Low Insulin-like Growth Factor-1 Research Articles

Low bone mass in Noonan syndrome children correlates with decreased muscle mass and low IGF-1 levels.

Although musculoskeletal abnormalities have long been described in patients with Noonan syndrome (NS), only a few studies have investigated the bone status of these patients. The aim of this retrospective observational study was to describe the bone health of children with NS. Thirty-five patients with a genetically confirmed diagnosis of NS were enrolled. We analyzed the axial skeleton (lumbar spine) using dual energy X-ray absorptiometry and the appendicular skeleton (hand) with the BoneXpert system. Bone metabolism markers, including mineral homeostasis parameters, serum 25-hydroxy vitamin D (25-OHD) levels and markers of bone formation and resorption were also reported. Compared to the general population, axial and appendicular bone mass was significantly decreased in children with NS (p<0.0001). Serum 25-OHD levels were low in about half of the patients and were negatively correlated with age (r=-0.52; p<0.0001). Patients with NS exhibited reduced bone formation marker levels and increased bone resorption marker levels (p<0.0001). No gender difference or genotype-phenotype correlations were found for the different bone parameters. Muscle mass and, to a lesser extent, serum insulin-like growth factor 1 (IGF-1) levels were independent predictors of whole-body bone mineral content (p<0.0001 for both parameters; adjusted R2=0.97). In conclusion, bone mass is reduced in children with NS and correlates with decreased muscle mass and low serum IGF-1 levels. These data justify addressing all potential threats to bone health including sufficient calcium and vitamin D intake, regular physical exercise, and hormone replacement therapy.

Evaluation of Serum Levels of Insulin-Like Growth Factor 1 and Insulin-Like Growth Factor-Binding Protein 3 in Patients With Colorectal Cancer: A Case-Control Study.

Background/aim: Limited information is available about the relationship between colorectal cancer (CRC) and serum concentration of insulin-like growth factor 1 (IGF1) and insulin-like growth factor-binding protein 3 (IGFBP3). This study aims to compare the serum levels of IGF1and IGFBP3 in colorectal cancer cases and controls and to assess the relationship between their level and the demographic and histopathological characteristics.Methods: A case-control study in which 50 patients with colorectal cancer and 50 controls matched by gender and age were compared regarding the demographic characteristics and the level of both IGF1 and IGFBP3. The correlation with different clinicopathological features was assessed.Results: Levels of IGF1 were significantly higher while levels of IGFBP3 were significantly lower among cases compared to control. IGF1 was significantly higher among patients with liver metastasis, lymph node (LN) spread, and lymphovenous invasions and did not show significant association with gender, smoking status, family history, or primary site of colorectal cancer. Lower IGFBP3 was significantly high among patients with liver and lymph node metastasis, lymphovenous invasion, and patients with positive family history. This significant negative correlation was also detected between IGFBP3 levels and the size of the tumor.Conclusions: High IGF1 levels and low concentrations of IGFBP3 are related to colorectal cancer and were significantly associated with liver metastasis, lymph node spread, and lymphovenous invasions. Further research is recommended to investigate if circulating IGF1 and IGFBP3 levels can be used to identify people at high risk of colorectal cancer and to investigate potential lifestyle or pharmaceutical ways to lower IGF1 bioactivity as a risk reduction strategy.

Abstract 10895: Biomarkers of Physical Frailty in Heart Failure

Introduction: Physical frailty is highly prevalent and associated with worse outcomes among adults with heart failure (HF). However, the biological mechanisms underlying physical frailty in HF are poorly understood. The aim was to identify biomarkers associated with physical frailty in HF using a multimarker strategy to reflect multiple physiological processes. Hypothesis: We hypothesized that biomarkers of neurohormonal activation, inflammation, insulin resistance, and adipose and skeletal muscle dysfunction would differentiate physically frail from non-physically frail adults with HF. Methods: We collected data and plasma samples from adults with New York Heart Association Functional Class I-IV HF. Physical frailty was measured with the Frailty Phenotype Criteria. Plasma biomarkers assayed were: N-terminal pro-B-type natriuretic peptide, norepinephrine, dihydroxyphenolglycol, soluble tumor necrosis factor alpha receptor 1, adiponectin, insulin, glucose, insulin-like growth factor-1, and myostatin. Comparative statistics and multivariate linear regression were used. Results: The average age of the participants (n = 113) was 63.5±15.7 years, half (48%) were women, and most had a non-ischemic etiology of HF (73%). Physical frailty was identified in 42% of the sample and associated with female gender, higher body mass index, more comorbidities, and HF with preserved ejection fraction. After adjusting for Seattle HF Model projected survival scores, comorbidities, body mass index, and gender, those physically frail had significantly lower plasma adiponectin, lower insulin-like growth factor-1, and lower myostatin compared with those non-physically frail (all p &lt; 0.05). There were no significant differences in other biomarkers between physical frailty groups. Conclusions: Biomarkers involved in adipose tissue and skeletal muscle development, maintenance, and function were significantly different between those physically frail and non-physically frail. Physical frailty in HF may be, in part, underpinned by dysfunctional peripheral processes involving the adipose tissue and skeletal muscle.

Associations of Serum Insulin-Like Growth Factor 1 with New Cardiovascular Events and Subsequent Death in Hemodialysis Patients: The DREAM Cohort.

Aim: Patients with chronic kidney disease (CKD) have elevated risk of death from cardiovascular disease (CVD). A low serum insulin-like growth factor 1 (IGF-1) level is known to predict higher risk for all-cause mortality in incident dialysis patients, although it is unknown whether IGF-1 predicts cardiovascular outcomes. Methods: This was a prospective cohort study of maintenance hemodialysis patients followed up for 5 years. Serum IGF-1 levels were measured at baseline, and patients were divided into IGF-1 tertiles. The key outcomes were all-cause mortality, a composite of new CVD, and death after new CVD events. Additional outcomes were hospitalization for infection and subsequent death. Association was analyzed using Cox proportional hazards models. Results: In the 516 patients that were analyzed, we identified 106 all-cause deaths, 190 new CVD events, and 61 subsequent deaths. In addition, there were 169 hospitalizations for infection and 47 subsequent deaths. The risk of all-cause death was the highest in the lowest IGF-1 tertile, and this association remained significant in multivariable-adjusted models. Regarding CVD outcomes, IGF-1 was not associated with new CVD events but significantly associated with subsequent death in adjusted models. Similarly, IGF-1 was not an independent predictor of hospitalization for infection, but it predicted subsequent death. Conclusions: A low IGF-1 level was not a significant predictor of new CVD events but an independent predictor of subsequent death in hemodialysis patients. Since similar associations with infection outcomes were observed, IGF-1 may be a biomarker of fragility or frailty in this population.

Reduced Insulin-Like Growth Factor 1 Is Associated with Insulin Resistance in Obese Prepubertal Boys.

As one of the most common features of obesity, insulin resistance is central to the pathogenesis of the metabolic syndrome. Low insulin-like growth factor 1 (IGF-1) levels have been proven to be associated with many traditional cardiovascular risk factors, but it still remains controversial with the relationship between IGF-1 and insulin resistance. Accordingly, the main purpose of this study is to investigate the relationship between IGF-1 and insulin resistance in obese prepubertal boys. We used the whole-body insulin sensitivity index (WBISI) to represent insulin resistance. 70 obese prepubertal boys were included in the study, and the obese subjects were divided into two groups by using 1.285 as a threshold value for WBISI. Clinical examination and laboratory examinations were assessed for all participants. Among obese boys, the group of children with WBISI ≤ 1.285 had lower IGF-1 standard deviation scores (SDS) (p = 0.021) than the WBISI > 1.285 group. The results of multiple linear analyses show that lg WBISI was positively correlated with IGF-1 SDS (p = 0.031) after adjusting for traditional cardiovascular risk factors. IGF-1 SDS was negatively associated with insulin resistance in obese prepubertal boys, independent of other traditional cardiovascular disease risk markers.

Pituitary Macroadenoma and Severe Hypothyroidism: The Link between Brain Imaging and Thyroid Function

In case of primary hypothyroidism, reactive pituitary hyperplasia can manifest as pituitary (pseudo) macroadenoma. We report the case of a 12-year-old boy who was evaluated for impaired growth velocity and increased body weight. Because of low insulin-like growth factor 1 levels and poor response to the growth hormone stimulation test, brain magnetic resonance imaging was performed and a pituitary macroadenoma was found. Treatment with levothyroxine was started, and thyroid function was evaluated approximately every 40 days to titrate the dosage. After few months of therapy, the size of the macroadenoma decreased and growth hormone secretion normalized. The pituitary returned to normal size in approximately 5 years. The boy went through puberty spontaneously and reached a normal adult height. In a patient affected by primary hypothyroidism, reactive pituitary hyperplasia can cause growth hormone deficiency; however, growth hormone secretion usually normalizes after starting levothyroxine treatment. Pituitary macroadenoma can be difficult to distinguish from severe pituitary hyperplasia; however, pituitary macroadenomas are rare in childhood, and our clinical case underlines how the hormonal evaluation is essential to achieve a correct diagnosis and prevent unnecessary surgery in a context of pituitary mass.

A low serum IGF-1 is correlated with sarcopenia in subjects with type 1 diabetes mellitus: Findings from a post-hoc analysis of the iDIAMOND study

AimOur previous study revealed that sarcopenia was frequently observed in subjects with type 1 diabetes mellitus (T1DM). However, the factors associated with sarcopenia that are related to T1DM have not yet been clarified. Insulin-like growth factor-1 (IGF-1) has been shown to play a role in skeletal muscle growth, differentiation, and regeneration. The present study, therefore, investigated the association between the serum IGF-1 level and sarcopenia and low skeletal muscle mass in subjects with T1DM. MethodsThis cross-sectional study enrolled subjects with T1DM (n = 168) and without diabetes (n = 59) who had had their clinical data on serum IGF-1 collected in the iDIAMOND study. ResultsThe z-score of serum IGF-1 was significantly lower in the subjects with T1DM than that in those without diabetes (p < 0.001). Among subjects with T1DM, the z-score of serum IGF-1 was significantly lower in sarcopenic subjects than in non-sarcopenic subjects. The multivariable logistic regression analysis showed that the serum IGF-1 z-score was an independent determinant of sarcopenia and a low skeletal muscle mass index, but not low grip strength nor slow gait speed in subjects with T1DM. ConclusionsA low serum IGF-1 level is correlated with sarcopenia and low skeletal muscle mass in subjects with T1DM.

The Correlation Between Iron Overload and Endocrine Function in Adult Transfusion-Dependent Beta-Thalassemia Patients with Growth Retardation.

BackgroundIron overload is a major problem in patients with transfusion-dependent beta-thalassemia (TDT). Reports on the correlation between iron overload and endocrine function with growth retardation in such a population in Indonesia have not been established. Therefore, this study aims to obtain a profile of iron load and endocrine function of adult transfusion dependent beta-thalassemia patients and their correlation with growth retardation.MethodsA cross-sectional study was performed, involving adult homozygous and HbE beta-thalassemia patients receiving blood transfusions at the Cipto Mangunkusumo Hospital, Jakarta. Iron overload was represented by serum ferritin (FS) and transferrin saturation (TS), while the endocrine function was examined by the Thyroid Stimulating Hormone-sensitive (TSHs), free T4 (fT4), and insulin-like growth factor-1 (IGF-1). The results were analyzed using bivariate analysis plus Pearson and Spearman correlation tests.ResultsIn general, 58 subjects were selected from 224 adult transfusion dependent beta- thalassemia patients, consisting of 31 males (53.4%) and 27 females (46.6%). Furthermore, their median age was 21 (18–24) years, while the subclinical hypothyroid proportion was 32.7% and low IGF-1 levels were detected in 79.3% of the total population. There was a weak negative correlation between FS and fT4 (Spearman rho=−0.361; p=0.003), as well as IGF-1 (Spearman rho=−0.313; p=0.008), but FS and TSHs had no correlation (Spearman rho=0.074; p=0.29). Also, there was no correlation between ST with TSHs (Spearman rho=0.003; p=0.492), fT4 (Spearman rho=0.018; p=0.448), and IGF-1 (Spearman rho=−0.142; p=0.143).ConclusionBased on serum ferritin, iron overload is discovered to have a negative correlation with free T4 and insulin-like growth factor-1.

IGF-1 Haploinsufficiency Causes Age-Related Chronic Cochlear Inflammation and Increases Noise-Induced Hearing Loss

Insulin-like growth factor 1 (IGF-1) deficiency is an ultrarare syndromic human sensorineural deafness. Accordingly, IGF-1 is essential for the postnatal maturation of the cochlea and the correct wiring of hearing in mice. Less severe decreases in human IGF-1 levels have been associated with other hearing loss rare genetic syndromes, as well as with age-related hearing loss (ARHL). However, the underlying mechanisms linking IGF-1 haploinsufficiency with auditory pathology and ARHL have not been studied. Igf1-heterozygous mice express less Igf1 transcription and have 40% lower IGF-1 serum levels than wild-type mice. Along with ageing, IGF-1 levels decreased concomitantly with the increased expression of inflammatory cytokines, Tgfb1 and Il1b, but there was no associated hearing loss. However, noise exposure of these mice caused increased injury to sensory hair cells and irreversible hearing loss. Concomitantly, there was a significant alteration in the expression ratio of pro- and anti-inflammatory cytokines in Igf1+/− mice. Unbalanced inflammation led to the activation of the stress kinase JNK and the failure to activate AKT. Our data show that IGF-1 haploinsufficiency causes a chronic subclinical proinflammatory age-associated state and, consequently, greater susceptibility to stressors. This work provides the molecular bases to further understand hearing disorders linked to IGF-1 deficiency.

High Level of Maternal Low Density Lypoprotein and Insulin-Like Growth Factor Binding Protein 5 as a Risk Factor for Preeclampsia

High Level of Maternal Low Density Lypoprotein and Insulin-Like Growth Factor Binding Protein 5 as a Risk Factor for Preeclampsia

Covid-19 and Growth Hormone/Insulin-Like Growth Factor 1: Study in Critically and Non-Critically Ill Patients.

ObjectiveWe aimed to measure insulin-like growth factor 1 (IGF1) and growth hormone (GH) in critically and non-critically ill patients with Covid-19 and assess them vis-a-vis clinical and laboratory parameters and prognostic tools.Subjects and MethodsWe included patients who were admitted to the wards or the ICU of the largest Covid-19 referral hospital in Greece; patients with non-Covid-19 pneumonia served as controls. Apart from the routine laboratory work-up for Covid-19 we measured GH and IGF1 (and calculated normalized IGF-1 values as standard deviation scores; SDS), after blood sampling upon admission to the wards or the ICU.ResultsWe studied 209 critically and non-critically ill patients with Covid-19 and 39 control patients. Patients with Covid-19 who were ICU non-survivors were older and presented with a worse hematological/biochemical profile (including white blood cell count, troponin, glucose, aminotransferases and lactate dehydrogenase) compared to ICU survivors or Covid-19 survivors in the wards. Overall, IGF-1 SDS was higher in Covid-19 survivors compared to non-survivors (-0.96 ± 1.89 vs -2.05 ± 2.48, respectively, p=0.030). No significant differences were noted in GH between the groups. Nevertheless, in critically ill patients with Covid-19, the prognostic value of IGF-1 (raw data), IGF-1 (SDS) and GH for survival/non-survival was on a par with that of APACHE II and SOFA (with a marginal difference between GH and SOFA).ConclusionIn conclusion, our findings suggest that there might be an association between low IGF1 (and possibly GH) and poor outcome in patients with Covid-19.

High Prevalence of Nonalcoholic Fatty Liver Disease Among Adolescents and Young Adults With Hypopituitarism due to Growth Hormone Deficiency

ObjectiveTo investigate the prevalence of nonalcoholic fatty liver disease (NAFLD) in adolescents and young adults with hypopituitarism and to examine the associations of growth hormone (GH) deficiency with the occurrence of NAFLD. MethodsA cross-sectional study for the determination of NAFLD prevalence included 76 patients with childhood-onset hypopituitarism and 74 controls matched by age and body mass index (BMI). We investigated the prevalence of NAFLD in adolescent and young adult patients with hypopituitarism as well as the age- and BMI-matched controls. Among patients with hypopituitarism, anthropometric, clinical, and biochemical assessments using transient elastography and magnetic resonance imaging were performed. Logistic regression was used to identify the factors associated with NAFLD. ResultsThe adolescents and young adults with hypopituitarism exhibited higher prevalence of NAFLD than the age- and BMI-matched controls. Among patients with hypopituitarism, obesity and obesity-related metabolic derangements were significantly associated with liver steatosis and fibrosis, whereas lower insulin-like growth factor (IGF)-I standard deviation score (SDS) and IGF-I/IGF-binding protein 3 molar ratios were associated with steatosis. In regression analyses adjusted for BMI SDS, steatosis was found to be associated with a lower IGF-I SDS and IGF-I/IGF-binding protein 3 molar ratios, whereas liver fibrosis was found to be associated with a lower IGF-I SDS. ConclusionOur results suggest that GH deficiency contributes to the occurrence of NAFLD, along with obesity and obesity-related metabolic changes. Because NAFLD occurs early in patients with hypopituitarism, the surveillance, weight control, and timely replacement of deficit hormones, including GH, are essential.

Acromegaly: achieving timely diagnosis and improving outcomes by personalized care.

Discuss recent literature regarding clinical manifestations and comorbidities in acromegaly, with focus on early diagnosis and customized care. The mean interval between onset of clinical manifestations and diagnosis is currently 3-5 years. Women, especially younger than 50 years of age, experience longer delays, have lower insulin-like growth factor 1 (IGF-1) levels and larger tumors than men. Development of comorbidities usually precedes the diagnosis and is influenced by age, sex, and biochemical disease activity. Comorbidities other than irreversible osteoarticular structural changes usually improve after acromegaly treatment. In patients with diabetes, the course of hyperglycemia not only depends on biochemical control but also on specific acromegaly therapies. Quality of life is influenced by sex, as well as by acromegaly symptoms, biochemical activity, and treatment. Quality of life remains lower than general population despite biochemical remission. Early diagnosis can be achieved by suspecting acromegaly based on suggestive clinical scenarios rather than obvious changes in appearance. Personalized care entails a proactive multidisciplinary approach to identify and treat comorbidities while carefully monitoring the effects of acromegaly treatment.

Clinical laboratory tests and five-year incidence of major depressive disorder: a prospective cohort study of 433,890 participants from the UK Biobank

Prevention of major depressive disorder (MDD) is a public health priority. Identifying biomarkers of underlying biological processes that contribute to MDD onset may help address this public health need. This prospective cohort study encompassed 383,131 white British participants from the UK Biobank with no prior history of MDD, with replication in 50,759 participants of other ancestries. Leveraging linked inpatient and primary care records, we computed adjusted odds ratios for 5-year MDD incidence among individuals with values below or above the 95% confidence interval (<2.5th or >97.5th percentile) on each of 57 laboratory measures. Sensitivity analyses were performed across multiple percentile thresholds and in comparison to established reference ranges. We found that indicators of liver dysfunction were associated with increased 5-year MDD incidence (even after correction for alcohol use and body mass index): elevated alanine aminotransferase (AOR = 1.35, 95% confidence interval [1.16, 1.58]), aspartate aminotransferase (AOR = 1.39 [1.19, 1.62]), and gamma glutamyltransferase (AOR = 1.52 [1.31, 1.76]) as well as low albumin (AOR = 1.28 [1.09, 1.50]). Similar observations were made with respect to endocrine dysregulation, specifically low insulin-like growth factor 1 (AOR = 1.34 [1.16, 1.55]), low testosterone among males (AOR = 1.60 [1.27, 2.00]), and elevated glycated hemoglobin (HbA1C; AOR = 1.23 [1.05, 1.43]). Markers of renal impairment (i.e. elevated cystatin C, phosphate, and urea) and indicators of anemia and macrocytosis (i.e. red blood cell enlargement) were also associated with MDD incidence. While some immune markers, like elevated white blood cell and neutrophil count, were associated with MDD (AOR = 1.23 [1.07, 1.42]), others, like elevated C-reactive protein, were not (AOR = 1.04 [0.89, 1.22]). The 30 significant associations validated as a group in the multi-ancestry replication cohort (Wilcoxon p = 0.0005), with a median AOR of 1.235. Importantly, all 30 significant associations with extreme laboratory test results were directionally consistent with an increased MDD risk. In sum, markers of liver and kidney dysfunction, growth hormone and testosterone deficiency, innate immunity, anemia, macrocytosis, and insulin resistance were associated with MDD incidence in a large community-based cohort. Our results support a contributory role of diverse biological processes to MDD onset.

Biomarkers representing key aging-related biological pathways are associated with subclinical atherosclerosis and all-cause mortality: The Framingham Study.

Increased oxidative stress, leukocyte telomere length (LTL) shortening, endothelial dysfunction, and lower insulin-like growth factor (IGF)-1 concentrations reflect key molecular mechanisms of aging. We hypothesized that biomarkers representing these pathways are associated with measures of subclinical atherosclerosis and all-cause mortality. We evaluated up to 2,314 Framingham Offspring Study participants (mean age 61 years, 55% women) with available biomarkers of aging: LTL, circulating concentrations of IGF-1, asymmetrical dimethylarginine (ADMA), and urinary F2-Isoprostanes indexed to urinary creatinine. We evaluated the association of each biomarker with coronary artery calcium [ln (CAC+1)] and carotid intima-media thickness (IMT). In multivariable-adjusted linear regression models, higher ADMA levels were associated with higher CAC values (βADMA per 1-SD increase 0.25; 95% confidence interval [CI] [0.11, 0.39]). Additionally, shorter LTL and lower IGF-1 values were associated with higher IMT values (βLTL -0.08, 95%CI -0.14, -0.02, and βIGF-1 -0.04, 95%CI -0.08, -0.01, respectively). During a median follow-up of 15.5 years, 593 subjects died. In multivariable-adjusted Cox regression models, LTL and IGF-1 values were inversely associated with all-cause mortality (hazard ratios [HR] per SD increase in biomarker, 0.85, 95% CI 0.74-0.99, and 0.90, 95% CI 0.82-0.98 for LTL and IGF-1, respectively). F2-Isoprostanes and ADMA values were positively associated with all-cause mortality (HR per SD increase in biomarker, 1.15, 95% CI, 1.10-1.22, and 1.10, 95% CI, 1.02-1.20, respectively). In our prospective community-based study, aging-related biomarkers were associated with measures of subclinical atherosclerosis cross-sectionally and with all-cause mortality prospectively, supporting the concept that these biomarkers may reflect the aging process in community-dwelling adults.

A Clinical Audit on Diagnosis and Management of Hypopituitarism in Scarborough General Hospital

Objectives: The main objective was to evaluate the use and compliance to the guidelines issued by the Endocrine Society in diagnosis and management of hypopituitarism and their impact on the clinical practice in Scarborough General Hospital (SGH). Design: A retrospective review of secondary data of patients with a diagnosis of hypopituitarism in SGH. Methodology: The data was collected from both patients’ case notes and electronic medical records. Data analysis was performed using Microsoft excel. Results: 18 patients with the diagnosis of Hypopituitarism were identified. 5 patients were females and 13 were males. 11 patients aged between 60-80 years, 4 patients were between 51-60 years and 3 patients were between 31-50 years. All the patients had low cortisol levels; however, cortisol was checked at 9AM in only 4 patients. All the patients had their thyroid stimulating hormone levels checked, which were low in all of them. Free T4 levels were normal in 2 patients, and low in 16 patients. 17 patients had low follicular stimulating hormone levels, whereas 15 had low luteinising hormone levels. Testosterone levels were checked in 9 male patients out of which 7 had low levels. Insulin-like growth factor-1(IGF1) was done in all patients and levels were low in 10 patients. All those with low IGF1 had glucagon stimulation test. Serum sodium levels were low in 3 patients and high in 5 patients. Plasma osmolality was only checked in 8 patients (was high in 5 patients). Urine osmolality was checked in 10 patients, and it was low in 5 patients. Brain MRI was performed in 16 patients, and 2 patients had brain CT. The most common cause of hypopituitarism was non-functioning pituitary adenoma (44.4%), and the least common causes were empty Sella syndrome (5.6%) and craniopharyngioma (5.6%). All patients received glucocorticoid replacement therapy, 17 received thyroid hormone replacement therapy, 8 received testosterone replacement therapy, 3 received desmopressin (DDAVP) treatment, and one patient received growth hormone replacement therapy. Conclusion: This Audit shows that our practice in diagnosis and management of hypopituitarism is mostly in line with the recommendation of the Endocrine Society. However, cortisol levels were not always measured at 9:00 am and we are not compliant with performing Growth Hormone stimulation test in every patient.

The Association of Insulin-Like Growth Factor-1 With Bone Mineral Density in Survivors of Childhood Acute Leukemia

Abstract Background: The purpose of the current study is to investigate bone mineral deficit of children in survivors of childhood acute leukemia and examine the association of insulin-like growth factor-1 (IGF-1) with bone mineral density (BMD) status and the presence of osteoporosis. Methods: In a cross-sectional study of children diagnosed with different types of acute leukemia at age between 6 months and 18 years, serum IGF-1 and IGFBP-3, were assessed in relation to lumbar spine BMD (LSBMD) by using dual-energy x-ray absorptiometry and non-traumatic vertebral fracture by lateral thoracolumbar spine radiographs. Standard deviation scores (SDS) were calculated based on the age- and gender-adjusted population mean. Results: Among 189 children after completion of acute leukemia treatment, 22 (11.6%) children had LSBMD SDS less than -2.0 while 80 (42.3 %) children were diagnosed with osteoporosis. Mean areal BMD and LSBMD SDS of the subjects were 0.862±0.197 g/cm2 and -0.6±1.6, respectively. IGF-1 and IGFBP-3 were lower in children with LSBMD lower than -2.0 (P&amp;lt;0.05) and those with osteoporosis (P&amp;lt;0.05). LSBMD SDS showed linear correlation with serum IGF-1 (P=0.041). Low serum IGF-1 level (OR=0.724, P=0.042) and elder age of leukemia diagnosis (OR=1.089, P=0.023) were suggested risk factor of the occurrence of osteoporosis. Conclusions: Substantial number of survivors from childhood acute leukemia undergo bone mineral deficits, and serum IGF-1 status could be a prognostic factor associated with bone mass acquisition and future occurrence of osteoporosis.

Anorexia Nervosa and Osteoporosis

Patients with anorexia nervosa (AN) often experience low bone mineral density (BMD) and increased fracture risk, with low body weight and decreased gonadal function being the strongest predictors of the observed bone mineral deficit and fractures. Other metabolic disturbances have also been linked to bone loss in this group of patients, including growth hormone resistance, low insulin-like growth factor-1 (IGF-1) concentrations, low leptin concentrations, and hypercortisolemia. However, these correlations lack definitive evidence of causality. Weight restoration and resumption of menstrual function have the strongest impact on increasing BMD. Other potential treatment options include bisphosphonates and teriparatide, supported by data from small clinical trials, but these agents are not approved for the treatment of low BMD in adolescents or premenopausal women with AN.

An Overview of the Molecular Mechanisms Contributing to Musculoskeletal Disorders in Chronic Liver Disease: Osteoporosis, Sarcopenia, and Osteoporotic Sarcopenia.

The prevalence of osteoporosis and sarcopenia is significantly higher in patients with liver disease than in those without liver disease and osteoporosis and sarcopenia negatively influence morbidity and mortality in liver disease, yet these musculoskeletal disorders are frequently overlooked in clinical practice for patients with chronic liver disease. The objective of this review is to provide a comprehensive understanding of the molecular mechanisms of musculoskeletal disorders accompanying the pathogenesis of liver disease. The increased bone resorption through the receptor activator of nuclear factor kappa (RANK)-RANK ligand (RANKL)-osteoprotegerin (OPG) system and upregulation of inflammatory cytokines and decreased bone formation through increased bilirubin and sclerostin and lower insulin-like growth factor-1 are important mechanisms for osteoporosis in patients with liver disease. Sarcopenia is associated with insulin resistance and obesity in non-alcoholic fatty liver disease, whereas hyperammonemia, low amount of branched chain amino acids, and hypogonadism contributes to sarcopenia in liver cirrhosis. The bidirectional crosstalk between muscle and bone through myostatin, irisin, β-aminoisobutyric acid (BAIBA), osteocalcin, as well as the activation of the RANK and the Wnt/β-catenin pathways are associated with osteosarcopenia. The increased understandings for these musculoskeletal disorders would be contributes to the development of effective therapies targeting the pathophysiological mechanism involved.

Association of Low Muscle Density With Deteriorations in Muscle Strength and Physical Functioning in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is associated with low muscle density due to the accumulation of intramuscular fat. The present study was undertaken to identify predictors of changes in muscle density and to determine whether low muscle density predicted changes in strength and physical function. Patients with RA, ages 18-70 years, completed whole-body dual-energy x-ray absorptiometry and peripheral quantitative computed tomography 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. Muscle density was assessed at baseline in 107 patients with RA. Seventy-nine of these patients (74%) returned for a follow-up assessment at a median follow-up time of 2.71 years (interquartile range 2.35-3.57). Factors associated with declines in muscle density included female sex, higher disease activity, smoking, and lower insulin-like growth factor 1 (IGF-1) levels. Greater muscle density Z score at baseline (per 1 SD) was associated with less worsening per year according to HAQ, SPPB, and 4-meter walk time scores and a lower risk of a clinically important worsening in HAQ score (odds ratio [OR] 1.90 [95% confidence interval (95% CI) 1.06, 3.42]; P = 0.03) and walking speed (OR 2.87 [95% CI 1.05, 7.89]; P = 0.04). Worsening of skeletal muscle density occurred in patients with higher disease activity, in smokers, and in 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.