Characterization of bone metabolism in hungarian psoriatic arthritis patients: a case-control study.

BACKGROUND: Skeletal manifestations are predominant in psoriatic arthritis (PsA). The aim of this cross-sectional, case-control study is the complex assessment of areal and volumetric bone mineral density (BMD), fracture risk, vitamin D status and bone turnover markers, and its association with disease-related variables. METHODS: Lumbar spine (L1-L4) and femoral neck (FN) areal, and distal radius (DR) volumetric BMD, 10-year probability of major and hip osteoporotic fracture as assessed by the fracture risk assessment (FRAX) tool, markers of bone metabolism and disease activity were assessed. RESULTS: Upon comparison of the disease and age- and sex-matched control groups, there was a statistically significant difference in FN areal (0.952 (0.607-1.292) g/cm2 vs. 1.016 (0.760-1.550) g/cm2; p = 0.001) and DR total volumetric (284.3 (138.9-470.3) mg/cm3 vs. 367.0 (287.0-412.0) mg/cm3; p < 0.001) BMD, 10 year probability for major osteoporotic (3.7% (0.7-32%) vs. 2.6% (0-17.5%); p = 0.003) and hip (0.4% (0-16%) vs. 0.05% (0-6.1%); p = 0.002) fracture and 25-hydroxyvitamin D status (47.5 (10-120) nmol/L vs. 64 (10-137; p < 0.001) nmol/L). As compared to areal assessment, volumetric BMD measurements identified a significantly higher number of patients with low bone mineral density (T-Score ≤ - 1.00) (34% vs. 88%, p < 0.001). Upon multiple linear regression analysis, disease activity score, as determined by DAS28 assessment, was an independent predictor of 10-year probability for major osteoporotic fracture (B (95%CI) = 1.351 (0.379-2.323); p = 0.007). CONCLUSION: In the studied PsA cohort, disease activity was an independent predictor of 10-year probability for a major osteoporotic fracture, and complemented assessment of volumetric and areal BMD assured better efficacy at identifying those with low bone mineral density.

The role of hyperinsulinemia as a cardiometabolic risk factor independent of obesity in polycystic ovary syndrome.

The aim of this study was to utilize various insulin resistance measuring methods to determine whether insulin resistance and other parameters impact the serum lipid levels of polycystic ovary syndrome (PCOS) patients and how the serum lipid levels in these patients are affected by the body mass index (BMI). Our dataset included patients between the ages of 16 and 42 (N = 228) from the outpatient endocrinology clinic of the Department of Obstetrics and Gynecology, who demonstrated increased hair growth and bleeding disorders and came for a routine oral glucose tolerance test (OGTT). Differences in the serum lipid levels were evaluated by t-test and linear regression analysis after adjusting for BMI. A stepwise regression model was constructed to evaluate the influence of each variable on the lipid levels. In PCOS patients, we found that dyslipidemia is more prevalent among hyperinsulinemic women compared with normoinsulinemic women, even after normalizing for BMI. PCOS patients with insulin resistance, determined by the insulin sensitivity index (ISI) method, showed more significant lipid abnormalities such as low high-density lipoprotein (HDL) and apo-A levels and high total cholesterol, low-density lipoprotein (LDL) and apo-B levels than if insulin resistance (IR) determination was based on insulin level or homeostatic model assessment (HOMA).

Cystatin C as a potential predictor of osteoprotegerin levels in healthy men, a cross-sectional, observational study.

BACKGROUND: The aim of the present study is to evaluate serum osteoprotegerin (OPG) and soluble receptor activator of nuclear factor κB ligand (sRANKL) levels in a randomly selected male cohort over 50 years of age and its association with cystatin C, a cysteine proteinase inhibitor that decreases formation of osteoclasts by interfering at a late stage of pre-osteoclast differentiation, apart from being a marker of renal function independent of gender, muscle mass and age; in addition to known predictors such as age, sex hormones, vitamin D, bone mineral density (BMD) and biochemical markers of bone turnover. METHODS: We determined serum OPG and sRANKL levels and examined its relationship with cystatin C, age, osteocalcin, C-terminal telopeptides of type-I collagen, procollagen type 1 amino-terminal propeptide, 25-hydroxyvitamin D, parathyroid hormone, total 17ß-estradiol (E2), total testosterone and L1-L4 (LS) and femur neck (FN) BMD data available from 194 (age, range: 51-81 years) randomly selected ambulatory men belonging to the HunMen cohort. RESULTS: OPG correlated significantly with age (Spearman's rho (r) = 0.359, p < 0.001), cystatin C (r = 0.298, p < 0.001), E2 (r = 0.160, p = 0.028) and free testosterone index (FTI) (r = -0.230, p = 0.001). Compared to the middle-aged (age: ≤ 59 years, n = 98), older men (age > 59 years, n = 96) had significantly higher serum OPG (4.6 pmol/L vs. 5.4 pmol/L; p < 0.001), and lower sRANKL (0.226 pmol/L vs. 0.167 pmol/L; p = 0.048) levels. The older men showed a significant correlation between serum OPG levels and cystatin C (Spearman's rho = 0.322, p = 0.002), and E2 (Spearman's rho = 0.211, p = 0.043). Including cystatin C and E2 in a regression model showed that cystatin C (standard regression coefficient (ß) = 0.345; p = 0.002) was the only significant predictor of serum OPG levels in the older men. CONCLUSIONS: The results of this study demonstrated that in addition to age (which was the stronger predictor), other modifiable factors such as cystatin C, FTI and E2 were also significant predictors of OPG, and that the association between cystatin C and OPG was more evident with increased age (older age group). As such, cystatin C is a significant predictor of OPG independently of age, FTI and E2.

Comparison of Different Vascular Biomarkers for Predicting In-Hospital Mortality in Severe SARS-CoV-2 Infection.

Severe SARS-CoV-2 elicits a hyper-inflammatory response that results in intravascular inflammation with endothelial injury, which contributes to increased mortality in COVID-19. To predict the outcome of severe SARS-CoV-2 infection, we analyzed the baseline level of different biomarkers of vascular disorders in COVID-19 subjects upon intensive care unit (ICU) admission and prior to any vaccination. A total of 70 severe COVID-19 patients (37 survivors and 33 non-survivors) were included with 16 age- and sex-matched controls. Vascular dysfunction was monitored via soluble VCAM-1, E-selectin, ACE2 and Lp-PLA2, while abnormal platelet activation was evaluated by soluble P-selectin and CD40L in parallel. These results were correlated with routine laboratory parameters and disease outcomes. Among these parameters, VCAM-1 and ACE2 showed significantly higher serum levels in COVID-19 patients with early death vs. convalescent subjects. VCAM-1 was significantly correlated with the Horowitz index (r = 0.3115) and IL-6 (r = 0.4599), while ACE2 was related to E-selectin (r = 0.4143) and CD40L (r = 0.2948). Lp-PLA2 was altered in none of these COVID-19 subcohorts and showed no relationship with the other parameters. Finally, the pre-treatment level of VCAM-1 (≥1420 ng/mL) and ACE2 activity (≥45.2 µU/mL) predicted a larger risk for mortality (Log-Rank p = 0.0031 and p = 0.0117, respectively). Vascular dysfunction with endothelial cell activation is linked to lethal COVID-19, and highly elevated soluble VCAM-1 and ACE2 at admission to ICU may predict unfavorable outcomes.

Serum sclerostin levels in healthy men over 50 years of age.

The aim of this study is to evaluate the relationship of serum sclerostin levels with age, cystatin C, bone mineral density (BMD) and biochemical markers of bone turnover in healthy Hungarian men >50 years of age. We determined serum levels of sclerostin and examined its relationship to age, cystatin C, osteocalcin, C-terminal telopeptides of type-I collagen, procollagen type 1 amino-terminal propeptide, 25-hydroxyvitamin D, parathyroid hormone, and L1-L4 (LS) and femur neck (FN) BMD data available from 194 randomly selected ambulatory men belonging to the HunMen cohort. In the study population as a whole [n = 194; age (median, range) 59 (51-81) years], statistically significant correlation was found between sclerostin and age (r = 0.211; p = 0.003), cystatin C (r = 0.246; p = 0.001), FN BMD (r = 0.147; p = 0.041) and LS BMD (r = 0.169; p = 0.019). Compared to middle-aged men (age ≤59 years, n = 98), elderly men (age >59 years, n = 96) had significantly higher serum sclerostin levels (67.8 ± 15.9 vs 63.5 ± 14 pmol/L; p = 0.047). Among men with normal (T score >-1.0) FN BMD, the elderly had significantly higher serum sclerostin levels compared to the middle-aged men (70.4 ± 17 vs 63.9 ± 11.5 pmol/L; p = 0.019). Furthermore, among the elderly men cystatin C was the only significant predictor of serum sclerostin levels (standardized regression coefficient (ß) = 0.487; p < 0.001). In the studied healthy elderly cohort, this study reports a significant increase in sclerostin levels with increasing age and deteriorating kidney function as determined by plasma cystatin C levels.

Combined application of angiotensin converting enzyme and chitotriosidase analysis improves the laboratory diagnosis of sarcoidosis.

Establishing the diagnosis of sarcoidosis most often requires biopsy and histopathologic evaluation, since there is no single marker with sufficient specificity and sensitivity for the disease. Our aims were to determine and compare the diagnostic accuracies of several potential biomarkers and to develop a combined biomarker analysis tool for the diagnosis of sarcoidosis. 133 healthy individuals and 104 patients with suspected sarcoidosis and diagnostic thoracic surgery were enrolled into this study. Histopathologic results were contrasted to biomarker levels of chitotriosidase (CTO), serum amyloid-A (SAA), soluble interleukin-2 receptor (sIL-2R), lysozyme (LZM) or angiotensin converting enzyme (ACE). Sarcoidosis was confirmed by histopathology in 69 patients. CTO activity, sIL-2R concentration and ACE activity could discriminate between sarcoidosis and control patients, while SAA and LZM concentrations could not. A new combined parameter, which was derived from the multiplication of ACE by CTO activities (double product) showed the best diagnostic accuracy in this clinical study: (AUC = 0.898, sensitivity: 90.5%, specificity: 79.3%, positive and negative predictive values: 90.5% and 79.3%, respectively). Sarcoidosis can be diagnosed with the combined analysis of ACE and CTO activities more accurately than with single serum biomarkers in the absence of invasive biopsy in the majority of cases with pulmonary manifestation of sarcoidosis.

Bone metabolism and the 10-year probability of hip fracture and a major osteoporotic fracture using the country-specific FRAX algorithm in men over 50 years of age with type 2 diabetes mellitus: a case-control study.

The aim of the study was to evaluate the 10-year probability of hip fracture and a major osteoporotic fracture using the FRAX algorithm, vitamin D status, bone mineral density (BMD), and biochemical markers of bone turnover in men over 50 years of age with type 2 diabetes mellitus (T2DM). We estimated FRAX-predicted 10-year fracture probability, levels of 25-hydroxyvitamin D (25-OH-D), markers of bone turnover, and bone mineral density at the L1-L4 (lumbar spine (LS)) and femur neck (FN) in 68 men with T2DM and compared these with an age-matched group (n = 68). The mean (range) age of the T2DM group was 61.4 (51-78) years. The prevalence of hypovitaminosis D (25-OH-D <75 nmol/L) was 59 %. The mean (range) FRAX hip fracture and FRAX major osteoporotic fracture was 0.7 (0-2.8) and 3.2 (0-8.5) %, respectively. BMD at the FN (0.974 vs. 0.915 g/cm(2), p = 0.008) and LS (1.221 vs. 1.068 g/cm(2), p < 0.001) was significantly higher in the T2DM cohort as compared to the healthy age-matched males. 25-OH-vitamin D (67.7 vs.79.8 nmol/L, p < 0.001), crosslaps (0.19 vs. 0.24 µg/L, p = 0.004), and osteocalcin (13.3 vs. 15.7 µg/L, p = 0.004) were significantly lower in the T2DM group. There was no difference in FRAX-related fracture probability between the two groups. Acknowledging the limitations of our study size, we suggest that the increased BMD in T2DM and the noninclusion of T2DM as a secondary risk factor in the FRAX algorithm may be probable explanations for the discordance between literature-observed and FRAX-related fracture probabilities.