Increases in IGF-1 After Anti-TNF-? Therapy Are Associated With Bone and Muscle Accrual in Pediatric Crohn Disease.
ABSTRACT: Context:Low levels of insulinlike growth factor 1 (IGF-1) in pediatric and adolescent Crohn disease (CD) likely contribute to bone and muscle deficits. Objective:Assess changes in IGF-1 levels and associations with bone and muscle accrual following initiation of anti-tumor necrosis factor ? (TNF-?) therapy in pediatric and adolescent CD. Design and Participants:Participants (n = 75, age 5 to 21 years) with CD were enrolled in a prospective cohort study; 63 completed the 12-month visit. Main Outcome Measures:IGF-1 levels at baseline and 10 weeks, as well as dual-energy x-ray absorptiometry (DXA) and tibia peripheral quantitative computed tomography (pQCT) measures of bone and muscle at baseline and 12 months after initiation of anti-TNF-? therapy. Outcomes were expressed as sex-specific z scores. Results:IGF-1 z scores increased from a median (interquartile range) of -1.0 (-1.58 to -0.17) to -0.36 (-1.04 to 0.36) over 10 weeks (P < 0.001). Lesser disease severity and systemic inflammation, as well as greater estradiol z scores (in girls), was significantly associated with greater IGF-1 z scores over time. DXA whole-body bone mineral content, leg lean mass, and total hip and femoral neck bone mineral density (BMD) z scores were low at baseline (P < 0.0001 vs reference data) and increased significantly (P < 0.001) over 12 months. Greater increases in IGF-1 z scores over 10 weeks predicted improvement in DXA bone and muscle outcomes and pQCT trabecular BMD and cortical area. Adjustment for changes in muscle mass markedly attenuated the associations between IGF-1 levels and bone outcomes. Conclusions:Short-term improvements in IGF-1 z scores predicted recovery of bone and muscle outcomes following initiation of anti-TNF-? therapy in pediatric CD. These data suggest that disease effects on growth hormone metabolism contribute to musculoskeletal deficits in CD.
Project description:We conducted the first comparison of dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) outcomes in adolescent girls with anorexia nervosa. We observed deficits in bone density by both tools. pQCT assessments were associated with many of the same clinical parameters as have been previously established for DXA.Adolescents with anorexia nervosa (AN) commonly exhibit bone loss, but effects on bone geometry are less clear. We compared measures obtained by DXA and pQCT in girls with AN.Seventy females (age 15.5 ± 1.9 years ) with AN and 132 normal-weighted controls underwent tibial measures by pQCT including trabecular volumetric bone mineral density (vBMD) at the 3 % site, cortical vBMD and dimensions at the 38 % site, and muscle cross-sectional area (CSA) at the 66 % site. Participants with AN also underwent standard DXA measures. Independent t tests compared the pQCT results, while Pearson coefficient assessed correlations among DXA and pQCT measures.Trabecular vBMD Z-scores were lower in AN compared to controls (AN -0.31 ± 1.42 vs +0.11 ± 1.01, p = 0.01) and cortical vBMD Z-scores were higher (AN +0.18 ± 0.92 vs -0.50 ± 0.88, p < 0.001). Trabecular vBMD and cortical CSA Z-scores positively correlated with DXA BMD Z-scores (r range 0.57-0.82, p < 0.001). Markers of nutritional status positively correlated with Z-scores for trabecular vBMD, cortical CSA, section modulus, and muscle CSA (p < 0.04 for all).This study is the first to compare DXA and pQCT measurements in adolescent girls with AN. We observed deficits in BMD by both DXA and pQCT. pQCT assessments correlated well with DXA bone and body composition measures and were associated with many of the same clinical parameters and disease severity markers as have been previously established for DXA. The differences in cortical vBMD merit further study.
Project description:We examined the relationships between malnutrition, lifestyle factors, and bone health in anorexia nervosa (AN) via dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT).Seventy adolescent girls with AN and 132 normal-weighted controls underwent pQCT tibial measures including trabecular volumetric bone mineral density (vBMD), cortical vBMD, and cortical thickness. Participants with AN underwent DXA measures of the axial skeleton. We assessed the association of DXA and pQCT measures with clinical and lifestyle variables.Body mass index Z-score and ideal body weight percentage were positively correlated with trabecular vBMD, cortical CSA, and section modulus (p < .04). Exercise was associated with all pQCT measures but only with hip BMD by DXA. In AN, the use of antidepressants was associated with lower pQCT measures (p < .03).Antidepressants may negatively, and exercise positively, influence BMD in adolescents with eating disorders. These findings offer a provocative look at two longstanding questions.
Project description:Trabecular bone score (TBS) is a bone assessment tool that offers information beyond that afforded by dual-energy x-ray absorptiometry (DXA) bone mineral density (BMD) measurements. Adolescents with anorexia nervosa (AN) are known to exhibit compromised bone density and skeletal strength.This study aimed to determine TBS among adolescents with AN and evaluate the correlation with anthropometric, clinical and densitometric variables.Areal BMD spinal measures were analyzed for TBS. Findings were compared with clinical (height, weight, body mass index [BMI], age, pubertal development, 25-hydroxyvitamin D) and self-reported data (illness duration, amenorrhea, exercise, fracture, family history of osteoporosis, and antidepressant use), and BMD measures by DXA and peripheral quantitative computed tomography (pQCT).This was an urban adolescent program consisting of 57 females with AN, age 11-18 y.Interventions included DXA (absolute BMD and Z-score), pQCT (volumetric BMD [vBMD] and stress-strain index [SSI]), laboratory evaluation, and questionnaire administration.Main outcome measures included TBS, areal and vBMD, SSI, fracture history, disease duration.The TBS of six participants (11%) showed degraded and 19 (33%) partially degraded microarchitecture. Spinal TBS was correlated (P < .05) with age, height, weight, BMI, pubertal stage, BMD, and body composition by DXA, and BMD and SSI by pQCT. TBS was not correlated with disease duration, fracture, vitamin D status, race, or ethnicity, and self-reported health data.TBS showed evidence of degraded microarchitecture in over 40% of this study sample, and strongly correlated with anthropometric data and measures of BMD and skeletal strength. TBS is a novel tool that captures another dimension of bone health in adolescents with AN.
Project description:INTRODUCTION:In 2015, 11.9% of people with cystic fibrosis (CF) in the United States had osteopenia, 5.1% osteoporosis, and 0.3% experienced a fracture. Screening for CF-related bone disease starts in childhood, and dual energy x-ray absorptiometry (DXA) is the recommended method. It is unknown whether peripheral quantitative computed tomography (pQCT) can detect deficits earlier than DXA. This study compared pQCT and DXA scans in a group of pre-pubertal children with CF and healthy controls. METHODS:This was a cross-sectional study of children at Tanner stage 1. A pQCT scan of the radius at proximal and distal sites was performed plus a total body DXA scan. Serum C-reactive protein, interleukin-6 and tumor necrosis factor-alpha were also measured. RESULTS:A total of 34 subjects completed the study; 14 with CF and 20 controls. At the distal radius, pQCT showed a lower total bone mineral density (BMD) Z-score for the CF group (P = 0.01 and P = 0.03 for 2 different reference databases) compared to controls. At the proximal site, the polar strength-strain index was lower in the CF group (P = 0.017). Finally, the total body BMD Z-score by DXA was lower in the CF group, although it did not meet the definition of reduced bone density (P = 0.004). Biomarkers of inflammation were not different. CONCLUSIONS:In this group of pre-pubertal children with CF, measures of bone strength and density by both pQCT and DXA were reduced compared to healthy controls.
Project description:BACKGROUND:Patients diagnosed with inborn errors of metabolism (IBEM) often present with compromised bone health leading to low bone density, bone pain, fractures, and short stature. Dual-energy X-ray absorptiometry (DXA) is the current gold standard for clinical assessment of bone in the general population and has been adopted for monitoring bone density in IBEM patients. However, IBEM patients are at greater risk for scoliosis, short stature and often have orthopedic hardware at standard DXA scan sites, limiting its use in these patients. Furthermore, DXA is limited to measuring areal bone mineral density (BMD), and does not provide information on microarchitecture. METHODS:In this study, microarchitecture was investigated in IBEM patients (n = 101) using a new three-dimensional imaging technology high-resolution peripheral quantitative computed tomography (HR-pQCT) which scans at the distal radius and distal tibia. Volumetric BMD and bone microarchitecture were computed and compared amongst the different IBEMs. For IBEM patients over 16 years-old (n = 67), HR-pQCT reference data was available and Z-scores were calculated. RESULTS:Cortical bone density was significantly lower in IBEMs associated with decreased bone mass when compared to lysosomal storage disorders (LSD) with no primary skeletal pathology at both the radius and tibia. Cortical thickness was also significantly lower in these disorders when compared to LSD with no primary skeletal pathology at the radius. Cortical porosity was significantly greater in hypophosphatasia when compared to all other IBEM subtypes. CONCLUSION:We demonstrated compromised bone microarchitecture in IBEMs where there is primary involvement of the skeleton, as well as IBEMs where skeletal complications are a secondary outcome. In conclusion, our findings suggest HR-pQCT may serve as a valuable tool to monitor skeletal disease in the IBEM population, and provides insight to the greatly varying bone phenotype for this cohort that can be used for clinical monitoring and the assessment of response to therapeutic interventions.
Project description:Hemodialysis (HD) patients face increased fracture risk, which is further associated with elevated risk of hospitalization and mortality. High-resolution peripheral computed tomography (HR-pQCT) has advanced our understanding of bone disease in chronic kidney disease by characterizing distinct changes in both the cortical and trabecular compartments. Increased cortical porosity (Ct.Po) has been shown to be associated with fracture in patients with osteopenia or in postmenopausal diabetic women. We tested whether the degree of Ct.Po identifies hemodialysis patients with prevalent fragility fractures in comparison to bone mineral density (BMD) assessed by dual X-ray absorptiometry (DXA). We performed a post-hoc analysis of a cross-sectional study in 76 prevalent hemodialysis patients. Markers of mineral metabolism, coronary calcification score, DXA-, and HR-pQCT-data were analyzed, and Ct.Po determined at radius and tibia. Ct.Po was significantly higher in patients with fracture but association was lost after adjusting for age and gender (tibia p = 0.228, radius p = 0.5). Instead, femoral (F) BMD neck area (p = 0.03), F T-score neck area (p = 0.03), radius (R) BMD (p = 0.03), R T-score (p = 0.03), and cortical HR-pQCT indices such as cortical area (Ct.Ar) (tibia: p = 0.01; radius: p = 0.02) and cortical thickness (Ct.Th) (tibia: p = 0.03; radius: p = 0.02) correctly classified patients with fragility fractures. Area under receiver operating characteristic curves (AUC) for Ct.Po (tibia AUC: 0.711; p = 0.01; radius AUC: 0.666; p = 0.04), Ct.Ar (tibia AUC: 0.832; p<0.001; radius AUC: 0.796; p<0.001), and F neck BMD (AUC: 0.758; p = 0.002) did not differ significantly among each other. In conclusion, measuring Ct.Po is not superior to BMD determined by DXA for identification of HD patients with fragility fracture.
Project description:Background:In pediatric Crohn's disease, fat mass improves over time with treatment, but lean mass deficits persist. This observational study of the associations of physical activity and dietary intake with lean mass and muscle strength in children with Crohn's disease was ancillary to a previously reported randomized clinical trial of an intervention to improve bone health. Methods:In this study, 138 participants were followed at baseline and at 6, 12, and 24 months with evaluation of lean and fat mass using DXA, muscle strength (peak torque), Crohn's characteristics, dietary intake, time in moderate to vigorous physical activity (MVPA), and serum insulin-like growth factor-1 (IGF-1) and tumor necrosis factor-alpha (TNF-?). Race- and sex-specific Z-scores for leg lean mass and whole body fat mass were generated. Quasi least square regression evaluated determinants of changes in body composition and muscle strength. Results:Leg lean mass and muscle strength were positively associated with time in MVPA (P < 0.05) and negatively associated with increasing clinical disease activity (P < 0.05). Both leg lean mass and strength were positively associated with IGF-1 Z-score (P ? 0.03) but negatively associated with serum TNF-? (P ? 0.04). Neither lean mass nor muscle strength was associated with caloric or protein intake. Conclusions:Persistence of lean mass deficits was related to ongoing Crohn's disease activity but improved with greater time spent in moderate to vigorous physical activity. Future trials are needed to evaluate the efficacy of physical activity in improving lean mass in pediatric Crohn's disease.
Project description:Osteogenesis imperfecta (OI) is most often caused by mutations in the type I procollagen genes (COL1A1/COL1A2). We identified two children with substitutions in the type I procollagen C-propeptide cleavage site, which disrupt a unique processing step in collagen maturation and define a novel phenotype within OI. The patients have mild OI caused by mutations in COL1A1 (Patient 1: p.Asp1219Asn) or COL1A2 (Patient 2: p.Ala1119Thr), respectively. Patient 1 L1-L4 DXA Z-score was +3.9 and pQCT vBMD was+3.1; Patient 2 had L1-L4 DXA Z-score of 0.0 and pQCT vBMD of -1.8. Patient BMD contrasts with radiographic osteopenia and histomorphometry without osteosclerosis. Mutant procollagen processing is impaired in pericellular and in vitro assays. Patient dermal collagen fibrils have irregular borders. Incorporation of pC-collagen into matrix leads to increased bone mineralization. FTIR imaging confirms elevated mineral/matrix ratios in both patients, along with increased collagen maturation in trabecular bone, compared to normal or OI controls. Bone mineralization density distribution revealed a marked shift toward increased mineralization density for both patients. Patient 1 has areas of higher and lower bone mineralization than controls; Patient 2's bone matrix has a mineral content exceeding even classical OI bone. These patients define a new phenotype of high BMD OI and demonstrate that procollagen C-propeptide cleavage is crucial to normal bone mineralization.