Expert opinion on the management of patients with osteoporosis with anabolic drugs in Italy.

OBJECTIVE: Fragility fractures (FF) resulting from osteoporosis pose a significant public health challenge in Italy, with considerable socio-health and economic implications. Despite the availability of safe and effective drugs, osteoporosis remains underdiagnosed and undertreated, leaving over 2 million high-risk Italian women without treatment. This paper aims to identify and propose key improvements in the management of osteoporosis, focusing particularly on the critical issues related to the use of anabolic drugs in secondary prevention, according to the current Italian Medicines Agency (AIFA) Note 79. METHODS: The Expert Panel, composed of nine recognized Italian experts in rheumatology, analyzed current practices, prescribing criteria, and the most recent literature. Three main reasons for revising the indications on pharmacological treatment of osteoporosis were identified: inadequate treatment of osteoporosis, new evidence regarding frontline placement of anabolics in high-risk conditions, and emerging sequential or combined strategies. RESULTS: The proposed improvements include the adoption of the Derived Fracture Risk Assessment algorithm for accurate fracture risk assessment, revision of AIFA Note 79 to reflect current evidence, improved prescribing appropriateness, broader access to anabolic agents, and the provision of sequential therapies with antiresorptives for teriparatide. These changes aim to enhance patient outcomes, streamline healthcare processes, and address the high percentage of undertreated individuals. CONCLUSIONS: This expert opinion emphasizes the importance of the appropriate use of anabolic drugs to reduce FF and associated costs while ensuring the sustainability of the National Health Service. The proposed recommendations are in line with the latest scientific evidence, providing a comprehensive strategy to optimize the management of osteoporosis in Italy. On behalf of the Study Group on Osteoporosis and Skeletal Metabolic Diseases of the Italian Society of Rheumatology.

Osteoblast role in the pathogenesis of rheumatoid arthritis.

In the pathogenesis of several rheumatic diseases, such as rheumatoid arthritis, spondyloarthritis, osteoarthritis, osteoporosis, alterations in osteoblast growth, differentiation and activity play a role. In particular, in rheumatoid arthritis bone homeostasis is perturbed: in addition to stimulating the pathologic bone resorption process performed by osteoclasts in course of rheumatoid arthritis, proinflammatory cytokines (such as Tumor Necrosis factor-α, Interleukin-1) can also inhibit osteoblast differentiation and function, resulting in net bone loss. Mouse models of rheumatoid arthritis showed that complete resolution of inflammation (with maximal reduction in the expression of pro-inflammatory factors) is crucial for bone healing, performed by osteoblasts activity. In fact, abnormal activity of factors and systems involved in osteoblast function in these patients has been described. A better understanding of the pathogenic mechanisms involved in osteoblast dysregulation could contribute to explain the generalized and focal articular bone loss found in rheumatoid arthritis. Nevertheless, these aspects have not been frequently and directly evaluated in studies. This review article is focused on analysis of the current knowledge about the role of osteoblast dysregulation occurring in rheumatoid arthritis: a better knowledge of these mechanisms could contribute to the realization of new therapeutic strategies.

Occult HBV infection may negatively impact on drug survival in patients with rheumatoid arthritis on treatment with a first biologic drug. An appraisal from the Biologic Apulian Registry (BIOPURE).

We performed a retrospective analysis to evaluate the survival on first line biologic drug of rheumatoid arthritis (RA) patients with potential occult HBV infection (pOBI). We analysed longitudinal data of 486 consecutive RA patients starting a first biological drug in a time frame from 1st January 2008 to 31st December 2014. Demographic and disease related characteristics were collected at baseline and at the last observation visit. Baseline serological markers of HBV infection and causes of treatment discontinuation were also recorded. Primary endpoint was the influence of pOBI on drug survival, estimated by Kaplan-Meier life table analysis. Estimates hazard ratios (HRs) of drug discontinuation, adjusted for disease characteristics, biological drug class and HBcAb status were computed by Cox-regression models. The retention rate was significantly lower in pOBI positive patients (58.2%) when compared to pOBI negative ones (67.8%) and this data was confirmed also when only discontinuation due to ineffectiveness was considered (pOBI positive 66.4% vs pOBI negative 75.3%, long rank 7.93, p=0.005). Cox regression models showed a significant association between HBcAb-neg (HR 0.58, 0.41-0.84), higher ESR-DAS28 at baseline (HR 1.07, 1.03-1.11) or RF/ACPA-neg (HR 1.46, 1.04-2.06) and drug discontinuation. Occult HBV infection seems to influence negatively the effectiveness of biological therapies in RA patients.

The epidemiology of osteoporosis in Italian postmenopausal women according to the National Bone Health Alliance (NBHA) diagnostic criteria: a multicenter cohort study.

PURPOSE: The study was aimed at evaluating the prevalence of osteoporosis, defined by BMD and the National Bone Health Alliance (NBHA) criteria, and the prevalence of clinical risk factors for fractures in Italian postmenopausal women. METHODS: This is a cross-sectional, multicenter, cohort study evaluating 3247 postmenopausal women aged ≥ 50 and older in different areas of Italy in the period 2012-2014. All the participants were evaluated as far as anthropometrics; questionnaires for FRAX® and DeFRA calculation were administered and bone mineral density was measured at lumbar spine, femoral neck and total hip by DXA. RESULTS: The prevalence of osteoporosis, as assessed by BMD and NBHA criteria was 36.6 and 57%, respectively. Mean ± SD values of FRAX® and DeFRA were: 10.2 ± 7.3 and 11 ± 9.4 for major fractures, and 3.3 ± 4.9 and 3.9 ± 5.9 for hip fractures, respectively. Among clinical risk factors for fracture, the presence of previous fracture, particularly non-spine/non-hip fracture, parental history of hip fracture and current smoking were the most commonly observed. CONCLUSIONS: Our study showed that more that the half of postmenopausal women aged 50 and older in Italy has osteoporosis on the basis of the NBHA criteria. There is a relevant high risk of femur fracture, as assessed by the FRAX® and DeFRA and previous fracture, parental history of hip fracture and current smoking are the most common risk factors. The data should be considered particularly in relation to the need to increase prevention strategies on modifiable risk factors and therapeutic intervention.

Nailfold capillaroscopic changes in patients with idiopathic pulmonary arterial hypertension and systemic sclerosis-related pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) represents one of the main clinical expressions of the vascular changes in systemic sclerosis (SSc). Lung microvascular changes can play a role in the pathogenesis of idiopathic PAH (IPAH) also. The aim of this study is to investigate the presence of capillaroscopic abnormalities in patients with IPAH and to evaluate the differences in capillary nailfold changes between patients with IPAH and patients with SSc with and without PAH. METHODS: 39 SSc patients (19 with PAH - SSc-PAH and 20 without - SSc-noPAH), 21 subjects with IPAH and 20 healthy subjects were recruited. PAH was diagnosed by right heart catheterization. Nailfold videocapillaroscopy was performed (NVC) in all recruited subjects; capillary quantitative parameters (loops length and width, capillary density, neoangiogenesis) were evaluated and a semiquantitative scoring was used (normal, minor or major abnormalities for healthy controls and IPAH subjects and specific patterns - early, active and late - for SSc subjects) to define microvascular alterations. RESULTS: The presence of capillaroscopic abnormalities was detected in 38,1% subjects with IPAH; particularly, compared to healthy controls, capillary density was significantly lower (7,5±1,65loops/mm vs 9±1,37loops/mm p<0,05) and mean capillary width was significantly higher (21±13µm vs 17±3µm p<0,05). A more severe NVC pattern (active/late) was described. SSc-PAH patients compared to SSc-noPAH patients (73,2% vs 50% respectively, p<0,05), with a significantly lower capillary density (5,64±1,9loops/mm vs 6,5±1,3loops/mm p<0,05) and a significantly higher capillary width (55±7µm vs 35±8µm - p<0,05) and mean number of neoangiogenesis (N/mm) (1±0,33 vs 0,2±0,22 respectively p<0,05). CONCLUSIONS: These data, beyond to confirm the role of microvascular damage in SSc-related PAH, support the hypothesis of systemic microvascular involvement in IPAH also, which can be detected by NVC, although further studies are needed to establish whether the changes in the systemic microcirculation are causal or consequential to PAH.

The effect of parathyroid hormone (1-84) treatment on serum bone morphogenetic protein 4 and vascular endothelial growth factor in postmenopausal women with established osteoporosis.

PURPOSE: To investigate the effect of 18 months' parathyroid hormone 1-84 (PTH 1-84) treatment on serum levels of bone morphogenetic protein 4 (BMP4) and vascular endothelial growth factor (VEGF), in postmenopausal women with established osteoporosis. METHODS: Thirty-seven postmenopausal women with osteoporosis (mean age 72.9 ± 8.1 years old) and 23 healthy controls (mean age 68.9 ± 9.9 years old) were enrolled. Patients were treated with daily subcutaneous injections of PTH (1-84) 100 mcg for 18 months, plus calcium 1 gr and vitamin D 800 IU per os daily. Blood samples were taken every 6 months during the study. RESULTS: At baseline, there were no differences considering anthropometric parameters, co-morbidities, current medications used between patients and controls. Mean serum VEGF levels were significantly higher in osteoporotic patients compared to controls (436.7 ± 259.7 vs. 260.3 ± 184.3 pg/ml, p = 0.006), while there were no differences in mean serum values of BMP4 (5.3 ± 1.7 vs. 5.7 ± 1.6 pg/ml, p = 0.40). Serum VEGF levels increased by approximately 20% after 12 months of PTH (1-84) treatment compared to baseline (p = 0.03) and by 22% after 18 months (p = 0.01). A significant increase of 10% in mean serum BMP4 levels was observed after 18 months of PTH (1-84) treatment compared to baseline (p = 0.02). In the control group we found no differences after 18 months compared to baseline in BMP4 (5.7 ± 1.6 vs. 6.0 ± 1.5 pg/ml, p = 0.53) and VEGF (260.3 ± 184.3 vs. 257.4 ± 107.1 pg/ml, p = 0.94). CONCLUSIONS: PTH (1-84) treatment increased serum levels of VEGF and BMP4 in postmenopausal women with severe osteoporosis.

Osteoporosis and rheumatic diseases.

Numerous rheumatic diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, systemic sclerosis, dermatomyositis/polymyositis and vasculitis are characterized by osteoporosis and fragility fractures. Inflammatory cytokines, glucocorticoid treatment, immobilization and reduced physical activity due to painful joints and muscle weakness are considered the main risk factors that cause low body mass density values in these diseases. Emerging evidence highlights the role of inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, IL-7 and IL-17, in the regulation of the bone homeostasis. In fact, chronic inflammation is often characterized by an imbalance between bone formation and bone resorption with a net prevalence of osteoclastogenesis, which is an important determinant of bone loss in rheumatic diseases.

Melkersson-Rosenthal syndrome in a patient with psoriatic arthritis receiving etanercept.

Melkersson-Rosenthal syndrome is a rare granulomatous neuro-mucocutaneous systemic disease that is characterized by relapsing peripheral facial paralysis, orofacial edema and fissured tongue. The disease etiology is still not well known, but it has been hypothesized that a possible role is played by various causal agents such as infectious diseases, genetic causes, allergic conditions, benign lymphogranulomatosis, various associations with other pathological conditions, particularly with immune-mediated diseases and food contact allergies. In this report we describe the case of a woman, 42 years old, with psoriatic arthritis who developed neurological episodes related to MRS after treatment with anti-TNF therapy. This finding further supports the hypothesis that TNF-alpha blockade, and particularly the use of the TNF-alpha receptor, could trigger the development of granulomatous lesions in predisposed patients. The case we report further sustains the importance for the clinician to take into account this potential adverse event in patients receiving anti-TNF-alpha therapies.

Effect of endothelin inhibition on lung fibroblasts on patients with systemic sclerosis.

AIM: The aim of the study was to investigate the effect of selective ETRA Sitaxsentan on viability and differentiation into myofibroblasts of lung fibroblasts derived from SSc-ILD patients and the ability of this drug to modify the lung fibroblast synthesis of VEGF, type I collagen and fibronectin. METHODS: Primary human lung fibroblast cultures were obtained from BAL of SSc-ILD patients. Cell cultures were exposed for 48 h to crescent concentrations of Sitaxsentan (10 -6M to 10 -4M). In these experimental conditions we evaluated cell viability through crystal violet staining, the production and mRNA expression of VEGF, fibronectin and type I collagen respectively through ELISA and real-Time PCR. Further, we detected alpha-Smooth Muscle Actin (α-SMA) through immunocytochemical assay. RESULTS: The lowest concentration of sitaxsentan (10-6M) did not affect fibroblasts viability; conversely at higher concentrations, sitaxsentan induced a significant inhibition of cell viability. Synthesis and mRNA expression of VEGF, type 1 collagen and fibronectin were significantly reduced in treated lung fibroblasts compared to the untreated ones, in a dose-dependent manner. At higher concentrations, Sitaxsentan reduced the expression of α-SMA. CONCLUSION: The results of this study show that sitaxentan is able in vitro to reduce both cell viability than production of VEGF and extra-cellular matrix components in SSc lung fibroblasts, confirming the anti-fibrotic potential of ETRA in SSc. The decreased expression of α-SMA in treated cells indicate that sitaxsentan may inhibit the fibroblast differentiation toward a myo-fibroblast phenotype and further support the hypothesis that the selective ETRAs may be beneficial in patients with SSc-ILD as anti fibrotic agents.

Subclinical coronary atherosclerosis, detected by computer tomography with coronary calcium score, and the occurrence of major cardiovascular events at 5 years of follow-up in a cohort of patients with systemic sclerosis.

BACKGROUND: Spreading data describe cardiovascular disease (CVD) as a growing cause of hospitalization in systemic sclerosis (SSc) patients. Although interstitial lung disease and pulmonary arterial hypertension (PAH) remain the principal causes of mortality, the presence of CVD has been shown to further increase mortality in SSc patients. Few and contrasting data are available on cardiovascular impairment, particularly of subclinical coronary arteries disease, in SSc patients. The aims of this study were: 1) to determine the demographic, clinical, and cardiovascular differences between the groups of SSc patients with and without subclinical coronary atherosclerosis (SCA) assessed by coronary calcium score; 2) to verify the performance of cardiovascular risk scores in SSc for detection of SCA major cardiovascular events (MCVE); 3) to evaluate the risk factors associated to MCVE in 5 years of follow-up in this study group of patients. METHODS: Sixty-seven SSc patients were enrolled in this study. SCA was assessed using quantification of coronary calcium score by computerized tomography, reported as Agatson. Evaluation of common cardiovascular risk scores, carotid plaques by Doppler ultrasonography, the history of peripheral artery disease (PAD), lipid profiles, and clinical and laboratiristic characteristics of SSc were assessed at baseline visits for each patient. Factors associated with the presence of SCA were assessed by multivariate logistic analysis. A five years prospective study was performed for the evaluation of MCVE occurrence and its possible predictors. RESULTS: The prevalence of SCA was 42% (Agatston scores of 266.04 ± 455.9 units) in our group of SSc patients. Patients with SCA were principally older (p = 0.0001) and had higher rates of CENP-B antibodies (57% vs 26%; p = 0.009), pulmonary arterial hypertension (PAH) (25% vs 3%; p = 0.008), dysphagia (86% vs 61%; p = 0.027), and users of statins (36% vs 8%; p = 0.004), carotid plaque (82% vs 13%; p = 0.0001), PAD (79% vs 18%; p = 0.0001), and metabolic syndrome (25% vs 0%; p = 0.002) than patients without SCA. Metabolic syndrome (OR: 8.2, p = 0.0001), presence of a PAD (OR: 5.98, p = 0.031), and carotid plaque (OR: 5.49, p = 0.010) were the main factors associated with SCA in SSc patients, by multivariate regression analysis. MCVE occurred in 7 patients. By multivariate COX regression analysis unique predictor of MCVE in 5 years of follow-up in our SSc patients was the presence of PAH (HR: 10.33, p = 0.009). Of note, the contemporary presence of PAH and SCA (defined as "not pure" pattern of PAH) was observed in 71% of patients with the occurrence of MCVE CONCLUSION: This study evidenced the high presence of the new "not pure" pattern of PAH, which could worsen the outcome in SSc in a medium-term (5 years) observation period. Furthermore, our data confirmed a higher cardiovascular impairment in SSc due to the presence of both SCA, mainly associated with typical cardiovascular risk factors, and PAH, life-threatening complications of SSc, that is the principal cause of the occurrence of MCVE in our SSc patients. A careful assessment of cardiovascular involvement in SSc and a more aggressive therapeutic strategy for preventing CAD and treating PAH should be highly suggested to reduce MCVE in SSc patients.

Dose-dependent metabolic effect of zoledronate on primary human osteoblastic cell cultures.

OBJECTIVES: To evaluate the in vitro effect of the bisphosponate zoledronate on metabolic activity, proliferation and viability of human osteoblasts. METHODS: Primary human osteoblasts cultures were obtained from cancellous bone of healthy subjects undergoing bone marrow biopsy. Cell cultures were treated with crescent concentrations of zoledronate (10⁻¹°to 10⁻³), with and without 1,25(OH)2 vitamin D3. In these experimental conditions we evaluated cells viability and proliferation using the MMT colorimetric test, cell apoptosis by measurement of Caspase 3 activity and metabolic cell activity through alkaline phosphatase activity and osteocalcin production. RESULTS: Osteocalcin and alkaline phosphatase synthesis was significantly enhanced by 10⁻¹° M to 10⁻5 M zoledronate concentrations, whereas was dramatically decreased by higher drug concentrations. Vitamin D3 enhanced the positive metabolic effect of zoledronate. The effect of zoledronate on cell proliferation was variable and dose-dependent. While no effect was observed with lower drug concentrations (10⁻¹° M to 10⁻8 M), zoledronate 10⁻7 M increased cell proliferation. Conversely, concentrations higher than 10⁻7 M significantly reduced cell proliferation, in a dose-dependent manner. Osteoblast apoptosis was enhanced after treatment with the highest zoledronate concentrations. The maximum positive effect on osteoblasts metabolic activity and proliferation was observed with the zoledronate concentrations corresponding to those theoretically reached in bone microenvironment when zoledronate is used in clinical practice for post-menopausal osteoporosis treatment. CONCLUSIONS: The results of this study confirm that bisphosphonates exert different cellular biochemical effects depending on dosage and support the hypothesis that their positive effect on bone mineral density could be partially due to an anabolic action on bone forming cells.

[Anabolic therapy of induced osteoporosis in beta-thalassaemia major: case report and literature review]. / La terapia anabolica nella osteoporosi indotta da beta-talassemia major: caso clinico e revisione della letteratura.

Transfusion program and chelating therapy treatment has extended the life expectancy of thalassaemic patient; osteoporosis is considered an important cause of morbidity in adult patients who display increased fracture risk. This is a case report is about a thalassaemic young female with multiple spine fractures (D11, D12 e L2) and lumbar spine DEXA - T score = -3,1 and femoral = -3,4. This was in spite of therapy with alendronate 70 mg/week from January 2006 to September 2007. The patient was subsequentently treated for 18 months with 1-34 recombinant human parathyroid hormone and colecalciferol (100.000 U/monthly). After 4 months of therapy, the patient showed a decrease in spinal pain (Roland and Morris Disability Questionnaire) and an improvement of quality of life (Qualeffo) with normalization of osteocalcin and 25-OHcolecalciferol haematic levels after 6 months. Lumbar spine and femoral DEXA - Tscore, at 18 months, rose respectively to -2,5 and -2,4. Thalassaemia-induced osteoporosis is multifactorial and its management is very difficult. Bone marrow expansion, endocrine dysfunction, iron overload and genetic factors all seem to play important roles in the development of low bone mass in these patients. Bisphosfonates have been used in the management of thalassemia induced osteoporosis but there is no data about fracture risk. Anabolic therapy for thalassemic patients requests additional study on a large scale.

Glomerular filtration rate is associated with trabecular bone score in patients with type 2 diabetes mellitus.

AIMS: The present study aimed to evaluate the trabecular and cortical bone components using Trabecular Bone Score (TBS) and its association with estimated-Glomerular Filtration Rate (e-GFR) in T2DM patients. METHODS: An assessment both of bone mineral density (BMD) and vertebral bone microarchitecture was performed in all patients using TBS iNsight® software version 3.0.2.0. Furthermore, the total population was divided into two groups based on the value of the eGFR (eGFR < o > at 60 ml/min/1.73 m2). RESULTS: TBS value was lower in patients with low e-GFR than that in patients with higher e-GFR (1.246 ± 0.125 vs 1.337 ± 0.115, respectively, p = 0.013 adjusted by gender and age) while there was no difference in total BMD value between two groups. In the multivariate model taking into account several possible confounders, such as age, gender, duration of diabetes, BMI, LDL cholesterol, serum calcium and HbA1c, the correlation between e-GFR and TBS remained significant (p: 0.046). CONCLUSIONS: In individuals with T2DM and reduced kidney function, TBS provides information independent of BMD, age and gender. TBS may be a useful additional tool to predict fracture risk in this unique population.

Evaluation of the influence of social, demographic, environmental, work-related factors and/or lifestyle habits on Raynaud's phenomenon: a case-control study.

Raynaud's phenomenon (RP) is a clinical disorder characterized by recurrent, reversible episodes of digital vasospasm. RP can be classified as primary (pRP) or secondary, depending on whether it occurs as a benign condition (not disease-associated) or is associated with other diseases, mainly of the connective tissues. In both cases, it can be triggered by environmental factors, as indicated by the increased incidence of pRP episodes following exposure to cold, vibration injury or chemicals. The purpose of this prospective case-control study was to assess, in an Italian cohort of 132 pRP patients, the association of the phenomenon with demographic, lifestyle habits, environmental and work-related factors. Compared to healthy controls, pRP was found to be inversely associated with the use of contact lenses (OR = 0.4; p = 0.004) and of chlorous-based disinfectants (OR = 0.3; p < 0.001) and directly associated with the presence of prosthesis implants (OR = 5.3; p = 0.001) and the use of hydrogen peroxide-based compounds (OR = 2.6; p = 0.002), suggesting that the latter should be avoided in RP affected patients. Multivariate and multivariable analysis confirmed the associations. Further investigations are needed to understand the mechanism(s) underlying these findings.

Membranous nephropathy in rheumatoid arthritis: a case report.

Rheumatoid arthritis is a chronic disease characterized by inflammation, abnormal cellular and humoral immune responses, synovial hyperplasia and rarely by renal involvement, characterized principally by secondary amyloidosis and nephrotoxic effects related to drugs, while renal lesions directly due to the disease itself are infrequent. In this report we describe a patient with rheumatoid arthritis who developed membranous nephropathy associated with nephrotic syndrome while receiving adalimumab, an anti-tumour necrosis factor-alpha drug.

Normal and osteoporotic human osteoblast behaviour after 1,25-dihydroxy-vitamin D(3) stimulation.

In order to examine the effects of vitamin D on osteoblast function and to evaluate if osteoporotic and normal osteoblasts show a different behaviour in response to vitamin D, this report investigates the changes in osteocalcin production, after 1,25-dihydroxy-vitamin D(3) stimulation of cultured osteoblasts derived from osteoporotic patients. Our results indicate an inadequate osteoblastic function in osteoporosis and demostrate that 1,25-dihydroxy-vitamin D(3) can stimulate the metabolic activity of human osteoblasts in vitro. Considering that osteoporotic bone samples were representative of senile osteoporosis, our results may indicate a different metabolic phenotype in osteoporotic osteoblasts compared with normal osteoblasts. The increased osteocalcin production after 1,25-dihydroxy-vitamin D(3) stimulation of osteoporotic osteoblasts suggests a reduced, but not absent, anabolic function in senile osteoporotic osteoblasts. The results of this study confirm the validity of vitamin D(3) to treat senile osteoporosis and suggest the need of higher vitamin D(3) intake in senile osteoporotic patients than in younger subjects.

Clodronate inhibits angiogenesis in vitro and in vivo.

The effects of amino-bisphosphonate clodronate on endothelial cell functions involved in angiogenesis, namely proliferation and morphogenesis on matrigel were tested in vitro, whereas its effects on angiogenesis were studied in vivo. This was performed by using the chick embryo chorioallantoic membrane (CAM) assay. In vitro, clodronate inhibited the endothelial cell proliferation in a dose-dependent fashion, peaking at 30 microM. At the same concentration, clodronate inhibited the fibroblast growth factor-2 (FGF-2)-induced capillary-like tube formation in the morphogenesis assay on matrigel. In vivo, when tested with the CAM assay, clodronate again displayed the capability to inhibit FGF-2-induced angiogenesis. Overall, these results suggest that antiangiogenesis by clodronate can be used to treat a wide spectrum of angiogenesis-dependent diseases, including certain chronic inflammatory diseases and cancer.

Angiogenesis in vasculitides.

Vasculitides, including Wegener's granulomatosis, Takayasu's arteritis, giant cell arteritis, Kawasaki disease, Behçet disease, thromboangiitis obliterans and erythema elevatum diutinum, are inflammatory diseases of blood vessel wall characterized by myointimal proliferation, fibrosis and thrombus formation leading to stenosis or occlusion of the vascular lumen, and finally to tissue ischemia. In these diseases the hypoxic environment subsequent to stenosis or occlusion of the vascular lumen is a potent signal for the generation of new blood vessels. Angiogenesis may be a compensatory response to ischemia and to the increased metabolic activity and may be also a further inflammatory stimulus because endothelial cells of newly-formed vessels express adhesion molecules and produce colony-stimulating factors and chemokines for leukocytes.

[Adult Scheuermann's disease as cause of mechanic dorsalgia]. / La malattia di Scheuermann dell'adulto come causa di dorsalgia meccanica.

Scheuermann's disease (SD) or vertebral osteochondrosis is the most frequent cause of non postural kyphosis and one of more frequent cause of adolescent's dorsalgia. The criteria for the diagnosis are: more than 5 degrees of wedging of at least three adjacent vertebrae at the apex of the kyphosis; a toracic kyphosis of more than 45 of Cobb's degree; Schmorl's nodes and endplates irregularities. In addition to classic SD, there are radiological alterations that remain asymptomatic for a long time to reveal in adult age: in that case it speaks of adult Scheuermann's disease (ASD). We considered the diagnosis of patients came from April 2006 to April 2007 on Day Hospital in our Clinic. ASD was diagnosed, besides, in 10 of these patients. 7 patients had previous diagnosis such as: dorsal Spondiloarthrosis (4 subjects); Osteoporosis with vertebral fractures (3 subjects). All these diagnosis was not confirmed by us. In case of chronic dorsalgia of adult, ASD is rarely considered as differential diagnosis. Besides, the vertebral dorsalgia, even in absence of red flags as fever, asthenia,hypersedimetry, functional loss and aching spinal processes to tapping, could hide a serious scene that lead us to be careful in the differential diagnosis, because of similar radiological pictures of the MSA to other pathology as spondylodiscitis, primitive or metastasic spinal tumors, and brittleness vertebral fractures.