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.

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.

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.

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.

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.

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.

Growth and Body Composition in PKU Children-A Three-Year Prospective Study Comparing the Effects of L-Amino Acid to Glycomacropeptide Protein Substitutes.

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.

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.

Selective Loss of Levator Ani and Leg Muscle Volumes in Men Undergoing Androgen Deprivation Therapy.

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.

A Cross-Sectional and Longitudinal Analysis of Trabecular Bone Score in Adults With Turner Syndrome.

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.

Fat-Bone Interactions in Adults With Spina Bifida.

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.

Associations between systemic bone mineral density and early knee cartilage changes in middle-aged adults without clinical knee disease: a prospective cohort study.

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.

Low versus high dialysate calcium concentration in alternate night nocturnal hemodialysis: A randomized controlled trial.

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.

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.

Vitamin D in polycystic ovary syndrome: Relationship to obesity and insulin resistance.

SCOPE: Polycystic ovary syndrome (PCOS) is underpinned by insulin resistance (IR). In PCOS, the relationships between vitamin D, adiposity, and IR are unclear. We aim to explore these relationships in lean and overweight women with PCOS. METHODS AND RESULTS: This is a cross-sectional study conducted in a tertiary medical center. Participants included 42 women with PCOS and 34 controls without PCOS. Vitamin D and metabolic markers were measured. Detailed body composition and gold standard hyperinsulinemic euglycemic clamps were performed. The main outcome measures were plasma levels of vitamin D, adiposity measures, and glucose infusion rate. Vitamin D levels were lower in overweight women with PCOS compared with overweight controls (31.6 and 46.1 nmol/L, respectively, p = 0.01). Vitamin D was not associated with IR after adjustment for confounders; however, there was a significant interaction between PCOS and percentage body fat. Further analysis by PCOS status revealed that vitamin D was associated with IR in the PCOS group (ß coefficient 2.1, 95% CI 0.2-4.0, p = 0.03), but not in the non-PCOS group. CONCLUSION: Vitamin D is associated with IR in women with PCOS, but not in controls. Large intervention studies are needed to determine if vitamin D supplementation can improve IR in PCOS.

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.