Publications

Several new peripheral dual-energy X-ray absorptiometry (DXA) devices designed for assessment of bone and body composition in rodents have been developed. We compared the performance (accuracy and precision) of two of these devices, the InAlyzer and the iNSiGHT, to those of an established device, the PIXImus. We measured total body bone mineral content (BMC), bone mineral density (BMD), and body composition (lean and fat mass) on the three DXA devices in 18 male C57Bl/6 J mice (6 each of ages 8, 14, and 24 weeks, weighing 22 to 33 g). DXA body composition measures were compared to whole-body nuclear magnetic resonance (NMR) outcomes. BMC of the femur was also compared to ex vivo micro-computed tomography (microCT). Total body BMD from the InAlyzer and iNSiGHT devices was strongly correlated to that from PIXImus (R2 = 0.83 and 0.82, respectively), but was  25 % higher than PIXImus. Total body BMC measures by InAlyzer were strongly associated with those from PIXImus (R2 = 0.86), whereas those from iNSiGHT were only weakly correlated (R2 = 0.29). Femur BMC from InAlyzer was strongly correlated with microCT outcomes, whereas iNSiGHT was only weakly correlated. InAlyzer and iNSiGHT fat mass measures were very strongly correlated with PIXImus and NMR outcomes (R2 = 0.91 to 0.97), with slightly weaker associations for lean mass (R2 = 0.81 to 0.76). Short-term precision of InAlyzer and iNSiGHT measurements were excellent, and akin to those from the PIXImus for both body composition and bone measures, ranging between 0.39 and 3.2 %. With faster scan times, closed X-ray source and excellent precision, the new devices are both satisfactory replacements for the now discontinued PIXImus system. However, given the accuracy of the bone and body composition measures, the InAlyzer may be preferable for studies where musculoskeletal changes are the main interest.

BACKGROUND: Loss of muscle mass is a known feature of sarcopenia and predicts poor clinical outcomes. Although muscle metrics can be derived from routine computed tomography (CT) images, sex-specific reference values at multiple vertebral levels over a wide age range are lacking.

OBJECTIVE: The aim of this study was to provide reference values for skeletal muscle mass and attenuation on thoracic and abdominal CT scans in the community-based Framingham Heart Study cohort to aid in the identification of sarcopenia.

MATERIALS AND METHODS: This secondary analysis of a prospective trial describes muscle metrics by age and sex for participants from the Framingham Heart Study without prior history of cancer who underwent at least 1 CT scan between 2002 and 2011. Using 2 previously validated machine learning algorithms followed by human quality assurance, skeletal muscle was analyzed on a single axial CT image per level at the 5th, 8th, 10th thoracic, and 3rd lumbar vertebral body (T5, T8, T10, L3). Cross-sectional muscle area (cm 2 ), mean skeletal muscle radioattenuation (SMRA, in Hounsfield units), skeletal muscle index (SMI, in cm 2 /m 2 ), and skeletal muscle gauge (SMRA·SMI) were calculated. Measurements were summarized by age group (<45, 45-54, 55-64, 65-74, ≥75 years), sex, and vertebral level. Models enabling the calculation of age-, sex-, and vertebral-level-specific reference values were created and embedded into an open access online Web application.

RESULTS: The cohort consisted of 3804 participants (1917 [50.4%] males; mean age, 55.6 ± 11.8 years; range, 33-92 years) and 7162 CT scans. Muscle metrics qualitatively decreased with increasing age and female sex.

CONCLUSIONS: This study established age- and sex-specific reference values for CT-based muscle metrics at thoracic and lumbar vertebral levels. These values may be used in future research investigating the role of muscle mass and attenuation in health and disease, and to identify sarcopenia.

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.

BACKGROUND: Bone stress injuries (BSIs) are common in female runners, and recurrent BSI rates are high. Previous work suggests an association between higher impact loading during running and tibial BSI. However, it is unknown whether impact loading and fatigue-related loading changes discriminate women with a history of multiple BSIs. This study compared impact variables at the beginning of a treadmill run to exertion and the changes in those variables with exertion among female runners with no history of BSI as well as among those with a history of single or multiple BSIs.

METHODS: We enrolled 45 female runners (aged 18-40 years) for this cross-sectional study: having no history of diagnosed lower extremity BSI (N-BSI, n = 14); a history of 1 lower extremity BSI (1-BSI, n = 16); and diagnosed by imaging, or a history of multiple (≥3) lower extremity BSIs (M-BSI, n = 15). Participants completed a 5-km race speed run on an instrumented treadmill while wearing an Inertial Measurement Unit. The vertical average loading rate (VALR), vertical instantaneous loading rate (VILR), vertical stiffness during impact via instrumented treadmill, and tibial shock determined as the peak positive tibial acceleration via Inertial Measurement Unit were measured at the beginning and the end of the run.

RESULTS: There were no differences between groups in VALR, VILR, vertical stiffness, or tibial shock in a fresh or exerted condition. However, compared to N-BSI, women with M-BSI had greater increase with exertion in VALR (-1.8% vs. 6.1%, p = 0.01) and VILR (1.5% vs. 4.8%, p = 0.03). Similarly, compared to N-BSI, vertical stiffness increased more with exertion among women with M-BSI (-0.9% vs. 7.3%, p = 0.006) and 1-BSI (-0.9% vs. 1.8%, p = 0.05). Finally, compared to N-BSI, the increase in tibial shock from fresh to exerted condition was greater among women with M-BSI (0.9% vs. 5.5%, p = 0.03) and 1-BSI (0.9% vs. 11.2%, p = 0.02).

CONCLUSION: Women with 1-BSI or M-BSIs experience greater exertion-related increases in impact loading than women with N-BSI. These observations imply that exertion-related changes in gait biomechanics may contribute to risk of BSI.

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.

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.

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.

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.

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.

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.