Pilot Study of Low-dose Naltrexone for the Treatment of Chronic Pain Due to Arthritis: A Randomized, Double-blind, Placebo-controlled, Crossover Clinical Trial.

PURPOSE: Low-dose naltrexone (LDN) is commonly used to control pain and other symptoms, especially in patients with autoimmune diseases, but with limited evidence. This study tests the efficacy of LDN in reducing chronic pain in patients with osteoarthritis (OA) and inflammatory arthritis (IA), where existing approaches often fail to adequately control pain. METHODS: In this randomized, double-blind, placebo-controlled, crossover clinical trial, each patient received 4.5 mg LDN for 8 weeks and placebo for 8 weeks. Outcome measures were patient reported, using validated questionnaires. The primary outcome was differences in pain interference during the LDN and placebo periods, using the Brief Pain Inventory (scale, 0-70). Secondary outcomes included changes in mean pain severity, fatigue, depression, and multiple domains of health-related quality of life. The painDETECT questionnaire classified pain as nociceptive, neuropathic, or mixed. Data were analyzed using mixed-effects models. FINDINGS: Seventeen patients with OA and 6 with IA completed the pilot study. Most patients described their pain as nociceptive (n = 9) or mixed (n = 8) rather than neuropathic (n = 3). There was no difference in change in pain interference after treatment with LDN (mean [SD], -23 [19.4]) versus placebo (mean [SD], -22 [19.2]; P = 0.90). No significant differences were seen in pain severity, fatigue, depression, or health-related quality of life. IMPLICATIONS: In this small pilot study, findings do not support LDN being efficacious in reducing nociceptive pain due to arthritis. Too few patients were enrolled to rule out modest benefit or to assess inflammatory or neuropathic pain. CLINICALTRIALS: gov identifier: NCT03008590.

Physical Activity, Exercise Capacity, and Body Composition in U.S. Veterans with Chronic Obstructive Pulmonary Disease.

Rationale: Differences in body composition may contribute to variability in exercise capacity (EC) and physical activity (PA) in individuals with chronic obstructive pulmonary disease (COPD). Most studies have used bioimpedance-based surrogates of muscle (lean) mass; relatively few studies have included consideration of fat mass, and limited studies have been performed using dual X-ray absorptiometry (DXA) to assess body composition. Objectives: To determine whether DXA-assessed muscle (lean) and fat mass exhibit differential correlations with EC and PA in subjects with COPD. Methods: U.S. veterans with COPD (defined as forced expiratory volume in 1 second/forced vital capacity < 0.7 or emphysema on clinical chest computed tomography) had DXA-assessed body composition, EC (6-minute-walk distance), objective PA (average daily step counts), and self-reported PA measured at enrollment. Associations among EC, PA, and body composition were examined using Spearman correlations and multivariable models adjusted a priori for age, sex, race, and lung function. Results: Subjects (n = 98) were predominantly White (90%), obese (mean body mass index, 30.2 ± 6.2 kg/m2), and male (96%), with a mean age of 69.8 ± 7.9 years and moderate airflow obstruction (mean forced expiratory volume in 1 second percentage predicted, 68 ± 20%). Modest inverse correlations of EC and PA with fat mass were observed (Spearman's rho range, -0.20 to -0.34), whereas measures of muscle (lean) mass were not significantly associated with EC or PA. The ratio of appendicular skeletal muscle mass (ASM) to weight, which considers both muscle (lean) and fat mass, was consistently associated with EC (8.4 [95% confidence interval, 2.9-13.8] meter increase in 6-minute walk distance per 1% increase in ASM-to-weight ratio), objective PA (194.8 [95% confidence interval, 15.2-374.4] steps per day per 1% increase in ASM-to-weight ratio), and self-reported PA in multivariable-adjusted models. Conclusions: DXA-assessed body composition measures that include consideration of both lean and fat mass are associated with cross-sectional EC and PA in COPD populations. Clinical trial registered with www.clinicaltrials.gov (NCT02099799).

Performance of bioelectrical impedance analysis compared to dual X-ray absorptiometry (DXA) in Veterans with COPD.

We examined the performance of a commercially-available handheld bioimpedance (BIA) device relative to dual X-ray absorptiometry (DXA) to assess body composition differences among Veterans with chronic obstructive pulmonary disease (COPD). Body composition was measured using DXA and BIA (Omron HBF-306C) at a single time point. Correlations between BIA- and DXA-assessed percent fat, fat mass, and fat-free mass were analyzed using Spearman (ρ) and Lin Concordance Correlation Coefficients (ρc). Mean differences in fat mass were visualized using Bland-Altman plots. Subgroup analyses by obesity status (BMI < 30 versus ≥ 30) were performed. Among 50 participants (96% male; mean age: 69.5 ± 6.0 years), BIA-assessed fat mass was strongly correlated (ρ = 0.94) and demonstrate excellent concordance (ρc = 0.95, [95%CI: 0.93-0.98]) with DXA, with a mean difference of 2.7 ± 3.2 kg between BIA and DXA. Although Spearman correlations between BIA- and DXA-assessed percent fat and fat-free mass were strong (ρ = 0.8 and 0.91, respectively), concordance values were only moderate (ρc = 0.67 and 0.74, respectively). Significantly stronger correlations were observed for obese relative to non-obese subjects for total percent fat (ρobese = 0.85 versus ρnon-obese = 0.5) and fat mass (ρobese = 0.96 versus ρnon-obese = 0.84). A handheld BIA device demonstrated high concordance with DXA for fat mass and moderate concordance for total percent fat and fat-free mass.ClinicalTrials.gov: NCT02099799.

Correction: Plasma vitamin D, past chest illness, and risk of future chest illness in chronic spinal cord injury (SCI): a longitudinal observational study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Plasma vitamin D, past chest illness, and risk of future chest illness in chronic spinal cord injury (SCI): a longitudinal observational study.

STUDY DESIGN: Observational study. OBJECTIVE: Assess associations between vitamin D levels and other risk factors on future chest illness in a chronic spinal cord injury (SCI) cohort. SETTING: Veterans Affairs Boston and the Boston, MA community. METHODS: Between August 2009 and August 2017, 253 participants with chronic SCI were followed over a median of 3.2 years (up to 7.4 years) with two to four visits a median of 1.7 years apart. At each visit, plasma 25-hydroxyvitamin D level was obtained, spirometry performed, and a respiratory questionnaire assessing chest illnesses since last visit was completed. Repeated measures negative binomial regression was used to assess chest illness risk longitudinally. RESULTS: At entry, 25% had deficient vitamin D levels (<20 nanograms/milliliter (ng/ml)), 52% were insufficient (20 to <30 ng/ml), and 23% were sufficient (≥30 ng/ml). Over 545 study visits, chest illnesses (n = 106) were reported by 60 participants. In multivariable models (including previous chest illness history), deficient vitamin D levels (compared with those with sufficient levels) were associated with future chest illness though with wide confidence limits (relative risk (RR) = 1.36, 95% confidence intervals (CI) = 0.74, 2.47). The strongest association with chest illness during the follow-up period was in persons who reported pneumonia/bronchitis after injury and a chest illness in the three years before study entry (RR = 7.62; 95% CI = 3.70, 15.71). CONCLUSION: Assessed prospectively in chronic SCI, there was a suggestive association between deficient vitamin D levels and future chest illness. Past chest illness history was also strongly associated with future chest illness.

Associations between vitamin D and pulmonary function in chronic spinal cord injury.

CONTEXT/OBJECTIVE: Individuals with chronic spinal cord injury (SCI) have an increased risk of morbidity and mortality attributable to respiratory diseases. Previous studies in non-SCI populations suggest that vitamin D may be a determinant of respiratory health. Therefore, we sought to assess if lower vitamin D levels were associated with decreased pulmonary function in persons with chronic SCI. DESIGN: Cross-sectional study. SETTING: Veterans Affairs Medical Center. PARTICIPANTS: 312 participants (260 men and 52 women) with chronic SCI recruited from VA Boston and the community participating in an epidemiologic study to assess factors influencing respiratory health. METHODS: Participants provided a blood sample, completed a respiratory health questionnaire, and underwent spirometry. Linear regression methods were used to assess cross-sectional associations between plasma 25-hydroxyviatmin D and spirometric measures of pulmonary function. OUTCOME MEASURES: Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC. RESULTS: Adjusted and unadjusted for a number of confounders, there was no significant association between plasma vitamin D levels and FEV1, FVC, or FEV1/FVC. For example, in fully adjusted models, each 10 ng/ml increase in vitamin D was associated with a 4.4 ml (95%CI -64.4, 73.2, P = 0.90) ml change in FEV1. Conclusion: There was no significant cross-sectional association between plasma vitamin D and FEV1, FVC, or FEV1/FVC in this cohort of individuals with chronic SCI.

Vitamin D, diet, and lifestyle in a chronic SCI population.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: Determine dietary, lifestyle, and clinical factors associated with plasma 25-hydroxyvitamin D [25(OH)D] levels in persons with chronic spinal cord injury (SCI). SETTING: Veterans Affairs Medical Center in Boston, MA. METHODS: 174 participants completed food frequency and health questionnaires, provided a blood sample, and underwent dual x-ray absorptiometry (DXA) to assess %total body fat. Linear regression models were used to assess cross-sectional associations of personal, lifestyle, and nutritional factors with plasma 25(OH)D. RESULTS: Independent factors positively associated with higher plasma 25(OH)D included vitamin D intake, age, hours of planned exercise, female sex, white race, wine consumption, and if a never or former smoker. The most important predictor of 25(OH)D was supplement intake. The majority of subjects (98.9% for vitamin D and 74.1% for calcium) did not meet the recommended daily allowance for adults from their diet alone. Level and completeness of SCI, injury duration, mobility, %total body fat, time outside, and comorbid diseases were not associated with plasma 25(OH)D. CONCLUSIONS: Plasma 25(OH)D level in chronic SCI is not associated with clinical factors specific to SCI such as injury level and completeness, injury duration, and mobility mode, but related to supplement intake and other lifestyle factors.

Plasma Leptin and Reduced FEV1 and FVC in Chronic Spinal Cord Injury.

BACKGROUND: Adipose tissue produces leptin, which is pro-inflammatory, and adiponectin, which has anti-inflammatory properties. Participants with chronic spinal cord injury (SCI) have increased body fat and are at increased risk for respiratory illness. OBJECTIVE: To assess the associations between leptin and adiponectin with pulmonary function in a chronic SCI cohort. DESIGN: Cross-sectional study. SETTING: Veterans Affairs Medical Center. PARTICIPANTS: A total of 285 participants (237 men and 48 women) with chronic SCI with mean (standard deviation) injury duration 17.8 (13.2) years from the VA Boston and the community participating in an epidemiologic study assessing factors associated with respiratory health. METHODS: Participants (24.6% cervical American Spinal Injury Association Impairment Scale (AIS) level A, B, and C; 33.6% other AIS A, B, and C; 41.8% AIS D) provided a blood sample, completed a respiratory health questionnaire, and underwent spirometry. Linear regression methods were used to assess cross-sectional associations between plasma leptin and adiponectin with spirometric measures of pulmonary function adjusted for age, race, gender, and height. Level and severity of SCI, mobility mode, body mass index, smoking, chronic obstructive pulmonary disease, asthma, chest injury history, laboratory batch, and other potential confounders were also considered. MAIN OUTCOME MEASUREMENTS: forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC. RESULTS: There was a statistically significant inverse relationship between plasma leptin assessed in quartiles or as a continuous covariate with FEV1 and FVC. In fully adjusted models, each interquartile range (16,214 pg/mL) increase in leptin was associated with a significant decrease in FEV1 (-93.1 mL; 95% confidence interval = -166.2, -20.0) and decrease in FVC (-130.7 mL; 95% confidence interval = -219.4, -42.0). There were no significant associations between leptin and FEV1/FVC or between plasma adiponectin with FEV1, FVC, or FEV1/FVC. CONCLUSION: Plasma leptin in individuals with chronic SCI is inversely associated with FEV1 and FVC, independently of SCI level and severity and other covariates. This finding suggests that plasma leptin may contribute to reduced pulmonary function in chronic SCI. LEVEL OF EVIDENCE: II.

Associations between vitamin D, adiposity, and respiratory symptoms in chronic spinal cord injury.

Context/Objective Persons with chronic spinal cord injury (SCI) have an increased risk of respiratory-related morbidity and mortality and chronic respiratory symptoms are clinical markers of future respiratory disease. Therefore, we sought to assess potentially modifiable factors associated with respiratory symptoms, with a focus on circulating vitamin D and measures of body fat. Design Cross-sectional study. Setting Veterans Affairs Medical Center. Participants Three hundred forty-three participants (282 men and 61 women) with chronic SCI participating in an epidemiologic study to assess factors influencing respiratory health recruited from VA Boston and the community. Methods Participants provided a blood sample, completed a respiratory health questionnaire, and underwent dual x-ray absorptiometry (DXA) to assess % body fat. Logistic regression was used to assess cross-sectional associations between respiratory symptoms and plasma vitamin D and measures of body fat with adjustment for a number of potential confounders. Outcome Measures Chronic cough, chronic phlegm, any wheeze, persistent wheeze. Results After adjustment for a number of confounders (including smoking), participants with greater %-android, gynoid, trunk, or total body fat had increased odds ratios for any wheeze and suggestive associations with persistent wheeze, but not with chronic cough or phlegm. Vitamin D levels were not associated with any of the respiratory symptoms. Conclusion Increased body fat, but not vitamin D, was associated with wheeze in chronic SCI independent of a number of covariates.

Epilepsy and osteoporosis risk.

PURPOSE OF REVIEW: It is well-recognized that individuals with epilepsy have an increased risk of vertebral and nonvertebral fractures; this increased risk has been described to be secondary to an increased bone fragility and to an increased risk of falls. Osteoporosis is the most common bone disease which has been characterized by microarchitectural deterioration of trabecula and cortical bone mass with a decrease in bone mineral density and bone strength. Specific side effects of antiepileptic drugs (AEDs) on bone metabolism have been identified; recent research publications further characterized some of the specific side effects of AEDs on bone metabolism. It is the purpose of this review to describe recent advances on the knowledge of the effects of AEDs on bone metabolism and the cause of osteoporosis in the field of epilepsy. RECENT FINDINGS: Recent literature demonstrates that the increased risk of fractures in the epileptic patient population is likely multifactorial and includes seizure activity, injuries from falls, decreased bone strength, adverse effects from AEDs. Reviewed publications suggest that the mechanism of adverse effects on bone metabolism may differ among different AEDs. The impact of vitamin D deficiency or its metabolism in the epileptic population has also been a concern of several reviewed publications. SUMMARY: This is a review is of the recent epilepsy and osteoporosis literature published over the past 18 months, highlighting reports and studies concerning the cause, pathogenesis, and possible preventive measures and effects of AEDs on changes of bone metabolism, bone loss, and development of osteoporosis. In addition, we also reviewed articles focusing on issues of prevention and treatment of osteoporosis in individuals with epilepsy. We utilized the search engines of PubMed and Cochrane Reviews from January 2016 to June 2017.

Ultrasound-guided intravenous catheter insertion in a prone patient using a T probe in emergency setting.

INTRODUCTION: Central venous catheterizations are common intraoperative procedures.Central venous catheter (CVC) placements are usually performed with patients lying in the supine position using real-time ultrasound (US) guidance. CASE DESCRIPTION: A 43-year-old man underwent open right popliteal artery reconstruction in the prone position for a limb-threatening injury. Excessive continuous intraoperative bleeding, increased by a coexisting pelvic fracture, was temporarily stabilized by a T POD device, but with the need of external fixation, required the placement of CVC, which was not feasible whilst in the prone position without US help.A view of the left internal jugular vein (IJV) was obtained with pediatric T probe and a CVC was placed using real-time US guidance, without complications. CONCLUSIONS: We demonstrated the feasibility and safety of US-guided CVC placements in an emergency setting.

FEV1 and FVC and systemic inflammation in a spinal cord injury cohort.

BACKGROUND: Systemic inflammation has been associated with reduced pulmonary function in individuals with and without chronic medical conditions. Individuals with chronic spinal cord injury (SCI) have clinical characteristics that promote systemic inflammation and also have reduced pulmonary function. We sought to assess the associations between biomarkers of systemic inflammation with pulmonary function in a chronic SCI cohort, adjusting for other potential confounding factors. METHODS: Participants (n = 311) provided a blood sample, completed a respiratory health questionnaire, and underwent spirometry. Linear regression methods were used to assess cross-sectional associations between plasma C-reactive protein (CRP) and interleukin-6 (IL-6) with forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC. RESULTS: There were statistically significant inverse relationships between plasma CRP and IL-6 assessed in quartiles or continuously with FEV1 and FVC. In fully adjusted models, each interquartile range (5.91 mg/L) increase in CRP was associated with a significant decrease in FEV1 (-55.85 ml; 95% CI: -89.21, -22.49) and decrease in FVC (-65.50 ml; 95% CI: -106.61, -24.60). There were similar significant findings for IL-6. There were no statistically significant associations observed with FEV1/FVC. CONCLUSION: Plasma CRP and IL-6 in individuals with chronic SCI are inversely associated with FEV1 and FVC, independent of SCI level and severity of injury, BMI, and other covariates. This finding suggests that systemic inflammation associated with chronic SCI may contribute to reduced pulmonary function.

Analysis of skeletal muscle gene expression patterns and the impact of functional capacity in patients with systolic heart failure.

BACKGROUND: Declining physical function is common among systolic heart failure (HF) patients and heralds poor clinical outcomes. We hypothesized that coordinated shifts in expression of ubiquitin-mediated atrophy-promoting genes are associated with muscle atrophy and contribute to decreased physical function. METHODS: Systolic HF patients (left ventricular ejection fraction [LVEF] ≤40%) underwent skeletal muscle biopsies (nondominant vastus lateralis) and comprehensive physical assessments. Skeletal muscle gene expression was assessed with the use of real-time polymerase chain reaction. Aerobic function was assessed with the use of cardiopulmonary exercise and 6-minute walk tests. Strength capacity was assessed with the use of pneumatic leg press (maximum strength and power). Serologic inflammatory markers also were assessed. RESULTS: 54 male patients (66.6 ± 10.0 years) were studied: 24 systolic HF patients (mean LVEF 28.9 ± 7.8%) and 30 age-matched control subjects. Aerobic and strength parameters were diminished in HF versus control. FoxO1 and FoxO3 were increased in HF versus control (7.9 ± 6.2 vs 5.0 ± 3.5, 6.5 ± 4.3 vs 4.3 ± 2.8 relative units, respectively; P ≤ .05 in both). However, atrogin-1 and MuRF-1 were similar in both groups. PGC-1α was also increased in HF (7.9 ± 5.4 vs. 5.3 ± 3.6 relative units; P < .05). Muscle levels of insulin-like growth factor (IGF) 1 as well as serum levels of tumor necrosis factor α, C-reactive protein, interleukin (IL) 1ß, and IL-6 were similar in HF and control. CONCLUSION: Expression of the atrophy-promoting genes FoxO1 and FoxO3 were increased in skeletal muscle in systolic HF compared with control, but other atrophy gene expression patterns (atrogin-1 and MuRF-1), as well as growth promoting patterns (IGF-1), were similar. PGC-1α, a gene critical in enhancing mitochondrial function and moderating FoxO activity, may play an important counterregulatory role to offset ubiquitin pathway-mediated functional decrements.

Validation of the osteoporosis self-assessment tool in US male veterans.

The osteoporosis self-assessment tool (OST) is a screening instrument that uses age and weight as parameters to predict the risk of osteoporosis. This study was designed to evaluate OST in predicting osteoporosis in males. Male veterans aged 50yr and older with no prior diagnosis of osteoporosis and no prior bone densitometry (dual-energy X-ray absorptiometry [DXA]) testing were eligible for the study. Sociodemographic information, medical history, and risk factors for osteoporosis were recorded. Anthropometric measurements were taken and DXA testing performed. The OST index for each subject was calculated and predictive values and receiver operating characteristic (ROC) curves were evaluated for OST and osteoporosis. Five hundred eighteen subjects underwent DXA, 92 (17.8%) had osteoporosis, 281 (54.2%) had low bone mass, and 145 (28.0%) had normal bone mineral density. The OST index ranged from -8 to 23 with a mean of 4 (standard deviation ± 4.3). An OST index of 6 or lower predicted osteoporosis with a sensitivity of 82.6%, specificity of 33.6%, and an area under the curve for the ROC curve of 0.67. OST index performed better in non-Hispanic whites and males >65 yr. OST predicts osteoporosis with moderate sensitivity and poor specificity in men.

Adiponectin is a candidate biomarker of lower extremity bone density in men with chronic spinal cord injury.

Adipose tissue is a major regulator of bone metabolism and in the general population obesity is associated with greater bone mineral density (BMD). However, bone-fat interactions are multifactorial, and may involve pathways that influence both bone formation and resorption with competing effects on the skeleton. One such pathway involves adipocyte production of adipokines that regulate bone metabolism. In this study we determined the association between BMD, walking status, and circulating adipokines (adiponectin and leptin) in 149 men with chronic spinal cord injury (SCI). Although adipokine levels did not vary significantly based on walking status, there was a significant inverse association between adiponectin and BMD in wheelchair users independent of body composition. We found no association between adiponectin and BMD in the walkers and no association between leptin and BMD in either group. These findings suggest that for subjects with chronic SCI, walking may mitigate the effect of adiponectin mediated bone loss. For wheelchair users, adipose-derived adiponectin may contribute to SCI-induced osteoporosis because the osteoprotective benefits of obesity appear to require mechanical loading during ambulation.

Prevention of bone loss and vertebral fractures in patients with chronic epilepsy--antiepileptic drug and osteoporosis prevention trial.

PURPOSE: To evaluate whether use of a bisphosphonate (risedronate) in addition to calcium and vitamin D in male veterans with epilepsy who were taking antiepileptic drugs (AEDs) long term can prevent the loss of bone mass (BMD, bone mineral density) associated with AED use compared to patients who were treated with a placebo plus calcium and vitamin D. As a secondary end point we studied the incidence of new morphometric vertebral and nonvertebral fractures. METHODS: Antiepileptic drug and osteoporosis prevention trial (ADOPT) was designed as a prospective 2-year double-blind, randomized placebo controlled study involving 80 male veterans with epilepsy who were being treated with AEDs such as phenytoin, phenobarbital, sodium valproate, or carbamazepine for a minimum of 2 years. All enrolled participants received calcium and vitamin D supplementation, and were randomized to risedronate or matching placebo. Total body, bilateral proximal femora, and anteroposterior (AP) lumbar spine BMDs in addition to morphometric lateral vertebral assessments (LVAs) were evaluated by a dual energy x-ray absorptiometry (DXA) instrument. Comparisons of BMDs were made between baseline, 1 year, and after 2 years of enrollment in the study. The incidence of new vertebral and nonvertebral fractures was secondary end point. KEY FINDINGS: Of the 80 patients initially enrolled in the study, 53 patients completed the study. Baseline characteristics of the two groups were similar. At the end of the study, in the placebo plus calcium and vitamin D group, we observed a significant improvement in BMD at any of the evaluated sites when compared to their baseline scans in 69% (18/26) of the participants. In the risedronate plus calcium and vitamin D group, we observed significant improvement of BMDs in 70% (19/27) of the participants. At the end of the study, the risedronate group experienced a significant increase of BMD at the lumbar spine L1-4 (1.267-1.332 g/cm(2)), which was significantly larger than that seen in the placebo group) (1.229 g/cm(2) vs. 1.245 g/cm(2) ; p = 0.0066).There were nonsignificant differences between the two groups regarding changes of total body BMD or at the proximal bilateral femora. Five new vertebral fractures and one nonvertebral fracture were observed only in the placebo group. SIGNIFICANCE: Calcium and vitamin D supplementation or calcium and vitamin D supplementation in addition to risedronate improved BMD in more than 69% of male veterans with epilepsy who were taking AEDs. In the group receiving risedronate plus calcium and vitamin D there was a significant improvement of BMD at the lumbar spine as compared to the placebo group, which also received calcium and vitamin D. The use of risedronate plus calcium and vitamin D prevented the incidence of new vertebral fractures and one nonvertebral fracture in this cohort.

Adiposity facilitates increased strength capacity in heart failure patients with reduced ejection fraction.

BACKGROUND: Obesity is associated with relatively improved prognosis among heart failure (HF) patients. Mechanisms explaining this so-called "obesity paradox" have been unclear. We hypothesized that increased adiposity may contribute to increased strength capacity, and may thereby facilitate clinical benefits. METHODS AND RESULTS: In a controlled, cross-sectional study, adults aged ≥ 50 years with HF with reduced ejection fraction (HFREF) (LVEF ≤ 40%) were compared to age matched controls. Body composition was determined by dual-energy X-ray absorptiometry (DXA). Aerobic (cardiopulmonary exercise testing), maximum strength (one repetition maximum [1RM]), and power (submaximal resistance/time) were assessed. 70 adults (31 HFREF, 39 controls; mean age 66.2 ± 9.6 years) were studied. Peak oxygen consumption (VO2) (15.4 ± 4.2 vs. 23.4 ± 6.6 ml O2 · kg(-1) · min(-1), p<0.0001), 1RM (154.8 ± 52.0 vs. 195.3 ± 56.8 kg, p<0.01) and power (226.4 ± 99.2 vs. 313.3 ± 130.6, p<0.01) were lower in HFREF vs. controls. 1 RM correlated with total fat (r=0.56, p<0.01), leg fat (r=0.45, p<0.05) and arm fat (r=0.39, p<0.05) in HFREF. Moreover, among HFREF patients with a high (≥ 30 kg/m(2)) body mass index (BMI), 1RM and fat mass were significantly greater than those with lower (<30 kg/m(2)) BMIs. Correlations between 1 RM and total fat (r=0.65, p<0.05) and leg fat (r=0.64, p<0.05) were particularly notable in the high BMI subgroup. CONCLUSION: Increased adiposity correlates with relatively greater strength in HFREF patients which may explain some of the clinical benefits that result from obesity.

Spinal cord injury-induced osteoporosis: pathogenesis and emerging therapies.

Spinal cord injury causes rapid, severe osteoporosis with increased fracture risk. Mechanical unloading after paralysis results in increased osteocyte expression of sclerostin, suppressed bone formation, and indirect stimulation of bone resorption. At this time, there are no clinical guidelines to prevent bone loss after SCI, and fractures are common. More research is required to define the pathophysiology and epidemiology of SCI-induced osteoporosis. This review summarizes emerging therapeutics including anti-sclerostin antibodies, mechanical loading of the lower extremity with electrical stimulation, and mechanical stimulation via vibration therapy.