Evaluation of an alternative skeletal muscle index for skeletal muscle mass assessment in a group of Australian women.

BACKGROUND: Sarcopenia is assessed by several methods, including dual energy X-ray absorptiometry (DEXA), which provide a height-adjusted skeletal muscle index (H-SMI). A SMI 2 standard deviation below the young adult reference [1] combined with low muscle strength or performance is used to identify sarcopenia. As height declines with age, H-SMI may underestimate low skeletal muscle mass in the older population. Our study aims to evaluate an alternative SMI and to examine its relationship to grip strength in a group of Australian women. METHODS: Women from two cohorts were analysed. 2041 women had body composition data (112 had calf circumference, 137 had leg length measurements) without grip strength, and 49 women had grip strength measured (40 had body composition data).The relationship between leg length-adjusted SMI (LL-SMI) to grip strength and anthropometric variables to skeletal muscle mass by DEXA were examined by linear regression analysis. RESULTS: Cohort 1: Older women were compared to younger women. Older women were shorter but leg length did not differ between different age groups. H-SMI was not different between groups (P = 0.528). LL-SMI was lower in older women (P = 0.002). Cohort 2: LL-SMI was significantly associated with grip strength (P = 0.048) after adjustment for age. CONCLUSION: Older women were shorter, while leg length did not differ from the younger group. H-SMI may obscure and may underestimate low muscle mass in older individuals. LL-SMI may be a better measure of skeletal muscle mass in older individuals. These alternate SMI would benefit from further exploration in older individuals.

Measurement of Muscle Mass and Sarcopenia Using Anthropometry, Bioelectrical Impedance, and Computed Tomography in Surgical Patients with Colorectal Malignancy: Comparison of Agreement Between Methods.

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), mid-arm muscle circumference (MAMC), and computed tomography (CT) at the third lumbar vertebra (L3), for the measurement of muscle mass and identification of sarcopenia, in patients with colorectal cancer (CRC).Method: A comparison study of low SMI and sarcopenia determined by BIA and MAMC, compared to CT. Sensitivity, specificity and area under the curve (AUC) were calculated.Results: CT scans were obtained for 100 participants. Low SMI was identified in 29%, 57%, and 20% of participants using CT at L3, BIA, and MAMC, respectively. For low muscle mass BIA showed 60% of participants were correctly classified (AUC 0.619, sensitivity 80%, specificity 52%, kappa 0.241, P = 0.009) and for MAMC, 73% of participants were correctly classified (AUC 0.625, sensitivity 38%, specificity 88%, kappa 0.286, P = 0.005). There were 14%, 31%, and 10% of participants identified as having sarcopenia from CT, BIA, and MAMC, respectively.Conclusions: Both BIA and MAMC show a poor level of agreement for measuring muscle mass compared to CT scans using L3 in patients with CRC.

Longitudinal changes in bone density in adolescents and young adults with cerebral palsy: A case for early intervention.

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 <-2.0 at all sites - lumbar spine (LS), femoral neck (FN), total hip (TH) and total body (TB). The median change in aBMD was +1.2%-1.9% per year in all subjects but in those <20 years of age, the median change was 4%-8% per year. Z-scores across all sites remained stable over time. Reduced functional state as measured by the gross motor functional classification scale (GMFCS) had a small negative effect on aBMD over time. CONCLUSION: In adolescents with CP, low bone mass was evident from the baseline DXA. However, significant bone accrual occurred during the second decade, followed by bone maintenance in young adulthood. Future studies should focus on optimizing bone health from early childhood.

Effects of testosterone treatment on body fat and lean mass in obese men on a hypocaloric diet: a randomised controlled trial.

BACKGROUND: Whether testosterone treatment has benefits on body composition over and above caloric restriction in men is unknown. We hypothesised that testosterone treatment augments diet-induced loss of fat mass and prevents loss of muscle mass. METHODS: We conducted a randomised double-blind, parallel, placebo controlled trial at a tertiary referral centre. A total of 100 obese men (body mass index ≥ 30 kg/m2) with a total testosterone level of or below 12 nmol/L and a median age of 53 years (interquartile range 47-60) receiving 10 weeks of a very low energy diet (VLED) followed by 46 weeks of weight maintenance were randomly assigned at baseline to 56 weeks of 10-weekly intramuscular testosterone undecanoate (n = 49, cases) or matching placebo (n = 51, controls). The main outcome measures were the between-group difference in fat and lean mass by dual-energy X-ray absorptiometry, and visceral fat area (computed tomography). RESULTS: A total of 82 men completed the study. At study end, compared to controls, cases had greater reductions in fat mass, with a mean adjusted between-group difference (MAD) of -2.9 kg (-5.7 to -0.2; P = 0.04), and in visceral fat (MAD -2678 mm2; -5180 to -176; P = 0.04). Although both groups lost the same lean mass following VLED (cases -3.9 kg (-5.3 to -2.6); controls -4.8 kg (-6.2 to -3.5), P = 0.36), cases regained lean mass (3.3 kg (1.9 to 4.7), P < 0.001) during weight maintenance, in contrast to controls (0.8 kg (-0.7 to 2.3), P = 0.29) so that, at study end, cases had an attenuated reduction in lean mass compared to controls (MAD 3.4 kg (1.3 to 5.5), P = 0.002). CONCLUSIONS: While dieting men receiving placebo lost both fat and lean mass, the weight loss with testosterone treatment was almost exclusively due to loss of body fat. TRIAL REGISTRATION: clinicaltrials.gov, identifier NCT01616732 , registration date: June 8, 2012.

The interaction between physical activity and amount of baseline knee cartilage.

OBJECTIVES: Conflicting reports of the effect of physical activity on knee cartilage may be due to the heterogeneity of populations examined and, in particular, the underlying health of the knee joint. This study examined the influence of recreational and occupational physical activity on cartilage volume loss. METHODS: A total of 250 participants with no significant musculoskeletal disease were recruited. A gender-specific median cartilage volume split was used to define people in the lowest and highest 50% of baseline cartilage volume. Baseline recreational and occupational activity was examined by questionnaire, while cartilage volume was assessed by MRI at baseline and 2.4 years later. RESULTS: Significant interactions were demonstrable between physical activity and cartilage volume loss based on stratification of baseline cartilage volume (all P ⩽ 0.03). There was a dose-response relationship between frequently performed baseline occupational activities and medial cartilage volume loss in both the low (B = 0.2% per annum, 95% CI: 0.0, 0.04% per annum) and high (B = -0.2% per annum, 95% CI: -0.4, 0.0% per annum) baseline cartilage volume groups (P = 0.001 for interaction). Individuals with low baseline cartilage volume who were active in their occupation and/or recreational activity had greater medial cartilage volume loss than their more inactive counterparts (2.4% per annum vs 1.5% per annum, P = 0.02). CONCLUSION: Whereas people with less baseline cartilage volume are more at risk of structural knee damage with either heavy occupational or recreational workloads or both, individuals with high baseline cartilage volume may advantageously modify their risk for knee OA by participating in more frequent occupational physical activities.

Adherence to the gluten-free diet can achieve the therapeutic goals in almost all patients with coeliac disease: A 5-year longitudinal study from diagnosis.

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.

Weight change and change in tibial cartilage volume and symptoms in obese adults.

INTRODUCTION: There is a paucity of data examining the effects of weight change on knee joint structures and symptoms. This study examined the effect of weight change on change in knee cartilage volume and symptoms in an obese cohort. METHODS: 112 obese subjects (Body Mass Index ≥30 kg/m(2)) were recruited from various community sources to examine the effect of obesity on musculoskeletal health. Tibial cartilage volume, determined by MRI, and knee symptoms, determined by the Western Ontario and McMaster Osteoarthritis Index (WOMAC) were collected at baseline and an average of 2.3 years later. RESULTS: Percentage weight change was associated with change in medial tibial cartilage volume (ß -1.2 mm(3), 95% CI -2.3 to -0.1 mm(3), p=0.03) that was consistent throughout the spectrum of weight loss through to mild weight gain. Percentage weight change was not associated with change in the lateral tibial (p=0.93) or patella (p=0.32) cartilage volumes. Percentage weight change was associated with change in all WOMAC subscales (all p≤0.01): pain (ß -1.8 mm, 95% CI -3.2 to -0.4 mm), stiffness (ß -1.6 mm, 95% CI -2.5 to -0.7 mm) and function (ß -6.9 mm, 95% CI -11.6 to -2.1 mm). CONCLUSIONS: The linearity of effect implies that weight loss is associated with reduced medial cartilage volume loss and improved knee symptoms, while weight gain is associated with increased medial cartilage volume loss and worse knee symptoms. These results suggest that in obese people, small amounts of weight change may have the potential for a disease modifying effect on both knee joint structure and symptoms. While weight loss is an important primary management strategy in obese individuals, avoidance of further weight gain should also be a clinical goal.

The longitudinal relationship between changes in body weight and changes in medial tibial cartilage, and pain among community-based adults with and without meniscal tears.

INTRODUCTION: Meniscal tears are commonly found on MRI and increase the risk for radiographic knee osteoarthritis (OA). While meniscectomy is recommended when knee pain is severe or functionally disabling, it is unclear how to best treat meniscal tears without these symptoms. The aim of this longitudinal study was to examine the effect of weight change on knee cartilage and pain in a cohort of community-based adults with and without meniscal tears detected by MRI. METHODS: 250 adults with no history of knee OA or knee injury were recruited from the general community and weight-loss clinics. MRI of the knee, Western Ontario and McMaster University Osteoarthritis Index (WOMAC), weight and height were measured at baseline and again at follow-up approximately 2 years later. RESULTS: Medial meniscal tears were present in 36 (18%) of the cohort. In those with medial meniscal tears, after adjustment for confounders, percentage weight change was significantly associated with percentage change in medial tibial cartilage volume (ß 0.2% 95% CI 0.08% to 0.3% p=0.002) and knee pain (ß 11.6% 95% CI 2.1% to 21.1% p=0.02). That is, for every 1% gain in weight, there was an associated 0.2% increased loss of medial tibial cartilage volume and 11.6% increase in pain. In those with no medial meniscal tear, neither change in medial tibial cartilage volume (ß 0.02% 95% CI -0.01% to 0.10% p=0.53) or pain (ß 1.9% 95% CI -2.2% to 6.1% p=0.36) were significantly associated with change in weight. CONCLUSIONS: This study demonstrated that among adults with medial meniscal tears, weight gain is associated with increased cartilage loss and pain, while weight loss is associated with the converse. This suggests attention to weight is particularly important in the management of people with medial meniscal tears.

Polycystic ovary syndrome and anti-Müllerian hormone: role of insulin resistance, androgens, obesity and gonadotrophins.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder associated with insulin resistance, hyperandrogenism, obesity, altered gonadotrophin release and anovulatory infertility. Anti-Müllerian 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-Müllerian hormone levels were increased in women with PCOS (P <0·001) regardless of adiposity, with this increase associated with testosterone (P <0·001) rather than insulin resistance (P = 0·79), adiposity (P = 0·98) or gonadotrophins. In assessing the ability of AMH to predict PCOS, a value of 30 pmol/l or higher indicated 79% of women with PCOS were correctly identified as having the condition. CONCLUSION: Anti-Müllerian hormone appears primarily related to androgen status suggesting a direct and predominant role of androgens in the pathophysiology of reproductive dysfunction in PCOS. As AMH reflects PCOS status, it may also be useful in PCOS diagnosis.

Energy expenditure in obstructive sleep apnea: validation of a multiple physiological sensor for determination of sleep and wake.

PURPOSE: 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. METHODS: We studied 50 adults referred for routine overnight polysomnography. In addition to polysomnography, the SenseWear Pro3 Armband(TM) (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. RESULTS: 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 < 0.001 for all). Stepwise multiple linear regression however revealed that BMI, male gender, age, and average heart rate during sleep were independent predictors of EE (Model R (2) = 0.78). CONCLUSIONS: The SenseWear armband provides a reasonable estimation of sleep but a poor estimation of wake. Furthermore, in a selected population of OSA patients, increasing OSA severity is associated with increased EE during sleep, although primarily through an association with increased BMI. However, as our data are not adjusted for fat-free mass and the SenseWear has yet to be validated for EE in OSA patients, these data should be interpreted with caution.

The associations between body and knee height measurements and knee joint structure in an asymptomatic cohort.

BACKGROUND: It has been suggested that knee height is a determinant of knee joint load. Nonetheless, no study has directly examined the relationship between anthropometric measures of height and knee joint structures, such as cartilage. METHODS: 89 asymptomatic community-based adults aged 25-62 with no diagnosed history of knee arthropathy were recruited. Anthropometric data (knee height and body height) were obtained by standard protocol, while tibial cartilage volume and defects, as well as bone area were determined from magnetic resonance imaging. Static knee alignment was measured from the joint radiograph. RESULTS: All anthropometric height measures were associated with increasing compartmental tibial bone area (p ≤ 0.05). Although knee height was associated with tibial cartilage volume (e.g. ß = 27 mm³ 95% CI 7- 48; p = 0.009 for the medial compartment), these relationship no longer remained significant when knee height as a percentage of body height was analysed. Knee height as a percentage of body height was associated with a reduced risk of medial tibial cartilage defects (odds ratio 0.6; 95% confidence interval 0.4 - 1.0; p = 0.05). CONCLUSION: The association between increased anthropometric height measures and increased tibial bone area may reflect inherently larger bony structures. However the beneficial associations demonstrated with cartilage morphology suggest that an increased knee height may confer a beneficial biomechanical environment to the chondrocyte of asymptomatic adults.

Abnormal Trabecular Bone Score, Lower Bone Mineral Density and Lean Mass in Young Women With Premature Ovarian Insufficiency Are Prevented by Oestrogen Replacement.

Background: Low bone density (BMD) and fractures commonly affect women with premature ovarian insufficiency (POI). However, bone microarchitecture and body composition data are lacking. Objective: To assess and characterise musculoskeletal phenotype and effects of oestrogen replacement therapy (ERT) in women with POI. Method: Cross-sectional and longitudinal studies of 60 normal karyotype women with POI, aged 20-40 years, from 2005-2018. Dual x-ray absorptiometry (DXA)-derived spinal (LS) and femoral neck (FN) BMD, trabecular bone score (TBS), appendicular lean mass (ALM), total fat mass (TFM), and fracture prevalence were compared with 60 age-, and BMI-matched population-based controls. Longitudinal changes in bone and body composition variables and ERT effects were analysed using linear mixed models over a median duration of 6 years. Results: Women with POI were subdivided into spontaneous (s)-POI (n=25) and iatrogenic (i)-POI (n=35). Median(range) age of POI diagnosis was 34 (10-40) years with baseline DXA performed at median 1(0-13) year post-diagnosis. ERT was used by 82% women (similar for both POI groups). FN-BMD were lowest in s-POI (p<0.002). Low TBS was more common in s-POI [(44%), p=0.03], versus other groups. LS-BMD and ALM were lower in both s-POI and i-POI groups than controls (p<0.05). Fracture prevalence was not significantly different: 20% (s-POI), 17% (i-POI), and 8% (controls) (p=0.26). Longitudinal analysis of 23 POI women showed regular ERT was associated with ALM increment of 127.05 g/year (p<0.001) and protected against bone loss. However, ERT interruption was associated with annual reductions in FN BMD and TBS of 0.020g/cm2 and 0.0070 (p<0.05), respectively. Conclusion: Deficits in BMD, trabecular microarchitecture, and lean mass were present in women with POI. However, regular ERT protected against declines in bone variables, with an increase in ALM. Assessment of skeletal and muscle health, and advocating ERT adherence, is essential in POI to optimise musculoskeletal outcomes.

Novel Lipidomic Signature Associated With Metabolic Risk in Women With and Without Polycystic Ovary Syndrome.

CONTEXT: Dyslipidemia is a feature of polycystic ovary syndrome (PCOS) and may augment metabolic dysfunction in this population. OBJECTIVE: Using comprehensive lipidomic profiling and gold-standard metabolic measures, we examined whether distinct lipid biomarkers were associated with metabolic risk in women with and without PCOS. METHODS: Using preexisting data and biobanked samples from 76 women (n = 42 with PCOS), we profiled > 700 lipid species by mass spectrometry. Lipids were compared between women with and without PCOS and correlated with direct measures of adiposity (dual x-ray absorptiometry and computed tomography) and insulin sensitivity (hyperinsulinemic-euglycemic clamp), as well as fasting insulin, HbA1c, and hormonal parameters (luteinizing and follicle-stimulating hormones; total and free testosterone; sex hormone-binding globulin [SHBG]; and free androgen index [FAI]). Multivariable linear regression was used with correction for multiple testing. RESULTS: Despite finding no differences by PCOS status, lysophosphatidylinositol (LPI) species esterified with an 18:0 fatty acid were the strongest lipid species associated with all the metabolic risk factors measured in women with and without PCOS. Across the cohort, higher concentrations of LPI(18:0) and lower concentrations of lipids containing docosahexaenoic acid (DHA, 22:6) n-3 polyunsaturated fatty acids were associated with higher adiposity, insulin resistance, fasting insulin, HbA1c and FAI, and lower SHBG. CONCLUSION: Our data indicate that a distinct lipidomic signature comprising high LPI(18:0) and low DHA-containing lipids are associated with key metabolic risk factors that cluster in PCOS, independent of PCOS status. Prospective studies are needed to corroborate these findings in larger cohorts of women with varying PCOS phenotypes.

Sex differences in the relationship between bone mineral density and tibial cartilage volume.

OBJECTIVE: Although there is a well-established sex difference in the prevalence and severity of OA, the mechanism for this is not clear. The aim of this study was to examine the potential role of BMD and BMC in explaining gender differences in knee cartilage volume. METHODS: A total of 153 subjects aged 25-60 years, 81% female, were recruited. MRI was performed of the dominant knee. Cartilage volume was measured using validated methods. Total body BMD and content was measured using DXA. RESULTS: Total body BMC and BMD was significantly associated with medial cartilage volume in both sexes. However, the associations were stronger in men for BMC (B = 0.52; 95% CI 0.21, 0.83; P for difference = 0.001) and BMD (B = 2242; 95% CI 443, 4041; P for difference = 0.05). Similar results were obtained in the lateral tibial compartment. No significant association was obtained between total body BMD and BMC and patella cartilage volume in either men or women. CONCLUSIONS: In this relatively healthy population, we found a positive relationship between total body BMD and BMC and tibial cartilage volume in the medial and lateral compartments. These relationships were stronger in men than women. Thus, the results of this study may provide some insight into the sex differences in knee cartilage volume, which may in turn facilitate our understanding of the pathogenesis of OA.

Vascular function in the diagnostic categories of polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with increased risk of cardiovascular disease (CVD). However, it is unknown whether CVD risk is equivalent across the different diagnostic categories or phenotypes of PCOS, particularly in the new phenotypes that affect up to 50% of women with PCOS. Surrogate markers of CVD include endothelial function and arterial stiffness that are independent risk factors for CVD. The primary aim of this study was to assess whether milder phenotypes of PCOS have elevated CVD risk compared with controls. METHODS: This was a cross-sectional study, conducted in an academic medical centre, of overweight premenopausal women with either National Institute of Health (NIH) PCOS (n = 29) or milder non-NIH PCOS (n = 25) and controls without PCOS (n = 27). Primary outcomes were markers of vascular health, including endothelial function [peripheral arterial tonometry (PAT), asymmetric dimethylarginine (ADMA) and plasminogen activator inhibitor-1 (PAI-1)] and arterial stiffness [central pulse wave velocity (PWVc)]. Secondary outcomes were insulin resistance, glucose tolerance and inflammation (C-reactive protein). RESULTS: ADMA was significantly different across the three groups (P = 0.003). ADMA was similar for NIH and non-NIH PCOS (0.56 ± 0.01 versus 0.53 ± 0.02 µmol/l, P = 1.0) and higher for both NIH PCOS compared with controls (0.56 ± 0.01 versus 0.46 ± 0.02 µmol/l, P = 0.003) and non-NIH PCOS compared with controls (0.53 ± 0.02 versus 0.46 ± 0.02 µmol/l, P = 0.046). PAI-1 (P = 0.20), PAT (P = 0.95) and PWVc (P = 0.67) were similar for the three groups. All results were maintained after adjustment for age and body mass index where significant differences in these potentially confounding factors occurred between groups. CONCLUSIONS: Women with NIH and non-NIH PCOS have elevated ADMA compared with controls independent of age and adiposity. This suggests that CVD risk, reflected by endothelial dysfunction, is increased in both traditional NIH and new milder non-NIH PCOS phenotypes. However, no differences in other markers of endothelial function or arterial stiffness were apparent between phenotypes in this PCOS cohort.

Bone mineral content and density in Rett syndrome and their contributing factors.

This study used densitometry to investigate the areal bone mineral density (aBMD) and bone mineral content (BMC) in an Australian Rett syndrome cohort and to 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 standardized Z scores and CIs 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.R168× and p.T158M mutations as the strongest predictors of low aBMC and BMD for all bone outcomes. The strong relationship between genotype, BMC, and aBMD is likely underpinned by the strong relationship between LTM, mobility, and bone outcome measures.

Mental health diagnoses in adults with phenylketonuria: a retrospective systematic audit in a large UK single centre.

BACKGROUND: Recently published European Society for Phenylketonuria (ESPKU) guidelines have recommended a lifelong diet with phenylalanine (Phe) control ≤ 600 µmol/L for phenylketonuria (PKU) patients. This study aimed to identify whether PKU adult patients are at a higher risk of mental health diagnoses if their 2-year average Phe level is higher than the ESPKU European guidelines. Published studies identified by a literature review showed that related studies have been published in American and European PKU study populations but not in the United Kingdom (UK) study populations. Previous studies also involved a smaller number of participants due to this being a rare disease. RESULTS: We undertook a retrospective audit at a single large PKU centre in the UK. 244 adult PKU patients at the centre were included, 220 of which had a recorded Phe level. Approximately 75% of the patients in this study did not meet the ESPKU European guidelines for Phe control. A systematic search of the electronic patient record was undertaken looking for mental health diagnoses. Compared to two-year average Phe levels ≤ 600 µmol/L, PKU adult patients with two-year average Phe levels > 600 µmol/L were more likely to have diagnoses of low mood, depression, anxiety, or mood swings, but only low mood reached statistical significance (p < 0.05). CONCLUSIONS: PKU patients with two-year average Phenylalanine levels greater than ESPKU guidelines may be at greater risk of mental health diagnoses and symptoms. Many of these adult PKU patients will be lost to follow-up, and therefore may be receiving treatment for mental health conditions in the community. Multicentre UK studies and international collaborations are required to overcome low participant numbers in the study of this rare disease.

Multicomponent density models for body composition: Review of the dual energy X-ray absorptiometry volume approach.

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.

A Three-Year Longitudinal Study Comparing Bone Mass, Density, and Geometry Measured by DXA, pQCT, and Bone Turnover Markers in Children with PKU Taking L-Amino Acid or Glycomacropeptide Protein Substitutes.

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 5-16 years) and 29 subjects in the CGMP-AA group (median age 8.3, range 5-16 years). The CGMP-AA was further divided into two groups, CGMP100 (median age 9.2, range 5-16 years) (n = 13), children taking CGMP-AA only and CGMP50 (median age 7.3, range 5-15 years) (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.