Dysregulated systemic immune responses during infectious spondylodiscitis (IS) may impair microbial clearance and bone resorption. Therefore, the aim of the study was to examine whether circulating regulatory T cells (Tregs) are elevated during IS and whether their frequency is associated with alterations in T cells and the presence of markers of bone resorption in the blood. A total of 19 patients hospitalized with IS were enrolled in this prospective study. Blood specimens were obtained during hospitalization and 6 weeks and 3 months after discharge. Flow cytometric analysis of CD4 and CD8 T cell subsets, the percentage of Tregs and serum levels of collagen type I fragments (S-CrossLap) were performed. Out of 19 enrolled patients with IS, microbial etiology was confirmed in 15 (78.9%) patients. All patients were treated with antibiotics for a median of 42 days, and no therapy failure was observed. Next, a significant serum C-reactive protein (S-CRP) decrease during the follow-up was observed, whereas the frequencies of Tregs remained higher than those of controls at all-time points (p < 0.001). In addition, Tregs demonstrated a weak negative correlation with S-CRP and S-CrossLap levels were within the norm at all-time points. Circulating Tregs were elevated in patients with IS and this elevation persisted even after the completion of antibiotic therapy. Moreover, this elevation was not associated with treatment failure, altered T cells, or increased markers of bone resorption.

• MeSH
• antibakteriální látky terapeutické užití   metabolismus   MeSH
• biologické markery metabolismus   MeSH
• discitida * diagnóza   farmakoterapie   metabolismus   MeSH
• lidé MeSH
• prospektivní studie MeSH
• regulační T-lymfocyty * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Objective: Osteoporosis and fragility fractures represent serious complications for the solid organ transplant population. The recommended osteoporosis therapy for organ recipients involves supplementation with calcium and vitamin D and bisphosphonate administration. However, these options can prove limited for patients with impaired renal function. An alternative therapy option is offered by denosumab, a monoclonal antibody that targets receptor activator of nuclear factor kappa-B ligand. Patients and methods: We evaluated 63 patients with osteoporosis (23 males and 40 females, age 56.4 ± 13.1 years) following solid organ transplantation (15 diabetic patients after simultaneous transplantation of the kidney and pancreas, 34 patients after kidney transplantation, and 14 patients with liver grafts). Osteoporosis was diagnosed according to standard DEXA examination using the Lunar Prodigy apparatus. Transplanted patients with impaired renal function were treated for osteoporosis of the lumbar spine (L-spine) and/or proximal femur with calcium and vitamin D supplementation and 60 mg of denosumab every 6 months between the years 2012 and 2017. The mean duration of the therapy was 1.65 ± 0.7 years. Results: After denosumab therapy, L-spine T-scores improved across the whole group, ranging from -2.7 ± 0.09 to -1.8 ± 1.0 (p < 0.001). T-score values for the proximal femur increased from -2.5 ± 0.8 to -2.0 ± 0.7 after the therapy (p < 0.01). We observed only a mild, statistically insignificant improvement in distal forearm T-scores. The mean increase in L-spine bone mineral density (BMD) was 11.5 ± 6.2% in subjects with osteoporosis at this site and 10.4 ± 6.1% in the case of all patients. BMD of the proximal femur increased by 10.4 ± 8.3% in patients with osteoporosis and by 7.5 ± 7.3% in all patients. Denosumab therapy decreased the prevalence of osteoporosis in the L-spine from 75 to 27% (p < 0.001) and proximal femur osteoporosis from 54 to 36% (p < 0.05). Denosumab therapy reduced elevated levels of osteocalcin and beta-crosslaps (βCTX) in comparison with baseline levels (p < 0.001) across the whole group of graft recipients. Conclusion: Denosumab therapy was well-tolerated and improved bone density in our group of solid organ transplant recipients. The indications are that denosumab could be a viable therapeutic option for transplanted patients with osteoporosis, especially in those with renal function impairment or bisphosphonate intolerance.

• Publikační typ
• časopisecké články MeSH

Malignant melanoma is a malignancy located predominantly in the skin and the incidence of melanoma increases. We compared the markers of bone metabolism - osteocalcin (OC), beta-carboxyterminal cross-linked telopeptide of type I collagen (β-CrossLaps, β-CTx) and tumour marker - human epididymis protein 4 (HE4) in the serum with finding during the entry examination and the check-up of whole-body bone scintigraphy of the patient with a malignant melanoma. Serum concentrations of OC, β-CTx, HE4 were determined in 1 patient (female, age 64 years) with malignant melanoma and correlated with the presence of equivocal bone metastases detected by whole-body bone scintigraphy (the entry examination and check-up after 6 months). Concentrations of bone metabolism markers decreased during six months and we observed progress in bone metastases. The change of the markers levels during the entry examination and the check-up of the whole-body bone scintigraphy with equivocal finding of bone metastases could be a sign of a possible initiating progression of malignant melanoma despite a clinically negative finding that does not prove the progression of the disease.

• MeSH
• kolagen typu I krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• melanom krev   patologie   MeSH
• nádorové biomarkery krev   MeSH
• nádory kostí krev   diagnostické zobrazování   sekundární   MeSH
• nádory kůže krev   patologie   MeSH
• osteokalcin krev   MeSH
• peptidy krev   MeSH
• radioisotopová scintigrafie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Východisko: Cílenou a bezpečnou léčbu minerálové a kostní nemoci při chronickém onemocnění ledvin (MBD-CKD) je možné stanovit na základě komplexní histomorfometrie jednotlivých forem kostní choroby se zastoupením řadových složek. U pacientů s vysokým kardiovaskulárním rizikem lze očekávat v relativně vysokém procentu obě krajní formy renální osteopatie (RO) podle rychlosti kostního obratu, přičemž cílená léčba se zásadně liší. Cíl: Cílem otevřené, pilotní prospektivní studie je komplexní histomorfometrie renální osteopatie u chronicky dialyzovaných pacientů, posouzení vztahu mezi vybranými sérovými markery osteoresorpce/osteonovotvorby k histomorfometrickým parametrům RO, zavedení metody do rutinní praxe u rizikové skupiny nemocných s CHRI. Soubor: 12 chronicky dialyzovaných pacientů (N-12, 8 žen, 4 muži, průměrný věk 74 let, průměrná délka dialyzačního léčení 38 měsíců) s vysokým kardiovaskulárním kalcifikačním indexem (CCI). Metodika: Odběry kostní tkáně trepanobiopticky a její histomorfometrické zhodnocení se statickými a dynamickými parametry renální osteopatie. Statické parametry zahrnovaly stanovení objemu a síly složek trabekulární a spongiózní kosti. Dynamické parametry byly určeny identifikací tetracyklinových linií. Biochemická charakteristika souboru zahrnovala vyšetření sérových markerů ve vztahu k novotvorbě i osteoresorpci. Ostatní charakteristiky souboru tvořily objem příštitných tělísek, Z-skóre pomocí DEXA vyšetření, diagnóza diabetu mellitu a délka dialyzační léčby. Výsledky: Pozitivní signifikantní korelace na 0,01 hladině významnosti byly prokázány mezi objemem kostního trámce a prokolagenem 1 a kalcitoninem, mezi sílou osteoidu a prokolagenem 1 a mezi objemem trabekulární kosti a sérovou hodnotou osteokalcinu. Statistická souvislost byla dále mezi Cross-laps, C-tel. kolagenu 1 a Z-skóre dle DEXA vyšetření. Byl prokázán vztah mezi tetracyklinovými liniemi, objemem kostní tkáně a sílou kostního trámce a mezi objemem osteoidu a objemem kostního trámce s délkou dialyzační léčby. Prokázaná souvislost byla i mezi objemem PT a prokolagenem 1. Závěr: Mezi klinicky a patogeneticky významné komplikace CHRI (chronické renální insuficience) patří změny fosfokalciového metabolismu. Ve složitých případech a u rizikových pacientů zůstává zlatým standardem kostní biopsie s histomorfometrickým vyšetřením ke komplexnímu posouzení kostních změn MBD-CKD (doporučení K/DOQi, ERA-EDTA).

Background: Targeted and safe treatment of chronic kidney disease – mineral and bone disorder (CKD-MBD) can be determined on the basis of comprehensive histomorphometry of particular forms of bone disease with the presence of ordinary components. In patients with high cardiovascular risk both extreme forms of renal osteopathy (RO) can be expected in a relatively high percentage according to the rate of bone turnover with a fundamentally different therapy for each form. Objective: The aim of this open, prospective pilot study is a comprehensive histomorphometry of renal osteopathy in chronic dialysis patients, assessment of the relationship between selected serum markers of bone resorption and formation and histomorphometric parameters of RO, and introduction of this method into routine practice in the high-risk group of patients with chronic renal insufficiency. Patients: 12 chronic dialysis patients (N-12, 8 women and 4 men, average age 74 years, average duration of dialysis treatment 38 months) with high cardiovascular calcification index (CCI). Methods: Samples of bone tissue were obtained by trepanobiopsy and histomorphometrically evaluated using static and dynamic parameters of renal osteopathy. Static parameters include the determination of the volume and thickness of trabecular and spongiosa bone. Dynamic parameters were determined by identifying the tetracycline lines. Biochemical characteristics of the cohort included examination of serum markers related to bone formation and resorption. Other cohort characteristics comprised parathyroid gland volume, Z-score by DEXA examination, diagnosis of diabetes mellitus and duration of dialysis treatment. Results: Statistically significant positive correlations (p<0.01) were demonstrated between the volume of bone trabeculae and type I procollagen and calcitonin, between the osteoid thickness and type I procollagen and the trabecular bone volume and serum osteocalcin. Furthermore, a statistically significant association was found between the Crosslaps, type I collagen C-telopeptides and Z-score using DEXA examination. An association kostbetween the tetracycline lines, bone volume and trabecular thickness was found, as well as between osteoid volume and the volume of bone trabeculae with the duration of dialysis treatment. Moreover, a relationship was demonstrated between the PT volume and type I procollagen. Conclusion: Changes in calcium and phosphorus metabolism belong to the clinically and pathogenetically significant complications of chronic renal insufficiency. In complex cases and in patients at risk a bone biopsy with histomorphometrical examination for a comprehensive assessment of bone changes in CKD-MBD (K / DOQi, ERA-EDTA recommendations) remain the gold standard.

• Klíčová slova
• histomorfometrie kostní tkáně,
• MeSH
• biologické markery krev   MeSH
• biopsie metody   MeSH
• chronická renální insuficience komplikace   MeSH
• chronické selhání ledvin komplikace   metabolismus   MeSH
• dialýza ledvin MeSH
• financování organizované MeSH
• histologické techniky metody   MeSH
• kardiovaskulární nemoci komplikace   prevence a kontrola   MeSH
• kosti a kostní tkáň metabolismus   patofyziologie   MeSH
• kostní denzita MeSH
• lidé MeSH
• minerálová a kostní nemoc při chronickém onemocnění ledvin diagnóza   komplikace   patofyziologie   MeSH
• pilotní projekty MeSH
• prospektivní studie MeSH
• remodelace kosti fyziologie   MeSH
• resorpce kosti diagnóza   komplikace   MeSH
• senioři MeSH
• statistika jako téma MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH

Transient hyperphosphatasemia of infancy and early childhood (THI) is characterized by a temporary isolated elevation of serum alkaline phosphatase activity (ALP), predominantly its bone or liver isoform, in either sick or healthy children under 5 years of age. Return to normal ALP levels usually occurs within four months. Spontaneous rise of ALP might concern the physician, especially when treating seriously ill children. However, THI is considered a benign biochemical disorder with no clinical consequences. Some existing reports support the hypothesis that THI is a result of increased bone turnover. We present evidence of normal bone turnover in two children with THI. In a one-year-old girl and a boy of the same age, high ALP levels (31 and 109 µkat/L, respectively) were accidentally detected. The children had no signs of metabolic bone disease or of liver disease. The high ALP levels returned to normal in two months, thus fulfilling the diagnosis of THI. In both patients, serum parathyroid hormone and bone turnover markers, serum CrossLaps, and serum osteocalcin were neither elevated, nor did these markers follow the ALP dynamics, thus reflecting normal bone turnover in THI. Children with THI should be spared from extensive investigations and unnecessary vitamin D treatment.

• MeSH
• alkalická fosfatasa krev   MeSH
• biologické markery krev   MeSH
• kojenec MeSH
• lidé MeSH
• náhodný nález MeSH
• neprospívání etiologie   MeSH
• průjem etiologie   MeSH
• spontánní remise MeSH
• vývoj dítěte * MeSH
• vývoj kostí * MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Laboratorní příručka Ústavu klinické biochemie a patobiochemie slouží jako interní materiál pro pracovníky FN v Motole.

• MeSH
• biochemická analýza krve MeSH
• klinická chemie metody   MeSH
• klinické laboratorní techniky klasifikace   MeSH
• odběr biologického vzorku MeSH
• Publikační typ
• příručky MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• chemie, klinická chemie

Vascular calcifications (VCs) are frequently observed in chronic kidney disease (CKD) and haemodialysis (HD) patients. They have been associated with numerous factors, particularly hyperphosphataemia, excess calcium load, hypertension and increased mortality rate. The purpose of this study is to measure VCs in long-HD patients with good blood pressure and phosphate control, with the occasional use of sevelamer, using a plain radiological score to identify the associated factors and effects on the 1-year survival rate. METHODS: We studied HD patients from one centre using a semi-quantitative score ranging from 0 to 3 according to the severity and extent of VCs. The following patients' characteristics were compared according to their VC scores: medical history, treatments, blood pressure, standard biological data, fibroblast growth factor (FGF) 23, osteoprotegerin (OPG), whole PTH, beta-crosslaps, bone alkaline phosphatases and bone mineral density scores. One-year survival analyses were also performed. RESULTS: Among the 250 HD patients of the centre, 161 were studied; the mean age was 67.2 +/- 13 years, 45% of the subjects were females, 35% were diabetics, and they had been on dialysis for between 1-486 months (median: 45 months) with a 3 x 5-3 x 8 h dialysis schedule using 1.5 mmol/l dialysate calcium and providing a mean 2.25 +/- 0.5 Kt/V. Only 17% of the patients were free from VCs and 11% had severe VCs. The factors associated with VCs were classified into 'classic' (age, diabetes, male gender, tobacco use, inflammation, more frequent warfarin treatment and peripheral vascular and cardiac diseases) and 'non-traditional' (higher FGF-23 and OPG serum levels, low albumin serum levels and low alfacalcidol and CaCO(3) use). In logistic regression, only age, diabetes and FGF-23 serum levels were associated with VC scores of 2 and 3. The patients with a score of 3 had a higher 1-year mortality rate (RR 2.1; P = 0.01) as compared to patients with a 0 score. CONCLUSION: A plain radiological score showed the high prevalence (83%) of VCs in HD patients in spite of a long and intensive dialysis strategy and adherence to guidelines. The main associated factors were classic factors such as ageing and diabetes. No relationship was found with blood pressure and phosphataemia that remained well controlled in long dialysis; the association with FGF-23 serum levels may aggregate some non-traditional risk factors. The harmful effects of VCs on survival require their systematic assessment and optimization of the potentially modifiable associated factors in CKD and HD patients.

• MeSH
• chelátory terapeutické užití   MeSH
• chronická nemoc MeSH
• dialýza ledvin MeSH
• incidence MeSH
• kalcinóza epidemiologie   radiografie   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• nemoci ledvin komplikace   mortalita   terapie   MeSH
• onemocnění periferních cév epidemiologie   radiografie   MeSH
• polyaminy terapeutické užití   MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH

The aim of this study was to assess the effects of the antiresorptive treatments of alendronate (ALN), risedronate (RIS) and raloxifene (RLX) on the response of bone to endogenous parathyroid hormone (PTH) induced by acute hypocalcemia. Forty women (age, 55-80 years) with postmenopausal osteoporosis (treated with ALN, RIS and RLX or untreated-control group) were given infusions of sodium ethylenediaminetetraacetic acid (EDTA; 10 mg/kg of body weight). Serum ionized calcium (iCa), plasma intact PTH and marker of bone resorption, serum beta C-terminal telopeptide of type I collagen (beta-CTX; beta CrossLaps) were followed for 180 min. In all women, decrease in serum iCa following the EDTA load resulted in an acute increase in serum PTH. Between 60 and 180 min, plasma PTH in the ALN and RIS treated women remained significantly higher than in the control group. The integrated beta-CTX responses (area under curves, AUCs) to peaks of PTH were significantly lower in the ALN treated women than in those treated with RIS, RLX or control group. There was no significant difference in beta-CTX AUC response to PTH between RIS, RLX and control women. Taken together, these findings suggest that in women with postmenopausal osteoporosis treated with ALN, a substantial reduction of bone turnover blunts the acute bone resorbing effect of endogenous PTH.

• MeSH
• alendronát terapeutické užití   MeSH
• biologické markery krev   MeSH
• chelátory farmakologie   MeSH
• EDTA farmakologie   MeSH
• financování organizované MeSH
• hypokalcemie chemicky indukované   MeSH
• inhibitory kostní resorpce terapeutické užití   MeSH
• kolagen typu I účinky léků   MeSH
• kyselina etidronová analogy a deriváty   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• parathormon metabolismus   MeSH
• peptidy účinky léků   MeSH
• plocha pod křivkou MeSH
• postmenopauzální osteoporóza farmakoterapie   krev   MeSH
• raloxifen hydrochlorid terapeutické užití   MeSH
• remodelace kosti účinky léků   MeSH
• resorpce kosti metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH

Cíl studie: U 60 nemocných s karcinomem prsu jsme vyšetřovali sérové hladiny markeru novotvorby kostí, prokolagen typu 1 N-terminální propeptidu (P1NP) a markerů kostní resorpce, β-CrossLaps (β-CTX) a C-Telopeptid kolagenu typu I (ICTP). U 44 nemocných byly přítomny kostní metastázy a byly léčeny bisfosfonáty, 16 nemocných bylo bez přítomnosti metastatického procesu. Cílem studie bylo vyhodnotit senzitivitu a specifi citu vzhledem k přítomnosti kostních metastáz a efektu terapie bisfosfonáty. Metody: Sérové hladiny kostních markerů β-CrossLaps (CTX) a P1NP jsme stanovovali na analyzátoru Elecsys 2010 (Roche), ICTP byl stanovován manuální EIA metodou (Orion – Diagnostica). Nemocným s prokázanými kostními metastázami (n = 44) byla aplikována terapie bisfosfonáty (Zoledronat 4 mg/28 dní). Analýza kostních markerů byla prováděna před zahájením terapie a 14., 28. a 56. den terapie. Výsledky: Nejvyšší validitu vyšetření pro detekci kostních metastáz karcinomu prsu a reakci na terapii jsme prokázali pro ICTP (specifi cita 89,5% a senzitivita 79,5%). Závěr: Z dosažených výsledků se ICTP jeví jako specifi cký marker kostní remodelace a představuje citlivou a snadnou metodu detekce kostních metastáz i monitorování efektu jejich terapie.

Objective: Biochemical markers of bone formation such as procollagen of type 1 N-terminal propeptide (P1NP) and bone resorption such as beta-CrossLaps (β-CTX) and cross linked c-telopeptide of type I collagen (ICTP) are considered possible non-invasive markers of bone metastases. Our objective was to determine validity of bone markers in the detection of bone metastases and in response to bisphosphonate therapy. Methods: We investigated 60 patients with breast carcinoma: 16 without bone metastases and 44 with metastases treated with Zoledronat 4 mg/28 days. Serum concentrations of β-CTX and P1NP were measured using immunoanalyser Elecsys 2010 (Roche) and ICTP by manual competitive immunoassay (Orion Diagnostica). Determinations of bone markers were performed prior to bisphosphonate therapy and after 2 weeks, 1 month and 2 months during therapy. Results: ICTP proved to have the highest diagnostic validity in detection of bone metastases reaching (specifi city 89,5% and sensitivity 79,5%). Conclusion: ICTP is a highly specifi c marker of bone degradation useful in diagnosis of bone metastases and monitoring of therapeutical effect of bisphosphonate.

• MeSH
• bisfosfonáty aplikace a dávkování   terapeutické užití   MeSH
• financování organizované MeSH
• lidé MeSH
• metaloendopeptidasy diagnostické užití   MeSH
• metastázy nádorů diagnóza   MeSH
• monitorování léčiv MeSH
• nádorové biomarkery krev   MeSH
• nádory kostí farmakoterapie   sekundární   MeSH
• nádory prsu komplikace   MeSH
• resorpce kosti diagnóza   krev   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH

• MeSH
• aplikace orální MeSH
• bederní obratle metabolismus   MeSH
• kolagen krev   MeSH
• lidé MeSH
• parathormon krev   MeSH
• postmenopauza MeSH
• resorpce kosti metabolismus   MeSH
• vápník aplikace a dávkování   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH