The presented guidelines are an update of the position paper, endorsed by the International Osteoporosis Foundation (IOF), on nomenclature of bone markers published over 2 decades ago. Novel insight into bone biology and pathophysiology of bone disorders has highlighted the increasing relevance of new and known mediators implicated in various aspects of bone metabolism. This updated guideline proposes the nomenclature Bone Status Indices (BSI) as the comprehensive classification rather than bone turnover markers, bone markers, metabolic markers of bone turnover or metabolic markers of bone turnover, that are currently in use for the implicated molecules. On behalf of the IFCC Committee on Bone Metabolism and the Joint IOF Working Group and IFCC Committee on Bone Metabolism, the authors propose standardized nomenclature, abbreviations and measurement units for the bone status indices.

• Klíčová slova
• bone status indices, nomenclature, standardization,
• MeSH
• biologické markery * metabolismus   analýza   MeSH
• kosti a kostní tkáň * metabolismus   MeSH
• lidé MeSH
• osteoporóza diagnóza   metabolismus   MeSH
• terminologie jako téma * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• směrnice MeSH
• Názvy látek
• biologické markery * MeSH

PURPOSE: This study evaluated the efficacy, safety, pharmacodynamics (PD), pharmacokinetics (PK), and immunogenicity of SB16 versus reference denosumab (DEN) up to 18 months in postmenopausal osteoporosis (PMO) patients, and assessed outcomes after switching from DEN to SB16 compared to those who continued with DEN or SB16. METHODS: 457 PMO patients were initially randomized, with 407 re-randomized at Month 12 to either continue DEN (DEN+DEN), switch to SB16 (DEN+SB16), or continue SB16 (SB16 + SB16) through Month 18. Efficacy was assessed by the percent change from baseline in bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck. Safety, PD, PK, and immunogenicity were evaluated throughout the study period. RESULTS: Mean percent changes from baseline in lumbar spine, total hip, and femoral neck BMD at Month 18 were comparable across treatment groups, indicating comparable efficacy between SB16 and DEN. The mean percent change in lumbar spine BMD was 6.8 % (SB16 + SB16), 6.2 % (DEN+SB16), and 6.8 % (DEN+DEN). Total hip BMD increased by 4.4 %, 3.5 %, and 4.0 %, and femoral neck BMD by 3.4 %, 3.1 %, and 2.7 % for SB16 + SB16, DEN+SB16, and DEN+DEN, respectively. Safety profiles were similar among groups, with no new safety concerns identified after switching. Only one patient in the DEN+SB16 group developed non-neutralizing anti-drug antibodies by Month 18, indicating a low immunogenicity risk for SB16. CONCLUSION: Switching from DEN to SB16 demonstrated comparable efficacy, safety, PD, PK, and immunogenicity in PMO patients relative to those who continued DEN. SB16 was well tolerated over 18 months, demonstrating comparable outcomes to DEN.

• Klíčová slova
• Biosimilar, Bone mineral density, Clinical trials, Denosumab, Postmenopausal osteoporosis, SB16,
• MeSH
• bederní obratle účinky léků   MeSH
• denosumab * terapeutické užití   MeSH
• inhibitory kostní resorpce * terapeutické užití   MeSH
• kostní denzita * účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• postmenopauzální osteoporóza * farmakoterapie   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• denosumab * MeSH
• inhibitory kostní resorpce * MeSH

PURPOSE OF THE REVIEW: The purpose of this Review was to summarize the evidence on the associations among estrogen status, cellular senescence, the gut microbiome and osteoporosis. RECENT FINDINGS: Indicate that osteoporosis is a global public health problem that impacts individuals and society. In postmenopausal women, a decrease in estrogen levels is associated with a decrease in gut microbial diversity and richness, as well as increased permeability of the gut barrier, which allows for low-grade inflammation. The direct effects of estrogen status on the association between bone and the gut microbiome were observed in untreated and treated ovariectomized women. In addition to the direct effects of estrogens on bone remodeling, estrogen therapy could reduce the risk of postmenopausal osteoporosis by preventing increased gut epithelial permeability, bacterial translocation and inflammaging. However, in studies comparing the gut microbiota of older women, there were no changes at the phylum level, suggesting that age-related comorbidities may have a greater impact on changes in the gut microbiota than menopausal status does. Estrogens modify bone health not only by directly influencing bone remodeling, but also indirectly by influencing the gut microbiota, gut barrier function and the resulting changes in immune system reactivity.

• Klíčová slova
• Aging, Estrogen, Inflammation, Leaky gut, Microbiota, Osteoporosis, Ovariectomy,
• MeSH
• estrogeny * MeSH
• lidé MeSH
• osteoporóza MeSH
• postmenopauzální osteoporóza * MeSH
• remodelace kosti * MeSH
• stárnutí buněk MeSH
• střevní mikroflóra * MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• estrogeny * MeSH

Schimke immuno-osseous dysplasia is a rare multisystemic disorder caused by biallelic loss of function of the SMARCAL1 gene that plays a pivotal role in replication fork stabilization and thus DNA repair. Individuals affected from this disease suffer from disproportionate growth failure, steroid resistant nephrotic syndrome leading to renal failure and primary immunodeficiency mediated by T cell lymphopenia. With infectious complications being the leading cause of death in this disease, researching the nature of the immunodeficiency is crucial, particularly as the state is exacerbated by loss of antibodies due to nephrotic syndrome or immunosuppressive treatment. Building on previous findings that identified the loss of IL-7 receptor expression as a possible cause of the immunodeficiency and increased sensitivity to radiation-induced damage, we have employed spectral cytometry and multiplex RNA-sequencing to assess the phenotype and function of T cells ex-vivo and to study changes induced by in-vitro UV irradiation and reaction of cells to the presence of IL-7. Our findings highlight the mature phenotype of T cells with proinflammatory Th1 skew and signs of exhaustion and lack of response to IL-7. UV light irradiation caused a severe increase in the apoptosis of T cells, however the expression of the genes related to immune response and regulation remained surprisingly similar to healthy cells. Due to the disease's rarity, more studies will be necessary for complete understanding of this unique immunodeficiency.

• Klíčová slova
• Cytometry, Exhaustion, IL-7, Immunodeficiency, Lymphopenia, Peritoneal dialysis, RNA-seq, SIOD, Schimke Imunoosseous dysplasia, Schimke immuno-osseous dysplasia, Spectral Cytometry, T cell, Thymus,
• MeSH
• apoptóza genetika   MeSH
• arterioskleróza genetika   etiologie   imunologie   MeSH
• dítě MeSH
• DNA-helikasy genetika   MeSH
• lidé MeSH
• metabolické nemoci kostí etiologie   genetika   MeSH
• nefrotický syndrom etiologie   genetika   MeSH
• oprava DNA * genetika   MeSH
• osteochondrodysplazie * genetika   imunologie   MeSH
• plicní embolie genetika   etiologie   MeSH
• poruchy růstu genetika   etiologie   MeSH
• primární imunodeficience * genetika   diagnóza   imunologie   MeSH
• syndromy imunologické nedostatečnosti genetika   imunologie   MeSH
• T-lymfocyty imunologie   MeSH
• ultrafialové záření škodlivé účinky   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA-helikasy MeSH
• SMARCAL1 protein, human MeSH Prohlížeč

Denosumab is a monoclonal antibody used to reduce risk of fractures in osteoporosis. ROSALIA was a multicenter, double-blind, randomized, integrated phase I/phase III study comparing the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and safety of proposed biosimilar denosumab GP2411 with reference denosumab (REF-DMAb) (Prolia®; Amgen). Postmenopausal women with osteoporosis were randomized 1:1 to 2 60-mg doses of GP2411 or REF-DMAb, one at study start and one at week 26. At week 52, the REF-DMAb group was re-randomized 1:1 to a third dose of REF-DMAb or switch to GP2411. The primary efficacy endpoint was percentage change from baseline (%CfB) in LS-BMD at week 52. Secondary efficacy endpoints were %CfB in LS-BMD, FN-BMD, and TH-BMD at weeks 26 and 78 (and week 52 for FN-BMD and TH-BMD). Primary PK and PD endpoints were the area under the serum concentration-time curve extrapolated to infinity and maximum drug serum concentration at week 26, and the area under the effect-time curve of the %CfB in serum CTX at week 26. Secondary PK and PD endpoints included drug serum concentrations and %CfB in serum CTX and P1NP during the study period. Similar efficacy was demonstrated at week 52, with 95% CIs of the difference in %CfB in LS-BMD between treatment groups fully contained within prespecified equivalence margins. Similarity in PK and PD was demonstrated at week 26. Immunogenicity was similar between groups and was not impacted by treatment switch. The rate of new vertebral fractures was comparable. Treatment-emergent adverse events were comparable between groups (63.6% [GP2411/GP2411]; 76.0% [REF-DMAb/REF-DMAb]; 76.6% [REF-DMAb/GP2411]). In conclusion, ROSALIA showed similar efficacy, PK and PD, and comparable safety and immunogenicity of GP2411 to REF-DMAb in postmenopausal osteoporosis.

Denosumab is a biologic treatment that stops bone breakdown. This clinical trial evaluated how similar GP2411 (a denosumab biosimilar in development) is compared with European-approved reference denosumab in women with post-menopausal osteoporosis. Biosimilars are highly similar to the original treatment (‘reference denosumab’) and may have a lower price. 263 patients were randomly assigned to receive GP2411 and 264 to reference denosumab. Treatment was given at the study beginning, at Week 26 and at Week 52. 124 patients were re-assigned at Week 52 to test the effect of changing from reference denosumab to GP2411. The study showed similarity in how the body interacts with the treatments, what effects the treatment has (both measured over 26 weeks), and bone mineral density (measured over 78 weeks). Antibody responses to GP2411 were detected in similar proportions of patients on each treatment. Reported adverse events were similar between treatments before Week 52, and from Week 52 to 78, and <5% of patients experienced serious adverse events. A change of treatment from reference denosumab to GP2411 did not affect outcomes. These results showed similarity between GP2411 and reference denosumab in this population. In future, GP2411 may enable more patients to benefit from denosumab.

• Klíčová slova
• bone modeling and remodeling: biochemical markers of bone turnover, clinical trials, diseases and disorders of/related to bone: osteoporosis,
• MeSH
• biosimilární léčivé přípravky * škodlivé účinky   MeSH
• denosumab škodlivé účinky   MeSH
• dvojitá slepá metoda MeSH
• inhibitory kostní resorpce * terapeutické užití   MeSH
• kostní denzita MeSH
• lidé MeSH
• osteoporóza * farmakoterapie   MeSH
• postmenopauzální osteoporóza * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnocení ekvivalence MeSH
• klinické zkoušky, fáze I MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• biosimilární léčivé přípravky * MeSH
• denosumab MeSH
• inhibitory kostní resorpce * MeSH

PURPOSE: To report the genetic etiology of Lisch epithelial corneal dystrophy (LECD). DESIGN: Multicenter cohort study. METHODS: A discovery cohort of 27 individuals with LECD from 17 families, including 7 affected members from the original LECD family, 6 patients from 2 new families and 14 simplex cases, was recruited. A cohort of 6 individuals carrying a pathogenic MCOLN1 (mucolipin 1) variant was reviewed for signs of LECD. Next-generation sequencing or targeted Sanger sequencing were used in all patients to identify pathogenic or likely pathogenic variants and penetrance of variants. RESULTS: Nine rare heterozygous MCOLN1 variants were identified in 23 of 27 affected individuals from 13 families. The truncating nature of 7 variants and functional testing of 1 missense variant indicated that they result in MCOLN1 haploinsufficiency. Importantly, in the homozygous and compound-heterozygous state, 4 of 9 LECD-associated variants cause the rare lysosomal storage disorder mucolipidosis IV (MLIV). Autosomal recessive MLIV is a systemic disease and comprises neurodegeneration as well as corneal opacity of infantile-onset with epithelial autofluorescent lysosomal inclusions. However, the 6 parents of 3 patients with MLIV confirmed to carry pathogenic MCOLN1 variants did not have the LECD phenotype, suggesting MCOLN1 haploinsufficiency may be associated with reduced penetrance and variable expressivity. CONCLUSIONS: MCOLN1 haploinsufficiency is the major cause of LECD. Based on the overlapping clinical features of corneal epithelial cells with autofluorescent inclusions reported in both LECD and MLIV, it is concluded that some carriers of MCOLN1 haploinsufficiency-causing variants present with LECD.

• MeSH
• dědičné dystrofie rohovky * diagnóza   genetika   MeSH
• kationtové kanály TRP * genetika   MeSH
• kohortové studie MeSH
• lidé MeSH
• mukolipidózy * diagnóza   genetika   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Názvy látek
• kationtové kanály TRP * MeSH
• MCOLN1 protein, human MeSH Prohlížeč

OBJECTIVES: The aim of this study is to examine the knowledge levels, beliefs, and self-efficacies of men regarding osteoporosis according to the health belief model. METHODS: Men aged 55 years and older were included in the study. After the descriptive characteristics of the participants were recorded, the Male Osteoporosis Knowledge Quiz, Osteoporosis Health Belief Scale, Osteoporosis Self-Efficacy Scale, and Osteoporosis Knowledge Test were administered to the participants face-to-face. RESULTS: A total of 435 men with an average age of 67.3 ± 0.4 years participated in the study. When the participants were categorized according to age subgroups, it was found that marital status (p = 0.002), economic status (p = 0.016), and education level (p < 0.001) differed with age. The results of the osteoporosis-specific measurement tools used in data collection also differed with age (p < 0.05). It was observed that men's levels of osteoporosis knowledge decreased with increasing age (p < 0.05). The lowest scores for the exercise benefits and health motivation subdimensions of the Osteoporosis Health Belief Scale and the Osteoporosis Self-Efficacy Scale were obtained from the subgroup that included the oldest participants (p < 0.05). The highest scores for the calcium barriers subdimension of the Osteoporosis Health Belief Scale were obtained from younger participants (p = 0.036). The level of osteoporosis knowledge showed a low-to-moderate correlation with each question of the Osteoporosis Health Belief Scale (p < 0.05). Age, education, associating the role of physiotherapy with primary-secondary treatment approaches, and health beliefs were the factors that affected the osteoporosis knowledge levels of the participating men (p < 0.05). CONCLUSIONS: The knowledge of osteoporosis and preventive beliefs and behaviours of men need to be increased. Knowledge and perceptions of susceptibility to osteoporosis should be developed in men with appropriate education from an early age. We recommend that exercise and physiotherapy approaches should be utilized to a greater extent, especially for individuals in the at-risk age range.

• Klíčová slova
• health belief, knowledge, male, osteoporosis,
• MeSH
• cvičení MeSH
• lidé MeSH
• model zdravotního přesvědčení MeSH
• osteoporóza * MeSH
• průřezové studie MeSH
• senioři MeSH
• stupeň vzdělání MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

Osteomalacia with characteristic histomorphometric, radiographic, laboratory and clinical features is a prominent syndrome of disturbed bone mineralisation in adulthood. From an etiological point of view, osteomalacia is usually caused by substrate (calcium, phosphate) deficiency, presence of excess mineralization inhibitors or deficiency or ineffectivness of mineralization facilitator (vitamin D). In proportion to the high number of congenital and acquired causes of osteomalacia, its clinical and laboratory picture is heterogeneous and rarely fully expressed. The treatment of a particular case is determined by the cause of osteomalacia and may (but does not necessarily) include correction of the underlying disease, administration of calcium and various forms of vitamin D, as well as orthopaedic interventions. For some of the hereditary forms, biological or replacement therapy is prospectively available. The article attempts to cover the whole range of osteomalacia variants, mentioning a fact discussed only in recent years - the occurrence of oligosymptomatic, incompletely expressed forms.

• Klíčová slova
• bone matrix, bone mineral, mineralization, osteoid, osteomalacia,
• MeSH
• lidé MeSH
• nedostatek vitaminu D * MeSH
• osteomalacie * diagnóza   etiologie   MeSH
• syndrom MeSH
• vápník MeSH
• vitamin D terapeutické užití   MeSH
• vitaminy terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• vápník MeSH
• vitamin D MeSH
• vitaminy MeSH

Osteoporosis is a systemic metabolic disease of the skeleton characterized by low bone strength that results in an increased risk of fracture. Fractures are associated with serious clinical consequences, including pain, disability, loss of independence, and death, as well as high healthcare costs. Early identification and intervention with patients at high risk for fracture is needed to reduce the burden of osteoporotic fractures. The identification of a patient at high risk of fracture should be followed by evaluation for factors contributing to low bone mineral density (BMD) and/or low bone quality, falls, and fractures. Components of the osteological evaluation include an assessment of BMD by dual-energy X-ray absorptiometry, osteoporosis-directed medical history and physical exam, laboratory studies, and possibly skeletal imaging. Disorders other than osteoporosis, requiring other types of treatment, may be found. This overview summarizes the basic procedures for the diagnosis and differential diagnosis of osteoporosis, which are necessary before starting treatment.

• Klíčová slova
• diagnosis, differential diagnosis, fractures, osteoporosis, type 2 diabetes mellitus,
• MeSH
• absorpční fotometrie škodlivé účinky   metody   MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• kostní denzita MeSH
• lidé MeSH
• osteoporotické fraktury * diagnóza   etiologie   MeSH
• osteoporóza * komplikace   diagnóza   MeSH
• rizikové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Osteoporosis is a chronic disease with high unmet medical need. It is characterized by low bone mass and deteriorated bone architecture, leading to increased risk of fragility fractures, with vertebral and hip fractures representing the highest risk of morbidity and mortality. The baseline therapeutic approach to osteoporosis treatment has been based on adequate intake of calcium and supplementation of vitamin D. In this review, we focus on two approved monoclonal antibodies, romosozumab and denosumab, which have been shown to be efficient and safe options to prevent patient fractures. Romosozumab is a humanized monoclonal antibody IgG2 isotype that extracellularly binds sclerostin with high affinity and specificity. Denosumab is a fully human monoclonal antibody IgG2 isotype that binds RANK ligand (RANKL) and prevents the interaction of RANKL with its receptor RANK. Denosumab is an antiresorptive that has been used for more than a decade, and romosozumab has recently been approved for clinical practice worldwide.

• Klíčová slova
• Bone disorders, Denosumab, Metabolic diseases, Osteoporosis, Romosozumab,
• MeSH
• denosumab * terapeutické užití   MeSH
• humanizované monoklonální protilátky * terapeutické užití   MeSH
• imunoglobulin G MeSH
• lidé MeSH
• osteoporóza * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• denosumab * MeSH
• humanizované monoklonální protilátky * MeSH
• imunoglobulin G MeSH
• romosozumab MeSH Prohlížeč