Diagnosis and treatment of Paget's disease of bone: position paper from the Italian Society of Osteoporosis, Mineral Metabolism and Skeletal Diseases (SIOMMMS).

INTRODUCTION: Paget's disease of bone is a focal skeletal disorder causing bone deformities and impairing bone quality. Despite the prevalence of asymptomatic cases is increasing, the progression of the disease can lead to invalidating complications that compromise the quality of life. Doubts on clinical and therapeutic management aspects exist, although beneficial effects of antiresorptive drugs, particularly bisphosphonates are known. However, limited information is available from randomized controlled trials on the prevention of disease complications so that somewhat contrasting positions about treatment indications between expert panels from the main scientific societies of metabolic bone diseases exist. This task force, composed by expert representatives appointed by the Italian Society of Osteoporosis, Mineral Metabolism and Skeletal Diseases and members of the Italian Association of Paget's disease of bone, felt the necessity for more specific and up to date indications for an early diagnosis and clinical management. METHODS: Through selected key questions, we propose evidence-based recommendations for the diagnosis and treatment of the disease. In the lack of good evidence to support clear recommendations, available information from the literature together with expert opinion of the panel was used to provide suggestions for the clinical practice. RESULTS AND CONCLUSION: Description of the evidence quality and support of the strength of the statements was provided on each of the selected key questions. The diagnosis of PDB should be mainly based on symptoms and the typical biochemical and radiological features. While treatment is mandatory to all the symptomatic cases at diagnosis, less evidence is available on treatment indications in asymptomatic as well as in previously treated patients in the presence of biochemical recurrence. However, given the safety and long-term efficacy of potent intravenous bisphosphonates such as zoledronate, a suggestion to treat most if not all cases at the time of diagnosis was released.

Diagnostic accuracy of a velcro sound detector (VECTOR) for interstitial lung disease in rheumatoid arthritis patients: the InSPIRAtE validation study (INterStitial pneumonia in rheumatoid ArThritis with an electronic device).

BACKGROUND: Interstitial lung disease (ILD) is a severe systemic manifestation of rheumatoid arthritis (RA). High-resolution computed tomography (HRCT) represents the gold standard for the diagnosis of ILD, but its routine use for screening programs is not advisable because of both high cost and X-ray exposure. Velcro crackles at lung auscultation occur very early in the course of interstitial pneumonia, and their detection is an indication for HRCT. Recently, we developed an algorithm (VECTOR) to detect the presence of Velcro crackles in pulmonary sounds and showed good results in a small sample of RA patients. The aim of the present investigation was to validate the diagnostic accuracy of VECTOR in a larger population of RA patients, compared with that of the reference standard of HRCT, from a multicentre study. METHODS: To avoid X-ray exposure, we enrolled 137 consecutive RA patients who had recently undergone HRCT. Lung sounds of all patients were recorded in 4 pulmonary fields bilaterally with a commercial electronic stethoscope (ES); subsequently, all HRCT images were blindly evaluated by a radiologist, and audio data were analysed by means of VECTOR. RESULTS: Fifty-nine of 137 patients showed ILD (43.1%). VECTOR correctly classified 115/137 patients, showing a diagnostic accuracy of 83.9% and a sensitivity and specificity of 93.2 and 76.9%, respectively. CONCLUSIONS: VECTOR may represent the first validated tool for the screening of RA patients who are suspected for ILD and who should be directed to HRCT for the diagnosis. Moreover, early identification of RA-ILD could contribute to the design of prospective studies aimed at elucidating unclear aspects of the disease.

Secukinumab after anti-tumour necrosis factor-α therapy: a phase III study in active rheumatoid arthritis.

OBJECTIVE: To assess the efficacy and safety of secukinumab in patients with rheumatoid arthritis (RA) who failed to respond to tumour necrosis factor- α (TNF-α) inhibitors. METHOD: This phase III double-blind, double-dummy, placebo-controlled study (NCT01770379) randomized (1:1:1) patients to subcutaneous secukinumab 150 mg, secukinumab 75 mg, or placebo at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks. American College of Rheumatology (ACR) 20 response at week 24 was the primary endpoint. Secondary outcomes included the 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP), Health Assessment Questionnaire Disability Index (HAQ-DI), and ACR50 at week 24. Long-term treatment was planned for 5 years. RESULTS: ACR20 response rates at week 24 for the secukinumab 150 mg and 75 mg groups were not statistically superior to placebo. None of the secondary endpoints was met for either secukinumab dose. Although not statistically significant, compared with placebo, numerically greater differences in least squares mean changes from baseline in HAQ-DI score and numerically higher ACR50 response rates were observed at week 24 in both secukinumab treatment groups. No new or unexpected adverse events were observed in this study compared with the large secukinumab safety database across psoriasis, psoriatic arthritis, ankylosing spondylitis, and other RA studies. CONCLUSIONS: Given that other second-line therapies have demonstrated efficacy in RA patients who failed to respond to TNF-α inhibitors, these findings may suggest that interleukin-17A inhibition with secukinumab does not provide additional benefit to these patients. This study further confirms the well-characterized safety profile of secukinumab.

Persistence with denosumab therapy in women affected by osteoporosis with fragility fractures: a multicenter observational real practice study in Italy.

BACKGROUND: Persistence is commonly considered a key factor for the successful management of osteoporosis and fragility fractures. Denosumab is the first biologic agent developed for the treatment of osteoporosis with satisfying data regarding the persistence with this therapy. AIM: The purpose of this multicenter observational real practice study was to evaluate the persistence with denosumab treatment in post-menopausal women affected by osteoporosis. MATERIAL/SUBJECTS AND METHODS: Women were recruited in four specialized centers for the management of osteoporosis in North, Center and South of Italy. We included women with a diagnosis of post-menopausal osteoporosis, aged >50 years, able to obtain a prescription according to the Italian reimbursement criteria in force during the study period for anti-osteoporotic pharmacological treatment. They initiated a treatment with subcutaneous denosumab (Prolia®) 60 mg/every 6 months between November 2011 and May 2016. Women who had received aromatase inhibitors were excluded. Patients were assessed at baseline and every 6 months for all treatment length. Persistence data were evaluated for a total of 36 months. RESULTS: Eight hundred seventy women were enrolled; mean aged 70 years, with a mean body mass index of 24.8 ± 4.1 kg/m2. At the Dual-energy X-ray absorptiometry assessment, the mean lumbar spine T-score was -2.76 ± 1.14 standard deviations (SD) and the mean femoral neck T-score was -2.49 ± 0.80 SD. During the study, the total persistence was 91.4%. Total dropouts were 75 (8.6%), higher within the initial 6-month period of treatment. CONCLUSIONS: Persistence to denosumab treatment in our observational real practice study was very high. These results suggest that factors such as frequency of visits, pharmacological schedule, and opportunity to call the doctor might play an important role in the persistence and adherence to treatment to obtain maximum therapeutic effect and avoid further fragility fractures.

Prevalence and incidence of osteoporotic fractures in patients on long-term glucocorticoid treatment for rheumatic diseases: the Glucocorticoid Induced OsTeoporosis TOol (GIOTTO) study.

Osteoporosis and fractures are common and invalidating consequences of chronic glucorticoid (GC) treatment. Reliable information regarding the epidemiology of GC induced osteoporosis (GIOP) comes exclusively from the placebo group of randomized clinical trials while observational studies are generally lacking data on the real prevalence of vertebral fractures, GC dosage and primary diagnosis. The objective of this study was to evaluate the prevalence and incidence of osteoporotic fractures and to identify their major determinants (primary disease, GC dosage, bone mineral density, risk factors, specific treatment for GIOP) in a large cohort of consecutive patients aged >21 years, on chronic treatment with GC (≥5 mg prednisone - PN - equivalent) and attending rheumatology centers located all over Italy. Glucocorticoid Induced OsTeoporosis TOol (GIOTTO) is a national multicenter cross-sectional and longitudinal observational study. 553 patients suffering from Rheumatoid Arthritis (RA), Polymyalgia Rheumatica (PMR) and Connective Tissue Diseases (CTDs) and in chronic treatment with GCs were enrolled. Osteoporotic BMD values (T score <-2.5) were observed in 28%, 38% and 35% of patients with CTDs, PMR or RA at the lumbar spine, and in 18%, 29% and 26% at the femoral neck, respectively. Before GC treatment, prevalent clinical fractures were reported by 12%, 37% and 17% of patients with CTDs, PMR, or RA, respectively. New clinical fragility fractures during GC treatment were reported by 12%, 10% and 23% of CTDs, PMR and RA patients, respectively. Vertebral fractures were the prevailing type of fragility fracture. More than 30% of patients had recurrence of fracture. An average of 80% of patients were in supplementation with calcium and/or vitamin D during treatment with GCs. Respectively, 64%, 80%, and 72% of the CTDs, PMR and RA patients were on pharmacological treatment for GIOP, almost exclusively with bisphosphonates. The GIOTTO study might provide relevant contributions to clinical practice, in particular by highlighting and quantifying in real life the prevalence of GIOP and relative fractures, the frequency of the main risk factors, and the currently sub-optimal prevention. Moreover, these results emphasize the importance of the underlying rheumatic disease on the risk of GIOP associated fractures.

Are Dietary Supplements and Nutraceuticals Effective for Musculoskeletal Health and Cognitive Function? A Scoping Review.

OBJECTIVE: The aim of our scoping review was to summarize the state of the art regarding micronutrients in order to identify which of them might effectively improve health status in the areas typically impaired in older people: bone, skeletal muscle, and cognitive function. DESIGN: Scoping review. METHODS: The Italian Study Group on Healthy Aging by Nutraceuticals and Dietary Supplements (HANDS) performed this scoping review, based on the following steps: doing a list of micronutrients related with musculoskeletal or cognitive functions, included in dietary supplements and nutraceuticals commercialized in Italy; planning a research on PubMed, according to an evidence-based approach, in order to the most relevant positive study for each micronutrient into each of the three areas involved (bone, skeletal muscle and cognitive function); identifying the micronutrients effective in maintaining or achieving an adequate health status in older people, specifying the effective and safe daily doses, according to the selected studies. RESULTS: In literature we found 12 relevant positive studies (1 international society guidelines/recommendations, 1 systematic review, 7 randomized controlled trials, and 3 prospective cohort studies). We showed that only 16 micronutrients resulted to have appropriate scientific evidences in terms of improving musculoskeletal health and/or cognitive function in older people: beta-alanine, calcium, creatine, fluorides, leucine, magnesium, omega-3 fatty acids, potassium, vitamin B6, vitamin B9, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K2, and zinc. CONCLUSION: This scoping review showed that selected micronutrients in adequate doses might have an ancillary role in musculoskeletal health and cognitive functions in older people.

Guidelines for the diagnosis, prevention and management of osteoporosis.

Osteoporosis poses a significant public health issue. National Societies have developed Guidelines for the diagnosis and treatment of this disorder with an effort of adapting specific tools for risk assessment on the peculiar characteristics of a given population. The Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS) has recently revised the previously published Guidelines on the diagnosis, riskassessment, prevention and management of primary and secondary osteoporosis. The guidelines were first drafted by a working group and then approved by the board of SIOMMMS. Subsequently they received also the endorsement of other major Scientific Societies that deal with bone metabolic disease. These recommendations are based on systematic reviews of the best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on leading experts' experience and opinion, and on good clinical practice. The osteoporosis prevention should be based on the elimination of specific risk factors. The use of drugs registered for the treatment of osteoporosis are recommended when the benefits overcome the risk, and this is the case only when the risk of fracture is rather high as measured with variables susceptible to pharmacological effect. DeFRA (FRAX® derived fracture risk assessment) is recognized as a useful tool for easily estimate the long-term fracture risk. Several secondary forms of osteoporosis require a specific diagnostic and therapeutic management.

Fragility fractures: clinical and therapeutic aspects.

Osteoporosis is the most important bone metabolic disorder characterized by reduction of bone mass and micro-architectural deterioration associated to an increased risk for fragility fractures. It involves millions of worldwide-dispersed individuals of both sexes and, consequently, the elevated morbidity and mortality of fractured subjects and the increased socio-economic costs suggest it must be faced as a major health problem. Thus, there is a need for either a precocious identification of subjects with fragile “bones” or the institution of specific diagnostic-therapeutical strategies. Improvement in bone pathophysiology knowledge, together with progress in pharmaceutical development has led to an opportunity for early identification and therapy of subjects at high risk of fragility fractures. In this review, we briefly describe the recent acquisitions in bone pathophysiology as well as in the anti-fracture drug development with a brief excursus on those already well established.

Nail dystrophies, scalp and intergluteal/perianal psoriatic lesions: risk factors for psoriatic arthritis in mild skin psoriasis?

AIM: In the literature, clinical features of psoriasis associated with psoriatic arthritis (PsA) onset have not been clarified, even if high Psoriasis Area and Severity Index (PASI) was found to be directly related with PsA. METHODS: The study was conducted between November 2008 and April 2009 on consecutive psoriatic outpatients referred to a service of dermatological consultations, on indication of other hospital specialists. Participants were affected by mild skin psoriasis, in particular with nail dystrophies and/or scalp and/or intergluteal/perianal lesions. The questionnaire provided by the Classification of Psoriatic Arthritis (CASPAR) study group was proposed to all patients and we added a question about the time of psoriasis onset. RESULTS: Eighty-seven subjects (34 males and 53 females) aged between 18 and 91 years (mean age 48 years) with such psoriatic features were recruited. Other 30 refused to take part to the study. Forty-seven per cent of these participants were found to suffer from PsA, in particular 83% of those with nail and scalp psoriasis, 40% of subjects with intergluteal/perianal involvement and 37% of patients with just scalp lesions. We present the first exploratory and observational study focused on a population with mild skin psoriasis, in order to evaluate if nail dystrophies, scalp or intergluteal/perianal psoriatic lesions might be indicative of a higher risk of PsA even in cases with mild skin psoriasis. CONCLUSION: Nail psoriasis is probably a suggestive feature of joint involvement. The scalp psoriasis, as well as intergluteal/perianal psoriatic lesions, is likely to be less associated to PsA, but may be an important comorbidity factor for the development of PsA. Further investigations in a larger population are encouraged to assess a potential link between PsA, site-specific and mild skin psoriasis.

Regional differences of vitamin D deficiency in rheumatoid arthritis patients in Italy.

Vitamin D deficiency is very common in patients with rheumatoid arthritis (RA). Aim of this study was to evaluate the prevalence of vitamin D deficiency among the different Italian regions and whether these variations are associated with different severity of the disease. The study includes 581 consecutive RA patients (464 women), not taking vitamin D supplements, from 22 Italian rheumatology centres uniformly distributed across Italy. Together with parameters of disease activity (disease activity score 28), functional impairment (activities of daily living and health assessment questionnaire disability index) and mean sun exposure time, all patients had serum 25-hydroxyvitamin D (25OHD) measured in a centralized laboratory. Vitamin D deficiency (25OHD level <20 ng/mL) was very frequent among RA patients; its prevalence was 60%, 52% and 38% in southern, central and northern Italy, respectively. Mean disease activity and disability scores were worse in southern regions of Italy. These scores were inversely related to 25OHD levels and this correlation remained statistically significant after adjusting for both body mass index (BMI) and sun exposure time. However, disease severity remained significantly higher in southern regions versus central-northern Italy after adjustment also for serum 25OHD levels, age and BMI. In RA Italian patients there are significant regional differences in the prevalence of vitamin D deficiency explained by different BMI, and sun exposure time, and inversely associated with disease activity and disability scores.

Metabolic abnormalities in pain-processing regions of patients with fibromyalgia: a 3T MR spectroscopy study.

BACKGROUND AND PURPOSE: A growing body of evidence suggests the involvement of the brain in FM. The purpose of this proton MRS study was to test the hypothesis that there are metabolic alterations in some brain regions processing pain (VLPFC and thalamus) in patients with FM compared with HC. MATERIALS AND METHODS: Twelve patients with FM (30-54 years of age; mean age, 43.2 years), and 12 HC, matched for age and sex, underwent 1 session of single-voxel MRS performed on a 3T MR imaging scanner. MRS spectra were acquired with a PRESS for localization. The raw data from each spectrum was evaluated with an LCModel. T tests were used to evaluate differences of brain metabolites between groups. The Pearson correlation tested the relationship of metabolite ratios and clinical symptoms. RESULTS: Glx/Cr and Glu/Cr ratios within the VLPFC of both sides were significantly higher in patients than in HC (P < .01). No significant differences of metabolites between groups were found in the thalami. Positive correlations were found between Glu/Cr in the left thalamus and the VAS for pain (r = 0.730, P = .007) and between mIns/Cr in the right VLPFC and the VAS for pain (r = 0.607, P = .037) and the FIQ (r = 0.719, P = .008). CONCLUSIONS: The presence of elevated Glu/Cr levels in VLPFC strengthens the opinion that a complex neurophysiologic imbalance of different brain areas involved in pain processing underlies FM. These data may be useful in the diagnosis and development of more effective pharmacologic treatments.

Baseline characteristics of the population enrolled in the Italian Observational Study on Severe Osteoporosis (ISSO).

OBJECTIVES: Baseline characteristics of the population enrolled in the ISSO study, designed to evaluate the incidence of vertebral and non-vertebral fractures in Italian patients with severe osteoporosis treated according to clinical practice over 24 months observation. METHODS: Prospective observational study in 783 post-menopausal women and men entering 18-month treatment with teriparatide in a community setting at 57 centres in Italy. Characterisation included demographics, fracture risk factors, bone mineral density, fracture status, Health-Related Quality of Life (HRQoL) measured by the European Quality of Life Questionnaire, EQ-5D, and back pain assessed by VAS. RESULTS: Most patients were elderly women (90.5%), mean age±SD was 72.9±8.8 years. Nearly all (91.3%) had experienced ≥ 1 vertebral fracture (mean±SD, 3.6±2.2 per patient), 37.5% had ≥ 1 non-vertebral fracture (mean±SD, 1.4±0.7 per patient). Nearly all patients were suffering from back pain (94.9%), which had significantly restricted their daily activities (51.7%) and had likely or very likely been caused by vertebral fractures (29.2% and 55.8%, respectively). Mean EuroQoL EQ-5D index value was 0.58±0.25 and VAS score 49.2±23.6. Non-vertebral fractures, back pain and multiple vertebral fractures were associated with lower HRQoL (EuroQoL-5D Index both p<0.001, EQ-5D VAS score p=0.025 and p<0.016, respectively). Many patients were physically inactive (81.1%). One third (34.7%) of population had co-morbidities and 60.5% were on chronic concomitant treatments. Few subjects reported a maternal history of osteoporosis (15.5%), regular consumption of alcohol (13.3%) or were current smokers (11.5%). Nearly two-thirds (71.5%) had already been treated for osteoporosis, mainly with bisphosphonates. Calcium and vitamin D supplements were taken by 13% and 15.5% of the total population, respectively. CONCLUSIONS: At enrollment, the population of ISSO study mostly consisted in aging women, who had osteoporosis with high fracture risk, poor HRQoL and suffered from significant back pain. Most of them had already been treated by bisphosphonates but without calcium and vitamin D supplements. Back pain, as well as non-vertebral and multiple vertebral fractures, were associated with lower HRQoL.

Osteoporosis risk in patients with chronic obstructive pulmonary disease: the EOLO study.

Chronic obstructive pulmonary disease (COPD) appears to be associated with osteoporosis. The aim of the study was to evaluate the prevalence of osteoporosis risk (OP risk) in a sample of patients with COPD. In 3030 patients (1768 men and 1262 women) aged >50 yr, we evaluated COPD severity with spirometry and OP risk by using a quantitative ultrasound device. We analyzed several risk factors for osteoporosis, such as age, gender, body mass index (BMI), fracture history, smoking status, glucocorticoid (GC) treatment in univariate and in multinomial logistic regressions. The risk of osteoporosis was higher in women and in older participants, among those with more severe COPD, treated with GC. In multivariate analysis, we found interactions between fracture history and smoking and between age and gender. Significant associations were found with BMI and GC treatment, whereas only a tendency, not statistically significant, was found for very severe COPD being associated to high risk of osteoporosis. In COPD patients the risk of osteoporosis is high, in particular at severe stages of the disease, but seems to be due to traditional risk factors, such as older age, female gender, low BMI, history of smoking and fractures, GC treatment.

Validity and reliability of the Italian version of the ECOS-16 questionnaire in postmenopausal women with prevalent vertebral fractures due to osteoporosis.

OBJECTIVE: To investigate the reliability and validity of the Italian version of ECOS-16 (Assessment of health related quality of life in osteoporosis) in comparison to other questionnaires in postmenopausal women with osteoporosis. METHODS: A cross-sectional multicentre study was carried out among postmenopausal women with osteoporosis who were attending primary care centres and hospital outpatient clinics. The patient group included 234 females (mean age 69 years, range 48-89) who presented vertebral fractures due to osteoporosis. The control group consisted of 244 asymptomatic osteoporotic subjects matched for age with the patient group. The psychometric properties of the questionnaires were evaluated in terms of feasibility, validity (construct validity and discriminant validity) and internal consistency. Test-retest reliability was analysed for 196 outpatients who reported that their general health status due to osteoporosis had not changed after one week. In all patients the ECOS-16, the SF-36 (Medical Outcomes Study Short Form-36), EUROQoL (EQ-5D), mini-OQLQ (mini-Osteoporosis Quality of Life Questionnaire), and RMDQ (Roland-Morris Disability Questionnaire) were administered, and all clinical variables and sociodemographic variables were taken into account. Construct and discriminant validity were assessed by Spearman's correlations, the Wilcoxon rank sum test, the Kruskal Wallis test and by receiver operating characteristic (ROC) curves. Internal consistency was evaluated using Cronbach's alpha and the test-retest reliability was evaluated by intra-class correlation coefficients (ICCs). RESULTS: 96.9% of the patients answered all items of the ECOS-16 questionnaires. The mean administration time was 10 minutes. Factor analysis yielded two factors that accounted for 88.4% of the explained variance in the ECOS-16 questionnaire. The first factor was the ECOS-16 Physical Component Score (PCS) (45.9% of the explained variance) and the second factor was the ECOS-16 Mental Component Score (MCS) (42.4% of the explained variance). The inter-item correlation between the two factors was 0.48. Significant correlations were found between the scores of similar domains or subscales of the ECOS-16 and SF-36, EQ-5D and mini-OQLQ, supporting the concept of convergent construct validity. The total ECOS-16 score progressively increased with the number of prevelant vertebral fractures (p<0.001) and the effect of the first fracture was already statistically significant (p<0.01). On ROC curve analysis the total ECOS-16 score showed the highest performance among the different questionnaires in discriminating between patients with vertebral fractures and controls with no fractures. In the reliability study, internal consistency within the domain of ECOS-16 was generally good, with Chronbach's alpha values ranging from 0.81 to 0.89. Test-retest reliability was 0.87 for the total ECOS-16 score. CONCLUSION: The Italian version of the ECOS-16 questionnaire was demonstrated to have good psychometric properties and could offer a useful tool in research and routine clinical practice to evaluate HRQoL in post-menopausal women with osteoporosis. A full validation of the psychometric properties will require data on its sensitivity to change.

Diagnostic performance of tear function tests in Sjogren's syndrome patients.

OBJECTIVE: To evaluate the diagnostic performance of the tests included in primary Sjogren's syndrome (SS-I) diagnostic criteria (Schirmer I, break-up time, vital dye staining) and to compare them with other examinations related to the ocular surface status. METHODS: Clinical and cytological data were collected from 177 patients (62 SS-1, 56 non-SS autoimmune diseases, 59 Sicca syndrome). Tear tests included: a validated questionnaire on symptoms, Schirmer I, Jones test, Ferning test, BUT, corneal aesthesiometry, tear clearance test, lissamine green staining, impression conjunctival cytology. Data were statistically evaluated and sensitivity, specificity, likelihood ratio (LR+), receiver-operating characteristics (ROC) curves were calculated for each test. RESULTS: Data showed a poor diagnostic performance of Schirmer test I (sensitivity 0.42; specificity 0.76; LR+1.75) and BUT (sensitivity 0.92; specificity 0.17; LR+1.11) (area under the curve in ROC analysis <0.58). Validated subjective symptoms questionnaire (sensitivity 0.89; specificity 0.72; LR+3.18), Jones test (sensitivity 0.60; specificity 0.88; LR+5), corneal aesthesiometry (sensitivity 0.80; specificity 0.67; LR+2.42), and tear clearance test (sensitivity 0.63; specificity 0.84; LR+3.93), all exhibited a high diagnostic performance (area under the curve in the ROC analysis always >0.70). Lissamine green staining exhibited the best performance (sensitivity 0.63; specificity 0.89; LR+5.72) but the result could be distorted by an incorporation bias. CONCLUSIONS: Our data suggest to implement the items for ocular signs and symptoms contained in many SS-I diagnostic criteria with the use of a validated questionnaire, performance of Jones test, corneal aesthesiometry measurement, and tear clearance rate evaluation.

A proposal of new ocular items in Sjögren's syndrome classification criteria.

OBJECTIVE: To verify whether ocular surface tests other than those included in primary Sjögren's syndrome (SS-I) classification criteria (Schirmer I, Break up Time, vital dye staining) may contribute to SS I diagnosis. METHODS: Two hundred and sixty-two patients (78 SS-1, 91 non-SS autoimmune diseases, 93 Sicca syndrome) filled a validated questionnaire on symptoms and were evaluated by Schirmer test without (Schirmer I) and with (Jones test) topical anaesthesia, Break Up Time (BUT), corneal aesthesiometry, tear clearance rate, vital dye (lissamine green) staining, impression conjunctival cytology, concentration of tear lysozyme and lactoferrin. Thresholds were selected from Receiver Operating Curves; sensitivity, specificity, likelihood ratio (LR+), predictive values were calculated for each test. A logistic regression model was constructed representing the best diagnostic index for SS. RESULTS: Data showed a poor diagnostic performance of Schirmer test I (LR+ 1.38) and BUT (LR+ 1.05); results from lissamine green staining may be unreliable due to incorporation bias. Tear lactoferrin (LR+ 4.52), Jones test (LR+ 6.24), tear lysozyme (LR+ 8.0), symptom questionnaire (LR+ 8.62), tear clearance rate (LR+ 18.73) and corneal aesthesiometry (LR+ 20.96) exhibited high diagnostic performance also taken together in the regression model. CONCLUSION: Because many of the tests we have screened in this study can be carried out by a trained ophthalmologist in any clinical setting, we recommend that ocular surface impairment is studied with the combination of tests proved to be helpful for the SS I diagnosis.

Differences in proximal femur geometry distinguish vertebral from femoral neck fractures in osteoporotic women.

Bone mineral density (BMD) is generally used to predict the risk of fracture in osteoporotic subjects. However, femoral neck BMD and spine BMD have been reported not to be significantly different among patients with hip or vertebral fractures, suggesting that other risk factors are needed to determine the different fracture types. Proximal femur geometry (PFG) parameters, such as hip axis length (HAL), femoral neck-shaft angle (NSA) and femoral neck diameter (FND) have also been shown to predict the risk of hip fracture. These parameters are statistically different in spine fractures compared with both types of hip fractures (trochanteric and femoral neck) when considered together. We wanted to assess the difference in these parameters by comparing spine fractures with a homogeneous group of hip fractures, i.e. femoral neck fractures. 807 post-menopausal women were divided into three groups; those with vertebral fractures (182), those with femoral neck fractures (134) and a control group without fractures (491). Dual X-ray absorptiometry (DXA) scans of the spine and hip were carried out to measure BMD and define the PFG parameters of the hip. Data were statistically analysed. In agreement with other authors, we found that women with femoral neck fractures had longer HAL, wider FND and larger NSA than controls, whereas there were no statistically significant differences in PFG between women with spine fractures and controls. Logistic regression showed HAL and NSA could predict the risk of femoral neck but not vertebral fracture. These data indicate specificity of some PFG parameters for hip fracture risk.

[Ocular surface analysis in patients affected with rheumatic diseases]. / Analisi della superficie oculare in pazienti affetti da malattie reumatiche.

OBJECTIVE: The international criteria for primary Sjögren's Syndrome (SS I) diagnosis (Vitali et al. 2002) include the Schirmer test I and vital dye staining as tests for ocular surface involvement, but diagnosis can be reached also when the item for ocular signs is not satisfied. The purpose of our study was to evaluate the ocular surface in patients with Sjögren's Syndrome, non-Sjögren's autoimmune diseases and Sicca Syndrome, to understand whether the SS I diagnosis can be targeted also on other tests related to the ocular surface status. METHODS: Clinical and cytological data were collected from 122 patients: 40 patients had diagnosis of Primary Sjögren's Syndrome, 51 a non Sjögren's autoimmune disease and 31 had symptoms of dry eye. A validated questionnaire on symptoms was filled by each patient; clinical tests included: Schirmer test I, Jones test, Ferning test, Break Up Time, corneal aesthesiometry, tear clearance test, vital dye staining of the ocular surface, scraping and impression conjunctival cytology. Data were statistically evaluated by using SPSS software and Mann-Whitney analysis on unpaired data. RESULTS: Data show that the subjective symptoms score, tear production, tear turnover, corneal sensitivity and ocular surface integrity are affected in SS I patients, with a statistically significant difference when matched to the other two groups. CONCLUSIONS: Our results suggest to enlarge the spectrum of ocular surface analysis, to support and orient a differential diagnosis among the autoimmune diseases.