IntroductionPatients in later stages of chronic kidney disease (CKD) have a 2- to 14-fold increase in fracture risk. Bone mineral density (BMD) assessment is limited due to the inability to measure trabecular and cortical bone characteristics and the interference of aortic calcifications.Study objectiveThis study aimed to assess the trabecular bone score (TBS) and three-dimensional dual-energy X-ray absorptiometry (3D-DXA) in participants across all CKD stages.Patients and methodsIn total, 64 CKD patients (consisting of 28 female participants and 36 male participants, with an average age of 69.5 years) were included. There were 9, 12, 8, 9, 11, and 15 participants in stages G1, G2, G3a, G3b, G4, and G5 of CKD, respectively. BMD at the lumbar spine (LS) and proximal femur, as well as the LS TBS, were analyzed. The proximal femur parameters such as cortical and trabecular volumetric (v)BMD, cortical thickness (CTh), and surface (s)BMD at the total hip (TH) and femoral neck (FN) were analyzed using 3D-Shaper software.ResultsComparison between the earlier stages (G1-G3a) and the later CKD stages (G3b-G5) showed significant differences in carboxy terminal collagen crosslinks (CTx) (386 vs.1053 ng/L), TH areal bone mineral density (aBMD; 0.991 vs. 0.859 g/cm2), cortical TH vBMD (831 vs. 795 mg/cm3), FN (837 vs. 788 mg/cm3), TH cortical sBMD (170 mg/cm2), and TH Cth (2.03 vs. 1.92 mm; all p < 0.05). Cross-sectional comparisons between each CKD stage showed a gradual decrease in the LS BMD, TH cortical vBMD, sBMD (FN and TH), and TH Cth. Strong positive associations between the glomerular filtration rate (GFR) and cortical parameters (FN/TH vBMD and TH Cth) were observed (p < 0.01).ConclusionIn conclusion, advanced stages of CKD (G3b–G5) were associated with lower cortical bone parameters. The majority of the cortical parameters were correlated with the GFR, demonstrating a direct relationship between the kidney function and bone structure.

Background Osteoporosis is a chronic, systemic skeletal disease characterized by decreased bone mass and microarchitectural deterioration, leading to increased fracture risk. In Slovakia, its prevalence is estimated at 6%, with substantial health, social, and economic burdens. Objective The Slovak national guideline provides an overview for the diagnosis, prevention, and treatment of osteoporosis in Slovakia, reflecting recent scientific advances and recommendations from international bodies. Methods The guidelines were developed by a multidisciplinary expert panel and officially adopted by the Ministry of Health of the Slovak Republic. They are based on current evidence and international standards, including FRAX, IOF, ISCD, and ESCEO recommendations. Results Diagnosis involves clinical risk assessment, biochemical testing, and imaging—primarily DXA and trabecular bone score. FRAX with or without BMD enhances risk stratification. Osteoporosis is categorized as primary or secondary. Prevention strategies include lifestyle modification, calcium and vitamin D supplementation, and fall risk reduction. Pharmacologic treatment includes antiresorptive agents (bisphosphonates, denosumab, SERMs), osteoanabolic (teriparatide, romosozumab), and hormone therapy when indicated. Sequential treatment strategies are emphasized, particularly in high-risk individuals. Treatment monitoring includes bone turnover markers and periodic DXA. Conclusions The Slovak guidelines provide a comprehensive and pragmatic approach for the management of osteoporosis across all stages, emphasizing early diagnosis, personalized treatment, and long-term fracture prevention. They align with European and global best practices and support clinical decision-making across specialties.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and destruction of synovial joints. The RANK/RANKL/OPG system is critical in regulating bone metabolism and immune responses, making it a potential target for RA treatment. This review summarizes the current understanding of RANK/RANKL/OPG signalling in RA pathogenesis, highlighting its potential as a biomarker for disease activity and treatment response. We discuss the roles of various immune cells and cytokines in the inflammatory process, emphasizing the impact of RANKL on osteoclast differentiation and bone resorption. Additionally, we explore the therapeutic potential of targeting RANKL with denosumab, a monoclonal antibody that inhibits osteoclastogenesis. Finally, we examine the role of RANK/RANKL/OPG as a predictor of treatment success in patients with RA.

IntroductionAcromegaly is associated with increased vertebral fracture (VF) risk regardless of bone mineral density (BMD). However, the vertebral trabecular compartment is still low; a possible contributor to this may be impaired glucose metabolism (GM) which frequently complicates acromegaly. Additionally, soft tissue thickness may confound bone imaging in acromegaly patients.ObjectiveThis study aims to assess the association of GM with BMD, trabecular bone score adjusted for BMI (TBSBMI), and trabecular bone score adjusted for tissue thickness (TBSTT) among acromegaly subjects.Patients and methodsA cross-sectional study was performed among 70 consecutive acromegaly patients (24 male/46 female, aged 55.1 years) divided in two subgroups: abnormal GM (n = 35) and normal GM (n = 35). Using DXA, BMD, TBSBMI, TBSTT, and VF screening were performed.ResultsIn all subjects, TBSTT was higher (mean 9.5%) than TBSBMI. Abnormal GM subjects had lower TBSBMI (1.166 ± 0.15) than normal GM subjects (1.232 ± 0.12; p < 0.05). No between-group difference in TBSTT or BMD was observed. In a multiple regression model, the best predictor of TBSTT was HbA1c (p = 0.002). None of the DXA measures or GM parameters was a significant predictor of VF (n = 7).ConclusionThe abnormal GM acromegaly subjects had lower TBSBMI than those with normal GM. TBSTT was higher than TBSBMI, and no between-group difference based on GM status was observed. TBSTT was significantly associated with GM parameters, notably HbA1c. The relationship of TBSTT with GM parameters may imply an effect of GM on trabecular bone microstructure in patients with acromegaly; a further study is indicated.

Abstract Disclosure: M. Kuzma: None. J. Payer: None. P. Vanuga: None. I. Sagova: None. D. Pavai: None. P. Jackuliak: None. Z. Killinger: None. Introduction: Previously, it was thought that increased risk of vertebral fractures (VF) in acromegaly is associated with impaired trabecular bone. More recently, cortical bone was proposed as one of the fracture risk determinant. However, trabecular compartment is still decreased. Glucose intolerance is a frequent complication of acromegaly and is directly attributable to the excess circulating growth hormone and IGF-1 concentrations and thus possibly lead to trabecular bone detoriation.Objectives: To assess effect of glucose metabolism on DXA-derived bone parameters, such as bone mineral density (BMD), trabecular bone score (TBS), cortical and trabecular vBMD, surface BMD and cortical thickness of proximal femur among patients with acromegaly. Patients and methods: In total, 70 consecutive patients (24 males/56 female, mean age = 55.6 years) with acromegaly based on current ADA guidelines were divided in two subgroups according to glucose metabolism(GM): abnormal GM (n=35; 14 males/21 females; 15 with active disease) and normal GM (n=35;10 Males /25 Females; 11 with active disease). Subjects were prospectively followed up for two years. At baseline and year 2; all subjects had pituitary hormonal measures, fasting plasma glucose (FPG), HBA1c, C-peptide, insulin resistance index (IRI) and DXA measurement performed. From DXA, BMD, TBS and 3D-Shaper parameters were derived. Results: At baseline; subjects with abnormal GM had lower TBS (1.166±0.15) in comparison to normal GM subjects (1.232±0.12; p<0.05). Insulin like growth factor 1 (IGF-1), FPG, HBA1c, C-peptide, IRI and bone parameters was correlated in simple regression model. FPG, HBA1c, C-peptide and IRI was negatively associated with TBS. No correlation between GM parameters and other bone measures was observed. Multiple regression model of all GM parameters weighted by IGF-1 revealed HBA1c as a significant predictor of TBS value (Estimate =-0,054; p=0.04). At year 2; FPG and HBA1c was negatively associated with TBS. In multiple regression IGF-1-weighted model, no significant predictor of TBS was observed. Conclusion: Acromegaly subjects with abnormal GM have lower TBS in comparison to those with normal GM. The best GM parameter to predict TBS in acromegaly was HBA1c. This study showed that trabecular bone microstructure, as indirectly assessed by TBS, is likely resulting of impaired glucose metabolism. Presentation: Thursday, June 15, 2023

Abstract Background and Aims Newer markers of kidney damage and mineral and bone changes in chronic kidney disease (CKD) are needed. The fracture risk increases with worsening of CKD with highest incidence in later stages. Thus methods for early bone status assessment and laboratory marker of kidney function is needed. Aim of the study was to evaluate bone mineral density (BMD) and trabecular bone score (TBS) – a novel surrogate of trabecular bone microstructure, in relationship with newer laboratory markers of CKD, such as fibroblast growth factor 23 (FGF23) and klotho. Method A cross-sectional study during July 2018-July2019 was conducted. Plasma levels of soluble klotho and FGF23 were determined by ELISA (enzyme-linked immuno -assay). All patients undergone bone mineral density (BMD) and trabecular bone scores (TBS) measurement. Patients were divided into 2 groups as follows: A - patients in stages G1 - G3; B - patients in stages G4 – 5 accoridng to KDIGO. Results A total of 74 CKD patients (42 males and 32 females; mean age 68.8 years) were included in the study. Greater FGF23 levels in group B(N = 15) in comparison to group A (N = 59)(p = .001) were observed. FGF23 was associated with glomerular filtration (GF)(R = -0.43; p = 0.003), with greater levels of FGF23 at GF less than 0.8 ml/s. Significant difference in TBS within first 3 CKD stages (mean TBS in G1 = 1.374 vs. G2 = 1.304 vs. G3a = 1.24; p = 0.03) and negative correlation of FGF23 and TBS (R = -0.33; p = 0.05) and a positive correlation between klotho and TBS (R = 0.419; p = 0.04) was observed. Conclusion This study confirmed that FGF23 is associated with TBS. However, TBS reflects kidney function decline only in first 3 stages of CKD. Thus, FGF23 together with TBS are promising markers of early trabecular bone impairment in CKD.

Objectives There is no consensus on specific serum 25-hydroxy vitamin D (25(OH) D) levels associated with higher risk of severe outcome in patients with coronavirus disease 2019 (COVID-19). According to the literature patients with serum 25(OH) D levels <12 ng/ml are clearly deficient at all ages. Our aim was to assess COVID-19 mortality in the settings of severe 25(OH) D deficiency. A cohort study of 357 patients with COVID-19 was conducted. Subjects were monitored until discharge or in-hospital death. At admission, severity parameters (C-reactive protein (CRP), IL-6, Charlson comorbidity index, etc.) were assessed. These parameters were compared regarding 25(OH) D levels threshold 12 ng/ml, where values below 12 ng/ml were considered absolute vitamin D deficiency. Results 25(OH) D levels at the time of admission were independently associated with mortality (p <0.05). Nonsurvivors (N = 168) had lower 25(OH) D levels, SO2, higher age, CRP, viral load, and Charlson comorbidity index in comparison to survivors. Patients with serum 25(OH) D levels <12 ng/ml had higher mortality (55% vs 45 %), viral load (21.5 vs 23.1), and Charlson comorbidity index (5.3 vs 4.4) than those with serum 25(OH) D levels >12 ng/ml (p <0.05). Conclusions Patients with COVID-19 with serum 25(OH) D levels <12 ng/ml have higher mortality. Among other factors, severe vitamin D deficiency likely leads to poor outcome.

Administration of biological therapy (BT) in rheumatoid arthritis (RA) patients is often associated with hematological complications, which result in switching among therapies. Thus, there is an instant need for suitable screening parameters that will help to individualize the therapy and minimize the onset of adverse effects. We analyzed the hematological profile of 99 RA patients receiving TNFα (Adalimumab - ADA, Golimumab - GOL, Etanercept - ETA) or IL-6 receptor (Tocilizumab - TCZ) inhibitors in order to find possible indicators to improve personalization of RA therapy. BTs significantly affect the levels of observed hematological parameters. In contrast to TNF-α inhibitors, TCZ normalized almost all monitored hematological parameters to values of healthy donors. Only GOL from the TNF-α inhibitors studied, was able to normalize neutrophil counts, as well as platelet indicators. Importantly, effects on the blood parameters (e.g. lymphocytes or platelet count) differ even within the same therapeutic group (anti-TNFα). Variable effects of individual biological agents in RA treatment point to importance to evaluate the patient's hematological profile to improve the selection of suitable BT. It will help to personalize the administration of BT and prevent unnecessary switching from an effective therapy just because of provocation of avoidable hematological complications.

In contrast to postmenopausal women diagnostic process and treatment of premenopausal osteoporosis in young women reamin poorly defined. A low bone mineral density in premenopausal women is not associated with the same risk of fractures as in postmenopausal women, therefore diagnosis requires not only densitometric examination but depends on the consideration of other risk factors. Most cases of premenopausal osteoporosis are associated with chronic diseases affecting bone metabolism. Treatment of the underlying disease may improve bone density as well as bone quality. Rarely, a bone-specific antiporotic therapy may be used, although quality evidence is scarce. This article will review current opinion on definition, diagnosis and treatment of premenopausal osteoporosis.

Abstract Introduction: Vertebral fractures (VFs) in patients with acromegaly are not associated with bone mineral density (BMD) decrease. Previous studies showed impaired trabecular bone parameters among acromegaly patients. However, recent studies suggest that cortical bone could also play a role in VF development. Objective: Evaluate the utility of dual energy x-ray absorptiometry (DXA) BMD and bone structural parameters to determine VF risk among acromegaly patients. Patients and Methods: A single-center two years prospective follow up of acromegaly patients regardless of age, gender, disease activity or associated treatments was conducted. Pituitary hormones, glucose metabolism and bone turnover markers in all subjects were assessed. Each subject had L1-4 spine, femoral neck (FN) and total hip (TH) BMD measured using DXA, and TBS measurement performed ± 7 days from blood sampling. 3D Shaper was used to assess proximal femur trabecular and cortical volumetric (v) BMD, cortical surface (s) BMD and cortical thickness (Cth). VF assessment was performed using the lateral spine imaging IVA™ mode with a Hologic Horizon® densitometer using semi-quantitative approach. Study outcomes were assessed at two time points - baseline and month 24. Results: Seventy subjects (34 M/36F), mean age 55.1 years, including 26 with active disease were studied. After two years a significant decrease in IGF-1 (-30%), osteocalcin (-18%) and TH cortical vBMD (-3%; all p≤0.05) was observed. During follow-up, 13 patients nine of them with controlled disease, developed VF; these patients had greater increase in CTx and decrease in TBS, sBMD, cortical and trabecular vBMD at TH and neck. Multivariate analysis of fracture prediction showed cortical vBMD at TH and neck as best parameters for fracture prediction with AUC 0.766 and 0.774; respectively. TBS was negatively associated with fasting plasma glucose (FPG), HBA1c at each time period. Conclusions: Decrease in cortical vBMD was the most sensitive and specific predictor of incident VF suggesting that cortical bone is involved in fracture development among acromegaly patients. In addition, TBS was strongly negatively associated with glucose metabolism, suggesting glucose intolerance could lead to trabecular bone impairment.

Microscopic polyangiitis is a rare, systemic, necrotizing, pauci-immune, ANCA associated small vessel vasculitis, with no evidence of granulomatous inflammation. Diagnosing microscopic polyangiitis is often difficult because of it´s presentation by a number of non-specific symptoms. We treated a 35-year old patient, who was admitted for migrating arthritis and fever with papulous rash. In this case, we want to point out the importance of considering the diagnosis of MPA and similar rare diseases in the process of differential diagnosis, mainly in patients presenting with non-specific symptoms, because the mortality of this disease without adequate treatment is alarmingly high.

Abstract Introduction: Adult growth hormone deficiency (AGHD) is associated with lower bone mass and likely with increased risk of fragility fractures. GH replacement leads to increase in bone mineral density (BMD).However, only few studies longer than 2 years exist. Aim: To assess long-term effect of recombinant GH replacement on BMD and bone turnover markers duringperiod of 8 years. Patients & Methods: Prospective follow-up of all (N=63) AGHD patients at one single center. All patients with adult GHD followed at single center. All participants were replaced with daily injection of recombinant human (rh) GH in IGF-1 normalizing regimen according to Endocrine Society Guidelines. Every 2 years, lumbar spine (L-spine) and total hip (TH) BMD using dual X-ray absorptiometry on Hologic Discovery device, was assessed. All patients were assessed for bone turnover markers; carboxy-terminal collagen crosslinks (CTx) and osteocalcin (OC), and 25(OH)D levels. Deficiencies of other pituitary axes were treated if necessary. All patients were supplemented with 800 IU /day of cholecalciferol and 1000-1200mg/day of calcium as recommended by International Osteoporosis Foundation. Results: Study group consisted of 38 males and 25 females (35 with adult onset (AO) /28 with childhood onset (CO); mean age at diagnosis 25,1 yrs) AGHD patients. All patients ended 8 years follow-up period without any treatment discontinuation during this period. Treatment was well tolerated, without any serious adverse event. IGF-1 has reached the normal ranges during first 6 months and remains normal during whole study period documenting good adherence to treatment (average dose of rhGH=0,4 mg/day). Both, L-spine and TH BMD increased significantly after 8 years of GH replacement (+8 % for L-spine BMD, +7,7% for TH BMD, both p<0,01). The highest peak of BMD was observed after 6 years of treatment. CTx increased by 35% (p<0,05) and remain stable, and no significant change in OC was observed during study period. Levels of 25(OH)D increased by 32% (p<0,05) from baseline. No clinical fractures were observed. Conclusion: Long-term GH replacement in adult GHD together with sufficient levels of vitamin D levels led to increase in BMD and CTx. This study supported fact that GH has sustained effect on bone mass and bone turnover and is safe and well -tolerated for the long time period.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

The relationship between inflammation and formation of reactive oxygen species (ROS) is still not completely understood and excessive inflammatory reaction is attributed to increased yet also to reduced ROS formation. To compare ROS formation in severe and low inflammation, neutrophil oxidative burst was analyzed in rheumatic patients before and during therapy with TNFα- or interleukin-6 receptor-neutralizing antibodies.Intracellular and extracellular ROS productions were evaluated on the basis of luminol- and isoluminol-enhanced chemiluminescence in isolated peripheral neutrophils. Disease activity score DAS28 and platelet to lymphocyte ratio were used as markers of arthritis activity and the intensity of systemic inflammation.Biological therapy effectively reduced the intensity of inflammation. Of the twenty-six patients studied eighteen achieved remission or low disease activity. Highly active arthritis persisted only in one patient, though prior to the therapy it was evident in all subjects tested. In patients receiving biological therapy, intracellular chemiluminescence was significantly higher than in patients before this therapy; ROS produced by neutrophils extracellularly were not affected.The increased ROS formation associated with reduced inflammation supports the need to revise the view of the role of ROS in inflammation - from toxic agents promoting inflammation towards a more complex view of ROS as regulators of immune pathways with inflammation-limiting capacity. From this perspective, the interference with neutrophil-derived oxidants may represent a new mechanism involved in the anti-inflammatory activity of biological therapy.

Cardiovascular diseases (CVD) are the most common causes of mortality and morbidity in Slovakia, and therefore early assessment of cardiovascular risk profile for asymptomatic subjects remains one of the major medical problems. Recently, in addition to assessing standard cardiovascular risk factors (CV), attention on to the evaluation of abdominal aortic calcifications is focused. Several studies have shown incidence of aortic calcification as an independent risk factor of developing CV mortality, including ischemic stroke. To quantify aortic calcifications several scoring systems have been developed and many authors have shown that high aortic calcification index positively correlates with CV risk, independently of the presence of classical CV risk factors. Increased interest in their evaluation was also enhanced by the broadening of methods used for identifying calcifications in vessels such as USG, X­ray and CT, but also the use of a bone densitometry (DXA), which became a widely available method. To detect aortic calcifications by DXA a lateral projection could be used, similarly to detection of asymptomatic vertebral fracreviews | přehledové články | prehľadové články Received | Doručeno do redakce | Doručené do redakcie 4. 6. 2019 Accepted | Přijato po recenzi | Prijaté po recenzii 17. 6. 2019 proLékaře.cz | 1.11.2019