Nazzarena Malavolta

Treatment of complex regional pain syndrome type I with neridronate: a randomized, double-blind, placebo-controlled study

OBJECTIVE Complex regional pain syndrome type I (CRPS-I) is a severely disabling pain syndrome for which no definite treatment has been established. The aim of this multi-centre, randomized, double-blind placebo-controlled trial was to test the efficacy of the amino-bisphosphonate neridronate in patients with CRP-I. METHODS Eighty-two patients with CRP-I at either hand or foot were randomly assigned to i.v. infusion of 100 mg neridronate given four times over 10 days or placebo. After 50 days the former placebo patients were given open label the same regimen of neridronate. RESULTS Within the first 20 days, visual analogue scale (VAS) score decreased significantly more in the neridronate group. In the following 20 days, VAS remained unchanged in the placebo group and further decreased in the active group by 46.5 mm (95% CI -52.5, -40.5) vs 22.6 mm (95% CI -28.8, -16.3) for placebo group (P < 0.0001). Significant improvements vs placebo were observed also for a number of other indices of pain and quality of life. During the open-extension phase in the formerly placebo group the results of treatment were superimposable on those seen during the blind phase in the active group. A year later none of the patients was referring symptoms linked to CRPS-I. CONCLUSION In patients with acute CRPS-I, four i.v. infusions of neridronate 100 mg are associated with clinically relevant and persistent benefits. These results provide conclusive evidence that the use of bisphosphonates, at appropriate doses, is the treatment of choice for CRPS-I. TRIAL REGISTRATION EU Clinical Trials Register, https://www.clinicaltrialsregister.eu/, 2007-003372-18.

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

ObjectiveTo evaluate the diagnostic performance of the tests included in primary Sjogrens 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.MethodsClinical 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.ResultsData 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.ConclusionsOur 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.

The relationship of vitamin D status to bone mineral density in an Italian population of postmenopausal women

Several authors have found a relationship between vitamin D status and bone mineral density (BMD). To our knowledge, no previous studies on this topic have been carried out on the Italian postmenopausal population. We studied this relationship retrospectively in 156 Italian postmenopausal women. We also investigated the relationship between parathyroid hormone (PTH) and BMD. Measurements of BMD were taken at the lumbar spine and upper femur by dual X-ray absorptiometry. Serum 25(OH)D (calcidiol), 1,25(OH)2D (calcitriol), PTH, calcium, phosphorus, creatinine, osteocalcin and urinary calcium and phosphorus were measured according to the current laboratory methods of analysis. We found a positive statistically significant correlation between BMD, both at the spine and hip, and 25(OH)D, and a negative statistically significant correlation between BMD and PTH. No statistically significant correlation was found between BMD and 1,25(OH)2D. Crude logistic regression showed age, 25(OH)D and PTH were significant predictors of low BMD, while 1,25(OH)2D was not. Backward logistic regression showed 25(OH)D was the best predictive model for spine osteoporosis together with age, and on its own it was the best predictive model for femoral neck osteoporosis.

Quantitative ultrasound and bone densitometry to evaluate the risk of nonspine fractures: a prospective study.

Abstract: The ability of quantitative ultrasound (QUS) to estimate the risk of osteoporotic fractures was evaluated in a prospective study over a mean time of 5.47 years in 254 postmenopausal women (mean age 58.06 ± 7.67 years). Baseline measurements of ultrasound transmission velocity (UTV) and bone mineral density (BMD) were taken at the distal radius (DR). UTV was also measured at the patella (P). Fifty nonspine fractures due to minor trauma were detected during annual check-ups with an incidence of 3.59/year. Fractures occurred in older women with a lower BMD and QUS. Using Cox regression analysis the relative risk (RR) per 1 standard deviation (SD) decrease in the unadjusted QUS and BMD measurements was: BMD-DR = 3.56, 95% confidence interval (CI) 1.57–8.09; UTV-DR = 5.35, 95% CI 2.07–13.83; UTV-P = 4.49, 95% CI 2.08–9.68. The relationship between BMD and QUS variables and fracture risk persisted after adjusting for potential confounders apart from previous fractures, giving the following RR: BMD-DR = 2.99, 95% CI 1.06–8.41; UTV-DR = 3.69, 95% CI 1.18–11.49; UTV-P = 3.89, 95% CI 1.53–9.90. Correcting also for previous fractures, only UTV-P remained an effective predictor of fracture risk even after QUS measurement correction for BMD. Wrist fractures were best related to BMD-DR (RR 7.33, 95% CI 1.43–37.50) and UTV-DR (RR 10.94, 95% CI 1.10–108.45), while hip and ankle fractures were significantly associated only with UTV-P (hip: RR 32.14, 95% CI 1.83–562.80; ankle: RR 17.60, 95% CI 1.78–173.79). The combined use of BMD and QUS is a better predictor of fracture risk than either technique used separately. Comparison of the areas under the receiver operating characteristic (ROC) curves did not show differences in the ability of BMD and QUS to correctly distinguish fractures. In conclusion, QUS predicts fracture risk in osteoporotic women at least as well as BMD. UTV-DR and BMD-DR are good predictors of wrist fractures, while UTV-P is strongly related to hip and ankle fractures. QUS and BMD combined improve the diagnostic ability of each technique individually.

Validity of internal expression of the major histocompatibility complex class I in the diagnosis of inflammatory myopathies

Objective The inflammatory myopathies (IMs) are a group of disorders characterised by weakness and inflammation of the skeletal muscles. Muscle biopsy is the most crucial test to confirm the clinical diagnosis, but also the most common cause of misdiagnosis. There are currently no markers specific or sensitive enough to distinguish IMs from other diseases with similar clinical and morphological features, and an international multidisciplinary effort is under way to develop new classification criteria for IMs. Methods Standards for Reporting of Diagnostic Accuracy recommendations to validate a diagnostic test based on the quantification of internal major histocompatibility complex class I (MHC-I) positive fibres were adopted. MHC-I immunostained specimens from 64 patients were scored by two independent blinded investigators, and the percentage of positive fibres was determined. Agreement between investigators was evaluated with the k-weighted statistic. The receiver operating characteristic curve, area under the curve, sensitivity, specificity, and positive and negative predictive values of each percentage range of positive fibres versus the diagnosis of IM were calculated. Results The main difference between IM and non-inflammatory samples was the number of internal MHC-I positive fibres. The k-weighted value was 0.89 for a percentage of MHC-I positive fibres above 50%; the positive predictive value was 100%, and the negative predictive value was 94%. Conclusions This is the first study on the validity of a quantitative analysis of internal MHC-I positive fibres for an IM diagnosis performed according to Standards for Reporting of Diagnostic Accuracy recommendations. The interobserver agreement was almost perfect, thus making the method reproducible. Applying an MHC-I cut-off above 50% is an optimal marker for polymyositis (PM) and dermatomyositis (DM) diagnosis.

Liver hemangioma and vascular liver diseases in patients with systemic lupus erythematosus.

AIM To investigate whether systemic lupus erythematosus (SLE) is associated with benign focal liver lesions and vascular liver diseases, since these have been occasionally reported in SLE patients. METHODS Thirty-five consecutive adult patients with SLE and 35 age- and sex-matched healthy controls were evaluated. Hepatic and portal vein patency and presence of focal liver lesions were studied by colour-Doppler ultrasound, computerized tomography and magnetic resonance were used to refine the diagnosis, clinical data of SLE patients were reviewed. RESULTS Benign hepatic lesions were common in SLE patients (54% vs 14% controls, P < 0.0001), with hemangioma being the most commonly observed lesion in the two groups. SLE was associated with the presence of single hemangioma [odds ratios (OR) 5.05; 95% confidence interval (CI) 1.91-13.38] and multiple hemangiomas (OR 4.13; 95% CI 1.03-16.55). Multiple hemangiomas were associated with a longer duration of SLE (9.9 ± 6.5 vs 5.5 ± 6.4 years; P = 0.04). Imaging prior to SLE onset was available in 9 patients with SLE and hemangioma, showing absence of lesions in 7/9. The clinical data of our patients suggest that SLE possibly plays a role in the development of hemangioma. In addition, a Budd-Chiari syndrome associated with nodular regenerative hyperplasia (NRH), and a NRH associated with hepatic hemangioma were observed, both in patients hospitalized for abdominal symptoms, suggesting that vascular liver diseases should be specifically investigated in this population. CONCLUSION SLE is associated with 5-fold increased odds of liver hemangiomas, suggesting that these might be considered among the hepatic manifestations of SLE.

Are dietary supplements and nutraceuticals effective for musculoskeletal health and cognitive function? A scoping review

ObjectiveThe 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.DesignScoping review.MethodsThe 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.ResultsIn 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.ConclusionThis scoping review showed that selected micronutrients in adequate doses might have an ancillary role in musculoskeletal health and cognitive functions in older people.

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.

Differential characteristics of bone quality and bone turnover biochemical markers in patients with hip fragility fractures and hip osteoarthritis: results of a clinical pilot study.

Background and aims: Bone density and quality alterations worsen the ability of osteoporotic bone to support prosthetic implants. The aim of our study was to evaluate potential differences in bone quality and bone turnover markers in aged individuals undergoing surgery for hip fragility fracture or hip osteoarthritis. Methods: Eighteen subjects with hip fragility fractures (Hip Fracture Group), 35 subjects with osteoarthritis of the hip (Hip Osteoarthritis Group) and 19 subjects with normal femoral bone mineral density (Control Group) were evaluated. Serum and urinary bone markers were assayed preoperatively in all surgical patients, and within 48 hours after fracture in the Hip Fracture, Osteoarthritis and Control groups. Histomorphometric analysis was performed on surgical samples. Results: A significant alteration in calcium and PTH serum levels with hyperparathyroidism was observed in the Hip Fracture Group compared with Hip Osteoarthritis and Control Groups. C-Terminal telopeptides of type I-collagen (CTx) and tartrate resistant-acid phosphatase (TRAP), markers of bone resorption, were increased in the Hip Fracture Group compared with both Osteoarthritis and Control Groups (CTx: p<0.0007 and p<0.0039 respectively; TRAP: p<0.002 and p<0.0007). All subjects were vitamin D3-deficient, but no differences were found among the different groups. In addition, histomorphometric data showed better maintained connectivity in the Osteoarthritis Group compared with the Hip Fracture Group (p<0.0001). Conclusions: Our data show significant differences in bone turnover markers in patients undergoing hip prosthesis for fragility fractures, compared with patients operated for hip osteoarthritis.

Ocular surface and intraocular inflammation are related in SS-I and rheumatoid arthritis patients

The purpose of this study is to evaluate the intraocular inflammation at a sub clinical level, in patients suffering from Sjogren’s syndrome (SS-I) and Rheumatoid Arthritis (RA), to relate it with the ocular surface status and to verify the diagnostic performance of the method. Twenty-eight patients suffering from SS-I, 31 patients suffering from RA and 31 normal subjects matched in age and gender were included in the study. A Kowa 500F laser cell flare meter was utilized to quantify the aqueous cells and flare in vivo, ocular surface inflammation was graded by conjunctival cytology and dosage of serum albumin in tears, eye dryness was scored with Tear Function Index. All data resulted significantly different in both SS-I and RA patients vs. control group and also different comparing SS-I vs. RA patients group, except for the Flare values. A blood-aqueous barrier breakdown occurs either in SS-I and RA patients; the degree of the damage is related with ocular surface inflammation and dryness. We recommend the aqueous flare be analysed in those rheumatic patients where an ocular surface inflammation has been documented.