Anterior cingulate metabolite levels, memory, and inhibitory control in abstinent men and women with alcohol use disorder.

Alcohol use disorder (AUD) has been shown to have harmful cognitive and physiological effects, including altered brain chemistry. Further, although men and women may differ in vulnerability to the neurobiological effects of AUD, the results of existing studies have been conflicting. We examined brain metabolite levels and cognitive functions in a cross-section of men with AUD (AUDm) and women with AUD (AUDw) to determine the degree of abnormalities after extended periods of abstinence (mean, 6 years) and to evaluate gender differences in neuropsychological and metabolite measures. Participants were 40 abstinent individuals with AUD (22 AUDw, 18 AUDm) and 50 age-equivalent non-AUD comparison participants (26 NCw, 24 NCm). Proton magnetic resonance spectroscopy (MRS) was employed at 3 Tesla to acquire metabolite spectra from the dorsal anterior cingulate cortex (dACC). Brain metabolites N-acetyl aspartate (NAA), choline (Cho), myo-Inositol (mI), and glutamate & glutamine (Glx) were examined relative to measures of memory and inhibitory control. Metabolite levels did not differ significantly between AUD and NC groups. Memory and inhibitory-control impairments were observed in the AUD group. There also were significant group-specific associations between metabolite ratios and measures of inhibitory control. There were no group-by-gender interactions for the four metabolite ratios. These findings demonstrate that brain metabolite levels in men and women with AUD, following long-term abstinence, do not differ from individuals without AUD. The data also provide preliminary evidence of sustained associations between metabolite levels and measures of inhibitory control, a functional domain important for curtailing harmful drinking.

Baseline bone turnover marker levels can predict change in bone mineral density during antiresorptive treatment in osteoporotic patients: the Copenhagen bone turnover marker study.

Anti-resorptive osteoporosis treatment might be more effective in patients with high bone turnover. In this registry study including clinical data, high pre-treatment bone turnover measured with biochemical markers was correlated with higher bone mineral density increases. Bone turnover markers may be useful tools to identify patients benefitting most from anti-resorptive treatment. INTRODUCTION: In randomized, controlled trials of bisphosphonates, high pre-treatment levels of bone turnover markers (BTM) were associated with a larger increase in bone mineral density (BMD). The purpose of this study was to examine this correlation in a real-world setting. METHODS: In this registry-based cohort study of osteoporosis patients (n = 158) receiving antiresorptive therapy, the association between pre-treatment levels of plasma C-telopeptide of type I Collagen (CTX) and/or N-terminal propeptide of type I procollagen (PINP) and change in bone mineral density (BMD) at lumbar spine, total hip, and femoral neck upon treatment was examined. Patients were grouped according to their pre-treatment BTM levels, defined as values above and below the geometric mean for premenopausal women. RESULTS: Pre-treatment CTX correlated with annual increase in total hip BMD, where patients with CTX above the geometric mean experienced a larger annual increase in BMD (p = 0.008) than patients with CTX below the geometric mean. The numerical pre-treatment level of CTX showed a similar correlation at all three skeletal sites (total hip (p = 0.03), femoral neck (p = 0.04), and lumbar spine (p = 0.0003)). A similar association was found for PINP where pre-treatment levels of PINP above the geometric mean correlated with a larger annual increase in BMD for total hip (p = 0.02) and lumbar spine (p = 0.006). CONCLUSION: Measurement of pre-treatment BTM levels predicts osteoporosis patients' response to antiresorptive treatment. Patients with high pre-treatment levels of CTX and/or PINP benefit more from antiresorptive treatment with larger increases in BMD than patients with lower pre-treatment levels.

Osteogenesis imperfecta and the teeth, eyes, and ears-a study of non-skeletal phenotypes in adults.

Osteogenesis imperfecta (OI) is a disease causing bone fragility; however, it potentially affects all organs with a high content of collagen, including ears, teeth, and eyes. The study is cross-sectional and compares non-skeletal characteristics in adults with OI that clinicians should be aware of when caring for patients with OI. INTRODUCTION: Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder. The skeletal fragility is pronounced; however, OI leads to a number of extra-skeletal symptoms related to the ubiquity of collagen type 1 throughout the human body. The vast majority of knowledge is derived from studies performed in the pediatric population. Thus, we aimed to investigate the nature and prevalence of ophthalmologic, odontologic, and otologic phenotypes in an adult population with OI. METHODS: The study population comprises 85 Danish OI patients (age 44.9 ± 15.9 years). Fifty-eight patients had OI type I, 12 OI type III, and 15 OI type IV according to the classification by Sillence. Audiometric evaluations and dental examinations were performed in 62 and 73 patients, respectively. Ophthalmologic investigations were performed in 64 patients, including measurements of the central corneal thickness. RESULTS: All patients, except two, had corneal thickness below the normal reference value. Patients with OI type I and patients with a quantitative collagen defect had thinner corneas compared to patients with OI type III and other patients with a qualitative collagen defect. One patient in this cohort was diagnosed with and treated for acute glaucoma. Dentinogenesis imperfecta was diagnosed in one fourth of the patients, based on clinical and radiographic findings. This condition was predominately seen in patients with moderate to severe OI. Hearing loss requiring treatment was found in 15 of 62 patients, of whom three were untreated. The most prevalent type of hearing loss (HL) was sensorineural hearing loss, whereas conductive HL was solely seen in patients with OI type III. The patients with the most severe degrees of HL were patients with mild forms of OI. Age was associated with increased HL. CONCLUSION: Although significant health problems outside the skeleton are frequent in adult patients with OI, the patients are not consistently monitored and treated for their symptoms. Clinicians treating adult patients with OI should be aware of non-skeletal health issues and consider including regular interdisciplinary check-ups in the management plan for adult OI patients.

A 'complex' of brain metabolites distinguish altered chemistry in the cingulate cortex of episodic migraine patients.

Despite the prevalence of migraine, the pathophysiology of the disease remains unclear. Current understanding of migraine has alluded to the possibility of a hyperexcitable brain. The aim of the current study is to investigate human brain metabolite differences in the anterior cingulate cortex (ACC) during the interictal phase in migraine patients. We hypothesized that there may be differences in levels of excitatory neurotransmitters and/or their derivatives in the migraine cohort in support of the theory of hyperexcitability in migraine. 2D J-resolved proton magnetic resonance spectroscopy ((1)H-MRS) data were acquired on a 3 Tesla (3 T) MRI from a voxel placed over the ACC of 32 migraine patients (MP; 23 females, 9 males, age 33 ± 9.6 years) and 33 healthy controls (HC; 25 females, 8 males, age 32 ± 9.6 years). Amplitude correlation matrices were constructed for each subject to evaluate metabolite discriminability. ProFit-estimated metabolite peak areas were normalized to a water reference signal to assess subject differences. The initial analysis of variance (ANOVA) was performed to test for group differences for all metabolites/creatine (Cre) ratios between healthy controls and migraineurs but showed no statistically significant differences. In addition, we used a multivariate approach to distinguish migraineurs from healthy subjects based on the metabolite/Cre ratio. A quadratic discriminant analysis (QDA) model was used to identify 3 metabolite ratios sufficient to minimize minimum classification error (MCE). The 3 selected metabolite ratios were aspartate (Asp)/Cre, N-acetyl aspartate (NAA)/Cre, and glutamine (Gln)/Cre. These findings are in support of a 'complex' of metabolite alterations, which may underlie changes in neuronal chemistry in the migraine brain. Furthermore, the parallel changes in the three-metabolite 'complex' may confer more subtle but biological processes that are ongoing. The data also support the current theory that the migraine brain is hyperexcitable even in the interictal state.

Hyponatremia, a risk factor for osteoporosis and fractures in women.

SUMMARY: Hyponatremia has been linked to an increased risk of osteoporosis and fractures. We found an increased hazard ratio of major osteoporotic fractures adjusted for potential confounders, including osteoporosis and medication. A reduced BMD was not sufficiently explaining the association. Our data indicate that hyponatremia should be considered a risk factor for osteoporosis and fractures. INTRODUCTION: Hyponatremia is the most common electrolyte disorder in clinical practice and could be a risk factor for both osteoporosis and fractures. Mild hyponatremia has traditionally been regarded as a benign and asymptomatic condition; however, data from large population and animal studies have led to a reappraisal of this view. The purpose of this study was to evaluate the association of hyponatremia with osteoporosis and major osteoporotic fractures (MOF) in women. METHODS: This is a historical cohort study with fracture follow-up. The study consisted of 5610 patients with available serum sodium and a bone density measurement. Information on potential risk factor was obtained through a questionnaire. Additional information on medication, comorbidities, and fractures was obtained through national registries. RESULTS: Hyponatremia was associated with significant lower T-scores at total hip and a borderline significant lower T-score at femoral neck in the multivariate analysis. No association was found between hyponatremia and the lumbar spine T-score. Hyponatremia was associated with an increased hazard ratio of sustaining a MOF in the period from 6 months prior to 12 months after serum sodium measurement. Finally, data showed a relationship with increasing serum sodium and an increasing T-score estimate and a decreasing hazard ratio of MOF. CONCLUSIONS: Our data suggest that hyponatremia in women increases the risk of osteoporosis and MOF. The increased risk of MOF was independent of osteoporosis.

[Inpatient Salivary Gland Surgery in Germany: A DRG-Based Nationwide Analysis, 2007-2011]. / Stationäre Speicheldrüsenoperationen in Deutschland Eine DRG-basierte Analyse der Jahre 2007-2011.

BACKGROUND: This is the first population-based analysis of inpatient salivary gland surgery across Germany. METHODS: Nationwide Diagnosis-Related Groups (DRG) statistics for 2007 to 2011 were analyzed regarding indications for salivary gland surgery based on ICD-10 codes. Age specific surgery rates were calculated for both sexes. RESULTS: Inpatient salivary gland surgical rates in 2007-2011 amounted for incisions (OPS [Classification of Operations and Procedures] code 5-260) 1.43 per 100 000 population, for excisions (5-261) 2.06 per 100 000, for salivary gland resections (5-262) 2.06 per 100 000, and for external incisions (5-270) 0.43 per 100 000. Regarding the mentioned four OPS codes, the surgical rates for benign tumors accounted to 10.08 per 100 000, for sialadenitis (without sialoliths) to 4.00 per 100 000, for malignant tumors to 3.90 per 100 000, and for sialolithiasis to 2.09 per 100 000. The increase of surgical rates from 2007 to 2011 was significant for malignant and benign tumors as well as for salivary stones. The surgical rates were highest for patients>60 years. DISCUSSION: Especially surgery for malignant tumors was more frequent than expected. In spite of the introduction of minimal invasive technique the rates for salivary gland resections in case of sialadenitis or sialolithiasis still seem to be high.

Subsequent fracture rates in a nationwide population-based cohort study with a 10-year perspective.

SUMMARY: Fractures after the age of 50 are frequently observed in Denmark, and many of these may be osteoporotic. This study examined the incidence of all and subsequent fractures in a 10-year period from 2001 to 2011. The incidence of subsequent fractures was high, especially following hip fracture. INTRODUCTION: The purpose of this study is to examine patterns of subsequent fractures and mortality rates over a 10-year period in patients already suffering from fracture. METHODS: The study was designed as a nationwide, register-based follow-up study. Patients were included if diagnosed with an index fracture (ICD-10 codes: S22.x, S32.x, S42.x, S52.x, S62.x, S72.x, S82.x, S92.x, T02.x, T08.x, T10.x and T12.x) between January 1st, 2001 and December 31st, 2001 and if older than 50 years at time of fracture. The patients were investigated for future subsequent fractures from January 1st, 2002 to December 31st, 2011. RESULTS: In this study, we demonstrated that patients with fractures (especially hip fractures) have a high risk of subsequent fractures, especially hip fracture. Other fractures, which are not commonly considered as osteoporotic fractures, such as lower leg, were frequently observed in the 10 years following index fracture. The cumulative incidence proportion (CIP) of subsequent fractures during the 10-year follow-up period was high for all recurrent fractures (9-46 %). Subsequent hip fracture, regardless of index fracture, had the highest CIP across the study period, ranging from 9 to 40 %. Appendicular fractures were often followed by a recurrent fracture, or subsequent fractures at a more proximal location in the same limb, i.e. forearm fractures were followed by humerus fractures. These results have not been previously demonstrated to this extent, and according to our knowledge, no previous studies have estimated cumulative 10-year subsequent fracture incidences for any non-hip fractures. CONCLUSION: Patients suffering a fracture (and especially a hip fracture) have a high incidence of subsequent fracture. Fractures after the age of 50 may be considered an early warning of increased risk for future fractures in many patients.

Newborn regional body composition is influenced by maternal obesity, gestational weight gain and the birthweight standard score.

AIM: This study investigated whether newborn body composition is influenced by prepregnancy obesity and gestational weight gain (GWG) and explored any associations between body composition and birthweight standard score (z-score), categorised by size for gestational age. METHODS: We recruited 231 obese and 80 normal weight mothers and their newborn infants and assessed the babies' body composition using dual-energy X-ray absorptiometry. RESULTS: The total and abdominal fat masses of infants born to mother who were obese before pregnancy were 135 g (p < 0.001) and 18 g (p < 0.001) higher than the offspring of normal weight mothers. The infants' fat mass increased by 11 g (p < 0.001) for every kilogram of GWG. There were no associations between prepregnancy obesity and fat-free mass. The fat percentage was significantly higher in infants who were large for gestational age (15.3%) than small for gestational age (5.2%) and appropriate for gestational age (9.8%) (p < 0.001). Lower birthweight z-score was associated with a higher proportion of abdominal fat mass (p = 0.009). CONCLUSION: Infants born to obese mothers had higher fat mass at birth, with abdominal fat accumulation. Low birthweight was associated with a lower crude abdominal fat mass, but a higher proportion of total fat mass placed abdominally.

The impact of recombinant parathyroid hormone on malignancies and mortality: 7 years of experience based on nationwide Danish registers.

UNLABELLED: We used Danish registers to identify patients with osteoporosis, who had been treated with parathyroid hormone and evaluated the probability of developing cancer. We did not find an increased risk of cancer among the patients treated with parathyroid hormone. INTRODUCTION: We evaluated the incidences of malignancies and mortality in osteoporotic patients treated with rPTH. METHODS: Using Danish nationwide registers, we identified patients diagnosed with osteoporosis in the period 1995 through 2010. Each patient treated with rPTH ("case") was compared with 10 gender- and age-matched patients who did also have osteoporosis but did not receive rPTH ("control"). RESULTS: A total of 4,104 cases (80.3 % females) were identified. The mean age at the beginning of rPTH treatment was 70.9 (SD 9.7) years. During a follow-up time of 10,118 person-years for the cases and 88,005 person-years for the controls, a total of 255 cases (6.2 %) compared with 2,103 controls (5.1 %) experienced a cancer (Chi square, p = 0.003). We found an adjusted cancer related HR of 1.1 (95 %CI 0.9-1.4) among the cases. Lung cancer was the only cancer type with a significantly increased rate among patients receiving rPTH (HR 1.7; 95 % CI 1.3-2.3). No cases developed osteosarcomas and nine controls developed osteosarcoma. During follow-up, 627 (15.3 %) cases died and 4,175 (10.2 %) controls died, which yielded an excess mortality risk of 26 % (95 % CI 16-37 %). This could be due to differences in the prevalence of vertebral fractures between the rPTH-treated and non-treated patients. CONCLUSION: This study did not support the hypothesis describing a possible link between rPTH treatment and the development of cancer. We also conclude that osteosarcoma has not been diagnosed in any Danish patient receiving rPTH since the year 2003 when it was introduced on the market.

A longitudinal pilot proton MRS investigation of the manic and euthymic states of bipolar disorder.

Several lines of evidence implicate dysfunction in brain energy production as a key component of bipolar disorder. In particular, elevated brain lactate levels observed in this condition suggest a shift from aerobic to anaerobic metabolism, possibly as a result of mitochondrial abnormalities. Most prior imaging studies of brain metabolites were performed in either euthymic or depressed bipolar patients or compared different populations in different mood states. We sought to measure brain metabolite concentrations in the same patients in both manic and euthymic states. Given the dramatic changes in clinical state of bipolar disorder patients, we hypothesized that previously observed abnormalities in lactate concentrations in bipolar disorder might show state dependent changes. In this study 15 patients (mean age 36.1 years) diagnosed with bipolar I disorder underwent proton magnetic resonance spectroscopy of the anterior cingulate cortex and parieto-occipital cortex during hospitalization for acute mania (mean Young Mania Rating Scale (YMRS) 22.1). Seven of these subjects returned (mean interval 21.16 months) to have imaging repeated while euthymic (mean YMRS 2.0). A group of age- and gender-matched control participants (N=6) were scanned as well. We report that during mania, bipolar disorder subjects had lactate levels comparable to healthy control subjects but during euthymia these levels were significantly reduced. No significant change was observed for other metabolites. These results implicate mood dependent alterations in energy metabolism in the biology of bipolar disorder. Additionally, this finding has potential use as a biomarker for both evaluating novel treatments as well as diagnostic clarification between mood disorders.

Effects of paracetamol, non-steroidal anti-inflammatory drugs, acetylsalicylic acid, and opioids on bone mineral density and risk of fracture: results of the Danish Osteoporosis Prevention Study (DOPS).

UNLABELLED: Pain medication has been associated with fractures. We found higher weight in paracetamol and non-steroidal anti-inflammatory drugs (NSAID) users and lower vitamin D levels in opioid and acetylsalicylic acid users. None of the pain medications influenced bone mineral density or loss. NSAID were associated with an increased fracture risk. INTRODUCTION: To study the effects of use of paracetamol, non-steroidal anti-inflammatory drugs (NSAID), acetylsalicylic acid (ASA), and opioids on bone mineral density (BMD) and risk of fractures. METHODS: Two-thousand sixteen perimenopausal women followed for 10 years as part of a partly randomised comprehensive cohort study on hormone therapy (HT). BMD was measured at baseline and after 10 years by DXA (Hologic). RESULTS: Paracetamol users were heavier (70.4 ± 13.4 vs. 67.7 ± 11.9 kg, 2p < 0.01) than non-users. NSAID users were heavier (71.6 ± 15.6 vs. 67.8 ± 11.9 kg, 2p = 0.04) than non-users. ASA users had lower 25-hydroxy-vitamin D (25OHD) levels (21.9 ± 9.3 vs. 25.3 ± 12.4 ng/ml, 2p < 0.01) than non-users. Opioid users had lower 25OHD (21.4 ± 8.4 vs. 25.2 ± 12.3 ng/ml) and lower intake of vitamin D (2.2 ± 1.1 vs. 3.1 ± 3.0 µg/day, 2p < 0.01) than non-users. Despite these differences, no baseline differences were present in spine, hip, forearm or whole body BMD. Over 10 years, no differences were present in BMD alterations except a small trend towards a higher BMD gain in the spine in users of paracetamol, NSAID, ASA, and opioids compared to non-exposed. After adjustment, NSAID exposed sustained more fractures (HR = 1.44, 95% CI 1.07-1.93) than non-users. For users of paracetamol and opioids, a non-significant trend towards more fractures was present after adjustment. For ASA users, no excess risk of fractures was present. CONCLUSION: Significant differences exist between subjects exposed to pain medications and non-users. Despite an absence of an effect over time on BMD, users of NSAID experienced more fractures than expected. The reasons for this have to be explored in further studies.

Fusarium head blight of cereals in Denmark: species complex and related mycotoxins.

Quantitative real-time polymerase chain reaction differentiating 10 Fusarium spp. and Microdochium nivale or M. majus was applied to a total of 396 grain samples of wheat, barley, triticale, oat, and rye sampled across Denmark from 2003 to 2007, along with selected samples of wheat and barley from 1957 to 2000, to determine incidence and abundance of individual Fusarium spp. The mycotoxins deoxynivalenol (DON), nivalenol, zearalenone, T-2, and HT-2 were quantified using liquid chromatography-double mass spectrometry. Major differences in the Fusarium species complex among the five cereals as well as great yearly variation were seen. Fusarium graminearum, F. culmorum, and F. avenaceum were dominant in wheat, with DON as the dominant mycotoxin. F. langsethiae, F. culmorum, and F. avenaceum were dominant in barley and oat, leading to relatively high levels of the mycotoxins T-2 and HT-2. F. graminearum, F. culmorum, and F. avenaceum dominated in triticale and rye. The nontoxigenic M. nivale/majus were present in significant amounts in all cereal species. Wheat and barley samples from 1957 to 1996 exhibited no or very low amounts of F. graminearum, indicating a recent increase of this pathogen. Biomass and mycotoxin data exhibited good correlations between Fusarium spp. and their corresponding mycotoxins under field conditions.

Polymorphisms of the peroxisome proliferator-activated receptor γ (PPARγ) gene are associated with osteoporosis.

UNLABELLED: Stimulation of PPARγ turns mesenchymal stem cells into adipocytes instead of osteoblasts. We investigated the effect of polymorphisms in the PPARγ gene on BMD and fracture risk in two Danish cohorts and found opposing effects of certain SNPs and haplotypes in the two cohorts probably owing to environmental factors. INTRODUCTION: Stimulation of PPARγ causes development of mesenchymal stem cells to adipocytes instead of osteoblasts leading to decreased osteoblast number and BMD. The aim of this study was to examine the effect of PPARG polymorphisms on BMD and fracture risk in two Danish cohorts: AROS, a case-control population comprising 809 individuals and DOPS, a population comprising 1,716 perimenopausal women allocated to hormone therapy or not at baseline and followed for 10 years. On the basis of linkage disequilibrium between SNPs throughout the gene and previous studies we chose 10 polymorphisms for investigation. METHODS: In AROS, individuals heterozygous for the polymorphisms rs12497191, rs4135263, and rs1151999 had an increased risk of vertebral fractures (OR = 1.48-1.76, p = 0.005-0.04) compared with individuals homozygous for the common allele. In DOPS, individuals heterozygous for rs1151999 had an increased BMD at the hip sites (p ≤ 0.02). An interaction between rs1151999 and diet was found on BMD in both cohorts. RESULTS: For the polymorphism rs1152003 there was an interaction with body weight on BMD at all sites in both cohorts (p ≤ 0.07). Stratified analyses revealed that in the high weight group in AROS individuals homozygous for the variant allele had a decreased BMD (p ≤ 0.02), whereas the same pattern was found in the low weight group in DOPS (p ≤ 0.03). A number of haplotype associations were found as well, the direction of which was opposite in the two cohorts. CONCLUSION: Our study suggests an association SNPs in PPARG and haplotypes thereof and BMD and fracture risk. The effect however appears to be modifiable by environmental factors.

Polymorphisms in the ALOX12 gene and osteoporosis.

UNLABELLED: ALOX12 produces ligands for PPARγ thereby turning mesenchymal stem cells into adipocytes instead of osteoblasts. We investigated the effect of polymorphisms in the ALOX12 gene on BMD and fracture risk in two Danish cohorts and found four polymorphisms and a haplotype thereof to be associated with BMD and fracture risk. INTRODUCTION: Stimulation of the PPARγ with ligands produced by the ALOX enzymes drives mesenchymal stem cells in an adipocyte direction at the expense of osteoblasts leading to decreased osteoblast number and BMD. Previously, polymorphisms in the ALOX12 gene have been associated with osteoporosis. METHODS: We examined the effect of ALOX12 polymorphisms on BMD and the risk of fractures in two Danish cohorts: AROS, a case-control population comprising 809 individuals and DOPS, a population comprising 1,716 perimenopausal women allocated to hormone therapy or not at baseline and followed for up to 10 years. On the basis of linkage disequilibrium (LD) between SNPs throughout the gene and previous genetic association studies we chose ten polymorphisms for investigation. Genotyping was carried out using the Sequenom MassARRAY genotyping system and TaqMan assays. RESULTS: In AROS, individuals heterozygous for the polymorphisms rs3840880, rs9897850, rs2292350 and rs1126667 had a 3.0-4.7% decreased lumbar spine BMD (p = 0.02-0.06) and an increased risk of vertebral fractures (p < 0.05) compared with individuals homozygous for either allele. In DOPS, none of the individual SNPs were associated with BMD or incident fractures. In both cohorts, the above-mentioned SNPs comprised an LD-block (pairwise D´ = 1.0, r (2) = 0.45-0.97). A haplotype comprising all the common alleles (frequency 9%) was associated with decreased bone loss at the hip (p < 0.05) and decreased incidence of osteoporotic fractures (p < 0.05) in DOPS and increased femoral neck BMD in AROS (p < 0.05). CONCLUSION: Our study suggests that genetic variants in ALOX12 may influence BMD and fracture risk.

Long-term high-physiological-dose growth hormone reduces intra-abdominal fat in HIV-infected patients with a neutral effect on glucose metabolism.

OBJECTIVES: The aim of the study was to investigate the effect of long-term high-physiological-dose recombinant human growth hormone (rhGH) therapy on fat distribution and glucose metabolism in HIV-infected patients. METHODS: Forty-six HIV-infected Caucasian men on highly active antiretroviral therapy (HAART), with an age range of 21-60 years and no significant comorbidity, were included in this randomized, placebo-controlled, double-blind, single-centre trial. Twenty-eight subjects were randomized to 0.7 mg/day rhGH, and 18 subjects to placebo, administered as daily subcutaneous injections between 1 and 3 pm for 40 weeks. Endpoints included changes in visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), limb fat mass, percentage of limb fat, plasma lipids, insulin resistance and glucose tolerance. RESULTS: VAT and trunk fat mass decreased significantly in the GH group compared with the placebo group [-19 cm(2) (-11%) vs. 12 cm(2) (6%), P=0.03, and -548 g (-9%) vs. 353 g (6%), P<0.01, respectively]. The beneficial fat redistribution in the GH group occurred without concomitant changes in subcutaneous fat at the abdomen or extremities. rhGH therapy was well tolerated. Insulin resistance, glucose tolerance, and total plasma cholesterol and triglycerides did not significantly change during intervention. CONCLUSIONS: Daily 0.7 mg rhGH treatment for 40 weeks reduced abdominal visceral fat and trunk fat mass in HIV-infected patients. This treatment appeared to be safe with respect to glucose tolerance and insulin sensitivity.

No association between hip geometry and four common polymorphisms associated with fracture: the Danish osteoporosis prevention study.

Both osteoporosis and hip geometry are independently associated with fracture risk. There is a significant genetic contribution to the risk of osteoporosis, and evidence provided by twin studies has suggested that hip geometry may also in part be genetically programmed. Polymorphisms in a number of genes, including those coding for methylene-tetrahydrofolate reductase (MTHFR c.677C > T), the purinergic P2X(7) receptor (Glu496Ala and Ile568Asn), and the low-density lipoprotein receptor-related protein 5 (LRP5 exon 9 [c.266A > G]), have been associated with an increased fracture incidence and/or reduced bone mineral density (BMD). The aim of the present study was to test whether these polymorphisms influence hip structural geometry in perimenopausal women. The four polymorphisms were genotyped in 800 healthy recently perimenopausal women never using hormone replacement therapy. BMD of the femoral neck was measured using a Hologic QDR-2000 densitometer and femoral neck axis length, neck width, neck shaft angle, and femoral head diameter were measured from the screen images. Genotype frequencies were compatible with Hardy-Weinberg equilibrium. No significant differences between homozygotes for the minor allele and carriers of the common allele regarding parameters of hip geometry were demonstrated. According to the anthropometric characteristics of the subjects, only body height in the MTHFR TT genotype group was significantly different from the combined CT/CC genotype group (P < 0.05). The geometric dimensions of the proximal femur in perimenopausal women are not associated with the MTHFR c.677C > T, P2X(7) (Glu496Ala), P2X(7) (Ile568Asn), and LRP5 exon 9 (c.266A > G) polymorphisms.

Citicoline enhances frontal lobe bioenergetics as measured by phosphorus magnetic resonance spectroscopy.

Citicoline supplementation has been used to ameliorate memory disturbances in older people and those with Alzheimer's disease. This study used MRS to characterize the effects of citicoline on high-energy phosphate metabolites and constituents of membrane synthesis in the frontal lobe. Phosphorus ((31)P) metabolite data were acquired using a three-dimensional chemical-shift imaging protocol at 4 T from 16 healthy men and women (mean +/- SD age 47.3 +/- 5.4 years) who orally self-administered 500 mg or 2000 mg Cognizin Citicoline (Kyowa Hakko Kogyo Co., Ltd, Ibaraki, Japan) for 6 weeks. Individual (31)P metabolites were quantified in the frontal lobe (anterior cingulate cortex) and a comparison region (parieto-occipital cortex). Significant increases in phosphocreatine (+7%), beta-nucleoside triphosphates (largely ATP in brain, +14%) and the ratio of phosphocreatine to inorganic phosphate (+32%), as well as significant changes in membrane phospholipids, were observed in the anterior cingulate cortex after 6 weeks of citicoline treatment. These treatment-related alterations in phosphorus metabolites were not only regionally specific, but tended to be of greater magnitude in subjects who received the lower dose. These data show that citicoline improves frontal lobe bioenergetics and alters phospholipid membrane turnover. Citicoline supplementation may therefore help to mitigate cognitive declines associated with aging by increasing energy reserves and utilization, as well as increasing the amount of essential phospholipid membrane components needed to synthesize and maintain cell membranes.

Disproportional geometry of the proximal femur in patients with Turner syndrome: a cross-sectional study.

OBJECTIVE: Patients with Turner syndrome (TS) have altered growth and increased risk of osteoporosis due to oestrogen deficiency and possibly a host of other factors. Thus, TS patients have a 4.9-fold increased risk of femoral neck fractures. Most patients are treated with oestrogen during puberty and adolescence to facilitate pubertal development and prevent secondary osteoporosis. The geometry of the hip is a predictor for hip fractures independent of bone mineral density (BMD). The purpose of the present study was to investigate the variation of the geometry of the hip in patients with TS in comparison with healthy controls. PATIENTS: The study population comprised 58 patients with TS (aged 22-67 years) and 60 age-matched healthy women (aged 21-65 years). MEASUREMENTS: Hip axis length (HAL), neck width (NW), neck shaft angle (NSA), and femoral head-radius (HR) on dual-energy X-ray absorptiometry (DXA) screen images. These parameters related to age of oestrogen supplementation, menarche, and duration of oestrogen exposure. RESULTS: Height was 146.6 +/- 6.9 cm and 167.1 +/- 6.2 cm (P < 0.1) and weight 57.4 +/- 13.9 kg and 62.3 +/- 8.3 kg (P < 0.001) in patients and controls, respectively. After adjustment for differences in height, HAL was not significantly different (9.4 +/- 0.5 vs. 9.5 +/- 0.5 cm; NS) in TS compared with controls while NW was significantly increased (3.5 +/- 0.4 cm vs. 3.3 +/- 0.2 cm, P < 0.001), NSA was similar (129 +/- 4 degrees vs. 130 +/- 4 degrees , NS), and HR was significantly decreased (4.1 +/- 0.4 vs. 4.5 +/- 0.3 cm, P < 0.001). The duration of oestrogen exposure was significantly shorter among TS, but did not correlate significantly with the geometrical parameters in either TS or controls. CONCLUSION: Our data demonstrates that hip geometry is disproportionate in TS compared with normal controls. The altered hip geometry, however, cannot explain the increased risk of hip fracture in TS.

Geometry of the proximal femur in relation to age and sex: a cross-sectional study in healthy adult Danes.

PURPOSE: To describe the natural variation in hip geometry in relation to Danish population characteristics, and to establish normal reference values. MATERIAL AND METHODS: We included 249 healthy individuals (94 M and 155 F, aged 19-79 years) and measured hip-axis-length (HAL), neck-width (NW), neck-shaft-angle (NSA), and femoral head-radius (HR) on dual-energy X-ray absorptiometry (DXA) screen images. RESULTS: HAL, NW, HR, and NSA were higher in men than in women (10.9 +/- 0.7 vs. 9.5 +/- 0.6 cm (P<0.001), 3.8 +/- 0.3 vs. 3.3 +/- 0.3 cm (P<0.01), 2.5 +/- 0.3 vs. 2.3 +/- 0.2 cm (P< 0.001), and 131 +/- 5 vs. 129 +/- 5 degrees (P< 0.01). NSA was higher in post-menopausal than in pre-menopausal women (130 +/- 4 vs. 128 +/- 5 degrees (P<0.001)). In multiple regression analysis, HAL, NW, and HR were positively related to body height in both sexes (R = 0.20 to 0.63, P<0.05 to P<0.001). In females, NSA was positively related to body height (R = 0.20, P<0.05) and negatively to body weight (R = -0.30, P<0.01). NW increased with age in men (R = 0.34, P<0.01) but not in women. CONCLUSION: Hip dimensions differ between genders in the Danish population. HAL, NW, and HR depend on body height. Finally, NW increases with age in men but not in women.

Performance of four clinical screening tools to select peri- and early postmenopausal women for dual X-ray absorptiometry.

Several methods to select postmenopausal women for dual X-ray absorptiometry (DXA) have been proposed. We decided to compare the performance of three clinical decision rules (SCORE, ORAI, OST) with the usual case-finding strategy based on the presence of a major risk factor for future fracture (CFMRF). The study subjects were 2009 healthy, white, peri- or early postmenopausal women participating in the Danish Osteoporosis Prevention Study (DOPS). DXA results expressed as T-scores and scores on SCORE, ORAI, OST and CFMRF were extracted from the DOPS database. First, we evaluated the screening tools as originally described by the developers. The resulting sensitivities and specificities ranged from 18% to 92% and from 66% to 85%, respectively. Only OST achieved a high sensitivity (92%) with respect to femoral neck T-score < or = -2.5; however, the sensitivity with respect to lumbar spine T-score < or = -2.5 was only 51%. Next, the performance of the screening tools was evaluated against T-score < or = -2.0 (and T-score < or = -2.5) in at least one of the regions: femoral neck, total hip or lumbar spine. Using ROC curve analysis, we determined cut-offs yielding sensitivities as close as possible to 90%. The CFMRF and the ORAI tool were too coarse to yield 90% sensitivity. The performances of OST and SCORE were equal from a clinical perspective in that the sensitivities and the specificities varied from 89% to 94% and from 23% to 28%, respectively. The performance of CFMRF was no better than could be expected by chance, yielding a sensitivity of 19% and a specificity of 85%. Applying SCORE or OST 75% of the women would have to be referred for densitometry to identify 90% of the women with T-score < or = -2.0 (or T-score < or = -2.5) in at least one region. In conclusion, our results question the utility of all the evaluated tools for screening peri- and early postmenopausal women for low BMD. However, if a decision on referral has to be made, it may be based on the simple OST rule, which performed as well as or better than any of the other tools.