross-sectional analysis of girls ages 10-16 years with (n = 62) and without (n = 60) T1D. We measured Ca intake with a validated food-frequency questionnaire and BMD, microarchitecture, and strength estimates with dual-energy X-ray absorptiometry and high-resolution peripheral quantitative computed tomography. Total daily Ca intake did not differ between groups (950 ± 488 in T1D versus 862 ± 461 mg/d in controls, p = 0.306). Serum 25OHD was lower in T1D (26.3 ± 7.6 versus 32.6 ± 9.0 ng/mL, p = <0.001), and parathyroid hormone (PTH) was higher in T1D (38.9 ± 11 versus 33.4 ± 9.7 pg/mL, p = 0.004). Trabecular volumetric BMD and thickness at the tibia were lower in T1D (p = 0.013, p = 0.030). Ca intake correlated with trabecular BMD at the radius and tibia among T1D participants (β = 0.27, p = 0.047, and β = 0.28, p = 0.027, β = 0.28, respectively) but not among controls (pinteraction = 0.009 at the radius, pinteraction = 0.010 at the tibia). Similarly, Ca intake was associated with estimated failure load at the tibia in T1D but not control participants (p = 0.038, β = 0.18; pinteraction = 0.051). We observed the expected negative association of Ca intake with parathyroid hormone in controls (p = 0.022, β = -0.29) but not in T1D participants (pinteraction = 0.022). Average glycemia as measured by hemoglobin A1c did not influence the relationship of Ca and PTH among participants with T1D (pinteraction = 0.138). These data suggest that youth with T1D may be particularly vulnerable to dietary Ca insufficiency. Increasing Ca intake may be an effective strategy to optimize bone health in this population. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Hughes, Julie M, Kathryn M Taylor, Katelyn I Guerriere, Nathaniel I Smith, Jeffery S Staab, Leila A Walker, Janet E Staab, et al. (2023) 2023. “Changes in Distal Tibial Microarchitecture During Eight Weeks of U.S. Army Basic Combat Training Differ by Sex and Race.”. JBMR Plus 7 (4): e10719. https://doi.org/10.1002/jbm4.10719.

Basic combat training (BCT) is a physically rigorous period at the beginning of a soldier's career that induces bone formation in the tibia. Race and sex are determinants of bone properties in young adults but their influences on changes in bone microarchitecture during BCT are unknown. The purpose of this work was to determine the influence of sex and race on changes in bone microarchitecture during BCT. Bone microarchitecture was assessed at the distal tibia via high-resolution peripheral quantitative computed tomography at the beginning and end of 8 weeks of BCT in a multiracial cohort of trainees (552 female, 1053 male; mean ± standard deviation [SD] age = 20.7 ± 3.7 years) of which 25.4% self-identified as black, 19.5% as race other than black or white (other races combined), and 55.1% as white. We used linear regression models to determine whether changes in bone microarchitecture due to BCT differed by race or sex, after adjusting for age, height, weight, physical activity, and tobacco use. We found that trabecular bone density (Tb.BMD), thickness (Tb.Th), and volume (Tb.BV/TV), as well as cortical BMD (Ct.BMD) and thickness (Ct.Th) increased following BCT in both sexes and across racial groups (+0.32% to +1.87%, all p < 0.01). Compared to males, females had greater increases in Tb.BMD (+1.87% versus +1.40%; p = 0.01) and Tb.Th (+0.87% versus +0.58%; p = 0.02), but smaller increases in Ct.BMD (+0.35% versus +0.61%; p < 0.01). Compared to black trainees, white trainees had greater increases in Tb.Th (+0.82% versus +0.61%; p = 0.03). Other races combined and white trainees had greater increases in Ct.BMD than black trainees (+0.56% and + 0.55% versus +0.32%; both p ≤ 0.01). Changes in distal tibial microarchitecture, consistent with adaptive bone formation, occur in trainees of all races and sexes, with modest differences by sex and race. Published 2023. This article is a U.S. Government work and is in the public domain in the USA. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Alemi, Mohammad Mehdi, Jacob J Banks, Andrew C Lynch, Brett T Allaire, Mary L Bouxsein, and Dennis E Anderson. (2023) 2023. “EMG Validation of a Subject-Specific Thoracolumbar Spine Musculoskeletal Model During Dynamic Activities in Older Adults.”. Annals of Biomedical Engineering 51 (10): 2313-22. https://doi.org/10.1007/s10439-023-03273-3.

Musculoskeletal models can uniquely estimate in vivo demands and injury risk. In this study, we aimed to compare muscle activations from subject-specific thoracolumbar spine OpenSim models with recorded muscle activity from electromyography (EMG) during five dynamic tasks. Specifically, 11 older adults (mean = 65 years, SD = 9) lifted a crate weighted to 10% of their body mass in axial rotation, 2-handed sagittal lift, 1-handed sagittal lift, and lateral bending, and simulated a window opening task. EMG measurements of back and abdominal muscles were directly compared to equivalent model-predicted activity for temporal similarity via maximum absolute normalized cross-correlation (MANCC) coefficients and for magnitude differences via root-mean-square errors (RMSE), across all combinations of participants, dynamic tasks, and muscle groups. We found that across most of the tasks the model reasonably predicted temporal behavior of back extensor muscles (median MANCC = 0.92 ± 0.07) but moderate temporal similarity was observed for abdominal muscles (median MANCC = 0.60 ± 0.20). Activation magnitude was comparable to previous modeling studies, and median RMSE was 0.18 ± 0.08 for back extensor muscles. Overall, these results indicate that our thoracolumbar spine model can be used to estimate subject-specific in vivo muscular activations for these dynamic lifting tasks.

Banks, Jacob J, Mohammad Mehdi Alemi, Brett T Allaire, Andrew C Lynch, Mary L Bouxsein, and Dennis E Anderson. (2023) 2023. “Using Static Postures to Estimate Spinal Loading During Dynamic Lifts With Participant-Specific Thoracolumbar Musculoskeletal Models.”. Applied Ergonomics 106: 103869. https://doi.org/10.1016/j.apergo.2022.103869.

Static biomechanical simulations are sometimes used to estimate in vivo kinetic demands because they can be solved efficiently, but this ignores any potential inertial effects. To date, comparisons between static and dynamic analyses of spinal demands have been limited to lumbar joint differences in young males performing sagittal lifts. Here we compare static and dynamic vertebral compressive and shear force estimates during axial, lateral, and sagittal lifting tasks across all thoracic and lumbar vertebrae in older men and women. Participant-specific thoracolumbar full-body musculoskeletal models estimated vertebral forces from recorded kinematics both with and without consideration of dynamic effects, at an identified frame of peak vertebral loading. Static analyses under-predicted dynamic compressive and resultant shear forces, by an average of about 16% for all three lifts across the thoracic and lumbar spine but were highly correlated with dynamic forces (average r2 > .95). The study outcomes have the potential to enable standard clinical and occupational estimates using static analyses.

Bredella, Miriam A, Karan A Patel, Maire Leyne, Anne S Levy, Bakhos A Tannous, and Mary L Bouxsein. (2023) 2023. “Design and Implementation of a Leadership Development Program for Early-Stage Investigators: Initial Results.”. The Journal of Continuing Education in the Health Professions. https://doi.org/10.1097/CEH.0000000000000518.

INTRODUCTION: Leadership skills are essential for a successful career in medical research but are often not formally taught. To address these gaps, we designed a leadership development program for early-stage investigators.

METHODS: A 9-month virtual program with monthly 2-hour interactive sessions was designed, covering topics such as Leadership in Research, Mentoring, Building Diverse and Inclusive Teams, Managing Conflict, Influencing without Authority, Grant Administration, and Management. An anonymized survey was sent to participants before and after completion of the program, and the results were compared using the chi-squared test.

RESULTS: Over a 2-year period, we selected two cohorts of 41 and 46 participants, respectively. After completion of the program, 92% of survey respondents indicated that the program met their expectations and 74% had made use of skills they learned. Participants enjoyed meeting new people and discussing common challenges. There was an increase in participants' perceived understanding of personal leadership qualities, mentoring, communication, conflict resolution, grant management, and collaboration with industry (P < .05).

DISCUSSION: A leadership development program for early-stage investigators led to a significant increase in participants' perceived understanding of personal leadership qualities and competencies. It also offered participants the opportunity to meet other researchers in the institution and discuss common challenges.

Rosa-Caldwell, Megan E, Marie Mortreux, Anna Wadhwa, Ursula B Kaiser, Dong-Min Sung, Mary L Bouxsein, and Seward B Rutkove. (2023) 2023. “Sex Differences in Muscle Health in Simulated Micro- and Partial-Gravity Environments in Rats.”. Sports Medicine and Health Science 5 (4): 319-28. https://doi.org/10.1016/j.smhs.2023.09.002.

Skeletal muscle size and strength are important for overall health for astronauts. However, how male and female muscle may respond differently to micro- and partial-gravity environments is not fully understood. The purpose of this study was to determine how biological sex and sex steroid hormones influence the progression of muscle atrophy after long term exposure to micro and partial gravity environments in male and female rats. Male and female Fisher rats (n ​= ​120) underwent either castration/ovariectomy or sham surgeries. After two weeks recovery, animals were divided into microgravity (0g), partial-gravity (40% of weight bearing, 0.4g), or full weight bearing (1g) interventions for 28 days. Measurements of muscle size and strength were evaluated prior to and after interventions. At 0g, females lost more dorsiflexion strength, plantar flexion strength, and other metrics of muscle size compared to males; castration/ovariectomy did not influence these differences. Additionally, at 0.4g, females lost more dorsiflexion strength, plantar flexion strength, and other metrics of muscle strength compared to males; castration/ovariectomy did not influence these differences. Females have greater musculoskeletal aberrations during exposure to both microgravity and partial-gravity environments; these differences are not dependent on the presence of sex steroid hormones. Correspondingly, additional interventions may be necessary to mitigate musculoskeletal loss in female astronauts to protect occupational and overall health.

Bozzini, Brittany N, Vy T Nguyen, Marinaliz C Reynoso, Katelyn I Guerriere, Leila A Walker, Kathryn M Taylor, Stephen A Foulis, Mary L Bouxsein, Julie M Hughes, and Kristin L Popp. (2023) 2023. “The Risk of Menstrual Dysfunction Increases for Women During U.S. Army Basic Combat Training.”. Medicine and Science in Sports and Exercise 55 (9): 1533-39. https://doi.org/10.1249/MSS.0000000000003183.

PURPOSE: To determine whether changes in menstruation develop in female trainees during BCT and whether changes in body mass, body composition and/or physical activity are associated with menstrual interruption during BCT.

METHODS: Female trainees grouped according to self-reported menstrual status in the 12 months before BCT as having regular cycles (RC; n = 352) or MD ( n = 97) completed height, body mass, and body composition assessments and questionnaires before and after BCT. Fisher's exact test and Mann-Whitney U test were used to compare between-group differences in categorical and continuous variables, respectively. Among RC trainees, odds ratios were calculated to examine the influence of changes in body mass, lean mass, and fat mass on a trainee's likelihood to miss a period during BCT.

RESULTS: There were no differences in race, height, body mass, body mass index, or physical activity history at pre-BCT between RC and MD ( P > 0.05). Overall, 86% of trainees experienced changes to menstruation during BCT. RC were more likely than MD to have at least one period during BCT (81% vs 69%, respectively, P = 0.01). Among RC, gaining more body mass and lean mass and losing less fat mass were associated with increased odds of missing a period during BCT.

CONCLUSIONS: These findings demonstrate that most female trainees experience menstrual changes during BCT. Menstrual cycle interruptions do not appear to align with loss of body or fat mass.

Mitchell, Deborah M, Vibha Singhal, Abisayo Animashaun, Amita Bose, Brian Carmine, Fatima C Stanford, Thomas H Inge, et al. (2023) 2023. “Skeletal Effects of Sleeve Gastrectomy in Adolescents and Young Adults: A 2-Year Longitudinal Study.”. The Journal of Clinical Endocrinology and Metabolism 108 (4): 847-57. https://doi.org/10.1210/clinem/dgac634.

CONTEXT: Vertical sleeve gastrectomy (VSG) is an increasingly common tool to achieve weight loss and improve metabolic health in adolescents and young adults with obesity, although it may adversely affect bone health.

OBJECTIVE: This work aimed to evaluate the effect of VSG on bone health in youth.

METHODS: An observational 2-year study was conducted at a tertiary care center of 66 patients aged 13 to 24 years with moderate-to-severe obesity meeting criteria for VSG. The patients underwent VSG (n = 30) or nonsurgical (n = 36) management per the decision of patient and clinical team. Main outcome measures included dual-energy x-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HRpQCT) measures of bone mineral density (BMD), geometry, and microarchitecture.

RESULTS: VSG patients achieved 25.3 ± 2.0% weight loss at 2 years (P < .001) while control subjects gained 4.0 ± 2.0% (P = .026). Total hip BMD declined 8.5 ± 1.0% following VSG compared with 0.1 ± 1.0% gain in controls (P < .001), with similar results at the femoral neck (P < .001). Total volumetric BMD (vBMD) decreased both at the distal radius and tibia following VSG (P < .001) driven primarily by trabecular vBMD loss (P < .001). Two-year changes in cortical vBMD did not differ between groups, though cortical porosity decreased following VSG both at the radius and tibia (P = .048 and P < .001). Cortical thickness increased in controls but not in VSG (P = .022 and P = .002 for between-group comparisons at the radius and tibia, respectively). Following VSG, estimated failure load decreased at the radius and did not demonstrate the physiologic increases at the tibia observed in controls.

CONCLUSION: VSG leads to progressive changes in bone health over 2 years, and may lead to increased skeletal fragility in adolescents and young adults.