Osteoporoza u osób w wieku podeszłym — patogeneza, ocena ryzyka złamań i skuteczność przeciwzłamaniowa leków

Osteoporoza jest ważnym problemem zdrowotnym wieku podeszłego. Złamania osteoporotyczne, w większości przypadków będące pierwszą manifestacją choroby, są przyczyną obniżenia jakości życia, zwiększonej umieralności, a także mają poważne konsekwencje ekonomiczne. Gęstość mineralna kości, mierzona przy użyciu badania densytometrycznego, nie jest już jedynym determinantem progu interwencji farmakologicznej. Obecnie decyzję terapeutyczną należy podjąć w zależności od bezwzględnego ryzyka złamania. W ostatnich latach opracowano powszechnie akceptowaną metodę oceny ryzyka złamań osteoporotycznych (FRAX), która jest wykorzystywana w codziennej praktyce klinicznej. Służy ona wczesnemu rozpoczynaniu skutecznego postępowania, a tym samym zmniejszeniu częstości złamań i zwiększeniu efektywności kosztowej leczenia osteoporozy. W artykule autorzy prezentują specyfikę osteoporozy inwolucyjnej, metodę FRAX — narzędzie do oceny ryzyka złamań osteoporotycznych — oraz wyniki badań klinicznych, które wyłoniły leki o udowodnionej skuteczności przeciwzłamaniowej u pacjentów w podeszłym wieku. Medycyna Wieku Podeszłego 2011, 1 (1), 23–2

Vitamin D serum concentration is not related to the activity of spondyloarthritis : preliminary study

Objective: Vitamin D plays an important role in mineral turnover and bone remodeling and there are increasing data about its immunomodulatory potential in different rheumatologic disorders. Deficiency of vitamin D is frequent in patients with spondyloarthritis (SpA) and some data suggest its association with increased disease activity and structural damage. However, its exact role in the pathogenesis of SpA and its association with disease activity are still a matter of debate. Material and methods: A cross-sectional study of patients diagnosed with axial spondyloarthritis (axSpA) and peripheral spondyloarthritis (perSpA) according to Assessment of Spondyloarthritis International Society classification criteria was performed. The correlation between concentration of 25-hydroxyvitamin D - 25(OH)D - and disease activity scores (Bath Ankylosing Spondylitis Disease Activity Index - BASDAI, Ankylosing Spondylitis Disease Activity Score - ASDAS), inflammatory markers (C-reactive protein - CRP, erythrocyte sedimentation rate - ESR) and clinical symptoms (arthritis, enthesitis, dactylitis) was performed. Results: We included 40 patients with axSpA and 23 patients with perSpA. The mean concentration of 25(OH)D was 24.9 ng/ml (SD 12.49). Forty-seven (74.6%) patients had 25(OH)D below the recommended threshold (< 30 ng/ml). We found no statistically significant negative correlation between the level of 25(OH)D and disease activity of axSpA and perSpA in terms of clinical symptoms (arthritis, enthesitis, dactylitis), inflammatory markers (ESR, CRP) and disease activity scores (BASDAI, ASDAS). These results did not change after adjustment for supplementation of vitamin D and seasonal variation. Conclusions: Our data show no correlation between the concentration of 25(OH)D in the serum and disease activity in two subgroups of SpA. However, this does not exclude the potential role of vitamin D in pathogenesis of SpA. Further studies are required to evaluate the optimal range of 25(OH)D serum concentration in axSpA and perSpA patients with its possible immunomodulatory potential and influence on disease activity

The absolute number of circulating nonclassical (CD14+CD16++CD14^{+}CD16^{++}) monocytes negatively correlates with DAS28 and swollen joint count in patients with peripheral spondyloarthritis

A different clinical course and pattern of skeletal involvement in peripheral and axial spondyloarthritis (SpA) suggests a distinct pathophysiology of these 2 phenotypic manifestations of SpA. Monocytes, as part of the innate immune system, seem to play an important role in the pathogenesis of SpA, but the exact inflammatory pathways remain to be elucidated. Regulatory T lymphocytes ($T_{reg}$) and Th17 lymphocytes are also known to influence proinflammatory and anti‑inflammatory reactions. The aim of our study was to compare the absolute numbers of monocyte subpopulations, $T_{reg}$, and Th17 lymphocytes with clinical measures of disease activity in patients with peripheral and axial SpA. We enrolled 21 patients with peripheral SpA and 27 patients with axial SpA diagnosed according to the Assessment of SpondyloArthritis International Society classification criteria, as well as 23 healthy controls. Patients were under 45 years, naïve to synthetic and biological disease‑modifying antirheumatic drugs and without the administration of systemic glucocorticoids. The absolute numbers of classical, intermediate, nonclassical monocytes, $T_{reg}$, and Th17 in peripheral blood were analyzed. Disease activity was assessed using the Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Disease Activity Score 28 (DAS28). In patients with SpA, the number of circulating nonclassical monocytes was decreased in comparison with controls. Only in the peripheral SpA group, a significant negative correlation was found between the concentration of nonclassical monocytes and DAS28 and the number of swollen joints. The 3 groups did not differ in terms of the concentrations of classical or intermediate monocytes and $T_{reg}$ or Th17 lymphocytes. Nonclassical monocytes may play a role in induction and perpetuation of peripheral joint inflammation, at least in peripheral SpA, as cells infiltrating the synovium

Low-field magnetic resonance and high-resolution ultrasound imaging of the wrist, metacarpophalangeal and proximal interphalangeal joints combined with anticyclic citrullinated peptide antibodies and rheumatoid factors in the diagnosis of early rheumatoid arthritis in patients with undifferentiated polyarthritis

Cel pracy: Ustalenie przydatności wykonania niskopolowego rezonansu magnetycznego (MR) i ultrasonografii (USG) stawów nadgarstka, śródręczno-paliczkowych (MCP) i międzypaliczkowych bliższych (PIP), a także oznaczenia czynników reumatoidalnych w klasie IgG, IgA i IgM oraz przeciwciał antycytrulinowych w klasie IgG (aCCP2) i w klasach IgG/IgA (aCCP3) w surowicy w rozpoznawaniu wczesnego reumatoidalnego zapalenia stawów (RZS) u pacjentów z niezróżnicowanym zapaleniem wielostawowym, u których istnieje duże podejrzenie kliniczne RZS przy braku nadżerek w wyjściowym RTG rąk. Materiał i metody: Zastosowano następujące kryteria kwalifikacji: 1) wiek > 18 lat, 2) jednoczesne zapalenie > 4 stawów, 3) zapalenie stawów nadgarstka i/lub śródręczno-paliczkowych, i/lub międzypaliczkowych bliższych, 4) sztywność poranna > 30 min, 5) początek zapalenia stawów > 12 tyg., 6) brak nadżerek w dostarczonym RTG rąk. U 21 pacjentów wykonano MR, USG i RTG cyfrowe nadgarstków, MCP i PIP, oznaczono w surowicy czynniki reumatoidalne w klasie IgM, IgG i IgA oraz przeciwciała antycytrulinowe w klasach IgG (aCCP 2 generacji) i IgG/IgA (aCCP 3 generacji). Wyniki: Największą liczbę nadżerek stwierdzono w MR; średnia liczba nadżerek u jednego pacjenta w MR i USG wynosiła odpowiednio 11,85 i 2,42 (p < 0,05). W każdej z technik najwięcej nadżerek obrazowano w kościach nadgarstka; 83% w RTG, 49% w USG i 76% w MR. Korelacja okresu trwania objawów zapalenia z liczbą nadżerek była istotna statystycznie tylko dla badania techniką USG. U 12 pacjentów stwierdzono aCCP IgG, u 14 aCCP IgG/IgA; RF IgM u 14 pacjentów, RF IgA u 17 i RF IgG u 20. Porównanie wyników aCCP IgG z aCCP IgG/IgA wykazało istotną statystycznie różnicę na korzyść aCCP IgG/IgA. Nie udało się wykazać korelacji poszczególnych czynników reumatoidalnych z aCCP IgG lub aCCP IgG/IgA. Korelację liczby nadżerek wykrytych techniką MR ze stężeniem markerów immunologicznych (aCCP i RF) udało się określić tylko dla aCCP IgG (r = –0,5, p = 0,02); nie wykazano podobnych korelacji dla RTG i USG. Wnioski: Badanie stawów rąk techniką MR w niezróżnicowanym zapaleniu wielostawowym, w porównaniu z RTG i USG, najlepiej wykrywa nadżerki, szczególnie w stawach nadgarstkowych. Dodatnie wyniki aCCP3 (IgG/IgA) we krwi w niezróżnicowanym zapaleniu wielostawowym stwierdza się u większej liczby pacjentów i w większych stężeniach niż aCCP2 (IgG).Objective: The purpose of the study was to assess the utility of low-field magnetic resonance (MR) and high-resolution ultrasound (US) of the wrist, metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints, anti-cyclic citrullinated peptide antibodies (aCCP IgG, aCCP IgG/IgA) and rheumatoid factors (IgG, IgA, IgM) in the diagnosis of early rheumatoid arthritis (RA) in patients with undifferentiated polyarthritis with a strong clinical suspicion of RA with no erosions on hand X-ray. Material and methods: The following inclusion criteria were used: 1) age > 18 years, 2) inflammation > 4 joints, 3) inflammation of wrist, MCP or PIP joints, 4) morning stiffness > 30 min, 5) arthritis onset > 12 weeks, 6) lack of erosions on hand X-ray on referral. In 21 patients MR, US and digital X-ray of the wrist, MCP and PIP joints were performed along with blood RF IgM, RF IgG and RF IgA, aCCP IgG and aCCP IgG/IgA assessment. Results: The highest number of erosions was detected in MRI; the average number of erosions per patient in MRI and US was 11.85 and 2.42 respectively (p < 0.05). In each technique the majority of erosions were detected within the wrist: 83% in X-ray, 49% in US and 76% in MRI. Only for US was there a significant correlation between duration of joint inflammation and the number of erosions. aCCP IgG and aCCP IgG/IgA were found in 12 and 14 patients, respectively, and RF IgM in 14, RF IgA in 17 and RF IgG in 20 patients. The results of aCCP IgG and aCCP IgG/IgA revealed a statistically significant difference in favour of aCCP IgG/IgA. There was no correlation between rheumatoid factors and aCCP IgG or aCCP IgG/IgA. The correlation between the number of erosions in MRI and the concentration of immunological markers (aCCP and RF) in the blood was statistically significant only for aCCP IgG (r = –0.5, p = 0.02); no similar correlations were revealed for X-ray and US. Conclusions: The best technique for detection of erosions, especially in the wrist region in undifferentiated polyarthritis, is MRI in comparison to X-ray and US. Positive results of aCCP3 (IgG/IgA) in undifferentiated polyarthritis are more frequent and are present in higher values than positive results of aCCP2 (IgG)

Results from Polish Spondyloarthritis Initiative registry (PolSPI) : methodology and data from : the first year of observation

Objectives: Report on one-year results from the Polish Spondyloarthritis Initiative registry (PolSPI), containing the cross-sectional analysis of clinical and imaging data as well as database methodology. Material and methods: The PolSPI registry includes patients with axial (axSpA) and peripheral (per- SpA) spondyloarthritis according to ASAS classification criteria, and/or patients with ankylosing spondylitis according to modified New York criteria, psoriatic arthritis according to CASPAR criteria, arthropathy in inflammatory bowel disease, reactive arthritis, juvenile spondyloarthritis or undifferentiated spondyloarthritis. Epidemiologic data and history of signs, symptoms and treatment of spondyloarthritis are collected and assessment of disease activity is performed. Radiographic images of sacroiliac joint, cervical and lumbar spine, and results of bone densitometry are collected. Every 6 months blood samples for inflammatory markers, and for long-term storage are taken. Results: During a one-year period from September 2015 to August 2016, 63 patients were registered on an electronic database; 44 (69.8%) of patients were classified as axial spondyloarthritis (axSpA) and 19 (30.2%) as peripheral spondyloarthritis (perSpA) according to ASAS criteria. Statistically significant differences between axSpA and perSpA were discovered in the percentage of HLA-B27 antigen occurrence (92.6% and 50%, respectively), BASDAI (2.8% and 4.1%, respectively), DAS 28 (2.66% and 4.03%, respectively), percentage of peripheral arthritis (20% and 88.8%, respectively), enthesitis (26.7% and 70.6%, respectively), dactylitis (6.7% and 88.9%, respectively), as well as extra-articular symptoms: acute anterior uveitis (26.7% and 5.6% , respectively) and psoriasis (6.9% and 55.6%, respectively). Patients with axSpA had significantly higher mean grade of sacroiliac involvement according to New York criteria, higher mSASSS score, and lower T-score in femoral neck in bone densitometry. Conclusions: At the early stage of the disease patients with axSpA compared to those with perSpA, have more advanced structural damage of sacroiliac joints and spine, and lower bone mineral density in the femoral neck. In the upcoming years the PolSPI registry will prospectively follow-up patients with SpA, recording response to treatment and carrying out research on interaction of inflammation and bone remodelling

Monocyte subpopulations display disease-specific miRNA signatures depending on the subform of Spondyloarthropathy

Spondyloarthropathies (SpA) are a family of rheumatic disorders that could be divided into axial (axSpA) and peripheral (perSpA) sub-forms depending on the disease clinical presentation. The chronic inflammation is believed to be driven by innate immune cells such as monocytes, rather than self-reactive cells of adaptive immune system. The aim of the study was to investigate the micro-RNA (miRNA) profiles in monocyte subpopulations (classical, intermediate and non-classical subpopulations) acquired from SpA patients or healthy individuals in search for prospective disease specific and/or disease subtype differentiating miRNA markers. Several SpA-specific and axSpA/perSpA differentiating miRNAs have been identified that appear to be characteristic for specific monocyte subpopulation. For classical monocytes, upregulation of miR-567 and miR-943 was found to be SpA-specific, whereas downregulation of miR-1262 could serve as axSpA-differentiating, and the expression pattern of miR-23a, miR-34c, mi-591 and miR-630 as perSpA-differentiating markers. For intermediate monocytes, expression levels of miR-103, miR-125b, miR-140, miR-374, miR-376c and miR-1249 could be used to distinguish SpA patients from healthy donors, whereas the expression pattern of miR-155 was identified as characteristic for perSpA. For non-classical monocytes, differential expression of miR-195 was recognized as general SpA indicator, while upregulation of miR-454 and miR-487b could serve as axSpA-differentiating, and miR-1291 as perSpA-differentiating markers. Our data indicate for the first time that in different SpA subtypes, monocyte subpopulations bear disease-specific miRNA signatures that could be relevant for SpA diagnosis/differentiation process and may help to understand SpA etiopathology in the context of already known functions of monocyte subpopulations