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Children with osteogenesis imperfecta are often treated with intravenous bisphosphonates. We aimed to assess the safety and efficacy of risedronate, an orally administered third-generation bisphosphonate, in children with the disease. In this multicentre, randomised, parallel, double-blind, placebo-controlled trial, children aged 4–15 years with osteogenesis imperfecta and increased fracture risk were randomly assigned by telephone randomisation system in a 2:1 ratio to receive either daily risedronate (2·5 or 5 mg) or placebo for 1 year. Study treatment was masked from patients, investigators, and study centre personnel. Thereafter, all children received risedronate for 2 additional years in an open-label extension. The primary efficacy endpoint was percentage change in lumbar spine areal bone mineral density (BMD) at 1 year. The primary efficacy analysis was done by ANCOVA, with treatment, age group, and pooled centre as fixed effects, and baseline as covariate. Analyses were based on the intention-to-treat population, which included all patients who were randomly assigned and took at least one dose of assigned study treatment. The trial is registered with ClinicalTrials.gov, number NCT00106028. Of 147 patients, 97 were randomly assigned to the risedronate group and 50 to the placebo group. Three patients from the risedronate group and one from the placebo group did not receive study treatment, leaving 94 and 49 in the intention-to-treat population, respectively. The mean increase in lumbar spine areal BMD after 1 year was 16·3% in the risedronate group and 7·6% in the placebo group (difference 8·7%, 95% CI 5·7–11·7; p<0·0001). After 1 year, clinical fractures had occurred in 29 (31%) of 94 patients in the risedronate group and 24 (49%) of 49 patients in the placebo group (p=0·0446). During years 2 and 3 (open-label phase), clinical fractures were reported in 46 (53%) of 87 patients in the group that had received risedronate since the start of the study, and 32 (65%) of 49 patients in the group that had been given placebo during the first year. Adverse event profiles were otherwise similar between the two groups, including frequencies of reported upper-gastrointestinal and selected musculoskeletal adverse events. Oral risedronate increased areal BMD and reduced the risk of first and recurrent clinical fractures in children with osteogenesis imperfecta, and the drug was generally well tolerated. Risedronate should be regarded as a treatment option for children with osteogenesis imperfecta. Alliance for Better Bone Health (Warner Chilcott and Sanofi).

To examine several dimensions of health-related quality of life (HRQL) in postmenopausal women who report previous fractures, and to provide perspective by comparing these findings with those in other chronic conditions (diabetes, arthritis, lung disease). Fractures are a major cause of morbidity among older women. Few studies have examined HRQL in women who have had prior fractures and the effect of prior fracture location on HRQL. In this observational study of 57,141 postmenopausal women aged 55 years and older (enrollment from December 2007 to March 2009) from 17 study sites in 10 countries, HRQL was measured using the European Quality of Life 5 Dimensions Index (EQ-5D) and the health status, physical function, and vitality questions of the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). Reductions in EQ-5D health-utility scores and SF-36–measured health status, physical function, and vitality were seen in association with 9 of 10 fracture locations. Spine, hip, and upper leg fractures resulted in the greatest reductions in quality of life (EQ-5D scores, 0.62, 0.64, and 0.61, respectively, vs 0.79 without prior fracture). Women with fractures at any of these 3 locations, as well as women with a history of multiple fractures (EQ-5D scores, 0.74 for 1 prior fracture, 0.68 for 2, and 0.58 for ≥3), had reductions in HRQL that were similar to or worse than those in women with other chronic diseases (0.67 for diabetes, 0.69 for arthritis, and 0.71 for lung disease). Previous fractures at a variety of bone locations, particularly spine, hip, and upper leg, or involving more than 1 location are associated with significant reductions in quality of life.

TNFα inhibitors (TNFαI) exert positive effects on disease activity in rheumatoid arthritis (RA). Bone involvement is a major determinant of functional impairment in this disease. Here we investigated the short-term effects of TNFαI therapy on bone metabolism and density. We studied 54 patients with RA starting a TNFαI biologic drug, in whom any factor known to interfere with bone metabolism was excluded or rigorously accounted for. We measured at baseline and after 6-month therapy bone turnover markers: N -propeptide of type I collagen (P1NP), and bone alkaline phosphates for bone formation and serum C-terminal telopeptide of type I collagen (CTX) for bone resorption. We also evaluated bone mineral density (BMD) at hip and lumbar by dual-energy X-ray absorptiometry. All bone markers rose significantly and these changes were not dependent on steroid dosage. A significant decrease in femoral neck BMD was also observed. These results indicate that TNFαI therapy in RA over 6 months is associated with an early increase in bone turnover and a decline in hip BMD.

The pathogenic mechanisms of specific immune-mediated inflammatory diseases (IMIDs) are not fully understood, but are thought to involve activated T cells with the release of pro-inflammatory cytokines. Understanding the autoimmune inflammatory pathways has led to the development of biological agents that target specific components of effector immune mechanisms. Despite the availability of many effective drugs, a large proportion of patients with moderate to severe IMID do not receive adequate treatment, and many therapies show decreased efficacy over time. Therefore, there is a need for new therapies. One subset of T helper cells, Th17, and the cytokine interleukin-17 (IL-17) play a central role in the pathophysiology of autoimmune diseases such as psoriasis. IL-17 is involved in the modulation of pro-inflammatory cytokines, haematopoietic growth factors, antimicrobial peptides, chemokines, and molecules involved in tissue remodelling; the inflammatory cascades triggered by Th17 cells and IL-17 itself, when unregulated, can result in widespread inflammation-related damage. Evidence of increased Th17 activity and high levels of IL-17 has been found in psoriasis, as well as other inflammatory conditions, thereby signalling the potential utility of IL-17 as a therapeutic target. Clinical trials investigating IL-17 inhibitors, such as secukinumab, in patients with psoriatic disease have reported no significant safety concerns so far. It is hoped that these agents will improve the long-term prognosis of patients with these debilitating disorders.

Bone formation is influenced by the Wnt pathway through effects on osteoblast functionality, and these actions are opposed by two antagonists: sclerostin and Dickkopf-1 (DKK1). Decreased levels of serum sclerostin were found after treatment with the PTH analogue teriparatide and in patients with primary hyperparathyroidism (PHPT), while treatment with teriparatide of postmenopausal osteoporosis is associated with increases in serum DKK1. We studied mineral metabolism and Wnt pathway in 21 postmenopausal women affected by PHPT and in 42 age-matched healthy women. Mean serum calcium and PTH were significantly higher and serum phosphates significantly lower in the PHPT group compared with the control group. Serum 25-OH-vitamin D (25OHD) was lower in PHPT patients and 1,25 dihydroxy-vitamin D [1,25(OH) 2 D] was significantly higher. Patients with PHPT had significantly higher levels of bone alkaline phosphatase (BAP) and of serum C -terminal telopeptides of type I collagene (sCTX). Serum sclerostin in PHPT was significantly lower (−26 %) and serum DKK1 significantly higher (+57 %) than in healthy control subjects. Serum PTH was positively correlated with 1,25OH 2 D ( p  < 0.001), BAP ( p  = 0.036), sCTX ( p  = 0.003), and DKK1 ( p  = 0.007) and negatively with 25OHD ( p  = 0.002) and sclerostin ( p  = 0.02). In PHPT patients, serum sclerostin was negatively correlated with BAP ( p  = 0.038) and sCTX ( p  = 0.07). Patients with PHPT have significantly lower sclerostin and higher DKK1 levels compared with healthy postmenopausal control subjects. Further studies are warranted in order to verify whether the balance between these two opposite effects on Wnt function might help explain the variable bone involvement among patients with PHPT.

Adult-onset Still’s disease (AOSD) is a systemic inflammatory condition of unknown aetiology characterized by typical episodes of spiking fever, evanescent rash, arthralgia, leukocytosis and hyperferritinemia. Given the lack of data in Italian series, we promote a multicentric data collection to characterize the clinical phenotype of Italian patients with AOSD. Data from 245 subjects diagnosed with AOSD were collected by 15 centres between March and May 2013. The diagnosis was made following Yamaguchi’s criteria. Data regarding clinical manifestations, laboratory features, disease course and treatments were reported and compared with those presented in other published series of different ethnicity. The most frequent features were the following: arthritis (93 %), pyrexia (92.6 %), leukocytosis (89 %), negative ANA (90.4 %) and neutrophilia (82 %). As compared to other North American, North European, Middle Eastern and Far Eastern cohorts, Italian data show differences in clinical and laboratory findings. Regarding the treatments, in 21.9 % of cases, corticosteroids and traditional DMARDs have not been able to control the disease while biologics have been shown to be effective in 48 to 58 patients. This retrospective work summarizes the largest Italian multicentre series of AOSD patients and presents clinical and laboratory features that appear to be influenced by the ethnicity of the affected subjects.

To examine when, where and how fractures occur in postmenopausal women. We analyzed data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), including women aged ≥55 years from the United States of America, Canada, Australia and seven European countries. Women completed questionnaires including fracture data at baseline and years 1, 2 and 3. Among 60,393 postmenopausal women, 4122 incident fractures were reported (86% non-hip, non-vertebral [NHNV], 8% presumably clinical vertebral and 6% hip). Hip fractures were more likely to occur in spring, with little seasonal variation for NHNV or spine fractures. Hip fractures occurred equally inside or outside the home, whereas 65% of NHNV fractures occurred outside and 61% of vertebral fractures occurred inside the home. Falls preceded 68-86% of NHNV and 68-83% of hip fractures among women aged ≤64 to ≥85 years, increasing with age. About 45% of vertebral fractures were associated with falls in all age groups except those ≥85 years, when only 24% occurred after falling. In this multi-national cohort, fractures occurred throughout the year, with only hip fracture having a seasonal variation, with a higher proportion in spring. Hip fractures occurred equally within and outside the home, spine fractures more often in the home, and NHNV fractures outside the home. Falls were a proximate cause of most hip and NHNV fractures. Postmenopausal women at risk for fracture need counseling about reducing potentially modifiable fracture risk factors, particularly falls both inside and outside the home and during all seasons of the year.

Objectives Aim of the current study was to evaluate the relationships between the findings of 18F-fluoride PET/CT (F-PET/CT) reflecting osteo-proliferative processes and the clinical indexes related to the disease activity. The clinical indexes are Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS). Methods We studied 29 AS patients aged 26–69 years with a wide range of disease activity using F-PET/CT. The number of regions of high bone turnover or osteoarthritis features at the spine and at sacroiliac joints was counted. Results The number of F-PET/CT positive sites was significantly higher in patients with severe functional impairment and higher disease activity and it was positively related to both BASDAI ( r  = 0.336; P  = 0.036) and ASDAS ( r  = 0.408; P  = 0.014) while the number of degenerative features (osteoarthritis) was related neither with functional impact nor with disease activity. Conclusions With a single examination, F-PET/CT accurately identifies the functional impairment and the clinical involvement of AS. The good correlation we found between the number of F-PET/CT positive sites and disease activity candidates this technique also for follow-up of AS.

Hip fractures cause substantial disability and are associated with a high rate of death among elderly women, 1 but there have been few studies of the effects of drug treatment on the risk of hip fracture. Observational studies suggest that estrogen may reduce the risk of hip fracture. 2 – 4 Alendronate reduced the risk of hip fracture in postmenopausal women with low bone mass at the femoral neck or with previous vertebral fractures, but not in women without those risk factors. 5 , 6 Numerous risk factors for hip fracture have been identified. 7 – 13 In general, these risk factors can be categorized as skeletal . . .