Secukinumab retention rate is greater in patients with psoriatic arthritis presenting with axial involvement.

Psoriatic arthritis (PsA) is an inflammatory disease characterized by peripheral and axial involvement. Biological disease-modifying antirheumatic drugs (bDMARDs) are the mainstream treatment for PsA and bDMARDs retention rate is a proxy for the drug's overall effectiveness. However, it is unclear whether IL-17 inhibitors can have a higher retention rate than tumor necrosis factor (TNF) inhibitors, in particular in axial or peripheral PsA. A real-life observational study was conducted on bDMARD naïve PsA patients initiating TNF inhibitors or secukinumab. Time-to-switch analysis was carried out with Kaplan-Meyer curves (log-rank test) truncated at 3 years (1095 days). Sub-analyses of Kaplan-Meyer curves between patients presenting with prevalent peripheral PsA or prevalent axial PsA were also conducted. Cox regression models were employed to describe predictors of treatment switch/swap. Data on 269 patients with PsA naïve to bDMARD starting either TNF inhibitors (n=220) or secukinumab (n=48) were retrieved. The overall treatment retention at 1 and 2 years was similar for secukinumab and TNF inhibitors (log-rank test p NS). We found a trend towards significance in the Kaplan-Meyer at 3 years in favor of secukinumab (log-rank test p 0.081). Predominant axial disease was significantly associated with a higher chance of drug survival in secukinumab users (adjusted hazard ratio 0.15, 95% confidence interval = 0.04-0.54) but not in TNF inhibitor users. In this real-life, single-center, study on bDMARD naïve PsA patients, axial involvement was associated with longer survival of secukinumab but not of TNF inhibitors. Drug retention of secukinumab and TNF inhibitors were similar in predominantly peripheral PsA.

Association between exposure to fine particulate matter and osteoporosis: a population-based cohort study.

Long-term environmental air pollution exposure was associated with osteoporosis' risk in a cohort of women at high risk of fracture. Cortical sites seemed to be more susceptible to the exposure's effect. INTRODUCTION: Environmental air pollution has been associated with disruption of bone health at a molecular level. Particulate matter (PM) exposure can simultaneously stimulate bone resorption and halt bone formation. The primary aim of the present study is to describe the association between long-term exposure to PM and osteoporosis in a large cohort of women at high risk of fracture. METHODS: Clinical, demographic, and densitometric data were extracted from the DeFRAcalc79 dataset, which gathers data on women at risk for osteoporosis. Data on the monitoring of PM10 and PM2.5 concentrations were retrieved from the Italian institute of environment protection and research (Istituto Superiore per la Protezione e la Ricerca Ambientale, ISPRA). Generalized linear models with robust estimators were employed to determine the relationship between BMD and PM long-term exposure. RESULTS: A total 59,950 women from 110 Italian provinces were included in the study. PM 2.5 exposure was negatively associated with T-score levels at the femoral neck (ß -0.005, 95 CI -0.007 to -0.003) and lumbar spine (ß -0.003, 95% CI -0.006 to -0.001). Chronic exposure to PM2.5 above 25 µg/m3 was associated with a 16% higher risk of having osteoporotic T-score at any site (aOR 1.161, 95% CI 1.105 to 1.220), and exposure to PM10 above 30 µg/m3 was associated with a 15% higher risk of having osteoporotic T-score at any site (aOR 1.148, 95% CI 1.098 to 1.200). CONCLUSION: Long-term exposure to air pollution was associated with higher risk of osteoporosis. Femoral neck site seemed to be more susceptible to the detrimental effect of PM exposure than lumbar spine site. KEY MESSAGE: Exposure to air pollution is associated with osteoporosis, mainly at femoral site.

Combining role-play with interactive simulation to motivate informed climate action: Evidence from the World Climate simulation.

Climate change communication efforts grounded in the information deficit model have largely failed to close the gap between scientific and public understanding of the risks posed by climate change. In response, simulations have been proposed to enable people to learn for themselves about this complex and politically charged topic. Here we assess the impact of a widely-used simulation, World Climate, which combines a socially and emotionally engaging role-play with interactive exploration of climate change science through the C-ROADS climate simulation model. Participants take on the roles of delegates to the UN climate negotiations and are challenged to create an agreement that meets international climate goals. Their decisions are entered into C-ROADS, which provides immediate feedback about expected global climate impacts, enabling them to learn about climate change while experiencing the social dynamics of negotiations. We assess the impact of World Climate by analyzing pre- and post-survey results from >2,000 participants in 39 sessions in eight nations. We find statistically significant gains in three areas: (i) knowledge of climate change causes, dynamics and impacts; (ii) affective engagement including greater feelings of urgency and hope; and (iii) a desire to learn and do more about climate change. Contrary to the deficit model, gains in urgency were associated with gains in participants' desire to learn more and intent to act, while gains in climate knowledge were not. Gains were just as strong among American participants who oppose government regulation of free markets-a political ideology that has been linked to climate change denial in the US-suggesting the simulation's potential to reach across political divides. The results indicate that World Climate offers a climate change communication tool that enables people to learn and feel for themselves, which together have the potential to motivate action informed by science.

Why golimumab in the treatment of psoriatic arthritis, ankylosing spondylitis and rheumatoid arthritis?

Golimumab is an anti-TNF monoclonal antibody administred subcutaneously once a month and produced with an innovative technology that minimizes immunogenicity. This paper reviews and updates the main studies on the efficacy, safety and pharmacoeconomic aspects of treatment with golimumab of psoriatic arthritis, ankylosing spondylitis and rheumatoid arthritis.

Vitamin D and rheumatic diseases.

Vitamin D has some well-known effects on calcium, phosphate and bone metabolism, but it has recently shown to have many other effects, which may potentially be relevant to patients with extra-skeletal rheumatic diseases. Such effects may be justified by: 1) the presence of the vitamin D receptors also on extra-osseous cells, such as cartilage cells, sinoviocytes, muscle cells; 2) the proven role of vitamin D in the control of the transcription of genes involved in rheumatic diseases; 3) the evidence that vitamin D has multiple endocrine effects not only on calcium homeostasis; 4) the activation of vitamin D not only in the kidneys, but also in monocyte-macrophage and lymphocytic cell lines and in some epithelial cells with additional intracrine and paracrine effects. Vitamin D deficiency has been reported in numerous metabolic, degenerative, inflammatory and autoimmune rheumatic diseases. In some cases this association was also related to the risk of developing a rheumatic disease or the degree of disease activity. However there is no conclusive evidence of the efficacy of a preventive or therapeutic strategy based on vitamin D supplementation in extra-skeletal rheumatic diseases. This review aims to provide an overview of the latest evidence concerning the relationship between vitamin D and the most relevant rheumatic diseases.

[Risk factors for hip fracture in elderly persons]. / Fattori di rischio per frattura di femore in persone anziane.

OBJECTIVE: The aim of this observational study, promoted by the Health Authorities of the Regione Veneto (Italy), is to assess the prevalence of the most relevant environmental and individual risk factors in subjects with a recent hip fracture. METHODS: Patients aged more than 60 years of both genders with a recent hip fracture not associated with malignancies, were administered questionnaires on dietary habits, sun exposure, and disability score. A complete family, pharmacological and pathology history was collected together with information on previous falls, details of the fracture index, and anthropometric data. In all subjects, blood was taken for the measurement of serum 25 hydroxy-vitamin D (25OHD). RESULTS: The study included 704 patients (573 women and 131 men). Mean age was 81 ± 8 years (range 60-102). Severe pre-fracture disability was a common feature (58%) associated with multiple co-morbidities (84%), more frequently cardiovascular and neurological diseases, and specific medications. In a large proportion (86%) of the patients, environmental or individual risk factors for falling were found. Vitamin D insufficiency (serum 25OHD levels < 75 nmol/l) was quite common (70%), particularly in the regional Health Districts were strategies for preventing vitamin D deficiency were not implemented (91%). Only a small proportion (17%) of the study population had been evaluated and treated for osteoporosis. CONCLUSIONS: In senile patients with a recent hip fracture, pre-existing disability, multiple co-morbidities, high risk of falling and inadequate intake of calcium and vitamin D is relatively common. Community and case-finding interventions aimed at selecting subjects at high risk of osteoporosis, preventing vitamin D and dietary calcium deficiency, and increasing awareness on the environmental risks of falling are highly warranted.

[Vitamin D and fractures: a systematic review]. / Vitamina D e fratture: revisione critica della letteratura.

Vitamin D deficiency is a relevant problem particularly in south Europe and in over 65 year old subjects, that is often underestimated. Vitamin D deficiency represents a real medical emergency also for its role in the patho-physiology of muscular-skeletal diseases. Chronic vitamin D deficiency leads to severe bone and muscular outcomes including: osteoporosis, osteomalacia and proximal limb myopathy. These increase the risk of falling and fractures. The efficacy of vitamin D treatment in decreasing the fracture risk has been reporting in several studies. The negative results of some recent studies questioned the clinical vitamin D efficacy. However these studies have a number of methodological problems and even the interpretation of the results is questionable. In this paper we review all these aspects. This analysis permits to confirm that vitamin D treatment can be extremely cost-effective when given to people at high risk of deficiency. An acceptable compliance is obviously of critical importance.

[Rational and results of weekly treatment with calcidiol in postmenopausal and senile osteoporosis]. / Razionale e risultati del trattamento settimanale con calcifediolo nell'osteoporosi postmenopausale e senile.

Vitamin D plays a crucial role for the prevention and treatment of both postmenopausal and senile osteoporosis and possibly for a number of other conditions. The prevalence of vitamin D deficiency remains extremely high among elderly subjects. This indicates that both the perception of the problem and the interventions so far implemented remain inadequate. This is further complicated by the observation that the lower normal range of 25-hydroxycholecalciferol (calcidiol) and the minimum daily allowance of vitamin D have been recently set to values considerably higher. The association of calcidiol with the specific osteoporosis treatment, for example associating the two therapies on one specific day (once weekly) is an efficient way for increasing compliance and effectiveness of the osteoporosis therapy. The weekly dose of calcidiol may be adapted to individual needs, i.e 4,000 to 6,000 IU (or 20-30 drops) according to age or risk factors for vitamin D deficiency.

Intravenous neridronate in adults with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a heritable disease of connective tissue, characterized by increased bone fragility. Bisphosphonates currently seems to be the most promising therapy, at least in children. We tested IV neridronate, an amino-bisphosphonate structurally similar to alendronate and pamidronate in adults with OI. Twenty-three men and 23 premenopausal women with OI were randomized to either iv neridronate (100 mg infused intravenously for 30 minutes every 3 months) or no treatment with a ratio of 2 to 1. Control patients were given the same bisphosphonate therapy at the end of the first year. Clinical evaluation included bone densitometry measurements using dual energy X-ray absorptiometry (DXA), fasting serum and urinary biochemistry every 6 months, and radiographs of the spine taken at baseline and after 12 and 24 months of follow-up. Spine and hip bone mineral density rose by 3.0 +/- 4.6% (SD) and by 4.3 +/- 3.9%, respectively, within the first 12 months of treatment, whereas small insignificant changes were observed in the control group. During the second year of follow-up, additional 3.91% and 1.49% increases were observed at the spine and hip, respectively. Markers of skeletal turnover significantly fell during neridronate treatment. Fracture incidence during neridronate treatment was significantly lower than before therapy and compared with controls. Neridronate iv infusions, administered quarterly, significantly increase bone mineral density and lowered the risk of clinical fracture in adults with OI. Bisphosphonate therapy seems to provide clinical benefits, not only to children with OI, but also to adult patients.

Waist circumference and abdominal sagittal diameter as surrogates of body fat distribution in the elderly: their relation with cardiovascular risk factors.

OBJECTIVE: To evaluate the relationship between supine sagittal abdominal diameter (SAD) and other indicators of body fat distribution with cardiovascular (CVD) risk factors in the elderly. SUBJECTS: One-hundred and forty-six women aged from 67 to 78 y with a body mass index (BMI) ranging from 18.7 to 50.6 kg/m2 and 83 men aged between 67 and 78 y with BMI ranging from 19.8 to 37.1 kg/m2. MEASUREMENT: Body fat distribution was assessed using anthropometric indicators: waist circumference, SAD, waist-to-hip ratio (WHR), waist-to-height ratio and SAD-to-thigh ratio. RESULTS: In women, there was a negative correlation between HDL-cholesterol and body weight, BMI, waist, SAD, WHR, waist-to-height ratio and SAD-to-thigh ratio. A significant association was found between triglycerides, basal glucose, 2 h glucose during oral glucose tolerance test (OGTT), systolic blood pressure (SBP), diastolic blood pressure (DBP) and anthropometric variables. In men a negative correlation was found between HDL-cholesterol and all the anthropometric variables. A significant association was found between triglycerides, DBP and body weight, BMI, waist, SAD and waist-to-height ratio. In women, after adjusting for age and BMI, a significant correlation was observed between waist and HDL-cholesterol, triglycerides and basal glucose. This was also seen with SAD and SAD-to-thigh ratio and triglycerides, basal and 2 h glucose. In men, after adjusting for age and BMI a significant correlation was found between SAD and HDL-cholesterol and triglycerides. When adjustments were made for age and waist, the correlations between BMI and metabolic variables as well between BMI and SBP and DBP were no longer significant. CONCLUSIONS: Our study shows that indicators of body fat distribution are associated with CVD risk factors in the elderly independently of BMI. Our data also show that waist and SAD are the anthropometric indicators of fat distribution which are most closely related to CVD risk factors in old age.

Chronic intravenous aminobisphosphonate therapy increases high-density lipoprotein cholesterol and decreases low-density lipoprotein cholesterol.

Nowadays, bisphosphonates are considered the drugs of choice for the treatment of several bone disorders. Their exact mechanism of action is not clear but recently it has been reported that the aminobisphosphonates inhibit cholesterol biosynthesis and that this might be relevant for their actions on bone osteoclasts. The study includes 87 postmenopausal women with moderate to severe osteoporosis. The patients were randomly assigned to intravenous (iv) infusion of 50 mg of the aminobisphosphonate Neridronate dissolved in 100 ml of saline solution every 2 months for a year (44 patients). The remaining 43 served as controls. At the time of each infusion blood samples were obtained for the evaluation of total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-I (Apo A-I), apolipoprotein B (Apo B), and total and bone alkaline phosphatase (AP). Free deoxypyridinoline (f-DPD) was measured in fasting urine specimens. In the control group no significant changes were observed throughout the study period for any of the biochemical variables. In the Neridronate-treated patients both bone AP and f-DPD excretion fell significantly by 15-20%. In these patients serum total cholesterol and serum triglycerides showed marginal decreases, which were occasionally significant. LDL-C and Apo B fell by 5-6% and these changes were statistically significant at most time points. Apo A-I and HDL-C rose progressively with time. At the 12th month, HDL-C rose 17-18% (p < 0.0001) above the baseline values. Similar findings were obtained in four postmenopausal women given high iv doses of Pamidronate or Alendronate. In conclusion aminobisphophonates, at least when given iv, induce remarkable and unexpected effects on lipid metabolism with a final profile that might be clinically relevant.

Bisphosphonate therapy of reflex sympathetic dystrophy syndrome.

OBJECTIVE: The reflex sympathetic dystrophy syndrome (RSDS) is a painful limb disorder, for which a consistently effective treatment has not yet been identified. The disease is associated with increased bone resorption and patchy osteoporosis, which might benefit from treatment with bisphosphonates, powerful inhibitors of bone resorption. METHODS: Twenty patients with RSDS of foot and hand, were randomly assigned to blind administration of either alendronate intravenously (Istituto Gentili, Pisa, Italy) 7.5 mg dissolved in 250 ml saline solution or placebo saline infusions daily for three days. Two weeks later all patients had an identical treatment course with open labelled alendronate (7.5 mg/day for three days), independent from the results of the first blind treatment. RESULTS: In the patients treated with blind alendronate the diminution in spontaneous pain, tenderness, and swelling (circumference of the affected limb) and the improvement in motion were significantly different from baseline (p < 0.001), from those observed within the first two weeks in the control group (p < 0.01), and from week 2 to week 4 (p < 0.01). In the patients given blind placebo infusions no relevant symptomatic changes were observed after the first two weeks of follow up, but they responded to the open alendronate therapy given afterwards. In 12 patients with RSDS of the hand the ultradistal bone mineral content (BMC) of the affected arm was considerably lower than that of the controlateral arm (mean (SD)) (426(82) mg/cm versus 688(49)). Six weeks after the beginning of the trial BMC rose by 77(12) mg/cm (p < 0.001) in the affected arm, but it did not change in the controlateral. CONCLUSIONS: These results indicate that bisphosphonates should be considered for the treatment of RSDS, producing consistent and rapid remission of the disease.

Intermittent Etidronate partially prevents bone loss in hirsute hyperandrogenic women treated with GnRH agonist.

Treatment with gonadotropin-releasing hormone (GnRH) agonist leads to enhanced bone turnover and accelerated bone loss in premenopausal women with endometriosis, uterine leiomyomatomas and hirsutism. Sodium etidronate is a powerful inhibitor of bone resorption which had been proven efficacious in the prevention and treatment of postmenopausal osteoporosis. The objective of this study was to evaluate the skeletal effects of 6 months of therapy with the depot preparation of the GnRH agonist triptorelin (decapeptil 3.75 mg intramuscularly every 4 weeks) in 24 hirsute patients, aged 24-33 years, with hyperandrogenic chronic anovulation. Ten patients also received cyclical etidronate in an oral dose of 400 mg/day for 2 weeks, followed by an 11-week period of 500 mg/day elemental oral calcium (one cycle). The remaining 14 patients received 500 mg/day of elemental calcium continuously. After 6 months all treatments were discontinued for at least a further 6 months. Bone mineral density (BMD) at lumbar spine and hip (dual-energy X-ray absorptiometry, Sophos LXRA, France) and biochemical markers (serum alkaline phosphatase, osteocalcin, urinary N-telopeptide and hydroxyproline/creatinine ratio) were evaluated at baseline, 6 months and 12 months. In the group given GnRH agonist alone BMD fell significantly at all measured skeletal sites during the first 6 months. In the patients treated with etidronate a significant decrease in BMD was observed at lumbar spine but not in the femoral neck and trochanter, and the changes at lumbar spine and trochanter were significantly smaller than those in the control group. At 6 months bone turnover was also increased in patients treated with GnRH and calcium. Cyclical etidronate prevented the increase in biochemical markers of bone formation and resorption, with the exception of calcium/creatinine excretion, which was significantly increased in both groups. Six months after treatment withdrawal BMD did not recover in either group. Biochemical markers (N-telopeptide, serum alkaline phosphatase) remained increased in those patients previously treated with calcium alone while they remained close to baseline values in the patients treated with cyclical etidronate. Our study indicates that: (1) GnRH agonist therapy causes remarkable bone loss in young individuals with androgen excess who are expected to have increased bone mass; (2) this bone loss can be partially prevented by intermittent cyclical etidronate therapy.

Effect of aging on trabecular and compact bone components of proximal and ultradistal radius.

Bone densitometry has become a major tool for osteoporosis risk assessment. The traditional dual-energy X-ray absorptiometry (DXA) methods are able to evaluate the bone mineral content (BMC; mg/cm) and the areal density (BMD; mg/cm2), but only quantitative computed tomography (QCT) has the potential to measure the true volumetric bone density in the sense of mass per unit volume (mg/cm3). Peripheral QCT (pQCT) measurements were carried out at the nondominant radius using a Stratec XCT 960 (Unitrem, Roma) in 241 postmenopausal and 29 premenopausal women. The sites of evaluation were both the ultradistal and the proximal radius. The technique used has a coefficient of variation of 2% and it allows separation of the bone section into trabecular and cortical bone on the basis of density threshold. Bone mass of radius, hip and spine was also evaluated by DXA procedures. The bone density data obtained by pQCT were significantly correlated with all DXA measurements. The correlation coefficients between their respective BMD values ranged from 0.48 to 0.75, but for the BMC values of the radius the correlation coefficients ranged from 0.82 to 0.93. The BMD values measured by DXA, but not by pQCT, were positively related with patient heights. All pQCT density measurements, including those obtained at the proximal radius and containing exclusively cortical bone, where negatively related with age and years since menopause. A partial volume effect, which is increasingly relevant the thinner are the bone cortices, might explain that. However, by applying increasing density thresholds, cortical bone density seems to decrease with age as a consequence of a gradual density diminution from the inner part of the bone cortex outwards. Trabecular bone density decreases with aging, but its overall mass does not change as a consequence of an age-related enlargement of trabecular area. Thus, the proportion of trabecular bone over total bone rises, and this might be relevant for our understanding of the age-related changes in bone turnover and rate of bone loss.

[Rational bases for the treatment of osteoporosis]. / Basi razionali del trattamento dell'osteoporosi.

Bone tissue undergoes a continuous process of remodelling through resorption of damaged tissue by osteoclasts and apposition of new bone by osteoblasts, at the level of basic multicellular units (BMUs). The number of BMUs ultimately defines bone turnover and it is by itself a source of scarcely mineralized bone. In young healthy individuals bone resorption and bone formation are strictly coupled at the level of the individual BMU and thus of the entire skeleton. Bone loss in the elderly is due to both excess resorption over formation and increased turnover. The inhibitors of bone resorption diminishes the number of BMUs and this invariably decreases the rate of bone loss. However their effect at individual BMU is uncertain. Estrogen replacement therapy lessens the rate of bone loss in postmenopausal women but it does not seem to correct the imbalance between resorption and formation. In several studies bisphosphonates have been shown to induce a continuous positive balance, and this might indicate that these compounds are able to correct the basic alteration of bone metabolism leading to age-related bone loss.