IL-6–174G/C genotype is associated with the bone mineral density response to oestrogen replacement therapy in post-menopausal women

A reduction in interleukin-6 (IL-6) activity may contribute to the beneficial effects of hormone replacement therapy (HRT) on the menopausal decline in bone mineral density (BMD). We have examined this hypothesis using a genetic strategy. The –174C (rather than G) IL-6 gene variant is associated with lower IL-6 expression. As such, we might anticipate the C allele to be associated with a greater response to HRT. We have tested this hypothesis. Mean three-site [spine (L1-L4), neck of femur, and Wards triangle] BMD was measured in 65 women in a 1-year randomised controlled trial of HRT with 0.625 mg oestrogen/day and 0.15 mg norgestrel (n=30). Baseline BMD was genotype-independent for both the control and HRT group. In the control group, the percentage change in BMD after 1 year was similar between genotypes (P=0.45). In contrast, in the HRT group, the rise was genotype-dependent. Those homozygous for the G allele showed a 3.62 (2.14)% increase in BMD compared with 10.44 (4.68)% for the C-homozygous group. Heterozygotes had an intermediate BMD increase of 5.6 (2.82)% [P=0.006 (P value for interaction between HRT and genotype was 0.04)] Although the study was limited by its small sample size, these are the first data to demonstrate the importance of IL-6 genotype in determining response to oestrogen therapy, rather than its physiological withdrawal.     

Are prostatitis symptoms associated with an isoprostane-mediated vicious circle?

Prostatitis is a disease that seriously affects the quality of patients’ life. In the majority of cases, chronic prostatitis (chronic pelvic pain syndrome – CPPS) has an unclear pathogenesis. Anti-inflammatory and anti-infectious treatments have remained controversial. According to the latest research, prostatitis has been associated with oxidative stress (OxS) and/or OxS-related genetic polymorphisms. We have observed that prostatitis patients have systemic OxS in case of inflammation and pain. We propose a new explanation for the role of OxS in the pathogenesis of prostatitis and describe the putative OxS-related pathways in detail. The neural vicious circle starts by activation of primary sensory afferents. Glutamate mediates the signal to the neurons in the dorsal horn of the spinal cord, and facilitates calcium influx into their mitochondria. The latter causes an increased production of superoxide radicals. If the superoxide production is not effectively controlled by mitochondrial superoxide dismutase (Mn-SOD), then superoxide leads to OxS and lipid peroxidation. Consequent release of electrophilic lipid peroxidation products (LPP) from dorsal horn of the spinal cord causes pain by activating the primary sensory afferents, again. Additional LPP-mediated causes of pain include glutathione depletion and neuron sensitisation by isoprostanes. Excretion of LPP into urine may exert positive feedback as well. Currently, different information exists about chronic prostatitis (inflammation, pain, oxidative stress, neural sensitisation, lower urinary tract symptoms). The clear links between these data are actually absent. We propose that vicious circle based on LPP, especially isoprostanes, is the linking mechanism.     

Is there an association between inhaled corticosteroids and bone density in postmenopausal women?

BACKGROUND: During the last decades, there has been increased concern about the association between oral corticosteroid (OC) therapy and osteoporosis. OBJECTIVE: The question currently discussed is whether inhaled corticosteroids (ICs) in recommended doses have any clinically relevant effects on bone mineral density (BMD). METHODS: We compared BMD in postmenopausal women exposed to corticosteroids only in inhaled form (IC group, n = 106) with that in women not exposed to corticosteroids (unexposed group, n = 674). BMD was also studied in 49 women exposed to OCs, intra-articular injections, or both in addition to ICs (OC group). The women were recruited from a population-based prospective cohort study. METHODS: We used a dietary survey, bone density measurement of the forearm, and a health questionnaire including an interview about past and present medication use. RESULTS: Mean BMD did not significantly differ between the IC group (0.434 g/cm2) and the unexposed group (0.429 g/cm2). The mean duration and dose of ICs was 8.2 +/- 5.03 years and 853 microg daily. Within the IC group, BMD stratified for cumulative dose of IC, duration, or current dose greater than or less than 1000 microg did not differ. BMD in the OC group was lower than that in the IC group (0.408 vs 0.434 g/cm2). CONCLUSION: No difference in BMD was noted between the IC group and unexposed control subjects, nor was any dose-response relationship observed between IC therapy and BMD.     

Is there any association between leptin levels and bone mineral density in haemophiliac men?

Introduction

Conflicting data exist regarding the role of leptin in bone metabolism. The purpose of the present study was to investigate serum leptin concentrations in male patients with haemophilia A and B, a disease known to be associated with low bone mass.

Material and methods

Eighty-one male patients, aged 45.4 ±15 years, were screened. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) in lumbar spine (LS), femoral neck (FN) and total hip (TH).

Results

Low bone mass was diagnosed in 20 patients (24.7%). Serum leptin concentrations were strongly associated with body weight (r _s = 0.457, p = 0.0001) and body mass index (BMI) (r _s = 0.491, p = 0.0001). In unadjusted analysis leptin was inversely associated with BMD in LS (r _s = –0.255, p = 0.023), but not in FN and TH (r _s = –0.205, p = 0.068 and r _s = –0.191, p = 0.090, respectively). However, after adjusting for BMI and body weight, leptin was inversely associated with BMD in FN (F _1,76 = 7.727, p = 0.007, β = –0.371, ΔR ² = 0.089) and TH (F _1,76 = 4.533, p = 0.036, β = –0.290, ΔR ² = 0.054), but not in LS (F _1,75 = 2.076, p = 0.154, β = –0.202, ΔR ² = 0.026). No association was found between age, presence of HBV, HCV or HIV infection or alkaline phosphatase and leptin levels.

Conclusions

Our study showed a negative association between circulating leptin levels and bone mass in males, independently of body weight and BMI.     

What is the impact of osteoporosis education and bone mineral density testing for postmenopausal women in a managed care setting?

OBJECTIVE: To assess whether osteoporosis education, with and without bone mineral density (BMD) testing, increases the initiation of lifestyle changes and pharmaceutical treatment to prevent osteoporosis. DESIGN: A total of 508 women, aged 54-65, from a large managed care organization who were not on osteoporosis prevention therapy participated in an intervention study. Participants were randomly assigned to either an education class on osteoporosis (n = 301) or education plus BMD (n = 207). A control group of 187 women receiving no intervention were also surveyed to serve as comparison. Group differences and differences based on BMD test result were compared 6 months after education regarding self-reported changes in health behaviors using chi2 tests and logistic regression analyses. RESULTS: Of the 508 intervention participants, 455 (90%) responded to the follow-up survey. Initiation of hormone replacement therapy was reported by 9%, with 5% reporting starting alendronate. More than half reported changes in diet, exercise, or calcium intake. Forty-three percent increased their vitamin D intake. There were no significant group differences in behavior except with regard to pharmaceutical therapy; subjects with education plus BMD were three times more likely than those receiving education only to report starting hormone replacement therapy (p = 0.004). Low BMD scores were associated with increasing vitamin D intake (p = 0.03) and starting medication (p = 0.001). Women in the intervention groups were significantly more likely to report modifying their diet (p < 0.001), calcium (p < 0.01), and vitamin D intake (p < 0.0001) than women in the control group, not exposed to education. CONCLUSION: Education regarding osteoporosis prevention seems to encourage women to make lifestyle changes. The inclusion of BMD testing enhances the likelihood that women will consider pharmaceutical therapy.     

Are planning,working memory,and inhibition associated with individual differences in preschool ADHD symptoms?

The association between executive function (EF; planning, working memory, and inhibition) and individual differences in symptoms of attention deficit hyperactivity disorder (ADHD) was explored in a sample of preschool children. One hundred sixty children (between the ages of 3 years, 0 months and 5 years, 6 months), selected so as to oversample high ADHD scorers, performed 3 tasks previously shown to measure planning (Tower of London), working memory (Noisy Book) and inhibition ("Puppet Says..."). EF measures were reliable (kappa > .77) and were correlated with IQ (rs > .38) and age (rs > .59). Once IQ and age were controlled, planning and working memory (r = .41) were correlated. Planning and working memory were not correlated with inhibition (rs < .20). There was no association between ADHD and working memory or planning (rs < .12). There was a significant negative association between ADHD and conduct problems and inhibition (r = -.30 and r = -.25, respectively). Only the link with ADHD persisted after the effects of other factors were controlled for in a multiple regression. Specific deficits in inhibitory control rather than general EF deficits are associated with ADHD in the preschool period. This association is linear in nature, supporting the idea that ADHD is better seen as a continuum rather than a discrete category. This association provides evidence for Barkley's (1997) view that ADHD is underpinned by inhibitory deficits in the preschool period.     

Endochondral bone growth,bone calcium accretion,and bone mineral density: how are they related?

Endochondral bone growth in young growing mammals or adult mammals with persistent growth plates progresses from proliferation, maturation and hypertrophy of growth plate chondrocytes to mineralization of cartilaginous matrix to form an osseous tissue. This complex process is tightly regulated by a number of factors with different impacts, such as genetics, endocrine/paracrine factors [e.g., PTHrP, 1,25(OH)₂D₃, IGF-1, FGFs, and prolactin], and nutritional status (e.g., dietary calcium and vitamin D). Despite a strong link between growth plate function and elongation of the long bone, little is known whether endochondral bone growth indeed determines bone calcium accretion, bone mineral density (BMD), and/or peak bone mass. Since the process ends with cartilaginous matrix calcification, an increase in endochondral bone growth typically leads to more calcium accretion in the primary spongiosa and thus higher BMD. However, in lactating rats with enhanced trabecular bone resorption, bone elongation is inversely correlated with BMD. Although BMD can be increased by factors that enhance endochondral bone growth, the endochondral bone growth itself is unlikely to be an important determinant of peak bone mass since it is strongly determined by genetics. Therefore, endochondral bone growth and bone elongation are associated with calcium accretion only in a particular subregion of the long bone, but do not necessarily predict BMD and peak bone mass.     

How to determine the bone mineral density of the distal humerus with radiographic tools?

Introduction

The aim of this study was to investigate three methods of prediction of the bone quality of the distal humerus: dual-energy X-ray absorptiometry (DEXA), Ct-Scan and plain radiographs.

Materials and methods

The bone mineral density (BMD) of 21 cadaveric distal humerus was determined using DEXA at two levels. Then a CT-scan and anteroposterior radiographs were taken. The cancellous density was estimated with the CT-scan. The cortico-medullar index (CMI) was calculated as cortical thickness divided by total bone thickness on AP views.

Results

A significant positive correlation was found between the BMD of the epiphysis and the CMI of r = 0.61. The mean BMD of the distal humerus was 0.559 g/cm². Male specimens showed a significantly higher BMD than females. The mean CMI of diaphysis was 1.431 and the mean BMD of the metaphysis region was 0.444 g/cm².

Discussion

More than a direct evaluation of the bone density with a CT-scan, the CMI of the distal humerus diaphysis is a predictor of the bone quality of the distal humerus. This should be of great help for the surgeon’s decision making in case of fracture of the distal humerus, as open Reduction and Internal Fixation (ORIF) of fractures of the distal humerus can lead to failure due to poor bone quality.

Level of evidence

Basic Science Study, Anatomic Cadaver Study.

     

Are cytokines associated with neuropsychiatric syndromes in humans?

Traditional aetiological models in neuropsychiatry have placed little emphasis on the abnormal behavioural responses (decreased psychomotor activity, anorexia, weight loss, decreased social exploration and sexual behaviour, impaired cognitive function and increased somnolence) that are common to both psychiatric syndromes, notably depression, and the illness behaviour of sick animals. In recent years, the possible role of cytokines, as mediators of not only the immunological and metabolic responses to infection and inflammation but also a co-ordinated behavioural response, has been described. Further, a range of possible mechanisms for these effects has been postulated, notably involving corticotropin releasing factor (CRF) and prostaglandins of the E series (PgE) with the central nervous system (CNS). Here we outline a series of human clinical conditions where neuropsychiatric syndromes co-occur with a host response to infection or inflammation. These may be characterized by cytokine production (e.g. acute, recurrent and chronic viral illnesses, systemic autoimmune diseases and chronic fatigue syndrome). Other clinical situations characterized by exposure to or in vivo production of cytokines (e.g. treatment of chronic infections and malignancies, progression and/or recurrence of malignancies) are also discussed. We postulate that the stereotyped behavioural repertoire observed is mediated by cytokine-dependent mechanisms within the CNS. Systematic studies of the behavioural responses of such patient groups are suggested, noting specifically correlations between the time course and severity of immune and neuroendocrine and behavioural responses and dose-response effects.     

Is there a relation between vitamin D,interleukin-17, and bone mineral density in patients with inflammatory bowel disease?

IntroductionIn inflammatory bowel diseases (IBD), osteopenia and osteoporosis constitute a significant medical problem. Cytokines, especially IL-17, play an important role in the pathogenesis of IBD and osteoporosis. Vitamin D is a regulator of bone metabolism, and helps maintain immune system homeostasis.Material and methodsThe research sample consisted of 208 persons: 83 patients (age 35 ±11.99 years) with Crohn’s disease (CD); 86 patients (age 39.58 ±14.74 years) with ulcerative colitis (UC); and 39 persons (age 30.74 ±8.63 years) in the control group (CG). Clinical data on bone mineral density of the lumbar spine (L2-L4), bone mineral density of the femoral neck (FN), and body mass index (BMI) were collected. 25OHD and IL-17 serum concentrations were also measured.ResultsBody mass index (kg/m²) results: in CD, 21.51 ±3.68; in UC, 23.31 ±4.38; and in CG, 24.57 ±3.45 (p < 0.01). Densitometry results for L2–L4 T-score SD: in CD –0.83 ±1.45; in UC –0.47 ±1.15; in CG 0.09 ±0.70. Densitometry results for FN T-score SD: in CD –0.62 ±1.26; in UC –0.29±1.17; in CG 0.41 ±1.03 25OHD (ng/ml) serum concentrations: in CD, 21.33±12.50; in UC, 22.04±9.56; in CG, 21.56±9.11 (ns). IL-17 (pg/ml) serum concentrations: in CD, 8.55±10.99; in UC, 11.67±12.97; in CG, 5.16±9.11 (ns).ConclusionsInflammatory bowel diseases patients and persons from the CG did not differ in vitamin D or IL-17 levels. Patients with a mild course of the disease had a higher vitamin D concentration and bone mineral density. In UC, higher vitamin D concentrations were associated with lower IL-17 concentrations. The IBD patients with a severe course of the disease had a lower body mass than those in the CG and the patients with a mild course of the disease.     

Which symptoms matter? Self-report and observer discrepancies in repressors and high-anxious women with metastatic breast cancer

Clinicians working with cancer patients listen to them, observe their behavior, and monitor their physiology. How do we proceed when these indicators do not align? Under self-relevant stress, non-cancer repressors respond with high arousal but report low anxiety; the high-anxious report high anxiety but often have lower arousal. This study extends discrepancy research on repressors and the high-anxious to a metastatic breast cancer sample and examines physician rating of coping. Before and during a Trier Social Stress Test (TSST), we assessed affect, autonomic reactivity, and observers coded emotional expression from TSST videotapes. We compared non-extreme (N = 40), low-anxious (N = 16), high-anxious (N = 19), and repressors (N = 19). Despite reported low anxiety, repressors expressed significantly greater Tension or anxiety cues. Despite reported high anxiety, the high-anxious expressed significantly greater Hostile Affect rather than Tension. Physicians rated both groups as coping significantly better than others. Future research might productively study physician-patient interaction in these groups.     

Are dehydroepiandrosterone sulphate and lipids associated with erectile dysfunction?

OBJECTIVE: Considering the results of the Massachusetts Male Aging Study (1994) we undertook the current investigation in an attempt to clarify the role of dehydroepiandrosterone sulphate (DHEAS), testosterone and lipids on age related deterioration of erectile function. METHODS: Forty males (13 under 40 years of age and 27 over 40) with erectile dysfunction were investigated. Seventeen healthy subjects (8 under 40 and 9 over 40 years) volunteered as controls. Serum levels of DHEAS, testosterone, total cholesterol, high-density lipoprotein cholesterol (HDL-ch), low-density lipoprotein cholesterol (LDL-ch) and triglycerides were assessed in blood samples. RESULTS: Plasma levels of DHEAS in patients over 40 years of age (4.17 +/- 2.76 micromol/l) were significantly lower in comparison with the younger group of patients (10.49 +/- 3.87 micromol/l), P < 0.001. There was no statistically significant difference in the DHEAS levels between patients and controls in the same age group. DHEAS in the patients showed an inverse correlation with age (r = -0.705, P < 0.001) and a positive correlation with testosterone (r = +0.402, P < 0.01). The same was found in the controls. The HDL-ch results were in the reference range. The total cholesterol levels (5.35 +/- 0.74 mmol/l) and LDL-ch levels (3.58 +/- 0.76 mmol/l) of the patients with erectile dysfunction in the group under 40 years were significantly higher in comparison with the controls (4.21 +/- 0.69 and 2.46 +/- 0.74 mmol/l, respectively, P <0.01). CONCLUSION: The data indicates that the decline in DHEAS is an age-related process rather than a causative factor of erectile dysfunction; total cholesterol and mainly LDL-ch may contribute to erectile dysfunction, especially in younger men.     

Are stress and coping associated with WISC-III performance among children?

This study examined the association between stress/coping variables and the newly developed Wechsler Intelligence Scale for Children – III (WISC-III) among children. Subjects included 98 children (72 males, 26 females), who ranged in age from 6 to 16 years and who were referred for multidisciplinary diagnostic testing during 1992-93. Demographic, DSM-III-R diagnostic, and testing data from the WISC-III were obtained from patient charts. Results suggest that stress and coping are associated with WISC-III performance among referred children in this archival and correlational study. Implications for future research are discussed.