<p>Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a common therapy for pediatric hematologic malignancies. With improved supportive care, addressing treatment-related late effects is at the forefront of survivor long-term health and quality of life. We previously demonstrated that alloHSCT survivors had increased adiposity, decreased lean mass, and lower bone density and strength, 7 years (median) from alloHSCT compared to their healthy peers. Yet it is unknown whether these deficits persist. Our longitudinal study characterized changes in muscle and bone over a period of 3.4 (range 2.0 to 4.9) years in 47 childhood alloHSCT survivors, age 5-26 years at baseline (34% female). Tibia cortical bone geometry and volumetric density and lower leg muscle cross-sectional area (MCSA) were assessed via peripheral quantitative computed tomography (pQCT). Anthropometric and pQCT measurements were converted to age, sex, and ancestry-specific standard deviation scores, adjusted for leg length. Muscle-specific force was assessed as strength relative to MCSA adjusted for leg length (strength Z-score). Measurements were compared to a healthy reference cohort (n=921), ages 5 to 30 years (52% female). At baseline and follow up, alloHSCT survivors demonstrated lower height-, weight-, and leg length Z-scores compared to the healthy reference cohort. Deficits in MCSA, trabecular volumetric bone density, and cortical bone size and estimated strength (section modulus) were evident in survivors (all p&lt;0.05). Between the two study time points, anthropometric, muscle, and bone Z-scores did not change significantly in alloHSCT survivors. Approximately 15% and 17% of alloHSCT survivors had MCSA and section modulus Z-score less than -2.0, respectively, at baseline and follow up. Furthermore, those with a history of total body irradiation compared to those without demonstrated lower MCSA at follow up. The persistent muscle and bone deficits in pediatric alloHSCT survivors support the need for strategies to improve bone and muscle health in this at-risk population. This article is protected by copyright. All rights reserved.</p>

<p><strong>OBJECTIVE: </strong>We determined the prevalence of sarcopenic obesity in patients with rheumatoid arthritis (RA) using multiple methods and assessed associations with physical functioning.</p>

<p><strong>METHODS: </strong>This study evaluated data from three RA cohorts. Whole-body dual-energy absorptiometry (DXA) measures of appendicular lean mass index (ALMI, kg/m2) and fat mass index (FMI) were converted to age, sex, and race-specific Z-Scores and categorized using a recently validated method and compared it to a widely-used existing method. The prevalence of body composition abnormalities in RA was compared with two reference populations. In the RA cohorts, associations between body composition and change in the Health Assessment Questionnaire (HAQ) and the Short Physical Performance Battery (SPPB) in follow-up were assessed using linear and logistic regression, adjusting for age, sex, race, and study.</p>

<p><strong>RESULTS: </strong>The prevalence of low lean mass and sarcopenic obesity were higher in patients with RA (14.2; 12.6%, respectively) compared with the reference population cohorts (7-10%; 4-4.5%, respectively, all p&lt; 0.05). There was only moderate agreement among methods of sarcopenic obesity categorization (Kappa 0.45). The recently validated method categorized fewer subjects as obese, and many of these were categorized as low lean mass only. Low lean mass, obesity, and sarcopenic obesity were each associated with higher HAQ and lower SPPB at baseline and numerically greater worsening.</p>

<p><strong>CONCLUSION: </strong>RA patients had higher rates of low lean mass and sarcopenic obesity than the general population. The recently validated methods characterized body composition changes differently from traditional methods and were more strongly associated with physical function.</p>

<p><strong>PURPOSE: </strong>We determined associations between adipokines and abnormal body composition in patients with rheumatoid arthritis (RA).</p>

<p><strong>METHODS: </strong>Combining data from three RA cohorts, whole-body dual-energy absorptiometry measures of appendicular lean mass and fat mass indices were converted to age, sex, and race-specific Z-Scores. Lean mass relative to fat mass was determined based on prior methods. Independent associations between body composition profiles and circulating levels of adiponectin, leptin, and fibroblast growth factor(FGF)-21 were assessed using linear and logistic regression models adjusting for demographics and study cohort. We also determined the improvement in the area-under-the-curve (AUC) for prediction of low lean mass when adipokines were added to predictive models that included clinical factors such as demographics, study, and body mass index (BMI).</p>

<p><strong>RESULTS: </strong>Among 419 participants, older age was associated with higher levels of all adipokines while higher C-reactive protein was associated with lower adiponectin levels and higher FGF-21 levels. Greater fat mass was strongly associated with lower adiponectin levels and higher leptin and FGF-21 levels. Higher levels of adiponectin, leptin, and FGF-21 were independently associated with low lean mass. The addition of adiponectin and leptin levels to regression models improved prediction of low lean mass when combined with demographics, study, and BMI (AUC 0.75 v. 0.66).</p>

<p><strong>CONCLUSIONS: </strong>Adipokines are associated with both excess adiposity and low lean mass in patients with RA. Improvements in the prediction of body composition abnormalities suggest that laboratory screening could help identify patients with altered body composition who may be at greater risk of adverse outcomes.</p>

<p><strong>PURPOSE: </strong>Rheumatoid arthritis (RA) is associated with low muscle density due to accumulation of intramuscular fat. This study identified predictors of changes in muscle density and determined whether low muscle density predicted changes in strength and physical function.</p>

<p><strong>METHODS: </strong>Patients with RA, ages 18-70, completed whole-body DXA and peripheral quantitative CT (pQCT) to quantify lean and fat mass indices and muscle density. Dynamometry was used to measure strength at the hand, knee, and lower leg. Disability and physical function were measured with the Health Assessment Questionnaire (HAQ) and the Short Physical Performance Battery (SPPB). Assessments were performed at baseline and at follow-up. Regression analyses assessed associations between patient characteristics, muscle density, and deteriorations in strength and function.</p>

<p><strong>RESULTS: </strong>Muscle density was assessed at baseline in 107 patients with RA. Seventy-nine (74%) returned for a follow-up assessment at a median follow-up time of 2.71 years (IQR: 2.35-3.57). Factors associated with declines in muscle density included female sex, higher disease activity, smoking, and lower IGF-1 levels. Greater muscle density Z-Score at baseline (per 1 SD) was associated with less worsening per year of HAQ, SPPB, and 4-meter walk time and a lower risk of a clinically important worsening in HAQ [OR 1.90 (1.06,3.42) p=0.03] and walking speed [OR 2.87 (1.05,7.89) p=0.04].</p>

<p><strong>CONCLUSION: </strong>Worsening of skeletal muscle density occurred in patients with higher disease activity, smokers, and those with lower IGF-1. Low muscle density was associated with worsening of physical function. Interventions addressing reductions in muscle quality might prevent functional decline.</p>

<p>We previously reported significant gains in pQCT measures of tibia trabecular bone mineral density (BMD) and cortical structure following completion of therapy in children and adolescents with acute lymphoblastic leukemia (ALL). The objective of this study was to examine changes in DXA measures used in clinical practice and expressed as Z-scores using robust national reference data. Children and adolescents, ages 5 to 18 years were enrolled within 2 (median 0.8) years of completing ALL therapy. DXA total-body less-head bone mineral content (TBLH-BMC), and spine, total hip, femoral neck, and 1/3rd radius areal BMD (aBMD) were assessed in 45 participants at enrollment and 12-months later. Linear regression models examined correlates of changes in DXA Z-scores. Changes in DXA outcomes were compared to changes in tibia pQCT trabecular and cortical volumetric BMD (vBMD) and cortical area. At enrollment, DXA TBLH-BMC, spine and radius aBMD Z-scores were not significantly reduced in ALL survivors; however, total hip [median -0.74 (IQ range -1.51 to -0.04)] and femoral neck [-0.51 (-1.24 to 0.14)] aBMD Z-scores were lower (both p &lt; 0.01) compared to reference data. DXA Z-scores at all skeletal sites increased over 12 months. Despite improvement, total hip Z-score remained lower at -0.55 (-1.05 to 0.18). The increases in TBLH-BMC, total hip and femoral neck aBMD Z-scores were more pronounced in those enrolled within 6 months of completing ALL therapy, compared to those enrolled at &gt;6 months. Gains in TBLH-BMC, total hip, femoral neck and radius aBMD Z-scores were significantly associated with gains in tibia cortical area Z-scores (R = 0.56 to 0.67, p ≤ 0.001). Changes in TBLH and proximal femur sites were associated with gains in trabecular vBMD Z-scores (R = 0.37 to 0.40; p ≤ 0.01); these associations were not significant when adjusted for gains in cortical area. In summary, gains in DXA measures were most pronounced in total hip and femoral neck following ALL therapy. The gains in all DXA measures, with the exception of lumbar spine, reflected gains in cortical area. Overall, ALL survivors demonstrate skeletal recovery following completion of therapy; a small sub-group continue to demonstrate deficits and benefit from continued observation to ensure improvement over time.</p>

<p><strong>PURPOSE: </strong>Rheumatoid arthritis (RA) is associated with adverse body composition profiles, and low muscle density due to accumulation of intramuscular fat. This study assessed associations between muscle density, body composition, muscle strength, and physical functioning in patients with RA and a reference group.</p>

<p><strong>METHODS: </strong>Patients with RA, ages 18-70 years, and healthy control participants completed whole-body DXA and peripheral quantitative CT (pQCT) to quantify appendicular lean mass (ALMI, kg/m) and fat mass indices (FMI, kg/m), visceral fat area, and muscle density. Dynamometry was used to measure hand-grip strength and muscle strength at the knee and lower leg (ft-lbs). Disability and physical functioning were measured with the Health Assessment Questionnaire (HAQ) and the Short Physical Performance Battery (SPPB). Linear regression analyses assessed differences related to RA and associations between muscle density, strength, and function.</p>

<p><strong>RESULTS: </strong>The study consisted of 103 RA patients (51 men) and 428 healthy participants. Low muscle density was associated with greater disease activity, CRP, and Interleukin-6, greater total and visceral fat, lower ALMI Z-Scores, physical inactivity, and long-term use of glucocorticoids (&gt;1yr). Patients with low ALMI Z-Scores had lower muscle density Z-Score compared to reference participants with similarly low ALMI. Low muscle density was independently associated with lower muscle strength, higher HAQ, and lower SPPB after adjusting for ALMI and FMI Z-Scores.</p>

<p><strong>CONCLUSIONS: </strong>Low muscle density observed among patients with RA is observed in association with low muscle mass, excess adiposity, poor strength, and greater disability. Interventions to address poor muscle quality could potentially affect important functional outcomes. This article is protected by copyright. All rights reserved.</p>

<p><strong>OBJECTIVE: </strong>Rheumatoid arthritis (RA) is associated with low muscle mass and density. The objective of our study was to evaluate associations between 2 serum biomarkers [insulin-like growth factor 1 (IGF-1) and adiponectin] and skeletal muscle in RA.</p>

<p><strong>METHODS: </strong>Whole-body dual energy X-ray absorptiometry measures of the appendicular lean mass index (ALMI; kg/m(2)) and total fat mass index (kg/m(2)), as well as the peripheral quantitative computed tomography measures of the lower leg muscle and fat cross-sectional area (CSA; cm(2)) and muscle density (an index of fat infiltration) were obtained from 50 participants with RA, ages 18-70 years. Multivariable linear regression analyses evaluated associations between body composition and levels of adiponectin and IGF-1, adjusted for age, sex, and adiposity.</p>

<p><strong>RESULTS: </strong>Greater age was associated with higher adiponectin (p = 0.06) and lower IGF-1 (p = 0.004). Eight subjects had IGF-1 levels below the reference range for their age and sex. These subjects had significantly lower ALMI and muscle CSA in multivariable models. Lower IGF-1 levels were associated with greater clinical disease activity and severity, as well as low ALMI, muscle CSA, and muscle density (defined as 1 SD below normative mean). After adjusting for age and sex, greater adiponectin levels were associated with lower BMI (p = 0.02) as well as lower ALMI, and lower muscle CSA, independent of adiposity (p &lt; 0.05). Only greater Health Assessment Questionnaire scores were significantly associated with lower adiponectin levels.</p>

<p><strong>CONCLUSION: </strong>Low IGF-1 and greater adiponectin levels are associated with lower muscle mass in RA. Lower IGF-1 levels were seen in subjects with greater disease activity and severity.</p>

<p><strong>OBJECTIVE: </strong>Rheumatoid arthritis (RA) is associated with muscle loss, osteoporosis, and fracture. We examined associations between skeletal muscle mass, strength, and quality and trabecular and cortical bone deficits in patients with RA and healthy controls.</p>

<p><strong>METHODS: </strong>Participants, ages 18-75 years, completed whole-body dual-energy x-ray absorptiometry and peripheral quantitative computed tomography (pQCT) of the tibia to quantify appendicular lean mass and fat mass indices (ALMI, FMI), muscle density at the lower leg, trabecular bone density, and cortical bone thickness. Age-, sex-, and race-specific Z scores were calculated based on distributions in controls. Associations between body composition and pQCT bone outcomes were assessed in patients with RA and controls. Linear regression analyses assessed differences in bone outcomes after considering differences in body mass index (BMI) and body composition.</p>

<p><strong>RESULTS: </strong>The sample consisted of 112 patients with RA (55 men) and 412 controls (194 men). Compared to controls, patients with RA had greater BMI Z score (p &lt; 0.001), lower ALMI Z score after adjustment for FMI (p = 0.02), lower muscle strength Z score (p = 0.01), and lower muscle density Z score (p &lt; 0.001). Among RA, ALMI Z scores were positively associated with trabecular density [β: 0.29 (0.062-0.52); p = 0.01] and cortical thickness [β: 0.33 (0.13-0.53; p = 0.002]. Associations were similar in controls. Bone outcomes were inferior in patients with RA after adjusting for BMI, but similar to controls when adjusting for body composition. Radiographic damage and higher adiponectin levels were independently associated with inferior bone outcomes.</p>

<p><strong>CONCLUSION: </strong>Patients with RA exhibit deficits in cortical bone structure and trabecular density at the tibia and a preserved functional muscle-bone unit. A loss of mechanical loading may contribute to bone deficits.</p>

<p>Allogeneic hematopoietic stem-cell transplantation (alloHSCT) survivors treated with total body irradiation (TBI) exhibit bone deficits and excess adiposity, potentially related to altered mesenchymal stem cell differentiation into osteoblasts or adipocytes. We examined associations among fat distribution, bone microarchitecture, and insulin resistance in alloHSCT survivors after TBI. This was a cross-sectional observational study of 25 alloHSCT survivors (aged 12 to 25 years) a median of 9.7 (4.3 to 19.3) years after alloHSCT compared to 25 age-, race-, and sex-matched healthy controls. Vertebral MR spectroscopic imaging and tibia micro-MRI were used to quantify marrow adipose tissue (MAT) and trabecular microarchitecture. Additional measures included DXA whole-body fat mass (WB-FM), leg lean mass (Leg-LM), trunk visceral adipose tissue (VAT), and CT calf muscle density. Insulin resistance in alloHSCT survivors was estimated by HOMA-IR. AlloHSCT survivors had lower Leg-LM (p &lt; 0.001) and greater VAT (p &lt; 0.01), MAT (p &lt; 0.001), and fat infiltration of muscle (p = 0.04) independent of WB-FM, versus matched controls; BMI did not differ. Survivors had lower bone volume fraction and abnormal microarchitecture including greater erosion and more rod-like structure versus controls (all p = 0.04); 14 had vertebral deformities and two had compression fractures. Greater WB-FM, VAT, MAT, and muscle fat infiltration were associated with abnormal trabecular microarchitecture (p &lt; 0.04 for all). AlloHSCT HOMA-IR was elevated, associated with younger age at transplantation (p &lt; 0.01), and positively correlated with WB-FM and VAT (both p &lt; 0.01). In conclusion, the markedly increased marrow adiposity, abnormal bone microarchitecture, and abnormal fat distribution highlight the risks of long-term treatment-related morbidity and mortality in alloHSCT recipients after TBI. Trabecular deterioration was associated with marrow and visceral adiposity. Furthermore, long-term survivors demonstrated sarcopenic obesity, insulin resistance, and vertebral deformities. Future studies are needed to identify strategies to prevent and treat metabolic and skeletal complications in this growing population of childhood alloHSCT survivors.</p>