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Objective Mechanisms of insulin resistance in polycystic ovary syndrome (PCOS) remain ill defined, contributing to sub-optimal therapies. Recognising skeletal muscle plays a key role in glucose homeostasis we investigated early insulin signalling, its association with aberrant transforming growth factor β (TGFβ)-regulated tissue fibrosis. We also explored the impact of aerobic exercise on these molecular pathways. Methods A secondary analysis from a cross-sectional study was undertaken in women with (n = 30) or without (n = 29) PCOS across lean and overweight BMIs. A subset of participants with (n = 8) or without (n = 8) PCOS who were overweight completed 12 weeks of aerobic exercise training. Muscle was sampled before and 30 min into a euglycaemic-hyperinsulinaemic clamp pre and post training. Results We found reduced signalling in PCOS of mechanistic target of rapamycin (mTOR). Exercise training augmented but did not completely rescue this signalling defect in women with PCOS. Genes in the TGFβ signalling network were upregulated in skeletal muscle in the overweight women with PCOS but were unresponsive to exercise training except for genes encoding LOX, collagen 1 and 3. Conclusions We provide new insights into defects in early insulin signalling, tissue fibrosis, and hyperandrogenism in PCOS-specific insulin resistance in lean and overweight women. PCOS-specific insulin signalling defects were isolated to mTOR, while gene expression implicated TGFβ ligand regulating a fibrosis in the PCOS-obesity synergy in insulin resistance and altered responses to exercise. Interestingly, there was little evidence for hyperandrogenism as a mechanism for insulin resistance.

Accurate and precise body composition estimates, notably of total body adiposity, are a vital component of in vivo physiology and metabolic studies. The reference against which other body composition approaches are usually validated or calibrated is the family of methods referred to as multicomponent "body density" models. These models quantify three to six components by combining measurements of body mass, body volume, total body water, and osseous mineral mass. Body mass is measured with calibrated scales, volume with underwater weighing or air-displacement plethysmography, total body water with isotope dilution, and osseous mineral mass by dual-energy X-ray absorptiometry. Body density is then calculated for use in model as body mass/volume. Studies over the past decade introduced a new approach to quantifying body volume that relies on dual-energy X-ray absorptiometry measurements, an advance that simplifies multicomponent density model development by eliminating the need for underwater weighing or air-displacement plethysmography systems when these technologies are unavailable and makes these methods more accessible to research and clinical programs. This review critically examines these new dual-energy X-ray approaches for quantifying body volume and density, explores their shortcomings, suggests alternative derivation approaches, and introduces ideas for potential future research studies.

Funding Information: Funding: This research was funded by Vitaflo International as part of Ph.D. grant. Funding Information: Conflicts of Interest: A.D. research funding from Vitaflo International, financial support from Nutri-cia, Mevalia & Vitaflo International to attend study days & conferences. S.E. research funding from Nutricia, financial support from Nutricia & Vitaflo International to attend study days & conferences. A.P. has received an educational grant from Cambrooke Therapeutics and grants from Vitaflo International, Nutricia, Merck Serono, Biomarin and Mevalia to attend scientific meetings. C.A. received honoraria from Nutricia and Vitaflo International to attend study days and conferences. J.C.R. member of the European Nutritionist Expert Panel (Biomarin), the Advisory Board for Applied Pharma Research and Nutricia, and received honoraria as a speaker from APR, Merck Serono, Biomarin, Nutricia, Vitaflo, Cambrooke, PIAM and Lifediet. A.M. research funding & honoraria from Nutricia, Vitaflo International & Merck Serono, Member of European Nutrition Expert Panel (Merck Serono international), member of Sapropterin Advisory Board (Merck Serono international), member of the Advisory Board Element (Danone-Nutricia). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved. In patients with phenylketonuria (PKU), treated by diet therapy only, evidence suggests that areal bone mineral density (BMDa) is within the normal clinical reference range but is below the population norm. Aims: To study longitudinal bone density, mass, and geometry over 36 months in children with PKU taking either amino acid (L-AA) or casein glycomacropeptide substitutes (CGMP-AA) as their main protein source. Methodology: A total of 48 subjects completed the study, 19 subjects in the L-AA group (median age 11.1, range 5–6 years) and 29 subjects in the CGMP-AA group (median age 8.3, range 5–16years). The CGMP-AA was further divided into two groups, CGMP100 (median age 9.2, range 5–16years) (n = 13), children taking CGMP-AA only and CGMP50 (median age 7.3, range 5–15years) (n = 16), children taking a combination of CGMP-AA and L-AA. Dual X-ray absorptiometry (DXA) was measured at enrolment and 36 months, peripheral quantitative computer tomography (pQCT) at 36 months only, and serum blood and urine bone turnover markers (BTM) and blood bone biochemistry at enrolment, 6, 12, and 36 months. Results: No statistically significant differences were found between the three groups for DXA outcome parameters, i.e., BMDa (L2–L4 BMDa g/cm2 ), bone mineral apparent density (L2–L4 BMAD g/cm3 ) and total body less head BMDa (TBLH g/cm2 ). All blood biochemistry markers were within the reference ranges, and BTM showed active bone turnover with a trend for BTM to decrease with increasing age. Conclusions: Bone density was clinically normal, although the median z scores were below the population mean. BTM showed active bone turnover and blood biochemistry was within the reference ranges. There appeared to be no advantage to bone density, mass, or geometry from taking a macropeptide-based protein substitute as compared with L-AAs. publishersversion published

Background: Low skeletal muscle index (SMI) and sarcopenia adversely affect clinical outcomes in oncology patients. Study aims were to assess the agreement of bioelectrical impedance analysis (BIA)...

Protein quality and quantity are important factors in determining lean body (muscle) mass (LBM). In phenylketonuria (PKU), protein substitutes provide most of the nitrogen, either as amino acids (AA) or glycomacropeptide with supplementary amino acids (CGMP-AA). Body composition and growth are important indicators of long-term health. In a 3-year prospective study comparing the impact of AA and CGMP-AA on body composition and growth in PKU, 48 children were recruited. N = 19 (median age 11.1 years, range 5–15 years) took AA only, n = 16 (median age 7.3 years, range 5–15 years) took a combination of CGMP-AA and AA, (CGMP50) and 13 children (median age 9.2 years, range 5–16 years) took CGMP-AA only (CGMP100). A dual energy X-ray absorptiometry (DXA) scan at enrolment and 36 months measured LBM, % body fat (%BF) and fat mass (FM). Height was measured at enrolment, 12, 24 and 36 months. No correlation or statistically significant differences (after adjusting for age, gender, puberty and phenylalanine blood concentrations) were found between the three groups for LBM, %BF, FM and height. The change in height z scores, (AA 0, CGMP50 +0.4 and CGMP100 +0.7) showed a trend that children in the CGMP100 group were taller, had improved LBM with decreased FM and % BF but this was not statistically significant. There appeared to be no advantage of CGMP-AA compared to AA on body composition after 3-years of follow-up. Although statistically significant differences were not reached, a trend towards improved body composition was observed with CGMP-AA when it provided the entire protein substitute requirement. publishersversion published

Humans expend energy at rest (REE), and this major energy exchange component is now usually estimated using statistical equations that include weight and other predictor variables. While these formulas are useful in evaluating an individual's or group's REE, an important gap remains: available statistical models are inadequate for explaining underlying organ-specific and tissue-specific mechanisms accounting for resting heat production. The lack of such systems level REE prediction models leaves many research questions unanswered. A potential approach that can fill this gap began with investigators who first showed in animals and later in humans that REE reflects the summated heat production rates of individual organs and tissues. Today, using advanced imaging technologies, REE can be accurately estimated from the measured in vivo mass of 10 organ-tissue mass components combined with their respective mass-specific metabolic rates. This review examines the next frontier of energy expenditure models and discusses how organ-tissue models have the potential not only to better predict REE but also to provide insights into how perturbations in organ mass lead to structure-function changes across other interacting organ systems. The introductory ideas advanced in this review provide a framework for future human energy expenditure modelling research.

Objective: Turner syndrome (TS) is associated with hypogonadism, osteoporosis and fractures. We investigated the prevalence and risk factors for low bone density and fractures in a TS cohort.Methods: We included 76 TS patients (median age 28.5 years) attending a tertiary hospital between 1998 and 2015 who underwent dual-energy X-ray absorptiometry. Spine and femoral neck (FN) areal bone mineral density (aBMD) were compared with those of a control group. To adjust for smaller bone size, bone mineral apparent density (BMAD) was calculated.Results: Primary amenorrhea was common (83%) in the TS cohort; the median age of pubertal induction was 15 years (range 11–30 years), and non-continuous estrogen therapy (ET) recorded in 40%. Almost one-third of TS patients reported fractures. TS patients had lower median spinal aBMD (1.026 g/cm2 vs. 1.221 g/cm2) and BMAD (0.156 g/cm3 vs. 0.161 g/cm3) than controls, and lower median FN aBMD (0.850 g/cm2 vs. 1.026 g/cm2) (all p

SummaryBackground Excessive visceral adipose tissue has been associated with poorer outcomes in patients with inflammatory bowel disease. Aim To determine whether body composition is associated with outcome in a prospective study of post-operative Crohn's disease patients. Methods The POCER study evaluated management strategies for prevention of post-operative Crohn's disease recurrence; subjects were enrolled after resection of all macroscopic Crohn's disease and were randomised to early endoscopy and possible treatment escalation, or standard care. The primary endpoint was endoscopic recurrence at 18 months. 44 subjects with cross-sectional abdominal imaging were studied, and body composition analysis performed using established techniques to measure visceral adipose tissue area, subcutaneous adipose tissue area, and skeletal muscle area. Results The body composition parameter with the greatest variance was visceral adipose tissue. Regardless of treatment, all subjects with visceral adipose tissue/height2 >1.5 times the gender-specific mean experienced endoscopic recurrence at 18 months (compared to 47%) [relative risk 2.1, 95% CI 1.5–3.0, P = 0.012]. Waist circumference correlated strongly with visceral adipose tissue area (ρ = 0.840, P < 0.001). Low skeletal muscle was prevalent (41% of patients), but did not predict endoscopic recurrence; however, appendicular skeletal muscle indices correlated inversely with faecal calprotectin (ρ = 0.560, P = 0.046). Conclusions Visceral adiposity is an independent risk factor for endoscopic recurrence of Crohn's disease after surgery. Sarcopenia correlates with inflammatory biomarkers. Measures of visceral adipose tissue may help to stratify risk in post-operative management strategies.

Delayed treatment failure occurs in a significant proportion of inflammatory bowel disease (IBD) patients treated with tumor necrosis factor-alpha (TNF) antagonists. Identification of predictors of loss of response (LOR) may help to optimize therapy. We sought to determine whether body composition parameters at the commencement of anti-TNF therapy were associated with earlier treatment failure.A retrospective cohort study was performed on 68 patients who had undergone cross-sectional abdominal imaging coincident with the commencement of anti-TNF drugs. Analysis of the images at the third lumbar vertebra was performed using standard techniques to determine cross-sectional areas of skeletal muscle (SM), visceral adipose tissue, subcutaneous adipose tissue and intermuscular adipose tissue. Treatment failure was defined as: post-induction hospital admission or surgery for IBD, escalation of TNF dose or immunosuppressants for clinical LOR, emergence of a new fistula or Crohn's Disease Activity Index (CDAI)150.Two-thirds of patients had myopenia. Patients with less than gender-specific median SM area had a median time to failure of 520 (s.d. 135) days compared to 1100 (s.d. 151) days for those with more than median SM area (P=0.036). No difference was found in disease duration, inflammatory markers or CDAI between quartiles of SM area. No relation between outcomes and measures of adipose tissue, weight or body mass index was observed.Identifying low muscle mass at anti-TNF induction as a risk factor for treatment failure may contribute to a more tailored approach to IBD therapy.

CONTEXT Cerebral palsy (CP) is a motor disorder affecting movement, muscle tone and posture due to damage to the foetal or infant brain. The subsequent lack of ambulation, nutritional deficiencies, anticonvulsant use and hormonal deficiencies have been implicated in the low bone mass associated with this condition. OBJECTIVE To assess changes in areal bone mineral density (aBMD) during adolescence and young adulthood in individuals with CP. The effect of ambulation, nutrition, hypogonadism on longitudinal changes in aBMD is also examined. DESIGN Retrospective longitudinal study. SETTING AND PARTICIPANTS Forty-five subjects with CP who had longitudinal dual-energy X-ray absorptiometry (DXA) scans at a single tertiary hospital between 2006 and 2018. RESULTS Mean age at first DXA was 19.4 years (range: 10-36 years), 57.8% were male and 80% were nonambulatory. The mean Z-scores at baseline were

Introduction: Higher calcium dialysate is recommended for quotidian nocturnal hemodialysis (NHD) (≥6 nights/week) to maintain bone health. It is unclear what the optimal calcium dialysate concentration should be for alternate night NHD. We aimed to determine the effect of low calcium (LC) versus high calcium (HC) dialysate on cardiovascular and bone parameters in this population. Methods: A randomized controlled trial where participants were randomized to LC (1.3 mmol/L, n = 24) or HC dialysate (1.6 or 1.75 mmol/L, n = 26). Primary outcome was change in mineral metabolism markers. Secondary outcomes included change in vascular calcification (VC) scores [CT abdominal aorta (AA) and superficial femoral arteries (SFA)), pulse wave velocity (PWV), bone mineral density (BMD) and left ventricular mass index (LVMI) over 12 months. Findings: In the LC group, pre-dialysis ionised calcium decreased −0.12 mmol/L (−0.18–0.06, P = 0.0001) and PTH increased 16 pmol/L (3.5–28.5, p = 0.01) from baseline to 12 months with no significant change in the HC group. In both groups, there was no progression of VC in AA or SFA and no change in PWV, LVMI or BMD. At 12 months, calcimimetics were prescribed in a higher percentage in the LC vs. HC groups (45.5% vs. 10.5%) with a lower proportion of the HC group being prescribed calcitriol (31.5% vs. 72%). Discussion: Although dialysate calcium prescription influenced biochemical parameters it was not associated with difference in progression of VC between HC and LC groups. An important finding was the potential impact of alternate night NHD in attenuating progression of VC and inducing stabilisation of LVMI and PWV.

Crohn's Disease is associated with body composition changes, which have important treatment and prognostic implications. Measurement of body composition usually requires dedicated scanning or measurement, with retrospective analysis of existing datasets impossible. We sought to determine whether single slice analysis of abdominal scans, obtained during routine clinical care, in patients with Crohn's Disease accurately predicts body composition compartments.Abdominal CT images of patients with Crohn's disease were analyzed and comparison was made with total body fat-free mass, total body fat mass, femoral neck t-score, and other parameters reported from DXA, the reference method.Thirty-seven subjects were identified, 15 male and 22 female, with a mean age of 43.8 years. There was significant correlation (Pearson r = 0.923, p 0.001) between skeletal muscle area from CT and total fat-free mass measured by DXA. Similarly, total body fat mass correlated strongly (r = 0.928, p 0.0001) with subcutaneous fat area. In this cohort of ambulatory Crohn's Disease patients, low muscle mass/sarcopenia was prevalent and predictive of lower bone mineral density.Fat mass, fat-free mass, and appendicular skeletal muscle index can be predicted by analysis of a single CT slice in patients with Crohn's Disease. Similar to published data from healthy subjects, the L3 vertebral body level provided the most robust correlation with most parameters. This study represents the first published use of routinely obtained abdominal imaging to demonstrate this relationship - and to predict body composition components - in patients with inflammatory bowel disease.

Background Key aims of treatment of coeliac disease are to heal the intestinal mucosa and correct nutritional abnormalities. Aim We aim to determine prospectively the degree of success and time course of achieving those goals with a gluten-free diet. Methods Ninety-nine patients were enrolled at diagnosis and taught the diet. The first 52 were reassessed at 1 year and 46 at 5 years, 25 being assessed at the three time points regarding dietary compliance (dietitian-assessed), coeliac serology, bone mineral density and body composition analysis by dual energy X-ray absorptiometry, and intestinal histology. Results Mean age (range) was 40 (18–71) years and 48 (76%) were female. Dietary compliance was very good to excellent in all but one. Tissue transglutaminase IgA was persistently elevated in 44% at 1 year and 30% at 5 years and were poorly predictive of mucosal disease. Rates of mucosal remission (Marsh 0) and response (Marsh 0/1) were 37% and 54%, and 50% and 85% at 1 and 5 years, respectively. Fat mass increased significantly over the first year in those with normal/reduced body mass index. Lean body mass indices more slowly improved irrespective of status at diagnosis with significant improvement at 5 years. Bone mass increased only in those with osteopenia or osteoporosis, mostly in year 1. Conclusion Dietary compliance is associated with a high chance of healing the intestinal lesion and correction of specific body compositional abnormalities. The time course differed with body fat improving within 1 year, and correction of the mucosal lesion and improvement in lean mass and bone mass taking longer.

Context Androgen deprivation therapy (ADT) for prostate cancer (PCa) leads to a selective loss of leg muscle function during walking. Rodent models of ADT have demonstrated that the levator ani is exquisitely androgen sensitive. Objective To determine whether the high androgen responsiveness of the levator ani muscle documented in rodents is evolutionarily conserved and ADT is associated with a selective loss in leg muscle volume. Design Prospective longitudinal case-control study. Setting Tertiary referral hospital. Participants Thirty-four men newly beginning ADT and 29 age-matched controls with PCa. Main outcome measures The muscle volumes in liters of the levator ani and primary muscles involved in walking (iliopsoas, quadriceps, gluteus maximus, gluteus medius, calf). Results Compared with controls, during a 12-month period, men receiving ADT experienced a mean reduction in total testosterone from 14.1 to 0.4 nmol/L and demonstrated greater decreases in levator ani [mean adjusted difference (MAD), -0.005 L; 95% CI, -0.007 to -0.002; P = 0.002; -16% of initial median value], gluteus maximus (MAD, -0.032 L; 95% CI, -0.063 to -0.002; P = 0.017; -5% of initial median value), iliopsoas (MAD, -0.005 L; 95% CI, -0.001 to 0.000; P = 0.013; -5% of initial median value), and quadriceps (MAD, -0.050 L; 95% CI, -0.088 to -0.012; P = 0.031; -3% of initial median value). No substantial differences were observed in the gluteus medius and calf muscles. Conclusions The androgen responsiveness of the levator ani appears to be evolutionarily conserved in humans. ADT selectively decreases the volume of muscles that support body weight. Interventional strategies to reduce ADT-related sarcopenia and sexual dysfunction should assess whether targeting these muscle groups, including the pelvic floor, will improve clinical outcomes.

Context Turner syndrome (TS) is associated with short stature, gonadal failure, and fractures. Spinal trabecular bone score (TBS) is a novel bone imaging modality that has not been evaluated in TS. Objective To evaluate TBS in TS and its association with bone mineral density (BMD), prevalent fracture, and risk factors. Design and Setting Longitudinal study of TS from a single tertiary hospital between 2006 and 2017. Patients or Other Participants Fifty-eight subjects with TS aged 20 to 49 years who underwent dual-energy X-ray absorptiometry (DXA). Main Outcome Measures TBS, DXA parameters, and prevalent fractures were investigated. Results Normal, partially degraded, and degraded TBSs were observed in 39 (67%), 15 (26%), and four (7%) subjects, respectively. High rates of prescribed estrogen replacement therapy (ERT) with stable TBS and BMD were observed during follow-up. TBS was positively correlated with spine and femoral neck (FN) BMD and Z-scores (all P < 0.05) and negatively correlated with age (-0.004 per year; P = 0.014) and delay in ERT initiation in women with primary amenorrhea (-0.010 per year; P < 0.001). Fractures were present in 17 (31%) subjects. Low TBS had a significantly higher area under the receiver operator curve for predicting prevalent fracture than low bone mass at either the spine or FN (P < 0.05). Subjects with no history of fracture were more likely to have a normal TBS (P = 0.023). Conclusions BMD and TBS can be preserved with early initiation and continued use of ERT. TBS may provide additional fracture risk prediction to standard DXA parameters in TS and needs to be validated in larger prospective studies.

Background Percutaneous endoscopic gastrostomy (PEG) placement is performed in a patient group with high mortality in the short and medium term. For a significant proportion of patients, the procedure provides no increase in survival. There are no standardised assessment tools available to determine the clinical appropriateness of PEG placement, nor any to predict clinical outcome. Aim The study aims to determine whether clinical assessment, by a trained dietitian, of the appropriateness of PEG placement is predictive of mortality in the short and medium terms. Methods A prospective audit was undertaken of all requests for PEG placement at a single large, publicly funded Australian tertiary hospital. The clinical appropriateness of each request was assessed by a trained dietitian, and data on age, sex, reason for referral, comorbidities and satisfaction of assessment criteria were collected, and patient outcome and survival were compared for all patients according to whether a PEG was inserted or not. Main outcome measures were mortality at 30 and 150 days after referral. Results During the period 2005–2008, 198 patients were referred for PEG; 94 were assessed as appropriate referrals, 104 as inappropriate. Eighty-four patients who underwent gastrostomy, after being assessed as appropriate, had significantly reduced mortality at 30 days (96.4% vs 74.6%, P < 0.0001) and 150 days (82.1% vs 57.9%, P = 0.0001) compared with all other patients. Patients who received PEG despite contrary advice had no significant survival advantage, at 30 days or 150 days, over patients who did not receive PEG. Conclusion The application of selection criteria by trained assessors improves patient selection for PEG insertion and predicts mortality at early and later time points, by identifying patients unlikely to benefit from PEG. The group of patients who received a gastrostomy despite an adverse assessment had no mortality benefit – in these patients, the procedure may have been futile.

Excess adiposity is the main phenotypic feature that defines human obesity and that plays a pathophysiological role in most chronic diseases. Measuring the amount of fat mass present is thus a central aspect of studying obesity at the individual and population levels. Nevertheless, a consensus is lacking among investigators on a single accepted 'reference' approach for quantifying fat mass in vivo. While the research community generally relies on the multi-component body volume class of 'reference' models for quantifying fat mass, no definable guide discerns among different applied equations for partitioning the four (fat, water, protein and mineral mass) or more quantified components, standardizes 'adjustment' or measurement system approaches for model-required labelled water dilution volumes and bone mineral mass estimates, or firmly establishes the body temperature at which model physical properties are assumed. The resulting differing reference strategies for quantifying body composition in vivo leads to small, but under some circumstances, important differences in the amount of measured body fat. Recent technological advances highlight opportunities to expand model applications to new subject groups and measured components such as total body protein. The current report reviews the historical evolution of multi-component body volume-based methods in the context of prevailing uncertainties and future potential.

Context: Spina bifida (SB) can lead to changes in body composition and bone mineral density (BMD) through diminished ambulation, renal impairment, and anticonvulsant medication. With increased life expectancy, diseases such as obesity and osteoporosis are emerging comorbidities in SB, with limited data to guide management. Objective: To examine the relationship between cardiometabolic factors, body composition, BMD, and minimal trauma fractures (MTFs) in adults with SB. Design: Retrospective cross-sectional study. Setting and Participants: Forty-nine adults with SB (median age, 32.7 years; interquartile range, 22.6 to 39.0) who had undergone dual-energy x-ray absorptiometry imaging at a single tertiary hospital from 2004 to 2015. Results: The mean body mass index was 31.7 ± 7.5 kg/m2; 26 (53.1%) were obese. Using age- and sex-matched fat percentiles from the National Health and Nutrition Examination Survey III, 62.5% had a total body percentage fat greater than the 95th percentile. Low bone mass (defined as a Z-score of ≤−2.0) was present in 21.9% at the L1 vertebra and in 35.1% at the femoral neck. Ten (20.4%) had a history of MTFs. A BMD or Z-score at L1, femoral neck, or total body site did not correlate with the occurrence of MTF. Fat mass was significantly and positively associated with BMD after adjustment for age, sex, and height and accounted for 18.6% of the variance in BMD (P = 0.005). The prevalence of metabolic comorbidities, such as hypertension (20.4%) and obstructive sleep apnea (16.3%), was high. Conclusions: Obesity and low BMD are common in young adults with SB. An increased fat mass correlated significantly with BMD. The prevalence of metabolic complications in patients with SB is increased and deserves further study., Adults with SB are at high risk of both low BMD and obesity and their related comorbidities. Obesity might play a role in the skeletal phenotype of this population.

Background Osteoarthritis has a high prevalence in people with high bone mineral density (BMD). Nevertheless, whether high systemic BMD predates early structural features of knee osteoarthritis is unclear. This study examined the association between systemic BMD and knee cartilage defect progression and cartilage volume loss in middle-aged people without clinical knee disease. Methods Adults (n = 153) aged 25–60 years had total body, lumbar spine, and total hip BMD assessed by dual-energy X-ray absorptiometry at baseline (2005–2008), and tibial cartilage volume and tibiofemoral cartilage defects assessed by magnetic resonance imaging at baseline and follow up (2008–2010). Results Higher spine BMD was associated with increased risk for progression of medial (OR = 1.45, 95% CI 1.10, 1.91) and lateral (OR = 1.30, 95% CI 1.00, 1.67) tibiofemoral cartilage defects. Total hip BMD was also positively associated with the progression of medial (OR = 1.63, 95% CI 1.10, 2.41) and lateral (OR = 1.53, 95% CI 1.08, 2.18) tibiofemoral cartilage defects. Greater total body, spine, and total hip BMD were associated with increased rate of lateral tibial cartilage volume loss (for every 1 g/10 cm2 increase in total body BMD: B = 0.44%, 95% CI 0.17%, 0.71%; spine BMD: 0.17%, 95% CI 0.04%, 0.30%; total hip BMD: 0.29%, 95% CI 0.13%, 0.45%), with no significant associations for medial tibial cartilage volume loss. Conclusion In middle-aged people without clinical knee disease, higher systemic BMD was associated with increased early knee cartilage damage. Further work is needed to clarify the effect of systemic BMD at different stages of the pathway from health through to disease in knee osteoarthritis, as new therapies targeting bone are developed for the management of knee osteoarthritis.

Thalassemia is an inherited disorder of alpha or beta globin chain synthesis leading to ineffective erythropoiesis requiring chronic transfusion therapy in its most severe form. This leads to iron overload, marrow expansion, and hormonal complications, which are implicated in bone deformity and loss of bone mineral density (BMD). In this 19-year retrospective longitudinal study, the relationships between BMD (determined by dual-energy X-ray absorptiometry) and risk factors for osteoporosis in 277 subjects with transfusion-dependent thalassemia were examined. The mean age at first review was 23.2 ± 11.9 years and 43.7% were male. Hypogonadism was present in 28.9%. Fractures were confirmed in 11.6% of subjects and were more frequent in males (16.5%) compared with females (7.7%). Lumbar spine (LS), femoral neck (FN), and total body (TB) Z-scores were derived. Patients with transfusion-dependent thalassemia had a significant longitudinal decline in BMD at the FN and TB. In the linear mixed-model analysis of BMD and risk factors for bone loss, FN Z-score was more significantly associated with risk factors compared with the LS and TB. The rate of decline at the FN was 0.02 Z-score per year and was 3.85-fold greater in males. The decline in FN Z-score over the last 5 years (years 15 to 19) was 2.5-fold that of the previous 7 years (years 8 to 14) and coincided with a change in iron chelator therapy from desferrioxamine to deferasirox. Hemoglobin (Hb) levels positively correlated with higher TB and LS Z-scores. In conclusion, the FN is the preferred site for follow-up of BMD. Male patients with β-thalassemia experienced a greater loss of BMD and had a higher prevalence of fractures compared with females. Transfusing patients (particularly males) to a higher Hb target may reduce the decline in BMD. Whether deferasirox is implicated in bone loss warrants further study. © 2014 American Society for Bone and Mineral Research.

SummaryObjective Polycystic ovary syndrome (PCOS) is a complex endocrine disorder associated with insulin resistance, hyperandrogenism, obesity, altered gonadotrophin release and anovulatory infertility. Anti-Mullerian hormone (AMH) has been proposed as a marker of ovarian function and fertility. Across a cohort of lean and overweight women with and without PCOS, we investigated the association of AMH with insulin resistance and body composition using gold standard measures. A secondary aim was to examine whether AMH was useful to determine PCOS status. Design Cross-sectional study. Patients A total of 22 lean and 21 overweight women with PCOS and 19 lean and 16 overweight non-PCOS healthy controls were recruited. PCOS was diagnosed based on the Rotterdam criteria. Measurements Euglycaemic-hyperinsulinaemic clamp for assessing insulin resistance, dual energy X-ray absorptiometry and computed tomography for assessing adiposity, and blood sampling for the assessment of androgens, gonadotrophins and AMH. Results Anti-Mullerian hormone levels were increased in women with PCOS (P

Objectives Although mental health is related to the persistence of musculoskeletal pain, our understanding of the relationship between mental health and foot pain is limited. Subsequently, we conducted a three year longitudinal study to examine the relationship between mental health and foot pain in a community based population. Methods Eighty-three community dwelling participants (mean body mass index 35.3 kg/m2 ± 9.0) who had foot pain at study inception in 2008, and for whom measures of mental health (Mental Component Summary of the Short Form-36) were available, were invited to take part in this follow-up study in 2011. Change in foot pain was determined by the difference between the Manchester Foot Pain and Disability Index score at baseline and follow up; therefore, a decrease in the score indicates improved foot pain and an increase indicates deterioration in foot pain. Linear regression was used to determine the factors affecting change in foot pain. Results Of the 62 respondents (75% response rate, 49 females and 13 males), there were 27 (44%) whose foot pain deteriorated. A higher Mental Component Summary score of the Short Form-36 at baseline was associated with a slower progression of foot pain (beta coefficient -0.29, 95% confidence interval -0.42 to -0.01); adjusted for age, sex, body mass index and physical health. Conclusion Mental health is associated with changes in foot pain. Clinicians dealing with this population should consider the contribution of mental health in their management and treatment of foot pain.

OBJECTIVE To determine whether testosterone therapy improves glucose metabolism in men with type 2 diabetes (T2D) and lowered testosterone. RESEARCH DESIGN AND METHODS We conducted a randomized, double-blind, parallel, placebo-controlled trial in 88 men with T2D, aged 35–70 years with an HbA1c ≤8.5% (69 mmol/mol), and a total testosterone level, measured by immunoassay, of ≤12.0 nmol/L (346 ng/dL). Participants were randomly assigned to 40 weeks of intramuscular testosterone undecanoate (n = 45) or matching placebo (n = 43). All study subjects were included in the primary analysis. Seven men assigned to testosterone and six men receiving placebo did not complete the study. Main outcome measures were insulin resistance by homeostatic model assessment (HOMA-IR, primary outcome) and glycemic control by HbA1c (secondary outcome). RESULTS Testosterone therapy did not improve insulin resistance (mean adjusted difference [MAD] for HOMA-IR compared with placebo −0.08 [95% CI −0.31 to 0.47; P = 0.23]) or glycemic control (MAD HbA1c 0.36% [0.0–0.7]; P = 0.05), despite a decrease in fat mass (MAD −2.38 kg [−3.10 to −1.66]; P < 0.001) and an increase in lean mass (MAD 2.08 kg [1.52–2.64]; P < 0.001). Testosterone therapy reduced subcutaneous (MAD −320 cm3 [−477 to −163]; P < 0.001) but not visceral abdominal adipose tissue (MAD 140 cm3 [−89 to 369]; P = 0.90). CONCLUSIONS Testosterone therapy does not improve glucose metabolism or visceral adiposity in obese men with moderately controlled T2D and modest reductions in circulating testosterone levels typical for men with T2D.

OBJECTIVE: Foot pain is a common complaint in adults. Increased BMI and fat mass have been linked only to foot pain prevalence. Therefore, a longitudinal study to examine the relationship between body composition and incident foot pain over 3 years was conducted. DESIGN AND METHODS: Sixty-one community dwelling participants from a previous study of musculoskeletal health, who did not have foot pain at study inception in 2008, were invited to take part in this follow-up study in 2011. Current foot pain was determined using the Manchester Foot Pain and Disability Index, and body composition was measured using dual X-ray absorptiometry at study baseline. RESULTS: Of the 51 respondents (84% response rate, 37 females and 14 males), there were 11 who developed foot pain. BMI ranged from underweight to morbidly obese (17-44 kg/m2), mean 27.0 ± 6.0 kg/m2. Incident foot pain was positively associated with both fat mass (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.03-1.20) and fat-mass index (OR 1.28, 95% CI 1.04-1.57) in multivariate analysis. CONCLUSIONS: Fat mass is a predictor of incident foot pain. This study supports the notion that incident foot pain in overweight individuals is associated with fat mass rather than body mass alone.

Objective: Optimizing gestational weight gain (GWG) in early pregnancy is of clinical and public health importance, especially in higher risk pregnancies. Design and Methods: In a robustly designed, randomized controlled trial, 228 pregnant women at risk of developing gestational diabetes mellitus (GDM) were allocated to either control (written health information only) or intervention (four-session lifestyle program). All women received standard maternal care. Measures were completed at 12-15 and 26-28 weeks gestation. Measures included anthropometrics (weight and height), physical activity (pedometer and International Physical Activity Questionnaire), questionnaires (risk perception), and GDM screening. Results: The mean (SD) age [31.7 (4.5) and 32.4 (4.7) years] and body mass index [BMI; 30.3 (5.9) and 30.4 (5.6) kg/m2] were similar between control and intervention groups, respectively. By 28 weeks, GWG was significantly different between control and intervention groups [6.9 (3.3) vs. 6.0 (2.8) kg, P < 0.05]. When stratified according to baseline BMI, overweight women in the control group gained significantly more weight compared to overweight women in the intervention group [7.8 (3.4) vs. 6.0 (2.2) kg, P < 0.05], yet in obese women, GWG was similar in both groups. Physical activity levels declined by 28 weeks gestation overall (P < 0.01); however, the intervention group retained a 20% higher step count compared to controls [5,203 (3,368) vs. 4,140 (2,420) steps/day, P < 0.05]. Overall, GDM prevalence was 22%, with a trend toward less cases in the intervention group (P = 0.1). Conclusions: Results indicate that a low-intensity lifestyle intervention, integrated with antenatal care, optimizes healthy GWG and attenuates physical activity decline in early pregnancy. Efficacy in limiting weight gain was greatest in overweight women and in high-risk ethnically diverse women.

Thalassemia bone disease is well described, but the prevalence of nephrolithiasis has not been characterized. The association between nephrolithiasis, reduced bone density, and increased fractures has been demonstrated through this retrospective study of 166 participants with transfusion-dependent thalassemia. The findings support the need for increased vigilance of kidney and bone disease in this cohort. Previous studies have revealed that thalassemia is associated with reduced bone mineral density (BMD) and fractures. Many causes are implicated including hypogonadism, growth hormone deficiency, marrow expansion, and iron overload. Nephrolithiasis is associated with reduced BMD and increased fractures in the general population. However, the prevalence of nephrolithiasis and its association with bone density and fractures have not been characterized in thalassemia. We have addressed this question by performing a retrospective cohort study of 166 participants with transfusion-dependent thalassemia who had undergone dual-energy X-ray absorptiometry between 2009 and 2011. Logistic regression modeling was used to adjust for potential confounders. We found a high prevalence of kidney stones (18.1 %) which was greater in males compared to females (28.7 vs 9.7 %, respectively). Renal stones were associated with reduced femoral neck Z-score and fractures in men after adjusting for potential confounders. These results indicate that nephrolithiasis is highly prevalent in patients with transfusion-dependent thalassemia and is significantly associated with reduced BMD and increased fractures. The findings from this study strongly support the need for ongoing surveillance of BMD, fractures, and nephrolithiasis in the management of transfusion-dependent thalassemia.

Background Diet and body composition play unclear roles in the pathogenesis, activity and symptoms of inflammatory bowel disease (IBD). Evidence-based guidance regarding dietary modification in IBD is lacking. We aimed to determine the attitudes of IBD patients and clinicians to diet. Methods The present cross-sectional study comprised an online questionnaire distributed to members of a national IBD patient organisation, assessing demographics, anthropometry, disease phenotype and dietary beliefs. Dietitians, gastroenterologists and surgeons were targeted for a similar questionnaire as a result of membership of national professional bodies. Results Nine hundred and twenty-eight patients (72.2% female; mean age 39.5 years; age range 5–91 years) responded. Two-thirds of the patients had Crohn's disease. The mean reported body mass index was 24.9 kg m–2 and was significantly skewed to the right. Patients who had taken >10 courses of steroids were had a greater probability of being overweight or obese, independent of disease complications. Most patients (71%) assumed that their diet affected their IBD; 61% considered their IBD specialist disregarded the importance of diet. Of the 136 clinicians who responded, the majority felt that diet was a factor in symptoms and intestinal microbiota. More gastroenterologists (44%) than dietitians (17%) considered that diet had a role in the pathogenesis of IBD (P = 0.003). Twenty-six percent of patients reported receiving dietary advice from their IBD specialist, whereas 98% of gastroenterologists reported advice provision. Patients received diverse advice. Half of the patients followed recommendations provided by a clinician. Conclusions The present study demonstrates that IBD patients consider diet to be important in their disease. IBD clinicians from different disciplines have diverse views of the role of diet. Advice given to patients is heterogeneous, often perceived as inadequate and poorly followed.

Cerebral palsy (CP) increases fracture risk through diminished ambulation, nutritional deficiencies, and anticonvulsant medication use. Studies examining bone mineral density (BMD) in adults with CP are limited.To examine the relationship between body composition, BMD, and fractures in adults with CP. The effect of functional, nutritional, and endocrine factors on BMD and body composition is also explored.Retrospective cross-sectional study.Forty-five adults with CP (mean age, 28.3 ± 11.0 years) who had dual-energy x-ray absorptiometry imaging at a single tertiary hospital between 2005 and 2015.Seventeen (38%) had a past history of fragility fracture; 43% had a Z-score of ≤ -2.0 at the lumbar spine (LS) and 41% at the femoral neck (FN). In nonambulatory patients, every one unit decrease in FN Z-score increased the risk of fracture 3.2-fold (95% confidence interval, 1.07-9.70; P = .044). Stepwise linear regression revealed that the Gross Motor Function Classification System was the best predictor of LS Z-score (R(2) = 0.550; β = -0.582; P = .002) and FN Z-score (R(2) = 0.428; β = -0.494; P = .004); 35.7% of the variance in BMD was accounted for by lean tissue mass. Hypogonadism, present in 20% of patients, was associated with reduced lean tissue mass and reduced LS BMD. Lean tissue mass positively correlated with BMD in eugonadal patients, but not in hypogonadal patients.Low BMD and fractures are common in adults with CP. This is the first study to document hypogonadism in adults with CP with detrimental changes in body composition and BMD.

The classic rule stating that restricting intake by 3500 kcal/wk will lead to a 1-lb/wk rate of weight loss has come under intense scrutiny. Generally not a component of most weight loss prediction models, the "early" rapid weight loss phase may represent a period during which the energy content of weight change (ΔEC/ΔW) is low and thus does not follow the classic "rule." The current study tested this hypothesis. Dynamic ΔEC/ΔW changes were examined in 23 Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy Study overweight men and women evaluated by dual-energy x-ray absorptiometry during weight loss at treatment weeks 4 to 24. Changes from baseline in body energy content were estimated from fat and fat-free mass. Repeated-measures analysis of variance was used to determine if ΔEC/ΔW changed significantly over time. The evaluation was expanded with addition of the Kiel 13-week weight loss study of 75 obese men and women to test with adequate power if there are sex differences in ΔEC/ΔW. The analysis of variance CALERIE time effect was significant (P < .001), with post hoc tests indicating that ΔEC/ΔW (kilocalories per kilogram) increased significantly from week 4 (X ± SEM; 4, 858 ± 388) to 6 (6, 041 ± 376, P < .01) and changed insignificantly thereafter; ΔEC/ΔW was significantly larger for Kiel women (6, 804 ± 226) vs men (6, 119 ± 240, P < .05). Sex-specific dynamic relative changes in body composition and related ΔEC/ΔW occur with weight loss initiation that extend for 1 month or more. These observations provide new information for developing energy balance models and further define limitations of the 3500-kcal energy deficit → 1-lb weight loss rule.

Obstructive sleep apnea (OSA) may be associated with increased energy expenditure (EE) during sleep. As actigraphy is inaccurate at estimating EE from body movement counts alone, we aimed to compare a multiple physiological sensor with polysomnography for determination of sleep and wake, and to test the hypothesis that OSA is associated with increased EE during sleep. We studied 50 adults referred for routine overnight polysomnography. In addition to polysomnography, the SenseWear Pro3 ArmbandTM (Bodymedia Inc.) was placed on the upper right arm. Epoch-by-epoch agreement rate between the measures of sleep versus wake was calculated. Linear regression analyses were performed for EE against apnea–hypopnea index (AHI), 3% oxygen desaturation index (ODI), body mass index (BMI), waist–hip ratio (WHR), gender, age, and average heart rate during sleep. The epoch-by-epoch agreement rate was high (79.9 ± 1.6%) and the ability of the SenseWear to estimate sleep was very good (sensitivity, 88.7 ± 1.5%). However, it was less accurate in determining wake (specificity 49.9 ± 3.6%). Sleep EE was associated with AHI, 3% ODI, BMI, WHR, and male gender (p

Patients with β-thalassemia major require iron-chelation therapy to avoid the complication of iron overload. Until recently, deferoxamine (DFO) was the major iron chelator used in patients requiring chronic hypertransfusion therapy, but DFO required continuous subcutaneous therapy. The availability of deferasirox (Exjade®), an orally active iron chelator, over the past 4 years represented a necessary alternative for patients requiring chelation therapy. However, there have been increasing reports of proximal renal tubular dysfunction and Fanconi Syndrome associated with deferasirox in the literature. We report a case of hypophosphataemic osteomalacia secondary to deferasirox therapy. © 2012 American Society for Bone and Mineral Research

Objective To assess the Finnish Diabetes Risk Score in polycystic ovary syndrome (PCOS) and in different phenotypes of PCOS and controls. Design Cross-sectional study. Setting General community. Patient(s) Overweight premenopausal women with National Institutes of Health (NIH) PCOS (n = 29), non-NIH PCOS (n = 25), or controls (n = 27). Intervention(s) No intervention provided. Main Outcome Measure(s) Finnish Diabetes Risk Score, anthropometrics, oral glucose tolerance test (OGTT), glucose, insulin, and reproductive hormone levels. Result(s) The women with NIH PCOS had higher adiposity, abdominal adiposity and 120-minute OGTT glucose. The women with NIH and non-NIH PCOS had elevated 120-minute OGTT insulin compared with controls. The women with NIH (11.3 ± 0.7) and non-NIH PCOS (10.4 ± 0.7) had similar diabetes risk scores, but both had higher diabetes risk score compared with controls (7.6 ± 0.8) maintained on adjustment for age and body mass index (BMI). The women with NIH (4%) and non-NIH PCOS (12%) had a lower prevalence of low risk of diabetes scores compared with controls (50%). Conclusion(s) We report for the first time that women with NIH and non-NIH PCOS have similar Finnish Diabetes Risk Scores and elevated scores relative to controls independent of age and adiposity. Similar clinical screening and treatment practices for type 2 diabetes are warranted for both phenotypes of PCOS.

This study used densitometry to investigate the areal bone mineral density (aBMD) and bone mineral content (BMC) in an Australian Rett syndrome cohort and assess how factors such as genotype, epilepsy, BMI and mobility affect these parameters. The influence of lean tissue mass (LTM) and bone area (BA) on total body BMC (TBBMC) was also investigated. Participants, recruited from the Australian Rett Syndrome Database (ARSD), had TBBMC and lumbar spine (LS) and femoral neck (FN) aBMD measured using Dual energy X-ray absorptiometry. Mean height standardised z-scores and confidence intervals for the bone outcomes were obtained from multiple regression models. The mean height z-score for the FN aBMD was low at −2.20, while the LS aBMD was −0.72. The TBBMC mean height z-score was −0.62, although once adjusted for BA and LTM the mean was above zero, suggesting that low BMC can be explained by narrow bones and decreased muscle mass, likely secondary to decreased mobility. Multiple linear regression identified the p.R168X and p.T158M mutations as the strongest predictors of low aBMC and BMD for all bone outcomes. The strong relation between genotype, BMC and aBMD, is likely underpinned by the strong relation between LTM, mobility and bone outcome measures.

Julie L Woods1, Sandra Iuliano-Burns2, Susannah J King1, Boyd J Strauss1, Karen Z Walker11Nutrition and Dietetics Department, Monash University, Victoria, Australia; 2Endocrine Centre of Excellence, Department of Medicine, Austin Health, University of Melbourne, West Heidelberg, AustraliaPurpose: To determine the prevalence of sarcopenia and investigate relationships among body composition, muscle strength, and physical function in elderly women in low-level aged care.Subjects and methods: Sixty-three ambulatory women (mean age 86 years) participated in this cross-sectional study where body composition was determined by dual energy X-ray absorptiometry (DXA); ankle, knee, and hip strength by the Nicholas Manual Muscle Tester; and physical function by ‘timed up and go’ (TUG) and walking speed (WS) over 6 meters. Body composition data from a female reference group (n = 62, mean age 29 years) provided cut-off values for defining sarcopenia.Results: Elderly women had higher body mass index (P < 0.001), lower lean mass (P < 0.001), and higher fat mass (P < 0.01) than the young reference group. Only a small proportion (3.2%) had absolute sarcopenia (defined by appendicular skeletal muscle mass/height squared) whereas 37% had relative sarcopenia class II (defined by percentage skeletal muscle mass). Scores for TUG and WS indicated relatively poor physical function, yet these measures were not associated with muscle mass or indices of sarcopenia. In multivariate analysis, only hip abductor strength predicted both TUG and WS (both P = 0.01).Conclusion: Hip strength is a more important indicator of physical functioning than lean mass. Measurement of hip strength may therefore be a useful screening tool to detect those at risk of functional decline and requirement for additional care. Further longitudinal studies with a range of other strength measures are warranted.Keywords: aged care, body composition, muscle strength, sarcopenia&nbsp

Summary Objective Androgen deprivation therapy (ADT) for prostate cancer is associated with increases in fat mass and risk of type 2 diabetes; however, the relationship between sex steroid deficiency and abdominal fat distribution remains controversial. Design We conducted a 12-month prospective observational study at a tertiary referral centre. Patients and measurements We investigated changes in abdominal fat distribution and insulin resistance in 26 men (70·6 ± 6·8 years) with nonmetastatic prostate cancer during the first year of ADT. Results Twelve months of ADT increased visceral abdominal fat area by 22% (from 160·8 ± 61·7 to 195·9 ± 69·7 cm2; P

Polycystic ovary syndrome (PCOS) is an insulin-resistant (IR) state. Visceral fat (VF) is independently associated with IR.The objectives of the study were to explore mechanisms underpinning IR by assessing the effect of exercise training on IR and body composition in overweight PCOS and non-PCOS women.This was a prospective exercise intervention study.The study was conducted at an academic medical center. Participants included 20 overweight PCOS and 14 overweight non-PCOS women.The intervention included 12 wk of intensified aerobic exercise (3 h/wk).IR on euglycemic hyperinsulinemic clamp, body composition including abdominal visceral and sc fat distribution by computer tomography and lipids was measured.PCOS subjects were more IR (P = 0.02) and had more VF (P = 0.04 age adjusted) than non-PCOS women. In PCOS women, IR correlated with VF (r = -0.78, P0.01). With exercise training, both groups maintained weight but within PCOS, VF (-12.0 cm(2), P = 0.03) and within non-PCOS abdominal sc fat (-40.2 cm(2), P = 0.02) decreased. Despite exercise-induced improvement in IR within PCOS (+27.9 mg · m(-2) · min(-1), P = 0.03), no relationship with decreased VF (r = -0.08, P = 0.84) and no differential changes in IR and VF between groups were noted. Triglycerides decreased within PCOS (-0.27 mmol/liter, P = 0.02) and decreased differentially between groups (P0.01).Higher IR was related to increased VF in PCOS, suggesting an etiological role for VF in intrinsic IR in PCOS; however, changes with exercise intervention did not support a causal relationship. Triglycerides were modulated more by exercise training in PCOS than non-PCOS women. Within-group exercise-induced reductions in cardiometabolic risk factors including IR, triglycerides, and VF in PCOS were observed without significant weight loss and if confirmed in future controlled trials, suggest weight loss should not be the sole focus of exercise programs.

Ageing women may choose to drink soya milk to reduce menopausal symptoms. As fermentation enriches soya milk with isoflavone aglycones, its beneficial qualities may improve. To reduce osteoporotic risk, however, soya milk must be Ca enriched, and it is not known how fermentation affects Ca bioavailability. A randomised crossover pilot study was undertaken to compare the Ca absorption of fortified soya milk with that of fermented and fortified soya milk in twelve Australian osteopenic post-menopausal women. The fortified soya milk was inoculated with Lactobacillus acidophilus American Type Culture Collection (ATCC) 4962 and fermented for 24 h at 37°C. Ca absorption from soya milk samples was measured using a single isotope radiocalcium method. Participants had a mean age of 54·8 (sd 12·3) years, with mean BMI of 26·5 (sd 5·5) kg/m2 and subnormal to normal serum 25-hydroxyvitamin D (mean 62·5 (sd 19·1) nmol/l). Participants consumed 185 kBq of 45Ca in 44 mg of Ca carrier. The mean fractional Ca absorption (α) from soya milk and fermented soya milk was 0·64 (sd 0·23) and 0·71 (sd 0·29), respectively, a difference not of statistical significance (P = 0·122). Although fermentation of soya milk may provide other health benefits, fermentation had little effect on acute Ca absorption.

Summary Weight loss follows when adult humans enter a phase of negative energy balance brought about by reducing energy intake and/or increasing energy expenditure. The weight loss period is usually viewed as a continuous process, ending when energy equilibrium is achieved at a lower weight or with death following depletion of fuel stores. However, growing evidence supports the expanded view that induction of negative energy balance leads to well-defined physiological effects characterized by three discrete phases (I-III). At present there are no comprehensive reviews of the ‘early’ phase of weight loss, a gap highlighted by recent interest in rapidly testing new treatments with short-term protocols. Herein we show from earlier reports and with new data that weight loss during phase I is: mathematically quantifiable with a t1/2 < 1-week and 4- to 6-week duration; includes well-defined rapidly evolving body composition and energy expenditure changes; and is moderated by multiple factors including subject sex and activity level, nutrients ingested at baseline and during the negative energy balance period, and hormone and pharmacologic treatments. Our in depth review collectively characterizes phase I as a distinct weight loss period while revealing important knowledge gaps that can be filled with appropriately designed future studies.

Summary The aim of this study was to determine the variability in total testosterone (TT) levels in healthy, non-obese ageing men with symptoms of androgen deficiency. Men aged ≥55 years were recruited from the community. Morning TT levels were measured on four occasions in a 12-month period. In all, 96 men aged 62.7 ± 6.8 years were studied. Geometric mean values (95% confidence interval) of TT levels for the cohort at each time point were 14.5 (13.4–15.7), 14.6 (13.5–15.8), 15.5 (14.4–16.8) and 15.0 (13.9–16.2) nmol/L. The maximum intra-individual difference in TT between the four samples was 4.1 nmol/L (interquartile range: 2.9–6.4). Using the average of two baseline TT values reduces the maximum difference to 2.3 nmol/L (1.0–3.8). Only 1 of 25 men with a documented TT

Debate continues over the effectiveness of coronary risk factor screening as a strategy for the prevention of coronary heart disease in the community. We reviewed changes in risk factors one year after a community coronary risk factor screen and found highly significant reductions in the blood cholesterol (mean reduction of 0.6 mmol/l) and body mass index (mean reduction of 1.03 kg/m2) in those participants who at the initial screening were found to have elevated (greater than 6.5 mmol/l) blood cholesterol concentrations. Comparison of this group with a reference group not given health advice and a group of hypercholesterolaemic clinic attenders showed that the blood cholesterol reduction could not be accounted for solely by regression to the mean, and was as good as the blood cholesterol reduction achieved by regular clinic attendance. Although there were many factors that could account for these reductions, we found that participants who received risk factor measurement and counselling during the screening process and who sought medical follow-up after the screen had a greater reduction in risk factors.

Udgivelsesdato: 2009-Dec AIM: The effect on body composition of liraglutide, a once-daily human glucagon-like peptide-1 analogue, as monotherapy or added to metformin was examined in patients with type 2 diabetes (T2D). METHODS: These were randomized, double-blind, parallel-group trials of 26 [Liraglutide Effect and Action in Diabetes-2 (LEAD-2)] and 52 weeks (LEAD-3). Patients with T2D, aged 18-80 years, body mass index (BMI) < or =40 kg/m(2) (LEAD-2), < or =45 kg/m(2) (LEAD-3) and HbA1c 7.0-11.0% were included. Patients were randomized to liraglutide 1.8, 1.2 or 0.6 mg/day, placebo or glimepiride 4 mg/day, all combined with metformin 1.5-2 g/day in LEAD-2 and to liraglutide 1.8, 1.2 or glimepiride 8 mg/day in LEAD-3. LEAD-2/3: total lean body tissue, fat tissue and fat percentage were measured. LEAD-2: adipose tissue area and hepatic steatosis were assessed. RESULTS: LEAD-2: fat percentage with liraglutide 1.2 and 1.8 mg/metformin was significantly reduced vs. glimepiride/metformin (p < 0.05) but not vs. placebo. Visceral and subcutaneous adipose tissue areas were reduced from baseline in all liraglutide/metformin arms. Except with liraglutide 0.6 mg/metformin, reductions were significantly different vs. changes seen with glimepiride (p < 0.05) but not with placebo. Liver-to-spleen attenuation ratio increased with liraglutide 1.8 mg/metformin possibly indicating reduced hepatic steatosis. LEAD-3: reductions in fat mass and fat percentage with liraglutide monotherapy were significantly different vs. increases with glimepiride (p < 0.01). CONCLUSION: Liraglutide (monotherapy or added to metformin) significantly reduced fat mass and fat percentage vs. glimepiride in patients with T2D.

BACKGROUND Nutritional status predicts outcome in dialysis populations. Increased dialysis time and/or frequency reportedly improves nutritional status. We examined the impact of more intensive dialysis on body composition. METHODS A cross-sectional, matched study comparing home haemodialysis (HHD) patients (>15 h/week, n = 28) and conventional haemodialysis (CHD) patients (

SUMMARY Background: Cardiovascular disease in dialysis patients is associated with increased vascular calcification (VC) and arterial stiffness, both inversely correlated with bone mineral density (BMD). Few studies have correlated VC in the dialysis population with measurements of BMD and arterial compliance. Methods: We report cross-sectional data on 45 haemodialysis (HD) patients assessing the prevalence of VC and its associations. Patients had computed tomography scans through abdominal aorta and superficial femoral arteries (SFA) to determine VC, pulse wave velocity (PWV) using SphygmoCor device measuring arterial stiffness, and dual-energy X-ray absorptiometry (DXA) to determine BMD. Results: Patients, 64% male, 38% diabetic, had median age 58 years. Mean PWV was 8.7 ± 3.5 m/s and median aortic VC score 488.1 ± 298 Hounsfield units, with 91% having aortic VC present. In univariate linear regression analysis, aortic VC correlated positively with length of HD (P = 0.03) and diabetes (P = 0.06). Increasing PWV was positively associated with age (P = 0.001), diabetes (P = 0.05) and VC (aortic P = 0.08, SFA P = 0.01). In multivariate regression analysis, length of HD and diabetes were significantly associated with aortic VC, whereas age and diabetes were associated with SFA VC and PWV. Mean lumbar spine and femoral neck T-scores on DXA were 0.14 and −1.66 respectively. Conclusion: Increased VC and reduced arterial compliance, both closely related, are common in Australian HD patients. Both are associated with diabetes and increasing age, and greater aortic VC is seen with longer duration of dialysis.

Background and objectives: Vascular calcification (VC) contributes to increased cardiovascular (CV) disease in dialysis patients and is inversely correlated with bone mineral density (BMD). Screening for VC may determine patients at greater CV risk and bone densitometry may have dual role in assessing VC as well as BMD. The aim of this study was to determine measurement of VC using dual-energy x-ray absorptiometry (DXA) with correlation to gold standard computed tomography (CT). Design, setting, participants, & measurements: Forty hemodialysis patients had abdominal aortic CT and lateral DXA of lumbar spine to determine aortic VC and BMD. Semiquantitative measurement of aortic VC from lateral DXA was determined using previously validated 24- and 8-point scales and correlated with aortic VC with CT. Anteroposterior (AP) and lateral DXA-reported BMD was compared with BMD from L2 through L4 with CT. Results: Patients, 70% men, 38% diabetic, had median age 58.5 yr. Aortic VC was present in 94% with CT and 68% on lateral DXA. For 24- and 8-point scores, intraclass correlation coefficients for intrarater agreement were 0.93 and 0.88, respectively. DXA-measured VC correlated with CT. Sensitivity and specificity for CT aortic VC ≥ 500 HU was 50 and 86%, respectively, for DXA VC ≥ 6 on a 24-point scale. Lateral DXA-reported BMD significantly correlated with BMD from CT, but AP DXA did not. Conclusions: Lateral DXA may be useful because images may provide concurrent assessment of aortic calcification as well as more accurate lumbar spine BMD, avoiding some of the limitations of AP DXA.

To investigate the role of androgens in increasing bone density and improving low libido in postmenopausal women, we have studied the long-term effects of estradiol and testosterone implants on bone mineral density and sexuality in a prospective, 2 year, single-blind randomised trial. Thirty-four postmenopausal volunteers were randomised to treatment with either estradiol implants 50 mg alone (E) or estradiol 50 mg plus testosterone 50 mg (E&T), administered 3-monthly for 2 years. Cyclical oral progestins were taken by those women with an intact uterus. Thirty-two women completed the study. BMD (DEXA) of total body, lumbar vertebrae (L1–L4) and hip area increased significantly in both treatment groups. BMD increased more rapidly in the testosterone treated group at all sites. A substantially greater increase in BMD occurred in the E&T group for total body (P < 0.008), vertebral L1–L4 (P < 0.001) and trochanteric (P < 0.005) measurements. All sexual parameters (Sabbatsberg sexual self-rating scale) improved significantly in both groups. Addition of testosterone resulted in a significantly greater improvement compared to E for sexual activity (P < 0.03), satisfaction (P < 0.03), pleasure (P < 0.01), orgasm (P < 0.035) and relevancy (P < 0.05). Total cholesterol and LDL-cholesterol fell in both groups as did total body fat. Total body fat-free mass (DEXA, anthropometry, impedance) increased in the E&T group only. We concluded that in postmenopausal women, treatment with combined estradiol and testosterone implants was more effective in increasing bone mineral density in the hip and lumbar spine than estradiol implants alone. Significantly greater improvement in sexuality was observed with combined therapy, verifying the therapeutic value of testosterone implants for diminished libido in postmenopausal women. The favourable estrogenic effects on lipids were preserved in women treated with T, in association with beneficial changes in body composition.

Plants contain compounds with oestrogen — like action called phytoestrogens. Soy contains daidzin, a potent phytoestrogen, and wheat flour contains less potent enterolactones. We aimed to show in 58 postmenopausal women (age 54, range 30-70 years) with at least 14 hot flushes per week, that their daily diet supplemented with soy flour (n = 28) could reduce flushes compared with wheat flour (n = 30) over 12 weeks when randomised and double blind. Hot flushes significantly decreased in the soy and wheat flour groups (40% and 25% reduction, respectively