Health-related quality of life in breast cancer patients treated with CDK4/6 inhibitors: a systematic review.

BACKGROUND: Evaluation of health-related quality of life (HR-QoL) among cancer patients has gained an increasing importance and is now a key determinant of anticancer treatments' value. HR-QoL has been assessed in trials testing cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in breast cancer (BC), using various questionnaires at different timepoints. HR-QoL reports from BC patients treated with CDK4/6i in the real-world setting are also available. METHODS: We systematically reviewed the literature, searching for full-length articles, and selected conference abstracts reporting data on HR-QoL in BC patients at any stage and of any molecular subtype treated with abemaciclib, palbociclib or ribociclib. RESULTS: A total of 533 full-length articles and 143 abstracts were retrieved. After screening for eligibility, 38 records were included (31 clinical trials; 7 real-world reports). Assessment methods were heterogeneous across studies in terms of questionnaires, evaluation timepoints and endpoints. Overall, adding CDK4/6i to endocrine therapy did not worsen patients' HR-QoL, with a positive trend towards pain improvement. Gastrointestinal scores (diarrhea, nausea and appetite loss) statistically favored the control arm among metastatic BC patients receiving abemaciclib, whereas they were superimposable in the early setting. The combination of palbociclib and endocrine therapy showed similar HR-QoL outcomes compared with endocrine therapy alone, but determined better scores compared with chemotherapy. HR-QoL was specifically assessed in premenopausal patients treated with ribociclib, showing similar scores compared with postmenopausal patients. CONCLUSIONS: Despite methodological heterogeneity does not allow a proper comparison, HR-QoL was generally maintained with CDK4/6i. However, differences between abemaciclib, palbociclib and ribociclib exist and mainly rely on the distinct safety profiles of the compounds. These differences should be acknowledged and taken into account in the clinical practice.

Surgical treatment of traumatic thoracolumbar fractures: a retrospective review of 101 cases.

PURPOSE: To evaluate the outcomes of vertebral stabilisation after acute traumatic thoracolumbar fractures, correlating the outcome with patient clinical data, type and location of fracture, presence of neurological damage, timing of surgical intervention and number of instrumented levels. The results have been evaluated also through the AO classification and AOSIS score. METHODS: Retrospective analysis of 101 patients with traumatic thoracolumbar injuries from T3 to L5 operated 2011-2016 by posterior or antero-posterior fixation. The demographic data, trauma dynamics, number and type of fractures, associated lesions, timing of surgery, hospital stay, AOSIS score, RKA, SF-36 and ODI scores, pre- and post-operative neurological condition (ASIA grade), possible complications and re-interventions were evaluated for each patient. RESULTS: Fractures mainly involved the region between T11 and L2. The probability of medullary involvement increases with the increase in severity of the main fracture type with no relation with the vertebral region. Type B and C fractures were common in the thoracic region and rare in the thoracolumbar junction. ODI and SF-36 scores were significantly better in patients with a lower AOSIS score, specifically in lesions classified as type A, amyelic and with no comorbidity. No difference was found in the clinical scores between thoracic, thoracolumbar and lumbar fractures, nor between male and female patients. None of the 10 patients with ASIA A lesion at presentation achieved any degree of recovery: 50% of them had a thoracic lesion. Re-intervention rate was 15%. Hospital stay was significantly higher in patients with type C fractures, and complication rate was on average 14% (7% in type A fractures, 16% in B and 25% in C). CONCLUSIONS: This study confirmed the validity of the posterior approach in the surgical treatment of thoracolumbar fractures. Outcomes and complication risks are related to fracture severity. Surgical treatment can be recommended even with an AOSIS score of two or three. The combined antero-posterior approach could be useful in cases with LSC > 8, especially in the thoracolumbar region. The degree of neurological recovery depends on fracture type, location, ASIA score and presence of comorbidities. Early intervention in myelic patients allows for a better prognosis. Level of evidence III retrospective case series.

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.

Radiofrequency echographic multispectrometry compared with dual X-ray absorptiometry for osteoporosis diagnosis on lumbar spine and femoral neck.

An innovative, non-ionizing technique to diagnose osteoporosis on lumbar spine and femoral neck was evaluated through a multicenter study involving 1914 women. The proposed method showed significant agreement with reference gold standard method and, therefore, a potential for early osteoporosis diagnoses and possibly improved patient management. INTRODUCTION: To assess precision (i.e., short term intra-operator precision) and diagnostic accuracy of an innovative non-ionizing technique, REMS (Radiofrequency Echographic Multi Spectrometry), in comparison with the clinical gold standard reference DXA (dual X-ray absorptiometry), through an observational multicenter clinical study. METHODS: In a multicenter cross-sectional observational study, a total of 1914 postmenopausal women (51-70 years) underwent spinal (n = 1553) and/or femoral (n = 1637) DXA, according to their medical prescription, and echographic scan of the same anatomical sites performed with the REMS approach. All the medical reports (DXA and REMS) were carefully checked to identify possible errors that could have caused inaccurate measurements: erroneous REMS reports were excluded, whereas erroneous DXA reports were re-analyzed where possible and otherwise excluded before assessing REMS accuracy. REMS precision was independently assessed. RESULTS: In the spinal group, quality assessment on medical reports produced the exclusion of 280 patients because of REMS errors and 78 patients because of DXA errors, whereas 296 DXA reports were re-analyzed and corrected. Analogously, in the femoral group there were 205 exclusions for REMS errors, 59 exclusions for DXA errors, and 217 re-analyzed DXA reports. In the resulting dataset (n = 1195 for spine, n = 1373 for femur) REMS outcome showed a good agreement with DXA: the average difference in bone mineral density (BMD, bias ± 2SD) was -0.004 ± 0.088 g/cm2 for spine and - 0.006 ± 0.076 g/cm2 for femur. Linear regression showed also that the two methods were well correlated: standard error of the estimate (SEE) was 5.3% for spine and 5.8% for femur. REMS precision, expressed as RMS-CV, was 0.38% for spine and 0.32% for femur. CONCLUSIONS: The REMS approach can be used for non-ionizing osteoporosis diagnosis directly on lumbar spine and femoral neck with a good level of accuracy and precision. However, a more rigorous operator training is needed to limit the erroneous acquisitions and to ensure the full clinical practicability.

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.

The impact on disability of initial treatment with methotrexate in patients with rheumatoid arthritis: results from the MARI study.

The study aimed to assess in a population of subjects with rheumatoid arthritis (RA) treated with methotrexate (MTX) how the initial approach to the treatment influenced subsequent disability. We performed a cross-sectional analysis of data collected during the baseline visit of the MARI study, a multicenter observational study on patients with RA on treatment with MTX for at least 12 months. Subjects who fulfilled the Health Assessment Questionnaire (HAQ) were included in the evaluation. For every patient we retrospectively evaluated the disease duration, the duration of symptoms before the diagnosis, the time elapsed before first MTX treatment, the initial MTX dose, and the concomitant medications in the first six months of therapy. Disability was defined as a DI-HAQ score ≥1. The study population included 1015 subjects. Patients with a DI-HAQ score ≥1 had a longer duration of symptoms before diagnosis, a higher delay in treatment initiation, a lower initial dose of MTX and a more frequent co-treatment with symptomatic drugs. Disability was found less frequently in subjects treated with other concomitant disease modifying anti-rheumatic drugs (DMARDs) but not with biological agents. Logistic regression analysis identified as significant predictors of disability: older age, female sex, a longer time to complete diagnosis, a delay in starting MTX treatment higher than 6 months, and a concomitant treatment with symptomatic drugs, while a combination therapy with other DMARDs was associated with a lower risk of disability. A late diagnosis and a delay in starting a treatment with MTX are associated with poorer functional outcomes in patients with RA.

Safety of rituximab in the routine treatment of rheumatoid arthritis in Italy in patients refractory to anti-TNFa drugs: results from the observational retrospective-prospective RUBINO study.

The paper reports the results from the observational retrospective-prospective RUBINO study conducted in Italy to assess the safety of rituximab in the treatment of rheumatoid arthritis (RA) in routine clinical practice. The percentage of patients who manifested at least one grade 3 or 4 adverse event (AE) assessed by the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v.3) during the observation period (primary objective) was evaluated. The percentage of patients manifesting a severe AE (SAE), clinical response to rituximab treatment, clinical remission according to disease activity score for 28 joints (DAS28) criteria, markers of disease and quality of life were also assessed. Fifty-three Italian rheumatology centers took part in the study. Patients with a diagnosis of RA and inadequate response to anti-tumor necrosis factor b (anti-TNFa) drugs were enrolled. Participating patients had previously received at least one cycle of rituximab, and treatment was still ongoing at the time of recruitment. Out of 205 patients enrolled, 60% manifested no form of AE, 14.2% had at least one grade 3 or 4 AE, and 11.2% patients reported an SAE. The overall percentage of patients manifesting AEs (40%) was lower compared to the DANCER (81% and 85%), REFLEX (85%) and RESET (85% and 69%) studies, but higher than that observed in the CERERRA registry (from 10.2% to 13.9%). This difference may be due to the shorter observation period applied in the CERERRA registry (only 12 months) compared to the RUBINO study (up to 3 years). All parameters of RA activity (erythrocyte sedimentation rate, C-reactive protein, health assessment questionnaire score, DAS28) improved significantly during the study.

Raman spectroscopy and partial least squares analysis in discrimination of peripheral cells affected by Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder caused by trinucleotide CAG (Cytosine-Adenine-Guanine) expansion on the Huntingtin gene (HTT) encoding for the Huntingtin protein (Htt). The protein has been linked in peripheral fibroblasts with dysregulation of cellular components which are part of lipid rafts in plasma membrane sub-domains. Therefore the analysis of the plasma membrane might be a useful diagnostic biomarker for the detection of the presence and possible onset of HD in readily accessible peripheral cells. Here Raman spectroscopy has been used with a chemometric approach in the form of Partial Least Square (PLS) for an initial corroboration that the plasma membrane is indeed a sub-cellular biomarker discriminator for HD identification. Observations were made in the spectral regions from 400 to 1800 cm(-1) and 2700 to 3200 cm(-1) with the former region displaying the most significant differences and peak displacement between plasma membranes extracted from HD and control fibroblast cells. The major differences in plasma membrane composition reside in sub-cellular elements putatively associated to cholesterol, phospholipids (mainly phophatidylinositol) as well as proteins containing tyrosine. These findings are indicative of the plasma membrane as an amenable biomarker for HD for further in vitro research with possible applications in vivo models.

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.

Management of cutaneous discomfort in patients with scleroderma: a clinical trial.

Systemic sclerosis (scleroderma) is a disease of unknown cause, the hallmark of which is induration of the skin. This bad condition of the skin influences negatively the quality of life of patients with scleroderma. The aim of the study was to verify the efficacy of two formulations, specifically designed to wash, moisturize and soothe the scleroderma skin. An independent, randomized, double blind, controlled trial was conducted in the Department of Rheumatology of "A. Galateo" Hospital in San Cesario di Lecce. Forty-six women affected by scleroderma, and treated with Iloprost every month, were divided into two groups: group 1 followed a specific treatment with cleansing formulation only, group 2 followed a combined treatment with the cleansing solution and the moisturizing solution. In addition, a third group was evaluated: 14 women, who did not undergo intravenous Iloprost therapy, were treated simultaneously with the cleansing formulation and the moisturizing formulation. The three treatments lasted for 4 weeks. Reduction in trans epidermal water loss (TEWL), increase in moisturization of the stratum corneum, reduction in Skin Score and improvement in quality of life were assessed. Very significant improvement in quality of life occurred in each group. Group 2 obtained very significant improvement in hydration and reduction in skin score and TEWL. The study showed that the daily use of both formulations proved to be effective in washing, hydrating and soothing the skin of patients with scleroderma, especially in association with Iloprost therapy.

Non linear optical microscopy of adipose-derived stem cells induced towards osteoblasts and adipocytes.

Adipose-derived stem cells (ADSCs) are adult stem cells isolated from lipoaspirates. They are a good candidate for autologuous cell therapy and tissue engineering. For these applications, label-free imaging could be critical to assess noninvasively the efficiency of stem cell (SC) differentiation. We report on the development and application of a multimodal microscope to monitor and quantify ADSC differentiation into osteoblasts and adipocytes.

[Incidence and socioeconomic burden of hip fractures in Italy: extension study 2003-2005]. / Incidenza e costi delle fratture di femore in Italia: studio di estensione 2003-2005.

OBJECTIVES: We aimed to analyze incidence and costs of hip fractures in Italy. METHODS: We analyzed the Italian Ministry of Health national hospitalization and DRGs databases concerning fractures occurred in people > or =65 between 2003 and 2005. We have estimated incidence and direct costs sustained by the National Health Service for hospitalization and treatment of hip fractures on the basis of the value of the Diagnosis Related Groups (DRGs) referring to hip fractures. The expenses of rehabilitation and indirect costs were based on regional estimations. RESULTS: Between 2003 and 2005 we registered almost 90,000 hospital admissions per year (corresponding to 75,000 patients) because of hip fractures in people aged > or =65. Women accounted for the majority of hospital admissions due to hip fractures (78.0%; n=214,519). Among women, 84.3% of fractures (n=180,861) occurred in patients > or =75, which is known to be the age group with the highest prevalence of osteoporosis. Hospitalizations of both men and women showed an increasing trend across all the examined period. Hospital costs increased up to 467 million euros in 2005, while rehabilitation costs rose up to 531 million in the same year. CONCLUSIONS: Hip fractures in the Italian population are increasing and represent a major public health challenge.

"Twice-a-month" clodronate 200 mg IM: a new dosing regimen and improved therapy adherence in the treatment of postmenopausal osteoporosis.

INTRODUCTION: The identification of therapeutic strategies aimed both at preventing and treating osteoporosis and osteoporotic fractures has become increasingly important; in particular, it is essential to promote adequate patient adherence to treatment. The primary aim of this study was to evaluate the effects on lumbar and femoral bone mass density (BMD) after two different intramuscular (IM) dosing regimens of clodronate (CLD), a bisphosphonate shown to be efficacious in reducing the incidence of both vertebral and nonvertebral fractures. Secondary aims were the assessments of bone resorption markers, safety, tolerability, pain, and patient compliance. METHODS: Sixty women with postmenopausal osteoporosis were randomized to two groups: group A (CLD 100 mg IM weekly for 12 months), and group B (CLD 200 mg IM every 2 weeks for 12 months). All patients received 1 g of calcium supplemented with 800 IU vitamin D(3), orally, once daily for 12 months Lumbar and femoral BMD, measured by DEXA Norland XR-36 (Norland Co., Fort Atkinson, WI), and bone turnover markers were assessed at baseline and at 12 months. Each patient was administered a visual analog scale of pain at baseline and after 6 and 12 months of treatment. RESULTS: A significant increase of BMD in both groups and in both skeletal sites was observed at 12 months versus baseline. In group A (n=28), lumbar BMD increased by 3.5% and femoral BMD by 2.1%; in group B (n=32), lumbar and femoral BMD rose by 3.4% and 2.2%, respectively. No difference was observed between groups. Bone resorption markers significantly reduced from baseline. Pain significantly improved as early as after 6 months of therapy and even more after 12 months, although no significant difference between the two groups was observed. The most common side effect was pain at the injection site, particularly in group B. Six patients in group A discontinued treatment and failed adherence to the therapeutic protocol. Conversely, no patient from group B discontinued therapy. CONCLUSION: In agreement with published data, in our two groups of patients, therapy with IM CLD at the doses of 100 mg/week and 200 mg/2 weeks was shown to be effective in increasing BMD, without differences between the two dosing regimens in all assessed efficacy parameters. Therefore, the "twice-a-month" regimen with 200 mg IM CLD may well promote an improved adherence with the same clinical efficacy and safety profile.

Hip fractures in Italy: 2000-2005 extension study.

SUMMARY: A total of 507,671 people > or =65 experienced hip fractures between 2000 and 2005. In 2005, 94,471 people > or =65 were hospitalized due to hip fractures, corresponding to a 28.5% increase over 6 years. Most fractures occurred in patients > or =75 (82.9%; n = 420,890; +16% across 6 years), particularly in women (78.2%; n = 396,967). INTRODUCTION: We aimed to analyze incidence and costs of hip fractures in Italy over the last 6 years. METHODS: We analyzed the national hospitalization and DRG databases concerning fractures occurred in people > or =65 between 2000 and 2005. RESULTS: A total of 507,671 people > or =65 experienced hip fractures across 6 years, resulting in about 120,000 deaths. In year 2005 94,471 people aged > or =65 were hospitalized due to hip fractures, corresponding to a 28.5% increase over 6 years. The majority of hip fractures occurred in patients > or =75 (82.9%; n = 420,890; +16% across 6 years) and particularly in women (78.2%; n = 396,967). Among women, 84.2% of fractures (n = 334,223; +28.0% over 6 years) were experienced by patients > or =75, which is known to be the age group with the highest prevalence of osteoporosis, accounting for 68.6% of the overall observed increase in the total number of fractures. Hip fractures in men > or =75 increased by 33.1% (up to 16,540). Hospitalization costs increased across the six examined years (+36.1%) reaching 467 million euros in 2005, while rehabilitation costs rose up to 531 million in the same year. CONCLUSIONS: Hip fractures of the elderly are increasing and represent a major health problem in industrialized countries such as Italy.

Incidence and costs of hip fractures compared to acute myocardial infarction in the Italian population: a 4-year survey.

INTRODUCTION: Few data are available about the incidence and costs of hip fractures in Italy. We aimed to determine the impact of hip fractures vs. acute myocardial infarction (AMI). METHODS: We studied the national hospitalization database to calculate their incidence and costs in adults aged >or=45 between 1999 and 2002. RESULTS: In 2002, there were 86,719 hip fractures with a 10.0% increase over 4 years. We observed a predominance of women (77.1%) and a strong age effect: 92.7% of patients were >or=65 years old and 80% of fractures occurred in women aged >or=75, showing a clear relationship with the incidence of osteoporosis. Hospitalizations due to AMI after 45 years of age in 1999 were only 9% higher than those for hip fracture, although this difference increased over the 4 examined years up to 24%. Considering the DRGs costs, hip fractures resulted in being more expensive than AMI overall and concerning elderly people. CONCLUSIONS: This study shows that in the Italian population aged >or=45, hospitalizations following hip fracture and AMI between 1999 and 2002 were comparable, while hip fractures' direct costs were higher and grew faster than costs for AMI. Hip fractures in Italy are a serious medical problem and a leading health-cost driver.

Superiority of alfacalcidol compared to vitamin D plus calcium in lumbar bone mineral density in postmenopausal osteoporosis.

In a randomized multicenter, double-blind, double-dummy, parallel group study a comparison of the efficacy and safety of 1 microg alfacalcidol to 880 IU vitamin D plus calcium carbonate (1 g calcium) once daily per os was performed on 148 postmenopausal osteoporotic Caucasian patients with normal vitamin D serum levels for 18 months. Bone mineral density (BMD) was measured at baseline, 12 and 18 months. Safety parameters were followed during the entire study period. Sixty-nine (90.8%) in the alfacalcidol group and 67 (93.1%) in the vitamin D group were included in the ITT analysis. Lumbar BMD in the alfacalcidol group increased by 0.017 g/cm2 (2.33%) and 0.021 g/cm2 (2.87%) from baseline (P<0.001) at 12 and 18 months, respectively, whereas in the vitamin D plus calcium group the increase was 0.005 g/cm2 (0.70%) from baseline (N.S.) at both 12 and 18 months. The higher changes from baseline in the alfacalcidol group, as compared to the changes in the vitamin D plus calcium group at both 12 and 18 months, were found to be statistically significant (P=0.018, 0.005). A small increase of mean femoral BMD was achieved in both groups (N.S.). Adverse events were similar in both groups. No significant differences were noted between the groups in serum calcium. In conclusion, alfacalcidol was found to be superior in significantly increasing lumbar BMD as compared to vitamin D plus calcium while safety characteristics were found to be similar in both treatments.

[Osteoporosis and diabetes]. / Osteoporosi e diabete mellito.

Diabetes mellitus and osteoporosis are chronic diseases with an elevated and growing incidence in the elderly. Recent epidemiological studies have demonstrated an elevated risk of hip, humerus and foot fractures in elder diabetic subjects. While type 1 diabetes is generally associated with a mild reduction in bone mineral density (BMD), type 2 diabetes, more prevalent in old subjects, is frequently linked to a normal or high BMD. Studies on experimental models of diabetes have suggested an altered bone structure that may help to explain the elevated risk of fractures observed in these animals and may as well help to explain the paradox of an incremented risk of fractures in type 2 diabetic elderly in the presence of normal or elevated BMD. In addition, diabetic elderly have an increased risk of falls, consequent at least in part to a poor vision, peripheral neuropathy, and weaken muscular performance. Diabetes may affect bone tissue by different mechanisms including obesity, hyperinsulinemia, deposit of advanced glycosilation end products in collagen fibre, reduced circulating levels of IGF-1, hypercalciuria, renal function impairment, microangiopathy and chronic inflammation. A better understanding of these mechanisms may help implement the prevention of fractures in the growing population of mature diabetics.

Effect of raloxifene and clodronate on bone density in postmenopausal osteoporotic women.

The aim of the present study was to determine the safety and efficacy of combined therapy with raloxifene (RLX) and clodronate (CLD) in postmenopausal women. We enrolled 45 women with postmenopausal osteoporosis. The patients were randomly assigned to two different therapeutic groups: RLX 60 mg/day (n = 23) and RLX 60 mg/day plus CLD 100 mg intramuscularly (i.m.) once every 10 days (n = 22); 1 g of calcium and 800 IU of vitamin D3 were also given daily to both groups. Lumbar and femoral bone mineral density (BMD) were assessed at baseline and after 12 months of therapy using the dual X-ray absorptiometry technique (Norland XR36). We measured the bone turnover markers NTx and CTx, bone alkaline phosphatase (BAP) and osteocalcin at baseline and after 12 months of therapy. Our data demonstrate that 1 year of combined RLX+CLD therapy induced a higher increase in lumbar BMD than treatment with RLX alone as well as a major decrease in bone resorption markers, suggesting an additive effect of CLD on bone mass and inhibition of bone turnover. Furthermore, after 1 year of therapy levels of bone formation markers (osteocalcin and BAP) had increased in both groups, but the increase in osteocalcin and BAP was significantly higher in the RLX+CLD treated group, suggesting that, in addition to its inhibitory effects on resorption, CLD might also have stimulatory effects on mature osteoblast activity.

[Occupational injuries with biological risk]. / Incidenti occupazionali a rischio biologico.

The aim of the present study was to identify the way the occupational injuries with biological risk can happen in order to find the right measures of prevention and protection and to periodically verify their efficacy. The study started in January 1996 and ended in December 2001 and included 2750 subjects working in the sanitary field. A module (module A), was created to collect all the accident data. For every occupational injury with biological risk, a specific procedure is activated, including: Emergency Room, Sanitary Direction, Infective Diseases Division, Competent Physician. The injuries were classified, according to: sex, age, work qualify, division, object causing injury, modality, anatomical location, type of injury, working turn, and time phase. Most of the division underlined a higher risk the procedures that expose the subjects to accidental punctures with infected needle, such as injection therapy, blood tests, butterfly insertion and removal, etc. Old and bad attitudes, such as needle recapping are still used, even if the law is clear. None occupational injury showed serum conversion. It could be a consequence of the post exposition prophylaxis performed by the infectivologists and of the HBV prophylaxis.