Lower leptin concentration in Type 2 diabetic men

BackgroundLeptin is a hormone produced in adipocytes. It has been suggested that leptin directs metabolic fuels towards utilization and away from storage. Few related studies have been conducted on a homogeneous diabetic cohort. The aim of this study was to examine the gender differences in leptin level in a homogeneous Type 2 diabetic cohort and the factors contributing to such a difference.MethodsOut of 1306 registered diabetic patients, 116 subjects who met the following criteria, (1) aged between 35 and 74 years, (2) Chinese, (3) having Type 2 diabetes for more than 1 year and (4) having been taking gliclazide and metformin for more than 6 months, were enrolled into the study. The main variable studied was the plasma leptin levels in relation to quartiles of body mass index (BMI) and insulin levels in various age groups of men and women. Factors affecting plasma leptin level in men and women were determined using multiple linear regression analysis.ResultsThis study demonstrated that Type 2 diabetic women had higher plasma leptin concentrations than their male counterparts (p < 0.001). Insulin level (β = 0.50, p < 0.001), BMI (β = 0.44, p < 0.001) and triglyceride levels (β = 0.16, p = 0.04) were found to be the main predictors of leptin level for Type 2 diabetic men.ConclusionsThese initial findings reveal that men had lower leptin levels than women, and seem to indicate that insulin concentration is the main predictor of leptin level in both Type 2 diabetic men and women.     

Changes in vertebral bone marrow fat and bone mass after gastric bypass surgery: A pilot study

Bone marrow fat may serve a metabolic role distinct from other fat depots, and it may be altered by metabolic conditions including diabetes. Caloric restriction paradoxically increases marrow fat in mice, and women with anorexia nervosa have high marrow fat. The longitudinal effect of weight loss on marrow fat in humans is unknown. We hypothesized that marrow fat increases after Roux-en-Y gastric bypass (RYGB) surgery, as total body fat decreases. In a pilot study of 11 morbidly obese women (6 diabetic, 5 nondiabetic), we measured vertebral marrow fat content (percentage fat fraction) before and 6 months after RYGB using magnetic resonance spectroscopy. Total body fat mass declined in all participants (mean ± SD decline 19.1 ± 6.1 kg or 36.5% ± 10.9%, p < 0.001). Areal bone mineral density (BMD) decreased by 5.2% ± 3.5% and 4.1% ± 2.6% at the femoral neck and total hip, respectively, and volumetric BMD decreased at the spine by 7.4% ± 2.8% (p < 0.001 for all). Effects of RYGB on marrow fat differed by diabetes status (adjusted p = 0.04). There was little mean change in marrow fat in nondiabetic women (mean + 0.9%, 95% CI − 10.0 to + 11.7%, p = 0.84). In contrast, marrow fat decreased in diabetic women (− 7.5%, 95% CI − 15.2 to + 0.1%, p = 0.05). Changes in total body fat mass and marrow fat were inversely correlated among nondiabetic (r = − 0.96, p = 0.01) but not diabetic (r = 0.52, p = 0.29) participants. In conclusion, among those without diabetes, marrow fat is maintained on average after RYGB, despite dramatic declines in overall fat mass. Among those with diabetes, RYGB may reduce marrow fat. Thus, future studies of marrow fat should take diabetes status into account. Marrow fat may have unique metabolic behavior compared with other fat depots.     

High-sensitivity C-reactive protein is an independent risk factor for non-vertebral fractures in women and men: The Tromsø Study

Low-grade inflammation is associated with fractures, while the relationship between inflammation and bone mineral density (BMD) is less clear. Moreover, any gender differences in the sensitivity to inflammation are still poorly elucidated. We therefore tested the hypothesis that high-sensitivity C-reactive protein (CRP) is an independent risk factor for low BMD and non-vertebral fractures, in both genders, and whether there are gender differences in these associations.CRP levels and BMD at the total hip and femoral neck were measured in 1902 women and 1648 men between 55 and 74 years of age, at baseline in the Tromsø Study, Norway, in 2001–2002. Non-vertebral fractures were registered from hospital X-ray archives during an average of 7.2 years follow-up. Linear regression analyses were used for CRP association with BMD and Cox proportional hazards model for fracture prediction by CRP.During 25 595 person-years follow-up, 366 (19%) women and 126 (8%) men suffered a non-vertebral fracture. There was no association between CRP and BMD in women, but an inverse association in men (p = 0.001) after adjustment for age and body mass index. Each standard deviation (SD) increase in log-CRP was associated with an increased risk for non-vertebral fracture by 13% in women and 22% in men (hazard ratios (HRs) 1.13, 95% confidence interval (CI) 1.02–1.26, p = 0.026 and 1.22, 95% CI = 1.00–1.48, p = 0.046, respectively). After adjustment for BMD and other risk factors, women with CRP in the upper tertile exhibited 39% higher risk for fracture than those in the lowest tertile of CRP (HR = 1.39, 95% CI = 1.06–1.83, p = 0.017), while men in the upper tertile exhibited 80% higher risk (HR = 1.80, 95% CI = 1.10–2.94, p = 0.019).In summary, CRP was not associated with BMD in women but inversely associated in men, and predicted fractures in both genders. We infer that inflammation influence fracture risk in both women and men, although the biological mechanisms may differ between the genders.     

Systemic fat embolism and the patent foramen ovale—A prospective autopsy study

A fat embolism is a known and common complication of blunt force injuries, especially pelvic and long bones fractures. The aim of this study was to determine the importance of a patent foramen ovale (PFO) in developing systemic fat embolism (SFE) and eventually fat embolism syndrome (FES) in patients suffering from orthopaedic blunt injuries and consequent lung fat embolism. The sample was divided: 32 subjects with a sealed foramen ovale (SFO), and 20 subjects with a PFO. In our sample, there was no difference in either the incidence of renal fat embolism in subjects with PFO compared to those with SFO (Fisher's exact test 0.228, p = 0.154) or in the grade of renal fat embolism (Pearson Chi-square 2.728, p = 0.435). However, there was a statistically significant correlation between the grade of lung fat embolism and the number of fractured bones for the whole sample (Spearman's rho 0.271, p = 0.052), but no correlation between the grade of lung fat embolism and the ISS or NISS (Pearson correlation 0.048, p = 0.736, and 0.108, p = 0.445, respectively). In our study, the presence of fat emboli in the kidney, i.e. SFE, could effectively be predicted by the grade of lung fat embolism (the moderate and slight grades of lung fat embolism were better predictors than the massive one: logistic regression – Wald. Coeff. = 11.446, p = 0.003, Wald. Coeff. = 10.553, p = 0.001, and Wald. Coeff. = 4.128, p = 0.042), and less effectively by presence of PFO (Wald. Coeff. = 2.850, p = 0.091). This study pointed out that lung and SFE are not pure biomechanical events, so the role of a PFO is not crucial in developing a lung fat embolism into a systemic embolism: the fat embolism is more of a biochemical and pathophsyiological event, than a biomechanical one. The appearance of a patent foramen ovale associated with a systemic fat embolism should be less emphasised: maybe arteriovenous shunts and anastomosis between the functional and nutritive, i.e. systemic circulation of lungs play a more important role in developing a SFE than a PFO.     

Relationships between bone geometry,volumetric bone mineral density and bone microarchitecture of the distal radius and tibia with alcohol consumption

PurposeChronic heavy alcohol consumption is associated with bone density loss and increased fracture risk, while low levels of alcohol consumption have been reported as beneficial in some studies. However, studies relating alcohol consumption to bone geometry, volumetric bone mineral density (vBMD) and bone microarchitecture, as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), are lacking.MethodsHere we report an analysis from the Hertfordshire Cohort Study, in which we studied associations between HR-pQCT measures at the distal radius and tibia and alcohol consumption in 376 participants (198 men and 178 women) aged 72.1–81.4 years.ResultsA total of 30 (15.2%), 90 (45.5%) and 78 (39.4%) men drank minimal/none (< 1 unit/week), low (≥ 1 unit/week and < 11 units/week) and moderate/high (≥ 11 units/week) amounts of alcohol respectively. These figures were 74 (41.8%), 80 (45.2%) and 23 (13.0%) respectively in women for minimal/none (< 1 unit/week), low (≥ 1 unit/week and < 8 units/week) and moderate/high (≥ 8 units/week). At the distal radius, after adjustment for confounding factors (age, BMI, smoking status, dietary calcium intake, physical activity and socioeconomic status and years since menopause and HRT use for women), men that drank low alcohol had lower cortical thickness (p = 0.038), cortical vBMD (p = 0.033), and trabecular vBMD (p = 0.028) and higher trabecular separation (p = 0.043) than those that drank none/minimal alcohol. Similar differences were shown between minimal/none and moderate/high alcohol although these only reached statistical significance for the cortical parameters. Interestingly, after similar adjustment, women showed similar differences in the trabecular compartment between none/minimal alcohol and low alcohol at the distal tibia. However, women that drank moderate/high alcohol had significantly higher trabecular vBMD (p = 0.007), trabecular thickness (p = 0.026), and trabecular number (p = 0.042) and higher trabecular separation (p = 0.026) at the distal radius than those that drank low alcohol.ConclusionsOur results suggest that alcohol consumption (low and moderate/high) may have a detrimental impact on bone health in men in both the cortical and trabecular compartments at the distal radius with similar results in women in the trabecular compartment between none/minimal alcohol and low alcohol at the distal tibia suggesting that avoidance of alcohol may be beneficial for bone health.     

Changes in total body surface area and the distribution of skin surfaces in relation to body mass index

BackgroundA correct estimation of total burn surface area is important since it is used for determining fluid resuscitation volumes, nutritional estimates and hospital admission criteria. Wallace’s rule of nines is the most commonly used methods for this purpose. However, fat distribution is non-uniform and the total body surface area changes with obesity. The aim of this study was to determine if the rule of nines applies to all body mass index groups.MethodsA total of 217 individuals were included in the study. The patients were divided into 4 groups according to their BMI (18.5–25 kg/m² (60 persons)), 25–29.9 kg/m² (61 individuals)), 30–34.9 kg/m² (55 persons)), >35 kg/m² (41 persons)). Each patient underwent a complete duel-energy X-ray absorptiometry body scan to determine the surface area (cm²) of the various regions of the body.ResultsWe found no statistically significant variations between the Wallace body percentage distributions and our results in the men for all BMI ranges (head p = 0.331, arms p = 0.861, legs p = 0.282, trunk p = 0.696). In contrast, among women we found a statistically significant change in body surface area percentage distribution between the BMI groups and specific body regions (head p = 0.000, legs p = 0.000 and trunk p = 0.001).ConclusionThe Wallace rule of nines is a quick and acceptable method for estimating the total burn surface area percentage in men of all BMI ranges. However, for women, a more accurate method of burn area estimation is required as proposed by our BMI adjusted charts.     

Association Between Lean Mass and Handgrip Strength With Bone Mineral Density in Physically Active Postmenopausal Women

The present study evaluated 117 physically active postmenopausal women (67.8 ± 7.0 yr) who performed neuromotor physical tests (strength, balance, and mobility). Body composition (lean mass [g], fat mass [g], and % fat) and bone mineral density (BMD) of lumbar spine (L1–L4), femoral neck, and total body were measured by dual-energy X-ray absorptiometry. Following the World Health Organization criteria, osteoporosis was found in at least 1 analyzed site in 33 volunteers (28.2%): 30 (25.6%) in lumbar spine and 9 (7.7%) in femoral neck. Body weight was strongly and positively related to BMD in all sites, but the most important component of body composition was lean mass, also significantly related to all BMD sites, whereas fat mass was weakly related to the femoral neck BMD. Percent fat did not correlate with any BMD site. Of all the physical tests, the handgrip strength was most importantly related to lumbar spine, femoral neck, and total body (r = 0.49, p < 0.001; r = 0.56, p < 0.001; and r = 0.52, p < 0.001, respectively). The static body balance presented a weak but significant positive correlation only with lumbar spine. Our results suggest that strategies aiming to improve muscle strength and lean mass must contribute to the bone health of physically active postmenopausal women.     

Contribution of Fat-Free Mass and Fat Mass to Bone Mineral Density Among Reproductive-Aged Women of White,Black, and Hispanic Race/Ethnicity

The objective of the study was to evaluate the contribution of fat-free mass (FFM) and fat mass (FM) to bone mineral density (BMD) and bone mineral apparent density (BMAD) among reproductive-aged women. Dual-energy X-ray absorptiometry scans were performed on 708 healthy black, white, and Hispanic women, 16–33 yr of age. The independent effect of FFM and FM on BMD and BMAD and the interaction of body composition measurements with race/ethnicity and age, were evaluated. FFM correlated more strongly than FM with BMD at the lumbar spine (r = 0.52 vs r = 0.39, p < 0.01) and the femoral neck (r = 0.54 vs r = 0.41, p < 0.01). There was a significant positive association between bone density measures [ln(BMD) and ln(BMAD)] and both ln(FFM) and ln(FM). The association of FFM with spinal BMD was stronger in 16–24-yr-old women than in 25–33-yr-old women (p < 0.006). The effect of FFM on femoral neck BMD was greater in blacks (p < 0.043) than Hispanics, whereas the effect of FM on spinal BMD was less (p < 0.047). Both FM and FFM are important contributors to bone density although the balance of importance is slightly different between BMD and BMAD.     

Men suffer more complications from diabetes than women despite similar glycaemic control and a better cardiovascular risk profile: the ADCM study 2008

BackgroundGender differences in glycaemic control and diabetes’ complications have been well studied overseas but not locally. Gender is one of the non-modifiable factors for the diabetes patient but it is an important factor for effective personalized diabetes care. This paper examined the gender differences in glycaemic control and diabetes’ complications.MethodsThis was a registry-based observational study from May–December 2008. An online standard case record form was available for site data providers to register their diabetes patients aged 18 years old and above annually. Demographic data, diabetes duration, treatment modalities, as well as various risk factors and diabetes complications were reported. Multivariate analysis was performed.ResultsA total of 20,646 diabetes patients were included. The majority (99.2%) had been diagnosed with type 2 diabetes mellitus (T2D); 42.8% of the sample were men; 57.1% were Malay. The mean age was 58.0 years (standard deviation (SD) = 11.49) with 77.6% of the sample being 50 years old and above. Despite similar diabetes control (HbA1c < 6.5%), females suffered more microvascular complications (estimated glomerular filtration rate (eGFR) <60 mls/min: X² = 753.54, P = <0.001) while men suffered more from macrovascular complications (ischaemic heart disease (X² = 57.61, P = <0.001) and stroke (X² = 13.87, P = <0.001)). Multivariate logistic regression analyses showed that T2D men were more likely to suffer from stroke (odds ratio (OR) = 1.21, 95% confidence interval (CI) = 0.89–1.64), ischaemic heart disease (OR = 1.55, CI = 1.35–1.78) and nephropathy (OR = 1.59, CI = 1.44–1.75).ConclusionWe observed that men suffered more diabetes-related complications despite similar glycaemic control and better risk factor control. This finding requires further verification from future studies.     

Adiponectin and bone mass density: The InCHIANTI study

IntroductionAdiponectin serum concentration has been reported to be inversely correlated with bone mineral density (BMD) in humans. The data on this issue, however, are biased by small study sample size and lack of controlling for body composition.MethodsWe used data from the third follow-up of the InCHIANTI study, which included measurements of BMD using quantitative CT of the tibia and of body composition using bioimpedenziometry. Serum adiponectin was measured using radioimmunoassay. We excluded participants with diabetes, hyperthyroidism, using hormone replacement or corticosteroid therapy. We evaluated the correlation of adiponectin with total, trabecular, and cortical BMD using Pearson's coefficient, and linear regression models to estimate the association between adiponectin and BMD controlling for potential confounders (age, body mass index, alcohol intake, fat mass, smoking).ResultsOur sample was made up of 320 men (mean age: 67 years, SD: 15.8, range: 29–97 years) and 271 postmenopausal women (mean age: 76 years, SD: 8.2, range: 42–97 years). In men, serum adiponectin was not independently associated with BMD. In women, after correction for potential confounders, adiponectin was associated with total (β = ?0.626, P < 0.001), trabecular (β = ?0.696, P < 0.001), and cortical (β = ?1.076, P = 0.001) BMD.ConclusionOur results show that adiponectin is inversely associated with bone mass in women. Further studies are needed to confirm these findings prospectively and then to clarify the explanatory mechanisms.     

Comprehensive assessment of sensitizing events and anti-HLA antibody development in women awaiting kidney transplantation

BackgroundAlloimmunization remains a critical factor which affects the success of kidney transplantation. Patients awaiting solid organ transplantation may develop anti-HLA antibodies after pregnancies, transfusions and previous events of transplantations.AimWe evaluated the effects of different sensitizing events on the anti-HLA antibody production and the potential role of patient HLA alleles in the context of antibody development in both the overall and pregnancy sensitized groups.Material and methodsWe retrospectively stratified 411 women on waiting list for kidney transplantation by route of sensitization. The presence of anti-HLA antibodies was evaluated by Solid Phase Assay and HLA typing was performed by serological and molecular methods.ResultsIn our study population, 54% of women had anti-HLA antibodies. We found that the 51.6% of women with pregnancy only, 44% of women with transfusion only and 100% of women with a history of transplantation only developed anti-HLA antibodies. Pregnancy only resulted significantly associated with all anti-HLA antibody development such as anti-A, -B, -C, -DR, -DP as well as anti-DQB and -DQA antibodies. We investigated the influence of patient HLA alleles on the antibody development in the overall study population. Patients expressing HLA A*32 (p = 0.024, OR = 0.42), B*14 (p = 0.035, OR = 0.44), HLA-B*44 (p = 0.026, OR = 0.51) and DRB1*01 (p = 0.029, OR = 0.55) alleles produced anti-HLA antibodies less frequently compared to subjects with other alleles. In the pregnancy only group, B*14 (p = 0.010, OR = 0.12) and B*51 (p = 0.005, OR = 0.24) alleles were associated with a low risk of anti-HLA antibody development, while A*11 (p = 0.033, OR = 3.56) and DRB1*04 (p = 0.022, OR = 3.03) alleles seem to represent a higher risk.ConclusionsPregnancy still remains a strong sensitizing event in women awaiting kidney transplantation. The anti-HLA antibody development in pregnancy appears to be associated with the expression of particular HLA alleles.     

Quilty in biopsy is associated with poor prognosis after heart transplantation

We tested if Quilty (endocardial infiltration of lymphocytes) in routinely processed endomyocardial biopsy is associated with poor outcome after heart transplantation (HTx).Biopsies (n = 9829) harvested within the first post-transplant year from 938 patients (778 men, mean age 49 years) were evaluated for Quilty and acute cellular rejection (according to the International Society for Heart and Lung Transplantation, ISHLT, classification). Transplant vasculopathy was evaluated by coronary angiography, and severe stenosis was found in 19% of patients. Survival was tested by Kaplan–Meier and Cox regression analyses for all-cause mortality and major cardiac events (lethal acute cellular rejection, graft loss or myocardial infarction).We found 1840 (19%) Quilty-positive biopsies in 487 Quilty-positive patients (52%). Quilty was more prevalent in women (p = 0.038) and younger men (p = 0.001), and was correlated with ISHLT grade 1R (OR 1.45, 95% CI 1.36–1.55; p < 0.001) and ISHLT grade 2R (OR 2.48, 95% CI 2.21–3.41; p < 0.001). Quilty in any biopsy was associated with a higher all-cause mortality (log rank p = 0.045) due to a higher risk for major cardiac event (p = 0.0001). Multivariate regression analysis showed Quilty (RR 1.69, 95%CI 1.05–2.73) and transplant vasculopathy (RR 2.78, 95%CI 1.68–4.61) as risk factors for major cardiac events and treated hyperlipidemia as lowering the risk for major cardiac events (RR 0.47, 95%CI 0.28–0.77).Quilty is associated with graft loss and poor outcome post HTx. Index biopsy during the first post-transplant year is a useful tool to identify patients at risk and is recommended during routine post-transplant management.     

Genetic predictors of skeletal outcomes in healthy fertile women: The Bonturno Study

Skeletal traits as height (Ht) or bone mineral density (BMD) are strongly inherited. Low-density lipoprotein receptor-related protein 5 (LRP5) and farnesyl diphosphonate synthase (FDPS) are candidate genes for bone phenotypes. From Bonturno study, we genotyped 570 healthy Caucasian women aged 20 to 50 years (yrs) for LRP5 rs4988321 (A/G) and rs3736228 (C/T) and FDPS rs2297480 (A/C) single nucleotide polymorphisms. Serum C-telopeptide of type I collagen (CTX), osteocalcin (OC), and N-terminal propeptide of type I procollagen (P1NP) were measured in BMD-evaluated subjects at lumbar spine (LS), total hip (TH) and femoral neck (FN) sites. LRP5 rs4988321 locus correlated with FN-BMD (P = 0.0230), while LRP5 rs3736228 genotypes differed in LS-BMD (P = 0.0428). When clustered by age, lower FN-BMD was detected in LRP5 GG (P = 0.030) subjects of 41 to 50 years but not in younger. Both LRP5 GG and CC genotypes showed higher age-adjusted values of OC, CTX and P1NP. Increased CTX values were in LRP5 GGCC subjects than in those having at least one LRP5 A plus T alleles (P = 0.0190). LRP5 CC, GG or GGCC subjects with at least one FDPS C allele showed higher levels of CTX and OC in 31 to 40 yrs or older subjects. In conclusion, LRP5 and FDPS loci age-specifically affect skeletal traits in healthy fertile women.     

The association between physical activity in different domains of life and risk of osteoporotic fractures

A large body of epidemiological evidence suggests an inverse relationship between physical activity and risk of fractures. However, it is unclear how this association varies according to the domain of life in which the activity is undertaken. In this analysis of the European Prospective Investigation of Cancer-Norfolk study, we assessed total and domain-specific physical activity using a validated questionnaire (EPAQ2) in 14,903 participants (6514 men, mean age 62 year) who also underwent quantitative ultrasound of the heel. After a median follow-up of 7.5 years, there were 504 fractures of which 164 were hip fractures. In multivariable linear regression analysis, broadband ultrasound attenuation (BUA) was positively associated with total and leisure-time activities while showing no association with transportation and work activities. Home activities were associated with a lower BUA among younger participants. In multivariable Cox proportional-hazards models, moderate activities at home and in leisure time were associated with lower hip fracture risk among women (hazard ratios [HR] 0.51 and 0.55, p value 0.02 and 0.03, respectively). Among men, leisure-time activities were associated with lower risk of hip fracture (HR = 0.58; p for trend < 0.001) whereas activities at home were associated with higher risk of any fracture (HR = 1.25; p for trend = 0.008). Walking for leisure or transport was associated with lower risk of fracture in both men and women. Multivariable fractional polynomial modelling showed a U-shaped association between home activities and fracture risk especially among women. This study suggests that different domains of physical activity may relate differently to fracture risk and these relationships may vary by sex.     

Absence of association between inflammatory dietary pattern and low trauma fractures: Results of the French cohort NutriNet-Santé

IntroductionThe aim of our study was to assess the association between the Alternate Dietary Inflammatory Index (ADII) and the risk of fracture in a French cohort of women and men older than 50 years.MethodsA total of 15,096 participants were included from the French NutriNet-Santé cohort. The ADII score was calculated at inclusion. Incident low trauma fractures were retrospectively self-reported by participants on a specific additional questionnaire. Multivariate hazard ratio obtained from Cox proportional hazard regression models were used to characterize an association between ADII (in quartiles) and incident low trauma fractures.ResultsIn all, 12,046 participants (7607 (63.2%) women and 4439 (36.8%) men) were included in our study. For fractures, 806 (10.6%) and 191 (4.3%) low trauma fractures were recorded respectively in women and in men. Mean ADII was −1.23 (± 3.13) for women and −0.87 (± 3.64) for men. No association was detected between the ADII score and the risk of vertebral fracture (P = 0.21), major osteoporotic fracture (P = 0.93) and any low trauma fracture (P = 0.72) in women nor in men (P = 0.06 for major fracture and P = 0.10 for low trauma fracture) after adjustment for sociodemographic, lifestyle variables and for bone treatments.ConclusionThis study in postmenopausal women and men older than 50 years from the general population did not show any association between inflammatory dietary pattern measured using the ADII and the risk of incident low trauma fracture.     

Flow cytometric measurement of sperm nuclear DNA fragmentation in infertile men with normal standard sperm parameters

BackgroundMale-factor infertility plays a role in approximately 50% of infertile couples. In at least 30% of cases, repeated standard semen analyses of the male partner of an infertile couple reveal normal results. When diagnostic work-up of the female partner is also normal, they are classified as idiopathic. The objective of this study was to evaluate the levels of sperm nuclear DNA fragmentation in a population of infertile men with normal standard semen parameters and to compare their results with those from men who had abnormal semen parameters, as well as with a control group of fertile men.MethodsSemen samples were obtained from 202 infertile men and 30 fertile donors. Standard semen analysis was performed according to the World Health Organization guidelines. Flow cytometry has been extensively used to study sperm DNA fragmentation and the results are expressed as the percentage of sperm DNA fragmentation index (DFI).ResultsOf the 202 patients, 48 (23.8%) had normal standard sperm parameters, while 154 (76.2%) had an abnormality in one or more of these parameters. DFI in infertile men with normal sperm parameters was significantly higher than in fertile donors (p = 0.03), but not significantly different from infertile men with abnormal sperm parameters (p = 0.10). There were statistically significant negative correlations between DFI and the percentage of motile sperm from infertile men with abnormal and normal semen parameters, but not in fertile donors (r = ?0.26, p = 0.001 and r = ?0.48, p = 0.0001, respectively).ConclusionSperm from infertile men with normal standard sperm parameters may have significant levels of DNA fragmentation that are comparable to levels in infertile men with abnormal sperm parameters. Sperm DNA fragmentation analysis is an independent test of sperm quality and has an important diagnostic value in the evaluation of male infertility.     

Polymorphisms in inflammation associated genes ALOX15 and IL-6 are associated with bone properties in young women and fracture in elderly

PurposeALOX12 and ALOX15 encode arachidonate lipoxygenases which produce lipid metabolites involved in inflammatory processes. Metabolites generated by ALOX12 and ALOX15 can activate the expression of the potent pro-inflammatory cytokine IL-6, and produce endogenous ligands for PPARG. In this study, polymorphisms in ALOX12, ALOX15, IL6 and PPARG were investigated for association with bone properties in young and elderly Swedish women.MethodsThree SNPs in ALOX12, five in ALOX15, one each in IL6 and PPARG were genotyped in the cohorts PEAK-25 (n = 1061 women; all 25 y) and OPRA (n = 1044 women; all 75 y). Bone mineral density (BMD) and quantitative ultrasound (QUS) were analyzed in both cohorts; trabecular bone score (TBS) in PEAK-25; bone loss, fracture incidence and serum C-reactive protein (CRP) were assessed in OPRA.ResultsIn the elderly women ALOX15 (rs2619112) was associated with CRP levels (p = 0.004) and incident fracture of any type (p = 0.014), although not with BMD or ultrasound. In young women, carrying the common T allele (ALOX 15 rs748694) was associated with lower QUS values (p = 0.002–0.006). The IL6 SNP was associated with lower BMD in PEAK-25 (femoral neck p = 0.034; hip p = 0.012). TBS was not associated with variation in any gene. Variants in the ALOX12 and PPARγ were not associated with BMD in either cohort.ConclusionsThis study suggests that variation in inflammation related genes ALOX15 and IL6 was associated with bone microarchitecture and density in young adult women, but appears to be less important in the elderly, despite an observed association with CRP as a marker of inflammation and incident fracture.     

Associations between amino acids and bone mineral density in men with idiopathic osteoporosis

Idiopathic osteoporosis in middle-aged men is characterized by low-level bone formation. Inhibited anabolism may be involved in the pathogenesis of the disease and amino acids may be of importance. In the present study fasting amino acid profiles in plasma and erythrocytes were determined in 22 male idiopathic osteoporosis (MIO) patients and in 20 age-matched healthy men and associated with bone mineral density, bone histomorphometry and hormones.The osteoporotic patients had normal plasma essential amino acids but increased non-essential amino acids (p = 0.001), particularly glutamine and glycine. The ratio essential/non-essential amino acids, an index of protein nutritional status, was decreased in the MIO patients (0.59 (0.04) μmol/l, mean (SD)), compared to controls (0.66 (0.05), p = 0.001).In the MIO patients, the ratio essential/non-essential plasma amino acids (r = 0.60, p = 0.003) was positively correlated with lumbar spine bone mineral density.The erythrocyte amino acids represent a large proportion of the free amino acids in blood. A novel finding was the lower levels of erythrocyte tryptophan in MIO (12 (2) μmol/l) compared to controls (16 (3), p = 0.001) and decreased erythrocyte/plasma ratio (0.28 (0.07) vs. 0.33, (0.06), p < 0.01), suggesting an altered amino acid transport of tryptophan between plasma and erythrocytes. In the combined group of MIO and control men (n = 42), bone mineral density was positively correlated with erythrocyte tryptophan in both the lumbar spine (r = 0.45, p = 0.003) and femoral neck (r = 0.56, p < 0.001). The bone histomorphometric variables wall thickness, trabecular thickness and mineral apposition rate were all positively associated with erythrocyte tryptophan levels in the MIO patients.In the combined group of MIO and controls, a multiple regression analysis showed that erythrocyte tryptophan could explain 22% of the variation of lumbar spine and 30% of the variation in femoral neck bone mineral density.We conclude that men with idiopathic osteoporosis have changes in free amino acid profiles which indicate their altered utilization. The correlations between tryptophan and bone mineral density and bone histomorphometry suggest a link between tryptophan and osteoblast function which may be important for bone health.     

Objectively measured physical activity is associated with parameters of bone in 70-year-old men and women

As the world's population ages, the occurrence of osteoporosis-related fractures is projected to increase. Low areal bone mineral density (aBMD), a well-known risk factor for fractures, may be influenced by physical activity (PA). In this cross-sectional study, we aimed to investigate potential associations between objective measures of PA and bone properties, in a population-based cohort of 1228 70-year-old men and women. We measured volumetric BMD (vBMD, mg/cm³) together with cross-sectional area (CSA, mm²) by peripheral quantitative computed tomography at sites located 4% and 66% in the distal–proximal trajectory at the tibia and radius. We also measured aBMD (g/cm²) by dual energy X-ray absorptiometry at the femoral neck, lumbar spine (L1–L4) and radius. Participants wore triaxial accelerometers for 7 consecutive days to obtain objective estimates of PA. The intensity of the objective PA was divided into light (100–1951 counts/min [CPM]), moderate (1952–5724 cpm) and vigorous (≥ 5725 cpm). Maximal accelerations for the anterior–posterior (z), medio-lateral (x), and vertical (y) axes were also separately assessed. Associations were investigated using bivariate correlations and multiple linear regression, adjusted for height, weight and sex. Vigorous PA showed the strongest association with femoral neck aBMD (β = 0.09, p < 0.001), while both moderate and vigorous PAs were associated with cortical area and trabecular vBMD in the weight-bearing tibia (all p < 0.05). Peak vertical accelerations were associated significantly with cortical area (β = 0.09, p < 0.001) and trabecular vBMD (β = 0.09, p = 0.001) of the tibia, whereas peak anterior–posterior accelerations showed no correlation with these properties. No positive association was found between objectively measured PA and bone parameters of the radius. In conclusion, vertical accelerations and moderate to vigorous PA independently predict bone properties, especially in the weight-bearing tibia, in 70-year-old men and women.     

Evaluating the relationship between muscle and bone modeling response in older adults

Bone modeling, the process that continually adjusts bone strength in response to prevalent muscle-loading forces throughout an individual's lifespan, may play an important role in bone fragility with age. Femoral stress, an index of bone modeling response, can be estimated using measurements of DXA derived bone geometry and loading information incorporated into an engineering model. Assuming that individuals have adapted to habitual muscle loading forces, greater stresses indicate a diminished response and a weaker bone. The purpose of this paper was to evaluate the associations of lean mass and muscle strength with the femoral stress measure generated from the engineering model and to examine the extent to which lean mass and muscle strength account for variation in femoral stress among 2539 healthy older adults participating in the Health ABC study using linear regression. Mean femoral stress was higher in women (9.51, SD = 1.85 Mpa) than in men (8.02, SD = 1.43 Mpa). Percent lean mass explained more of the variation in femoral stress than did knee strength adjusted for body size (R² = 0.187 vs. 0.055 in men; R² = 0.237 vs. 0.095 in women). In models adjusted for potential confounders, for every percent increase in lean mass, mean femoral stress was 0.121 Mpa lower (95% CI: − 0.138, − 0.104; p < 0.001) in men and 0.139 Mpa lower (95% CI: − 0.158, − 0.121; p < 0.001) in women. The inverse association of femoral stress with lean mass and with knee strength did not differ by category of BMI. Results from this study provide insight into bone modeling differences as measured by femoral stress among older men and women and indicate that lean mass may capture elements of bone's response to load.