Simeon Grazio

Osteoporosis in psoriatic arthritis: Is there any?

ZusammenfassungZIELE: Obwohl es als ein Merkmal entzündlich-rheumatischer Erkrankungen angesehen wird, gibt es viel Kontroverse über die niedrige Knochenmasse bei Patienten mit psoriatischer Arthritis. Das Ziel dieser Querschnittsstudie war es, die Knochenmineraldichte bei Patienten mit psoriatischer Arthritis zu analysieren, sowie ihre mögliche Verbindung mit einigen Ausmaßen der Krankheitsaktivität und funktionaler Kapazität zu untersuchen. PROBANDEN UND METHODEN: Neunundsechzig Patienten, bei denen psoriatische Arthritis festgestellt wurde (Durchschnittsalter 56,20 ± 12,23 Jahre), und die nicht mit gezielten antiosteoporotischen Medikamenten behandelt wurden, wurden aus der klinischen Datenbank ambulanter Patienten angeworben. Die Knochenmineraldichte wurde an der Lendenwirbelsäule und an der linken Hüfte mittels Dualröntgenabsorptiometrie gemessen. Die Ausmaße der Krankheitsaktivität umfassten: Dauer der Morgensteifheit, schmerzende Gelenkschwellung, allgemeine Einschätzung durch den Patienten selbst und durch den Arzt, Manifestation von Daktylitis und/oder Enthesitis, ESR und CRP, und Krankheits-Aktivitäts-Score (DAS 28). Ein Fragebogen zur Beurteilung der Gesundheit (HAQ) wurde verwendet, um den funktionalen Status der Patienten zu beurteilen. ERGEBNISSE: Laut Definition der Weltgesundheitsorganisation wurde bei 7,2 % der Patienten Wirbelsäulenosteoporose, bei 1,4 % der Patienten Osteoporose des Hüftgelenks und bei 2,9 % der Patienten Osteoporose des Schenkelhalses festgestellt. Es gab keine signifikante Verbindung von keinem der Ausmaße der Krankheitsaktivität mit der Knochenmineraldichte an keinem der Messbereiche. Eine höhere HAQ Punktzahl wurde in Verbindung gebracht mit niedrigerer Knochenmineraldichte des Hüftgelenks. SCHLUSSFOLGERUNG: Anhand unserer Stichprobe der Patienten mit Psoriasis-Arthritis haben wir keine erhöhte Prävalenz der Osteoporose gefunden. Es gab keine Verbindung von Knochenmineraldichte mit Hinweisen auf Krankheitsaktivität, während negative Korrelation festgestellt wurde zwischen dem HAQ und der Knochenmineraldichte des Hüftgelenks.SummaryAIMS: Although considered as a feature of inflammatory rheumatic diseases, there is a lot of controversy around low bone mass in patients with psoriatic arthritis. The aim of this cross-sectional study was to analyze bone mineral density in patients with psoriatic arthritis, as well as to investigate its possible association with some measures of disease activity and functional capacity. SUBJECTS AND METHODS: Sixty-nine patients with established psoriatic arthritis (mean age 56.20 ± 12.23 years) and who have not been treated with specific antiosteoporotic drugs were recruited from the out-patient clinic database. Bone mineral density was measured by dual-energy X-ray absorptiometry at the lumbar spine and at the left hip. Disease activity measures included: duration of morning stiffness, tender and swollen joint count, patients and physicians global assessment, presence of dactylitis and enthesitis, ESR, CRP and Disease Activity Score 28. Health Assessment Questionnaire was used to assess functional status. RESULTS: According to WHO definition, spinal osteoporosis was found in 7.2% of patients, total hip osteoporosis in 1.4% of patients and femoral neck osteoporosis in 2.9% of patients. There was no significant association of any of the measures of disease activity with BMD at any site. Higher HAQ scores were associated with lower total hip BMD. CONCLUSIONS: In our sample of patients with psoriatic arthritis we did not find increased prevalence of osteoporosis. There was no association of BMD with indices of disease activity, while negative correlation was found between HAQ and total hip BMD.

Vitamin D Serum Level, Disease Activity and Functional Ability in Different Rheumatic Patients

Background:The aim of the study was to determine the serum vitamin D levels in patients with psoriatic arthritis (PsA) and compare it with patients with rheumatoid arthritis (RA) and with osteoarthritis (OA), as well as to explore the relationship of the vitamin D level with indices of disease activity and functional ability in a real-life setting in a South-European country. Methods:In a cross-sectional study, 120 adult patients with established diagnosis of PsA, RA and OA were consecutively enrolled. Serum 25-hydroxyvitamin D and intact parathyroid hormone were determined. Parameters of disease activity and functional ability were obtained using standard instruments. Results:Serum vitamin D insufficiency (⩽75 nmol/L) was found in 74% of patients with PsA, 94% patients with RA and 97% of patients with OA, whereas vitamin D deficiency (⩽25 nmol/L) was found in 13% of patients with PsA, 39% of patients with RA and in 38% of patients with OA. Compared with RA, patients with PsA had significantly higher serum vitamin D (P = 0.002), and when controlling for age and gender, their serum vitamin D level was significantly associated with disease activity and functional activity. Conclusions:In the group of rheumatic patients, a high prevalence of serum vitamin D insufficiency/deficiency was found regardless of the type of arthritis. Patients with PsA might have higher levels of vitamin D than patients with RA, and this was associated with disease activity and functional ability. The results of this study indicate that prophylactic supplementation with vitamin D might be recommended for all rheumatic patients.

Prevalence of vertebral fractures in an urban population in Croatia aged fifty and older.

SummaryAIM OF THE STUDY: To establish the prevalence of vertebral fractures according to age groups, sex and vertebral level in a sample of a Croatian urban population aged ≥50. We also tried to establish how many people had been diagnosed with osteoporosis by their family physician. PARTICIPANTS AND METHODS: Lateral thoracic and lumbar spinal radiographs were obtained in 425 ambulatory people (156 men and 269 women) aged ≥50 and living in the community as a random sample of the City of Zagreb (Croatia) population. An interviewer-administered questionnaire was used to obtain information on prior traumatic vertebral fractures and whether the person had been diagnosed with osteoporosis. Vertebral fractures in the population sample were defined using the morphometric method proposed by McCloskey et al., and normal values of the ratios of dimensions in non-fractured vertebrae with the iterative algorithm described by Melton et al. RESULTS: The prevalence of individuals with vertebral fractures was 11.8% (15.8% of men and 9.7% of women), ranking Zagreb mid-scale among other European cities. The prevalence of individuals with vertebral fractures rose with age. Sixty-nine (1.24%) of 5525 analysed vertebrae had been fractured. The most common fractures were those of lower thoracic and upper lumbar vertebrae. The elderly tend to sustain multiple fractures. Forty-one (9.6%) people had been previously diagnosed as having osteoporosis. Extrapolation to the Croatian population implies that approximately 90,000 men and 77,000 women aged ≥50 have vertebral fractures. CONCLUSION: Vertebral osteoporotic fractures are common in the Croatian population aged ≥50; however, awareness of osteoporosis appears to be low.

European multicentre pilot survey to assess vitamin D status in rheumatoid arthritis patients and early development of a new Patient Reported Outcome questionnaire (D-PRO)

OBJECTIVE To collect data on vitamin D (25(OH)D) serum levels in a large number of rheumatoid arthritis (RA) patients from different European countries, to investigate their relation with disease activity, disability, quality of life, and possibly to construct a new Patient Reported Outcome (PRO) questionnaire in order to self-estimate if they are at risk for vitamin D insufficiency/deficiency-related clinical implications (D-PRO). METHODS This was a European League Against Rheumatism (EULAR) supported cross-sectional study (project No CLI064) which involved 625 RA patients (mean age 55±11years, mean disease duration 11±9years), 276 age and sex matched healthy subjects, and rheumatologists working in academic institutions or hospital centres, as well as PARE organizations (patient representatives) from 13 European countries. Serum samples for 25(OH)D level measurement were collected during winter time and analyzed in a central laboratory using chemiluminescence immunoassay (DiaSorin). Patient past medical history was recorded. RA patients were provided with three questionnaires: the Rheumatoid Arthritis Impact Diseases score (RAID), the Health Assessment Questionnaire (HAQ), and the new D-PRO questionnaire at the time of 25(OH)D serum sampling. D-PRO questionnaire consisted of three domains, Symptom Risk Score (SRS), Habitus Risk Score (HRS) and Global Risk Score (SRS+HRS=GRS), constructed with items possibly related to vitamin D deficiency. D-PRO was correlated with both clinical and PRO scores. DAS28-CRP was also evaluated. Statistical analysis was performed by non parametric tests. RESULTS Mean serum concentration of 25(OH)D in RA patients (17.62±9.76ng/ml) was found significantly lower if compared to the levels obtained in matched controls (18.95±9.45ng/ml) (p=0.01), with statistically significant differences among several European countries. Negative correlations were found between 25(OH)D serum levels and DAS28-CRP (p<0.001), RAID (p=0.05) and HAQ (p=0.04) scores in the RA patients group. Negative correlations were also found in the cohort of enrolled RA patients between 25(OH)D serum concentrations and SRS (p=0.04), HRS (p=0.02) and GRS (p=0.02) domains of the D-PRO questionnaire. CONCLUSIONS This first multicentre European survey add new evidences that vitamin D insufficiency/deficiency is frequent in RA patients with statistically significant differences among several countries. Vitamin D serum concentrations seem to correlate negatively and significantly with the D-PRO Global Risk Score, clinimetric indexes for quality of life, disease activity and disability in present cohort of RA European patients.

Antibodies targeting mutated citrullinated vimentin in patients with psoriatic arthritis

Antibodies against mutated citrullinated vimentin (anti-MCV) are of a comparable diagnostic value in rheumatoid arthritis (RA) as antibodies targeting citrullinated peptides (anti-CCP). Anti-CCP are present in up to 15% of psoriatic arthritis (PsA) patients, while the prevalence of anti-MCV in PsA patients has been poorly investigated. The aim of the present study was to assess the prevalence and relevance of anti-MCV antibodies in PsA patients. The study included 56 PsA patients. Clinical features, disease activity, and functional ability were noted by an experienced rheumatologist. Serum samples of all patients were analyzed for anti-MCV and anti-CCP antibodies using enzyme-linked immunosorbent assay. Data on 92 patients with RA, 44 patients with other inflammatory rheumatic diseases, and 107 healthy controls from a previous study were used to compare the prevalence of anti-MCV antibodies in PsA patients. Anti-MCV antibodies were positive in only two out of 56 (3.6%) PsA patients, which was significantly lower compared to RA patients (63%). The anti-MCV level was moderately positive and borderline in one patient each. Both patients had asymmetric polyarthritis, dactylitis, moderate to high disease activity, and were anti-CCP and rheumatoid factor (RF) negative. There was no significant difference in anti-MCV levels according to clinical subtypes of PsA and no correlation of anti-MCV levels with anti-CCP, RF, disease activity variables, and functional ability indices. According to study results, anti-MCV antibodies can be detected in a very small proportion of PsA patients with polyarthritic disease and are primarily related to the polyarthritic pattern rather than the specific diagnosis of RA.

Validity of the rheumatoid arthritis impact of disease (RAID) score and definition of cut-off points for disease activity states in a population-based European cohort of patients with rheumatoid arthritis

OBJECTIVES To assess the validity of the rheumatoid arthritis impact of disease (RAID) for measuring disease activity of rheumatoid arthritis (RA) and to determine cut-off values for defining the disease activity states. METHODS A total of 622 RA patients from an European database have been included. Cross-validation was based on assessment of convergent and discriminant validity. Optimal cut-offs were determined against external criteria by calculating the respective 25th and 75th percentiles mean values of RAID. External criteria included definitions for remission (REM), low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA), cut-offs of the 28-joint disease activity score-C-reactive protein (DAS28-CRP) score. RESULTS The RAID showed a moderate degree of correlation with respect to DAS28-CRP (rho=0.417; P<0.0001). The receiver operating characteristic (ROC) curves to discriminate the ability of RAID to distinguish patients with active and non-active disease was very good with an area under the curve (AUC) of 0.847 (95% confidence interval [CI]: 0.816 to 0.878; P<0.0001). Based on the distributions of RAID in the different disease activity groups, we propose the following cut-off values for REM: RAID ≤3; for LDA: RAID >3 and ≤4; for MDA: RAID >4 and ≤6; for HDA: RAID >6. Mean RAID differed significantly between patients classified as REM, LDA, MDA or HDA (P=0.001). CONCLUSIONS The cut-offs revealed good measurement characteristics in cross-validation analysis, had great discriminatory performance in distinguishing patients with different levels of disease activity and are suited for widespread use in everyday practice application and research.

Muscle strength and bone density in patients with different rheumatic conditions: cross-sectional study

Aim To explore the relationship between muscle strength and bone density in patients with different rheumatic diseases and to examine whether inflammatory arthritis was more harmful for muscle strength and bone loss than degenerative joint diseases. Methods The study included 361 men and women with a mean ± standard deviation age of 60.5 ± 11.4 years and different rheumatic conditions: regional syndromes, osteoarthritis of the hands, shoulders, knees, and hips, and inflammatory arthritis. Maximum voluntary back strength was measured by isometric dynamometry. Bone mineral density (BMD; g/cm2) of the lumbar spine, femoral neck, and distal radius was measured by dual-energy x-ray absorptiometry. Anthropometry and lifestyle characteristics were also assessed. Results Back strength was lowest in patients with hand and shoulder osteoarthritis (20.0 ± 17.9 kg), followed by patients with inflammatory arthritis (24.8 ± 19.2 kg). Patients with inflammatory arthritis had the lowest BMD at the mid-radius (0.650 ± 0.115 g/cm2) and femoral neck (0.873 ± 0.137 g/cm2), while patients with hand and shoulder osteoarthritis had the lowest BMD at the mid-radius (0.660 ± 0.101). In both sexes, muscle strength was significantly lower in patients who had lower BMD (T score<-1.0). Multiple regression analysis identified significant predictors of back strength to be spine BMD (P = 0.024) and body mass index (P = 0.004) in men and femoral neck BMD in women (P = 0.004). Conclusion Muscle strength decline may be connected to bone loss in patients with rheumatic conditions, especially those with inflammatory joint diseases.

Epidemiology of Osteoporosis

Epidemiologija Osteoporoze U većini zemalja u svijetu, pa tako i u Hrvatskoj ne postoji jedinstveni sustav registriranja oboljelih od osteoporoze, kao ni osoba s osteoporotskim prijelomima. Podatci iz epidemioloških istraživanja pokazuju da je učestalost osteoporoze veća u azijskim zemljama u odnosu na europsko i sjevernoameričko stanovništvo bijele rase, u kojih prevalencija iznosi 10% do 15%. U Hrvatskoj je učestalost slična onoj u drugim europskim zemljama, dok je incidencija osteoporotskih prijeloma nešto veća od europskog prosjeka. Također je broj prijavljenih slučajeva osteoporoze i osteomalacije od primarne zdravstvene zaštite zadnjih 10 godina u stalnom porastu i u 2004. godini je iznosio 0,70% u odnosu na ukupan broj prijavljenih bolesti. Najvažniji rizični čimbenici bolesti su dob, naslijeđe, životne navike, postojanje kroničnih bolesti i hormonskih poremećaja te individualna fizikalna obilježja kosti. Kao u većine kroničnih bolesti, mjerama prevencije može se pravodobno spriječiti nastanak bolesti i njezinih komplikacija. Epidemiology of Osteoporosis In many countries, including Croatia, there is no disease registry for osteoporosis and osteoporotic fractures. Epidemiological data show that the prevalence of osteoporosis is much higher in Asian people than in white European or North American populations, where the prevalence ranges between 10 % and 15 %. Epidemiological characteristics of osteoporosis in Croatia are similar to other European countries, though the incidence of osteoporotic fractures is somewhat higher. According to the annual report of registered diseases, the number of patients with osteoporosis and osteoporotic fractures increased during the last 10 years. In 2004, 0.70 % of all registered diseases in Croatia referred to osteoporosis and osteomalacia. The most important risk factors for osteoporosis are age, heredity, lifestyle, chronic diseases, hormonal abnormalities and physical characteristics of bone. Like in other chronic diseases, prevention measures are most important for disease control.

Osteoporosis and polymorphisms of osteoprotegerin gene in postmenopausal women - a pilot study

Objectives Osteoprotegerin (OPG) has an important role in bone remodeling, and it has been proposed that the OPG gene might be a candidate gene for osteoporosis predisposition. Several studies have already assessed the connection between OPG gene polymorphism and bone mineral density (BMD). In this study we wanted to analyze the association of two polymorphisms in the OPG gene with BMD and bone turnover markers in women with and without osteoporosis. Material and methods In 22 postmenopausal women with osteoporosis (aged 65.6 ±12.6) and 59 women without osteoporosis (aged 60.8 ±8.7) we analyzed the association of two polymorphisms in the OPG gene with BMD, measured by dual energy absorptiometry and with bone turnover markers (crosslaps and osteoprotegerin). A163G, G209A, T245G and G1181C polymorphisms were determined. Results No significant differences in age, anthropometry, number of fractures, osteocalcin and cross-laps were found between women with and without osteoporosis. Women with osteoporosis were significantly longer in postmenopause. Significantly more women with osteoporosis had AG polymorphism (p = 0.038) compared to women without osteoporosis, while no significant difference was found in prevalence of TT and GG polymorphism between patients with and without osteoporosis. No relationship was found between investigated polymorphism and bone turnover markers. A significant negative correlation between total hip BMD and crosslaps (p = 0.046) as well as between total hip T score and crosslaps (p = 0.044) was found in women without osteoporosis Conclusions Postmenopausal women with osteoporosis had AG polymorphism more frequently than women without osteoporosis. Our results indicate that A163G polymorphism could have an impact on higher bone loss in postmenopausal women.

FRI0078 European Pilot Study on Vitamin D Serum Levels and Disease Activity in Rheumatoid Arthritis Patients

Background Several studies have demonstrated low 25(OH)D3 serum levels, which could influence pathogenesis and clinical outcomes of immune-mediated diseases such as rheumatoid arthritis (RA) (1,2). Objectives In order to investigate the necessity to implement specific vitamin D patient related outcomes we performed a pilot European multicentre study, involving individuals from different countries/latitudes, to explore 25(OH)D3 serum levels and their possible correlation with disease activity and related outcomes in RA patients during winter season. Methods We enrolled 270 RA patients (not treated with vitamin D supplementation) and 180 healthy subjects as controls (CNT), from Rheumatology centers in 10 European countries. RA patients mean disease duration was 10±9 years and mean age 56±10 years. Patients informed consent was obtained before collecting blood samples. Complete medical history, health assessment questionnaire (HAQ), rheumatoid arthritis impact disease score (RAID), disease activity scale (DAS28) were recorded. 25(OH)D3 serum levels were evaluated centrally using chemiluminescence immunoassay with an automatic analyser (LIAISON, DiaSorin), and classified as normal (>30 ng/ml), insufficient (between 20 and 30 ng/ml) or deficient (<20 ng/ml) (3). Results 25(OH)D3 serum levels were significantly lower in RA patients compared to controls (median 16 vs 20 ng/ml) (p<0.0001). In particular, we registered 25(OH)D3 deficiency (<20 ng/ml) in 25% and insufficiency in 70% of RA patients. Male and female RA patients showed similar 25(OH)D3 values (median 19 vs 17 ng/ml) (p=n.s.). We found statistically significant difference in 25(OH)D3 levels between some European countries such as significantly higher 25(OH)D3 serum levels in Spanish RA patients (Canaries Islands) compared to patients from Latvia, Lithuania, Romania, Croatia, Russia and Italy (p<0.01). In agreement with previous observations (4), we found in RA patients statistically significant negative correlations between 25(OH)D3 values and HAQ (r=-0.29, p=0.03), RAID (r=-0.32, p=0.02), and DAS28 scores (r=-0.41, p=0.003), respectively. Conclusions The results of this multicentre study confirms, at least in winter time, the presence of significantly lower 25(OH)D3 serum levels in RA patients than in healthy control subjects, which seem correlated with disease activity at all latitudes in Europe. The significant negative correlations observed between 25(OH)D3 serum levels and DAS28, HAQ and RAID scores justify the need to develop specific questionnaires for patient reported outcomes (PRO) vitamin D-related, and to validate them in a large European multicentre study. References 1. Cutolo et al. Autoimmun Rev 2011;11:84-87. Aranow C. J Investig Med. 2011; 59: 881–886. 3. Holick MF. N Engl J Med 2007;357:266-81. 4. Cutolo M. Ann Rheum Dis 2013;72:473-5. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4145