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VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic) syndrome is characterized by heterogeneous clinical manifestations. Due to the inflammatory nature of this condition, 18-FDG-PET (18-fluorodeoxyglucose-positron emission tomography) might be used to diagnose and monitor the disease. However, no data are available about the most common findings of PET imaging in this disease. For this reason, we summarised all the available reports of patients with VEXAS who underwent at least one PET scan and described 8 additional patients' PET from our centres. Overall, we described 35 patients' PET findings. All patients were male, with a median age of 70 years. The most frequent hypermetabolic sites on PET scans were the bone marrow (77.1%), lymph nodes (35.3%), lungs (28.6%), spleen and large vessels (22.9%), and cartilage (20%). Six patients underwent a PET scan 2.7 ± 1.5 years before VEXAS diagnosis, showing nonspecific uptake in the bone marrow. Four patients had a follow-up PET scan, showing a decrease or a disappearance of the previously identified hypermetabolic areas. In conclusion, although no specific uptake site has been found for VEXAS syndrome, PET imaging could help detect inflammatory foci that are not clinically evident. In addition, high metabolic activity in bone marrow might precede the clinical onset of the disease, shedding light on the pathogenesis of VEXAS., (© 2024. The Author(s).)

Background: Cystinuria is a rare genetic disease characterized by impaired tubular transport of cystine. Clinical features of cystinuria mainly include nephrolithiasis and its complications, although cystinuric patients may present with other comorbidities. There are currently no data on bone features of patients with cystinuria. Our aim is to characterize bone mineral density (BMD) in cystinuria., Methods: Our study included adult cystinuric patients with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m 2 followed at 3 specialized outpatient clinics in Italy (Rome, Naples and Verona). Markers of bone turnover were analyzed in a centralized laboratory. Clinical, biochemical and dual-energy X-ray absorptiometry (DEXA) data were collected from September 2021 to December 2022. Linear regression models were used to evaluate statistically significant deviations from zero of Z-scores., Results: Twenty-seven patients were included in the study. Mean (SD) age was 37 (15) years, 41% were women. Mean estimated glomerular filtration rate was 99 mL/min/1.73 m 2 . Serum parameters associated with bone turnover (parathyroid hormone, FGF23, calcium and phosphate) were all in the normal range, with only 4 patients showing mild hypophosphatemia. Prevalence of low bone mineral density, defined as Z-score ≤  - 2 at any site, was 15%. Average Z-scores were negative across most sites., Conclusions: Our study suggests that cystinuric patients have lower bone mineral density compared with individuals of the same sex and age, even when their kidney function is normal., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Bariatric surgery is associated with a postoperative reduction of 25(OH) vitamin D levels (25(OH)D) and with skeletal complications. Currently, guidelines for 25(OH)D assessment and vitamin D supplementation in bariatric patients, pre- and post-surgery, are still lacking. The aim of this work is to analyse systematically the published experience on 25(OH)D status and vitamin D supplementation, pre- and post-surgery, and to propose, on this basis, recommendations for management. Preoperatively, 18 studies including 2,869 patients were evaluated. Prevalence of vitamin D insufficiency as defined by 25(OH)D < 30 ng/mL (75 nmol/L) was 85%, whereas when defined by 25(OH)D < 20 ng/mL (50 nmol/L) was 57%. The median preoperative 25(OH)D level was 19.75 ng/mL. After surgery, 39 studies including 5,296 patients were analysed and among those undergoing either malabsorptive or restrictive procedures, a lower rate of vitamin D insufficiency and higher 25(OH)D levels postoperatively were observed in patients treated with high-dose oral vitamin D supplementation, defined as ≥ 2,000 IU/daily (mostly D3-formulation), compared with low-doses (< 2,000 IU/daily). Our recommendations based on this systematic review and meta-analysis should help clinical practice in the assessment and management of vitamin D status before and after bariatric surgery. Assessment of vitamin D should be performed pre- and postoperatively in all patients undergoing bariatric surgery. Regardless of the type of procedure, high-dose supplementation is recommended in patients after bariatric surgery., (© 2023. The Author(s).)

Background: The aim of this real-life cross-sectional explorative study was to compare radiofrequency echographic multi-spectrometry (REMS) with dual-energy X-rays absorptiometry (DXA) in the BMD assessment of patients receiving peritoneal dialysis (PD). Furthermore, we investigated the relationship between lumbar aortic calcifications (AOCs) and the DXA lumbar measurements., Methods: Consecutive patients referring to the PD clinic of our hospital were included. Lumbar spine and femur scans were acquired with both techniques (including lumbar laterolateral DXA scans). The risk assessment of two fracture risk algorithms (FRAX ® and DeFRA ® ) were compared. Cohen's k coefficients were used to assess the inter-technique agreement in the classification of patients as osteoporotic. Lumbar AOCs were estimated semi-quantitatively on laterolateral DXA scans., Results: 41 patients were enrolled. No significant differences were documented between the BMD T-scores measured through DXA or REMS at the femur. At the lumbar spine, the DXA anteroposterior mean T-score (- 0.49 ± 1.98) was significantly higher than both the laterolateral DXA (- 1.66 ± 0.99) and the REMS (- 2.00 ± 1.94) measurements (p < 0.01 vs both). No significant differences were found between the DXA and REMS fracture risk estimates with both algorithms. The inter-technique Cohen's k coefficient (for the worst T-score, any site) was 0.421, p < 0.001. The discrepancy between the DXA laterolateral and anteroposterior lumbar T-score was positively associated with the AOCs extent and severity (r = 0.402, p < 0.01)., Conclusions: Our data showed a promising agreement, in a real-life PD setting, between DXA and REMS BMD assessment and in the consequent fracture risk estimation and confirm the AOCs interference on the diagnostic accuracy of lumbar DXA., (© 2022. The Author(s).)

Systemic chronic inflammation may favor the onset of metabolic syndrome (MetS) which represents a risk factor for CV events. Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are disorders with high prevalence of MetS. We assessed the factors associated with MetS and its prognostic role in non-selected RA/AS/PsA patients. Between March 2014 and April 2016, 458 patients (228 RA, 134 PsA, 96 AS) selected for a primary prevention program for cardiovascular diseases were analyzed. Primary and co-primary end points were a composite of all-cause death/all-cause hospitalization and CV death/CV hospitalization, respectively. MetS was diagnosed according to the IDF Task Force on Epidemiology and Prevention. Patients were divided into MetS + (73 = 16%) and MetS - (385 = 84%). At multivariate logistic analysis, cancer, moderate/high disease activity, higher LV mass (LVM) and degree of LV diastolic dysfunction were independently associated with MetS. At 36-month follow-up, the event rate for primary/co-primary end point was 52/15% in MetS + vs 23/7% in MetS - (both p < 0.001). At multivariate Cox regression analysis, MetS was related to primary end point (HR 1.52 [CI 1.01-2.47], p = 0.04) together with higher LVM, disease duration and higher prevalence of biologic DMARDs refractoriness, and to co-primary end point (HR 2.05 [CI 1.16-3.60], p = 0.01) together with older age and higher LVM. The RA/AS/PsA phenotype MetS + is a subject with moderate/high disease activity, LV structural and functional abnormalities at increased risk for cancer. MetS + identifies RA/AS/PsA patients at higher risk for CV and non-CV events, independently of traditional CV risk factors analyzed individually and traditional indexes of inflammation.

In the present observational cohort study in 4902 men and 9804 women, we found that the factors associated with osteoporosis care utilization in men were comorbidities, adjuvant hormonal therapy for prostate cancer, vertebral or hip fractures, and glucocorticoid treatment., Introduction: Male osteoporosis is associated with an important clinical and economic burden worldwide; nevertheless, undertreatment of men with osteoporosis is common. Understanding the factors associated with referral to bone specialists may help to define future interventions to improve access to osteoporosis care for male patients., Methods: We conducted a retrospective analysis of a nationwide cohort (DeFRACalc79 database). DeFRACalc79 is a tool that estimates the fracture risk by considering clinical and densitometric risk factors, including the presence of prior hip or vertebral and non-vertebral or non-hip fractures. We compared the clinical characteristics of male individuals with an age-matched cohort of women. Propensity score generation with a 2:1 female-to-male ratio was performed using a logistic regression model to age-match the cohorts., Results: We analyzed a sample of 4902 men at high risk for osteoporosis. We found that the factors associated with osteoporosis care utilization in men were the presence of comorbidities (OR 1.939, 95% CI 1.799-2.090), adjuvant hormonal therapy for prostate cancer (OR 1.482, 95% CI 1.315-1.670), the presence of vertebral or hip fractures (OR 1.490, 95% CI 1.378-1.611), and glucocorticoid treatment (OR 2.573, 95% CI 2.274-2.832)., Conclusions: Men are more commonly referred to the bone specialist with a prevalent fragility fracture and/or diagnosis of secondary osteoporosis as compared with women. Our study suggests that there is a lack of screening for the primary prevention of osteoporosis in men as compared with that in women.

Inflammatory arthritis, including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), are associated with both cancer and cardiovascular (CV) adverse events. Cancer and CV abnormalities have coincident etiologic and pathophysiologic pathways in RA/PsA/AS patients. However, a comprehensive evaluation of CV system has never been performed in these patients in relation to the presence of cancer. This study was designed to assess the possible relationships between CV abnormalities and cancer among RA/PsA/AS patients. Between March 2014 and March 2015, 414 patients (214 RA, 125 PsA, and 75 SA) in sinus rhythm without known cardiac disease underwent clinical and color Doppler echocardiographic evaluation and were prospectively followed up. Patients had a mean age of 58 ± 12 years, 64% women. Forty-two patients (10.1%) had a diagnosis of cancer (made before enrollment in 24 cases and in 18 cases during the 36 months of follow-up). Skin cancer was the most frequent malignancy found, followed by thyroid, colon, pancreas, and breast cancer. Patients who had cancer were older with higher systolic blood pressure, more frequent hypertension and moderate/high disease activity, left ventricular (LV) hypertrophy, diastolic dysfunction, and higher ascending aortic stiffness index (AOSI) than those who had not. At multivariate logistic regression analysis, LV diastolic dysfunction and abnormally high AOSI emerged as conditions associated with cancer together with older age and hypertension. Cancer in RA/PsA/AS adults without history of CV disease is closely associated with specific asymptomatic CV abnormalities, such as LV diastolic dysfunction and reduced vascular elasticity, which are independent of age and hypertension.

The original published version of this article contained the incorrect Table 2 and are now presented correctly in this article.

Introduction and Objectives: The nail unit is a subject of interest in several diseases, often involving different medical fields. Even if few data are available for psoriasis and psoriatic arthritis, no data regarding ultrasonography and imaging are present for other degenerative and inflammatory conditions. The aim of this study was to explore through imaging the changes of nail and enthesis in inflammatory and degenerative conditions in order to find qualitative and quantitative changes related to distal interphalangeal joints., Methods: The study sample was composed of 51 patients affected by psoriatic arthritis, 31 affected by psoriasis, 37 subjects with rheumatoid arthritis, 34 with osteoarthritis and 50 healthy controls for a total of 203 individuals. Ultrasonography of the nails was performed after clinical evaluation in a cross-sectional study design by blinded ultrasonographers who were blind to patient data. Data about power Doppler signal of the nail bed, tendon entheses, thickness of nail plate and nail bed were recorded., Results: Patients affected by psoriasis and psoriatic arthritis differ from other subgroups, and power Doppler signal at the enthesis seems to be an exclusive feature of psoriatic arthritis (Pearson's chi-square of 5297 and p < 0.001 with adjusted residuals). Nail plate thickness also differs in psoriasis and psoriatic arthritis, but surprisingly in osteoarthritis, too, with similar results., Conclusions: This study provides qualitative and quantitative data regarding the ultrasonographic features of nails in several rheumatic diseases with a potential role of ultrasonography in characterising them.

Available studies reported contradictory results about serum levels Dickkopf-1 (DKK1), an inhibitor of Wnt signaling in patients with ankylosing spondylitis (AS). In previous studies, we observed in other conditions that parathyroid hormone (PTH) serum levels were an important determinant of DKK1 serum levels. The aim of the present study was to investigate it in patients with AS. We recruited 71 patients diagnosed with AS. Levels of C-reactive protein (CRP), DKK1, PTH, 25OH-vitamin D, and bone turnover markers (intact N-propeptide of type I collagen, P1NP, and C-terminal telopeptide of type I collagen, CTX) were measured and compared to healthy controls (HC). Dual X-ray absorptiometry at lumbar spine and proximal femoral site was used for bone mineral density (BMD) assessment and spine X-rays were also performed. PTH serum levels were found to be significantly higher in AS patients than in HC (33.8 ± 14.11 vs 24.8 ± 13 pg/ml, p = 0.002), while mean DKK1 serum levels were lower than in HC (23.3 ± 13.1 vs 29.8 ± 15.9 pmol/l, p = 0.009). A positive correlation between DKK1 and PTH (correlation coefficient + 0.25, p = 0.03) was observed; it remained significant in a multivariate analysis. In patients with longer disease duration, DKK1 was also positively correlated with CTX (coefficient 0.42, p = 0.01), and PTH was higher in those patients with low BMD (Z-score ≤ - 1) at any site (p = 0.04). Also in AS, PTH is an important determinant of DKK1 serum levels and should be evaluated in studies on DKK1. PTH might have a role in bone involvement in AS, also through the Wnt pathway.

Unfortunately, the author's first name and the family name were swapped and published in the original publication.

Overweight and obesity according to the definition of the WHO are considered as an abnormal or excessive fat accumulation that may impair health. Studies comparing fracture incidence in obese and non-obese individuals have demonstrated that obesity, defined on the basis of body mass index (BMI), is associated with increased risk of fracture at some sites but seems to be protective at others. The results of the studies are influenced by the distribution of BMI in the population studied; for example, in cohorts with a low prevalence of obesity, a predilection for certain fracture sites in obese individuals becomes difficult to detect, whereas, in populations with a high prevalence of obesity, previously unreported associations may emerge. Furthermore, obesity can bring with itself many complications (Type 2 diabetes mellitus, vitamin D deficiency, and motor disability) which, in the long run, can have a definite influence in terms of overall risk and quality of life, as well. This is a narrative review focusing on the relationship between bone metabolism and overweight/obesity and dealing with the fundamental dilemma of a disease (obesity) apparently associated with improved values of bone mineral density, part of a complicated relationship which revolves around obesity called "the obesity paradox".

Psoriatic Arthritis (PsA) is characterized by bone erosive damage often associated with exuberant bone formation especially in enthesial sites. Dkk-1 and sclerostin are the main inhibitors of the WNT/β-catenin signaling pathway and play a key role in the regulation of both bone formation and resorption. We performed this study in order to compare the serum levels of the WNT-pathway regulators along with bone turnover markers (BTM) and parathyroid hormone (PTH) between three different groups: one group of female patients affected by PsA, one group of female patients affected by rheumatoid arthritis (RA), and healthy female controls (HC). This is a cross-sectional study including 33 patients with PsA classified with the CASPAR criteria, 35 HC, and 28 patients with RA classified with the ACR/EULAR 2010 criteria. Intact N-propeptide of type I collagen (PINP), C-terminal telopeptide of type I collagen (CTX-I), Dickkopf-related-protein 1 (Dkk-1), sclerostin, PTH, and 25OH-vitamin D serum levels were dosed. The PsA group showed significantly lower Dkk-1 levels when compared to the HC and RA groups. Dkk-1 in the RA group was significantly higher than HC. A similar trend was documented for PTH. In the PsA group, CTX-I was found to be lower than in both the RA and HC groups. This study demonstrated for the first time that Dkk-1 levels in PsA are lower than HC, in contrast with RA, in which they are increased. These results might contribute to explain the different bone involvement of the two different diseases.

Paget disease of bone is a chronic metabolic bone disorder characterized by increased bone resorption and new bone formation. The aim of this study is defining the role of inhibitors of canonical Wnt/b-catenin signaling pathway in patients with Paget disease of bone. Scarce and contrasting results have been reported in literature. We studied 40 patients (15 females and 25 males) with radiological and scintigraphic evidence of Paget disease of bone and 40 healthy subjects matched by age and sex. N-propeptide of type I collagen, C-terminal telopeptide of type I collagen, sclerostin, and Dickkopf-related protein 1 (DKK1) were evaluated by blood samples in our laboratory. As expected, mean serum levels of bone turnover markers (N-propeptide of type I collagen and C-terminal telopeptide of type I collagen) were significantly higher in the Paget disease of bone group compared with the control group. No difference was observed between groups in Dickkopf-1 and sclerostin. Dickkopf-1 and sclerostin were never correlated with each other or with bone turnover markers. Sclerostin was positively correlated with age. In conclusion, our results suggest that the regulators of the Wnt-β catenin pathway are not altered in patients with Paget disease of bone. The positive correlation we found between sclerostin and age in Paget disease of bone patients indicates that in comparative studies, sclerostin serum levels must be adjusted for age.