Liyanage A.,National Hospital of Sri Lanka |
Lekamwasam S.,Center for Metabolic Bone Diseases
Lupus | Year: 2013
Studies on body composition and its determinants among SLE patients are limited. Estimation of body composition, analysis of determinants and associations of different body compartments are important in planning long-term care of these patients. The aim of the study was to identify the changes in body composition among SLE patients and assess the effect of corticosteroid use, patient and disease-related variables on body composition. We compared lean mass, fat mass, bone mineral density (BMD), and bone mineral content (BMC) determined by dual-energy x-ray absorptiometry technology, in a group of premenopausal women with SLE (n = 27) and an age-matched healthy group of women (n = 27). The median (IQR) duration of SLE was 3 (2-5) years while median (IQR) duration and dose of prednisolone therapy were 108 (88-172) weeks and 9730 (6160-15360) mg, respectively. No significant difference was observed in body mass index (BMI) or total fat mass between the two groups. SLE patients, however, had significantly lower lean mass (p < 0.001), BMD (p < 0.001) and BMC (p < 0.005) than healthy controls. Among cases, compared with lean mass, total body fat content showed stronger associations with total body BMD (r = 0.49, p < 0.01) and total body BMC (r = 0.63, p < 0.01). When a stepwise regression model was fitted, lean mass among controls and total fat mass among cases emerged as the best predictors of BMC/BMD. No significant correlations were found between the disease duration or cumulative glucocorticosteroid dose and total body BMD, total body BMC, lean mass or total fat content in SLE patients. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
Van Remoortel H.,University Hospitals Leuven |
Hornikx M.,University Hospitals Leuven |
Langer D.,University Hospitals Leuven |
Burtin C.,University Hospitals Leuven |
And 7 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2014
Rationale: There is little information about comorbidities and their risk factors in the preclinical stages of chronic obstructive pulmonary disease (COPD). Objectives: This study aims to investigate the prevalence of premorbid risk factors and comorbid diseases and its association with daily physical activity in subjects detected with COPD by spirometry screening. Methods: Sixty subjects with preclinical COPD (63 ± 6yr; 68% [n = 41] male) were compared with 60 smoking control subjects (62 ± 7 yr; 70% [n = 42] male) and 60 never-smoking control subjects (62 ± 6yr; 57% [n = 34] male). Comorbidities (cardiovascular, metabolic, and musculoskeletal disease) and daily physical activity (by multisensor activity monitor) were measured objectively. Measurements and Main Results: The prevalence of premorbid risk factors and comorbid diseases was significantly higher in preclinical COPD compared with age-matched never-smoking control subjects, but was similar to smoking control subjects not suffering from COPD. In preclinical COPD and smoking control subjects, the combination of cardiovascular disease and musculoskeletal disease was the most prevalent (15% [n = 9] and 12% [n = 7], respectively). In a multivariate logistic regression analysis, physical inactivity and smoking were found to be independent risk factors for having greater than or equal to two comorbidities. Conclusions: Premorbid risk factors and comorbid diseases were more prevalent in the preclinical stages of COPD and smokers without COPD. Physical inactivity and smoking were more strongly associated with the presence of comorbidities compared with airflow obstruction. Clinical trial registered with www.clinicaltrials.gov (NCT 01314807). Copyright © 2014 by the American Thoracic Society.
Jayasena A.,Lady Ridgeway Hospital for Children |
Atapattu N.,Lady Ridgeway Hospital for Children |
Lekamwasam S.,Center for Metabolic Bone Diseases
International Journal of Rheumatic Diseases | Year: 2015
Aims: The aim of this systematic review was to evaluate, critically, the treatment options used in the management of bone loss associated with glucocorticoid (GC) use among children. Methods: We performed a systematic search using PubMed, Cochrane clinical trial registry, Clinicaltiral.gov and Ovid databases (1 March, 2013). The search resulted in 34 eligible retrievals. Of them, seven clinical trials that fulfilled the inclusion and exclusion criteria were selected by two authors. Results: Four studies have compared the effectiveness of bisphosphonates in the treatment of GC-induced low bone mineral density (BMD) in children. Remaining studies were on menatretenone + alfacacidol versus alfacalcidol alone, calcium + vitamin D versus placebo and alfacalcidol versus menatetrenone. In the four studies, bisphosphonates have shown the ability either to improve BMD or prevent bone loss associated with GC use in children. However, alendronate either in oral or intravenous routes and oral pamidronate were the only bisphosphnates that have been studied in children. Vitamin K2 (menatetrenone) combined with alfacalcidol has also preserved BMD in children on long-term GC therapy. Calcium combined with alfacalcidol has also prevented bone loss, greater than menatetrenone. Calcitriol together with Calcium in conventional doses has retarded bone loss, although the combination could not completely prevent the process. Conclusions: Vitamin D derivatives such as calcitriol or alfacalcidol together with adequate calcium can be considered suitable treatment options to be started simultaneously when long-term GC therapy is needed in children. For children who have been on GCs or have already lost BMD, either oral pamidronate or alendronate in oral/intravenous routes can be considered based on the availability. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.
PubMed | Research Group for Musculoskeletal Rehabilitation, Arthritis Research Center for Epidemiology & Manchester Musculoskeletal Biomedical Research Unit Manchester, Clinical and Experimental Endocrinology, University of Manchester and 5 more.
Type: Journal Article | Journal: Journal of cachexia, sarcopenia and muscle | Year: 2015
In men, the long-term consequences of low serum levels of sex steroids, vitamin D metabolites, and insulin-like growth factor 1 (IGF-1) on the evolution of muscle mass, muscle strength, or physical performance are unclear. Moreover, there are no data about the relationship between these hormones and incident sarcopenia defined as low muscle mass and function. The aim of this study was to determine whether the baseline levels of sex hormones, vitamin D metabolites, and IGF-1 predict changes in muscle mass, muscle strength, physical performance, and incident sarcopenia.In 518 men aged 40-79 years, recruited for participation in the European Male Ageing Study, total, free, and bioavailable testosterone (T), oestradiol (E), sex hormone-binding globulin, IGF-1, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH)2D), and parathyroid hormone were assessed at baseline. Appendicular lean mass (aLM), gait speed, and grip strength were measured at baseline and after a mean follow-up of 4.3 years. Sarcopenia was defined by the definition of Baumgartner (relative aLM 7.26 kg/m(2)), the International Working Group on Sarcopenia (IWGS), and the European Working Group on Sarcopenia in Older People (EWGSOP).aLM significantly decreased from age 50 years, while gait speed and grip strength significantly decreased from age 70 years. The incidence of sarcopenia by the definitions of Baumgartner, IWGS, and EWGSOP was 8.1%, 3.0%, and 1.6%, respectively. After adjustment for age, centre, body mass index, smoking, and number of comorbidities at baseline, baseline levels of T and vitamin D metabolites were not associated with change in aLM, gait speed, and/or grip strength, while a high baseline level of total E2 was associated with a greater decrease in aLM. In men aged 70 years, low IGF-1 was associated with a greater decrease in gait speed. Baseline endocrine variables were not independently associated with an increased risk of incident sarcopenia by any definition.Low levels of T and 25OHD do not predict loss of muscle mass, gait speed, or grip strength in middle-aged and elderly community-dwelling European men. Low IGF-1 predicts change in gait speed in men aged 70 years.
News Article | October 28, 2016
ComplianceOnline, the leading governance, risk and compliance advisory network with over 500 experts in various regulatory subjects, today announced a seminar on Understanding the Statistical Considerations for Quantitative ICH Guidelines. The two day seminar led by Dr. Al Bartolucci will be held on December 8 and 9, 2016 in San Francisco, CA. This workshop will introduce the participants to a hands on approach to the different statistical techniques, how they are applied and reasonably interpreted and understood. The seminar will also address the various challenges facing pharmaceutical and biotechnology companies when it comes to quantifying results in a meaningful interpretable manner through tabulations and graphical presentations. For more information or to register for the seminar, please click here. Speaker Dr. Al Bartolucci is Emeritus Professor of Biostatistics at the University of Alabama where he also serves as a Senior Scientist at the Center for Metabolic Bone Diseases, AIDS Research Center and Cancer Center. His teaching experience includes areas such as clinical trials, survival analysis, multivariate analysis, regression techniques, environmental/industrial hygiene sampling and analysis, Bayesian statistics, and longitudinal data analysis. This course is designed for personnel responsible for developing, maintaining and improving clinical and laboratory monitoring programs. It will be beneficial for quality managers, assay development scientists, research scientists, clinical/laboratory data analysts and laboratory data managers. Date: Thursday, December 8, 2016 (8.30 AM- 4.30 PM) and Friday, December 9, 2016 (8.30 AM- 4.30 PM) Location: San Francisco, CA Registration Cost: $1,899.00 per registration Early bird discounts: For discounts on early registrations, please click here. Register by phone: Please call our customer service specialists at +1-888-717-2436 or email to customercare(at)complianceonline(dot)com For more information on ComplianceOnline or to browse through our trainings, please visit our website. ComplianceOnline is a leading provider of regulatory compliance trainings for companies and professionals in regulated industries. ComplianceOnline has successfully trained over 35,000 professionals from 9,000 companies to comply with the requirements of regulatory agencies. ComplianceOnline is headquartered in Palo Alto, California and can be reached at http://www.complianceonline.com. ComplianceOnline is a MetricStream portal. MetricStream (http://www.metricstream.com) is a market leader in Enterprise-wide Governance, Risk, Compliance (GRC) and Quality Management Solutions for global corporations. For more information please contact:
Helsen C.,Molecular Endocrinology Laboratory |
Kerkhofs S.,Molecular Endocrinology Laboratory |
Clinckemalie L.,Molecular Endocrinology Laboratory |
Spans L.,Molecular Endocrinology Laboratory |
And 4 more authors.
Molecular and Cellular Endocrinology | Year: 2012
The gene family of nuclear receptors is characterized by the presence of a typical, well conserved DNA-binding domain. In general, two zinc coordinating modules are folded such that an α-helix is inserted in the major groove of the DNA-helix displaying a sequence similar to one of two hexameric consensus motifs. Both zinc molecules coordinate four cysteines. Although the DNA-binding domains as well as the hormone response elements are very similar, each nuclear receptor will affect transcription of a specific set of target genes. This is in part due to some important receptor-specific variations on the general theme of DNA interaction.For most nuclear receptors, the DNA-binding domain dimerizes on DNA, which explains why most hormone response elements consist of a repeat of two hexamers. The hexamer dimers can be organized either as direct, inverted or everted repeats with spacers of varying lengths. The DNA can be bound by homodimers, heterodimers and for some orphan receptors, as monomer.Another key element for DNA binding by nuclear receptors is the carboxy-terminal extension of the DNA-binding domain extending into the hinge region. This part not only co-determines sequence specificity, but also affects other functions of the receptors like nuclear translocation, intranuclear mobility and transactivation potential. Moreover, allosteric signals passing through towards other receptor domains, explain why to some extent, the DNA elements can also be considered as controlling ligands. © 2011 Elsevier Ireland Ltd.
Lekamwasam S.,Center for Metabolic Bone Diseases
Archives of osteoporosis | Year: 2013
There is a wide variation in fracture probabilities estimated by Asian FRAX models, although the outputs of South Asian models are concordant. Clinicians can choose either fixed or age-specific intervention thresholds when making treatment decisions in postmenopausal women. Cost-effectiveness of such approach, however, needs to be addressed. This study examined suitable fracture probability intervention thresholds (ITs) for Sri Lanka, based on the Sri Lankan FRAX model. Fracture probabilities were estimated using all Asian FRAX models for a postmenopausal woman of BMI 25 kg/m2 and has no clinical risk factors apart from a fragility fracture, and they were compared. Age-specific ITs were estimated based on the Sri Lankan FRAX model using the method followed by the National Osteoporosis Guideline Group in the UK. Using the age-specific ITs as the reference standard, suitable fixed ITs were also estimated. Fracture probabilities estimated by different Asian FRAX models varied widely. Japanese and Taiwan models showed higher fracture probabilities while Chinese, Philippine, and Indonesian models gave lower fracture probabilities. Output of remaining FRAX models were generally similar. Age-specific ITs of major osteoporotic fracture probabilities (MOFP) based on the Sri Lankan FRAX model varied from 2.6 to 18% between 50 and 90 years. ITs of hip fracture probabilities (HFP) varied from 0.4 to 6.5% between 50 and 90 years. In finding fixed ITs, MOFP of 11% and HFP of 3.5% gave the lowest misclassification and highest agreement. Sri Lankan FRAX model behaves similar to other Asian FRAX models such as Indian, Singapore-Indian, Thai, and South Korean. Clinicians may use either the fixed or age-specific ITs in making therapeutic decisions in postmenopausal women. The economical aspects of such decisions, however, need to be considered.
Leslie W.D.,University of Manitoba |
Lix L.M.,University of Manitoba |
Morin S.N.,University of Manitoba |
Johansson H.,Center for Metabolic Bone Diseases |
And 3 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2015
Context: Bone mineral density (BMD) measurement from dual-energy X-ray absorptiometry (DXA) is widely used to assess skeletal strength in clinical practice, but DXA instruments can also measure biomechanical parameters related to skeletal shape. Objective: The objective of the study was to determine whether DXA-derived hip geometry measures provide information on fracture prediction that is independent of hip fracture probability determined from the fracture risk assessment tool (FRAX) algorithm. Design and Setting: This was a retrospective registry study using BMD results for Manitoba, Canada. Patients: Women aged 40 years and older with baseline hip DXA, derived hip geometry measures, and FRAX scores (n = 50 420) participated in the study. Main Outcome Measures: Hospitalized hip fracture (n = 1020) diagnosed during 319 137 person-years of follow-up (median 6.4 y) was measured. Results: Among the hip geometry measures, hip axis length (HAL) showed a consistent association with hip fracture risk when adjusted for age [hazard ratio (HR) 1.30 per SD increase, 95% confidence interval (CI) 1.22-1.38], and this was unaffected by further adjustment for BMD or FRAX score. Adjusted for FRAX score with BMD, there was a significant effect of increasing HAL quintile on hip fracture risk (linear trend P < .001); relative to quintile 1 (referent), the HR increased from 1.43 (95% CI 1.12-1.82) for quintile 2, 1.61 (95% CI 1.27-2.04) for quintile 3, 1.85 (95% CI 1.47-2.32) for quintile 4, and 2.45 (95% CI 1.96-3.05) for quintile 5. There was a modest but significant improvement in net reclassification improvement (1.5%) and integrated discrimination improvement (0.7%) indices. The effect of HAL was particularly strong among younger, nonosteoporotic women (FRAX adjusted HR 1.70 per SD increase, 95% CI 1.48-1.94). Conclusions: DXA-derived hip geometry measurements are associated with incident hip fracture risk, but many do not confer significant independent predictive information. HAL was found to predict hip fractures when adjusted for BMD or FRAX score and may be of clinical value in refining hip fracture risk. Copyright © 2015 by the Endocrine Society.
Lekamwasam S.,Center for Metabolic Bone Diseases
Journal of Clinical Densitometry | Year: 2010
The FRAX software developed by the World Health Organization provides a method to estimate fracture probability of old men and women based on their bone mineral density (BMD) and clinical risk factors (CRFs). The validity of 4 selected ethnic-specific FRAX tools in determining prevalent fracture or treatment decisions in a group of postmenopausal women from Sri Lanka was examined. Women with a history of fragility fracture/s and those who were detected to have femoral neck T-score < 2.5 were considered eligible for specific osteoporosis treatment. Ten-year all osteoporotic fracture (vertebral and nonvertebral) probability (10y-AOFP) of 481 postmenopausal women were estimated on US Caucasian, US Asian, Japanese, and Chinese FRAX tools, first using CRFs alone and then combining with femoral neck T-scores. At 20% 10y-AOFP, Chinese tool showed a very low sensitivity in detecting prevalent fracture or detecting women needing intervention (1.3%). Sensitivities observed with US Asian and Japanese tools ranged from 33% to 42%, showing their limitations in predicting prevalent fracture in this group of women. The US Caucasian tool, either with CRFs alone or with BMD incorporated, showed a relatively higher sensitivity in detecting fractures or identifying those needing interventions (71% and 76%, respectively). Furthermore, the US Caucasian tool showed a relatively high specificity (ranging from 70% to 87%). In conclusion, this analysis showed the limitations of the current FRAX tools in predicting fractures when applied to a different ethnic group. Until a separate FRAX tool is developed, the US Caucasian tool can be used to predict fractures in Sri Lankan postmenopausal women. © 2010 The International Society for Clinical Densitometry.
Lekamwasam S.,Center for Metabolic Bone Diseases
Archives of Osteoporosis | Year: 2013
There is a wide variation in fracture probabilities estimated by Asian FRAX models, although the outputs of South Asian models are concordant. Clinicians can choose either fixed or age-specific intervention thresholds when making treatment decisions in postmenopausal women. Cost-effectiveness of such approach, however, needs to be addressed. Purpose: This study examined suitable fracture probability intervention thresholds (ITs) for Sri Lanka, based on the Sri Lankan FRAX model. Methods: Fracture probabilities were estimated using all Asian FRAX models for a postmenopausal woman of BMI 25 kg/m2 and has no clinical risk factors apart from a fragility fracture, and they were compared. Age-specific ITs were estimated based on the Sri Lankan FRAX model using the method followed by the National Osteoporosis Guideline Group in the UK. Using the age-specific ITs as the reference standard, suitable fixed ITs were also estimated. Results: Fracture probabilities estimated by different Asian FRAX models varied widely. Japanese and Taiwan models showed higher fracture probabilities while Chinese, Philippine, and Indonesian models gave lower fracture probabilities. Output of remaining FRAX models were generally similar. Age-specific ITs of major osteoporotic fracture probabilities (MOFP) based on the Sri Lankan FRAX model varied from 2.6 to 18 % between 50 and 90 years. ITs of hip fracture probabilities (HFP) varied from 0.4 to 6.5 % between 50 and 90 years. In finding fixed ITs, MOFP of 11 % and HFP of 3.5 % gave the lowest misclassification and highest agreement. Conclusion: Sri Lankan FRAX model behaves similar to other Asian FRAX models such as Indian, Singapore-Indian, Thai, and South Korean. Clinicians may use either the fixed or age-specific ITs in making therapeutic decisions in postmenopausal women. The economical aspects of such decisions, however, need to be considered. © 2013 International Osteoporosis Foundation and National Osteoporosis Foundation.