Wnt pathway involvement and its response to treatment in the development of bone damage in different inflammatory and non-inflammatory rheumatic contidions

Inflammatory conditions such as Rheumatoid Arthritis (RA) are characterised by impaired bone health, with bone loss occurring both systemically and locally (erosions). Other conditions, such as Diffuse Idiopatic Skeletal Hyperostosis (DISH) are not usually associated with significant systemic inflammation but nonetheless can show signs of impaired bone health, in the form of osteoporosis and bone ectopic neoformation. The Wnt/B-catenin pathway is the master regulator of osteogenesis, and its role has been extensively investigated in the last years. The objective of the presen thesis is to investigate the role of the main Wnt pathway modulators (Dkk-1 and sclerostin) in inflammatory conditions such as RA and polymyalgia rheumatica and the effect of different treatment on their serum levels. Furthermore, the Wnt pathway dysregulation in a non-inflammatory conditions such as DISH will be investigated and discussed

Vitamin D and Osteogenesis Imperfecta in Pediatrics

Osteogenesis Imperfecta (OI) is a heterogeneous group of inherited skeletal dysplasias characterized by bone fragility. The study of bone metabolism, in these disease, is problematic in terms of clinical and genetic variability. The aims of our study were to evaluate the importance of Vitamin D levels in OI bone metabolism, reviewing studies performed on this topic and providing advice reflecting our experience using vitamin D supplementation. A comprehensive review on all English-language articles was conducted in order to analyze the influence of vitamin D in OI bone metabolism in pediatric patients. Reviewing the studies, contradictory data were found on the relationship between 25OH vitamin D levels and bone parameters in OI, and in several studies the baseline levels of 25OH D were below the threshold value of 75 nmol/L. In conclusion, according to the literature and to our experience, we highlight the importance of adequate vitamin D supplementation in children with OI

Systematic study on nail plate assessment: differences in nail plate shape, thickness, power Doppler signal and scanning approach

Ultrasonography (US) of the nail is raising interest in the last years and its feasibility, quickness and amount of descriptive data may provide valuable information. Different authors presented several scanning approaches to nail complex in different pathological conditions, such as psoriasis, but no scanning protocol was ever proposed using healthy subjects as population of reference. The aim of the study was to establish a protocol for the US of nail plate and to assess whether the measurement of the nail plate is influenced by longitudinal vs transverse scan, sex, digit and hand dominance. Using high frequency probe and a Canon Aplio i800 machine, ultrasonographers took scans of nail plates of the hands from healthy subjects. Nail plate shape, thickness and power Doppler signal (PDUS) were evaluated and scans were taken both on longitudinal and transverse axis, at distal, middle and proximal portion of the nail plate or at a fixed angles of - 45 degrees, 0 degrees or + 45 degrees. All the images were then revised and scored using a DICOM software, in order to allow good standards of accuracy and reproducibility. A total of 27 subjects (14 females and 13 males) were assessed. The measures did not result to differ in different portions or angles. Furthermore, no difference appears in sex or dominant vs not dominant hand. A decreasing and significant trend for nail plate thickness was found from the first to the fifth finger. Doppler signal was found in all but one subjects, with a range from almost absent to very evident. No difference was found between groups regarding PDUS. The data provided suggest that a proper scan protocol should include all the nails and evaluation should be done both on longitudinal and transverse axis. Since Doppler signal is highly variable in healthy subjects, its presence should be carefully considered as pathological finding. Observations provided by this study clarify important points of the scanning technique and solve doubts related to which nails should be scanned and where to evaluate quantitative parameters

Effects of secukinumab on serum adipocytokines: preliminary data

Psoriatic arthritis (PsA) is a chronic inflammatory disease that affects joints, connective tissues and the axial skeleton. Metabolic syndrome is an independent risk factor for psoriasis (Pso) development and is associated with more severe forms of Pso. Adipocytokines are secreted by white adipose tissue and are thought to link obesity with the development of metabolic and cardiovascular diseases. Secukinumab is a new monoclonal antibody with a different mechanism of action. This antibody selectively binds to and neutralizes interleukin-17 (IL-17) and it has shown efficacy in the treatment of PsA. The aim of this study was to evaluate the possible interferences of secukinumab on different adipocytokines. We enrolled 28 patients with PsA, classified with the CASPAR criteria. Serum samples were stored at baseline and then at the first, the third and the sixth month of therapy. Resistin, chemerin, adiponectin and C-reactive protein (CRP) were dosed. When tested globally, none of the adipokine tested showed any statistically significant variation. However, when the male group was tested, both resistin and chemerin at M6 showed a significant decrease from baseline. CRP did not show any variation at any time point. Our study demonstrated that treatment with secukinumab has little influence on the levels of adipokines tested within the first six months of treatment even though it might exert different influence between males and females from a metabolic perspective. Further studies with greater numbers of patients are needed to determine whether these preliminary results have clinical relevance

Drug-induced osteonecrosis of the jaw: the state of the art

Osteonecrosis of the jaw (ONJ) is a rare adverse event of antiresorptive drugs such as bisphosphonates (BP) and denosumab (DMAb). The diagnosis of ONJ is considered in cases where exposed bone in the maxillofacial region does not heal within 8 weeks in a patient previously treated with an antiresorptive agent. In patients with osteoporosis, ONJ is reported as a very rare adverse event while in oncologic patients with bone metastases or malignant hypercalcemia the incidence is significantly higher (up to the 1-10% of the patients). The pathophysiology of ONJ is still not completely understood but it is multi-factorial. ONJ is a condition associated with poor oral health, oral surgery, and use of antiresorptive agents. Prevention is of paramount importance especially in cancer patients, in whom the large majority of cases of ONJ (>90%) are reported, but it should also be considered in osteoporotic patients, especially during dental surgical procedure. Some simple prevention procedures are effective in reducing the risk of its appearance. When ONJ unfortunately occurs, the large majority of patients can be managed conservatively. In conclusion, ONJ is a rare condition associated with antiresorptive drugs. Both osteoporotic and oncologic patients should be well informed about its low absolute risk and regarding the fact that the benefits of antiresorptive therapy far outweigh this potential risk of ONJ

Correction to: Bone metabolism in patients with anorexia nervosa and amenorrhoea.

Unfortunately, the sixth author name was incorrectly spelled as "S. Fassio" instead of "A. Fassio" in the original publication

Osteoimmunology of Spondyloarthritis

: The mechanisms underlying the development of bone damage in the context of spondyloarthritis (SpA) are not completely understood. To date, a considerable amount of evidence indicates that several developmental pathways are crucially involved in osteoimmunology. The present review explores the biological mechanisms underlying the relationship between inflammatory dysregulation, structural progression, and osteoporosis in this diverse family of conditions. we summarize the current knowledge of bone biology and balance and the foundations of bone regulation, including bone morphogenetic protein, the Wnt pathway, and Hedgehog signaling, as well as the role of cytokines in the development of bone damage in SpA. other areas surveyed include the pathobiology of bone damage and systemic bone loss (osteoporosis) in SpA and the effects of pharmacological treatment on focal bone damage. Lastly, we present data relative to a survey of bone metabolic assessment in SpA from Italian bone specialist rheumatology centers. The results confirm that most of the attention to bone health is given to postmenopausal subjects and that the aspect of metabolic bone health may still be underrepresented. In our opinion, it may be the time for a call to action to increase the interest in and focus on the diagnosis and management of SpA

Sex-Specific Association of Left Ventricular Hypertrophy With Rheumatoid Arthritis

Objectives: Clinical expression of rheumatoid arthritis (RA) varies by gender, but whether cardiovascular disease (CVD) is gender related in RA is unknown. Left ventricular (LV) hypertrophy (LVH) is a hallmark of CVD in RA patients. We investigated whether the association of LVH with RA is gender driven.Methods: Consecutive outpatients with established RA underwent echocardiography with measurement of LVH at baseline and one follow-up. All participants had no prior history of CVD or diabetes mellitus. We assessed CVD risk factors associated with LVH at follow-up, including sex, age, arterial blood pressure, and body mass index (BMI). We also evaluated inflammatory markers, autoimmunity, disease activity, and the use of RA medications as predictors of LVH.Results: We recruited 145 RA patients (121 females, 83%) and reassessed them after a median (interquartile range) of 36 months (24–50). At baseline, women were more dyslipidemic but otherwise had fewer CVD risk factors than men, including less prevalent smoking habit and hypertension, and smaller waist circumference. At follow-up, we detected LVH in 42/145 (44%) RA patients. LV mass significantly increased only in women. In multiple Cox regression analysis, women with RA had the strongest association with LVH, independently from the presence of CVD risk factors (OR, 6.56; 95% CI, 1.34–30.96) or RA-specific characteristics (OR, 5.14; 95% CI, 1.24–21.34). BMI was also significantly and independently associated with LVH.Conclusion: Among established RA patients, women carry the highest predisposition for LVH