Stefano Gonnelli

Background/Objectives: Hypovitaminosis-D is a highly prevalent condition worldwide, associated with adverse skeletal and extra-skeletal outcomes. Increasing demand for serum 25-hydroxyvitamin D (25(OH)D) testing points toward the need for simple tools to identify individuals at risk and optimize laboratory use. We aimed to develop and validate a clinical risk score for predicting hypovitaminosis-D based on easily assessable risk factors. Methods: This cross-sectional study included 1408 adults aged ≥50 years (1286 women and 122 men) attending centers across Italy dedicated to osteoporosis and metabolic bone diseases. Demographic, clinical, lifestyle, and dietary data were collected through a standardized questionnaire. Overall, 1147 subjects (81.5%) were receiving cholecalciferol supplementation. Univariable and multivariable logistic regression analyses identified predictors of 25(OH)D < 20 ng/mL (primary outcome) and p < 0.001). A screening cut-off (10.3–10.7) ensured high sensitivity (87.0–92.7%), while 11.9–12.0 balanced sensitivity (~62%) and specificity (~80%). A second score for 25(OH)D < 30 ng/mL showed moderate discrimination (AUC: 69.6%). Performance remained stable across seasons and in untreated subjects (AUC: 72.7%). Female predominance, widespread vitamin D use, and the absence of external validation or impact analyses limit generalizability. Conclusions: The proposed data-driven clinical risk score may help identify individuals at risk of vitamin D deficiency and support targeted screening strategies, potentially reducing unnecessary testing in routine clinical practice.

Background: Bone Marrow Edema Syndrome (BMEs) encompasses primary clinical conditions characterized by pain and high-intensity signals on fluid-sensitive magnetic resonance imaging at the subchondral bone level. This study aimed to evaluate bone mineral density (BMD) and turnover markers in BMEs patients compared to a healthy control group. Methods: We selected from the records 165 patients—comprising Complex Regional Pain Syndrome type 1 (CRPS-1, n = 61), hip BMEs (n = 42), and knee BMEs (n = 62)—alongside 150 age- and sex-matched healthy controls. Assessments included bone turnover markers, vitamin D levels, and BMD at the lumbar spine and femur by Dual-Energy X-ray Absorptiometry. Trabecular Bone Score (TBS) was calculated to estimate bone microarchitecture. Results: BMEs patients demonstrated significantly lower BMD across all skeletal sites and reduced TBS values compared to controls. Osteoporosis prevalence was significantly higher in all BMEs subgroups, with CRPS-1 and hip BMES patients showing higher rates than those with knee BMEs. No significant differences were observed in vitamin D or bone turnover markers between groups. Conclusions: Patients with CRPS-1 and BMEs of the hip or knee exhibit a higher prevalence of osteoporosis and compromised bone microarchitecture. These findings highlight a significant association between BME-related conditions and altered BMD/TBS parameters, suggesting a potential shared pathophysiological link.

Background/Objectives: Hypovitaminosis-D is a highly prevalent condition worldwide, associated with adverse skeletal and extra-skeletal outcomes. Increasing demand for serum 25-hydroxyvitamin D (25(OH)D) testing points toward the need for simple tools to identify individuals at risk and optimize laboratory use. We aimed to develop and validate a clinical risk score for predicting hypovitaminosis-D based on easily assessable risk factors. Methods: This cross-sectional study included 1,408 adults across Italy. Demographic, clinical, lifestyle, and dietary data were collected through a standardized questionnaire. Univariable and multivariable logistic regression analyses identified predictors of 25(OH)D <20 ng/mL and <30 ng/mL. Risk scores were derived from models. Discriminative ability was assessed using ROC curves, and calibration by comparing predicted and observed probabilities. Results: Median age was 67 years, and 91.3% were female. Median 25(OH)D was 33.2 ng/mL; 9.8% had levels <20 ng/mL. Independent predictors of hypovitaminosis-D (25(OH)D <20 ng/mL) included higher body mass index, residence in Northern Italy, reduced summer sun exposure, sunscreen use, cardiovascular disease, glucocorticoid use, absence of cholecalciferol supplementation, and no prior vitamin D use. The score (range 9-18) showed good discrimination (Area under the curve; AUC: 79.1%, 95% CI 75.3-82.9) and excellent calibration (r=0.98, p<0.001). A screening cut-off (10.3-10.7) ensured high sensitivity (87.0-92.7%), while 11.9-12.0 balanced sensitivity (~62%) and specificity (~80%). A second score for 25(OH)D <30 ng/mL showed moderate discrimination (AUC: 69.6%). Performance remained stable across seasons and in untreated subjects (AUC: 72.7%). Conclusions: A simple, data-driven clinical risk score identifies individuals at risk of hypovitaminosis-D and may support targeted screening, reduce unnecessary testing, and improve cost-effectiveness in clinical practice.

Background: Dietary calcium and dairy products are hypothesized protective factors against metabolic syndrome (MetS), yet epidemiological evidence remains inconsistent. This systematic review and meta-analysis evaluated the association between total dietary calcium intake or dairy consumption and MetS prevalence in adults. Methods: Following PRISMA 2020 guidelines, PubMed, Cochrane Library, ClinicalTrials.gov, and SCOPUS were searched through to October 2025 for eligible cross-sectional studies assessing dietary calcium or dairy intake and MetS (NCEP ATP III, IDF, or JIS criteria). Longitudinal studies, non-English articles, and pediatric populations were excluded. Quality was assessed via an adapted Newcastle–Ottawa Scale. Random-effects meta-analyses pooled fully adjusted odds ratios (ORs) and 95% confidence intervals (CIs) comparing the highest versus lowest intake categories. Results: Twenty-four studies were included (12 for dietary calcium intake, 12 for dairy products). Higher dietary calcium intake was significantly associated with lower MetS odds (pooled OR: 0.85; 95% CI: 0.80–0.91), despite substantial heterogeneity (I² = 70.1%). Higher dairy consumption was also inversely associated with MetS (pooled OR: 0.78; 95% CI: 0.72–0.85; I² = 64.6%). While small-study effects were observed for dairy, trim-and-fill analysis confirmed the robustness of the findings. Higher calcium intake further correlated with favorable profiles in individual MetS components, including blood pressure, HDL cholesterol, waist circumference, triglycerides, and fasting glucose. Conclusions: Higher total dietary calcium intake and dairy product consumption are associated with a lower prevalence of MetS in adults. However, the cross-sectional nature of the included studies precludes any inference of causality between calcium intake and MetS. Therefore, although these findings suggest a protective role of calcium-rich diets, well-designed prospective and interventional studies are warranted to clarify whether this relationship is causal.

Background: Sport participation has been shown to have a positive impact on bone mineral density (BMD) in children and adolescents. In fact, the type, intensity, and duration of sports activities may influence the magnitude of the effect on BMD. The aim of this study was to examine the effect of different sports on BMD in children and adolescents. Methods: We studied 90 children and adolescents (age 10.21 ± 2.96 years): 43 soccer players, 27 vocational dancers, and 20 active controls. In all subjects, bone mineral density at the lumbar spine (BMD-LS), at the femoral neck (BMD-FN), and at the total femur (BMD-TH) was measured. Moreover, their daily dietary calcium intake was assessed, and the presence of prior fractures was reported. Results: The values of the BMD-LS Z-score adjusted for height did not differ between the three groups: controls (BMD-LS Z-score values were 0.41 ± 1.26, 0.16 ± 0.94, and −0.14 ± 0.96 for soccer players, vocational dancers, and active controls, respectively). On the contrary, BMD-FN and BMD-TH were significantly higher in the soccer players group compared to the vocational dancers and active controls groups (BMD-FN Z-score values, adjusted for height, were 0.49 ± 1.35, −0.04 ± 0.84, and −0.63 ± 1.25 for soccer players, vocational dancers, and active controls, respectively). Soccer players with a history of fractures showed no reduced BMD values compared to those without previous fractures, whereas vocational dancers and active controls with fracture history had reduced BMD values. Conclusions: Consistent athletic involvement during the pre-pubertal and pubertal years significantly enhances bone mineral acquisition. Specifically, youth soccer players demonstrate superior BMD at the proximal femur compared to less active peers, underscoring the site-specific osteogenic effect of sport-related mechanical strain.

Background/Objectives: A significantly higher fracture risk characterizes Type 2 diabetes mellitus (T2DM) patients when compared to the non-diabetic population, even though their average bone mineral density (BMD) tends to be normal or high. This elevated risk is primarily driven by defective bone quality. The trabecular bone score (TBS) and radiofrequency echographic multispectrometry (REMS) have recently been proposed to improve the assessment of bone quality in T2DM individuals. This study aimed to evaluate whether TBS and REMS can improve the identification of osteoporosis and fracture risk in these patients. Methods: BMD was measured in 223 consecutive T2DM patients (126 women and 97 man) and 102 controls. BMD values for the lumbar spine (LS), femoral neck (FN), and total hip (TH) were obtained via both dual-energy X-ray absorptiometry (DXA) and radiofrequency echographic multi-spectrometry (REMS). In all patients, TBS and Fragility Score (FS) by REMS were measured and prior major osteoporotic fractures (MOF) were assessed. Results: All BMD T-scores measured by REMS were significantly lower than those obtained by DXA at both lumbar and femoral sites. T2DM patients with previous MOF exhibited lower T-scores for both BMD-LS and BMD-TH, as assessed by DXA and REMS, compared with patients without fractures. However, these differences reached statistical significance for BMD-TH with both techniques and for BMD-LS with REMS, but not for BMD-LS with DXA. Moreover, patients with a history of MOF had significantly lower TBS values (p < 0.05) and significantly higher FS values at both lumbar (p < 0.05) and femoral (p < 0.01) sites compared with those without fractures. Conclusions: The results of this study suggest that the parameters obtained using REMS technology (BMD and FS) may be valuable tools for improving the diagnosis of osteoporosis and assessing fracture risk in patients with T2DM.

Background: Calcium is the most abundant mineral in the human body and is essential not only for bone health but also for many other physiological functions. In fact, dietary calcium intake is important not only for bone health but also for fat mass and overall body composition. This study aimed to evaluate the potential effects of dietary calcium intake on bone mineral density (BMD), body composition, and fragility fractures. Methods: In a cohort of 173 consecutive elderly men and 939 women aged 55 and over, living in Siena, Italy, daily dietary calcium intake was evaluated using a food frequency questionnaire (FFQ) specifically validated for the Italian population. Bone mineral density at various skeletal sites and body composition were measured in all participants using a Lunar Prodigy densitometer. Additionally, the serum levels of vitamin D and bone turnover markers were assessed, and the presence of prevalent atraumatic fractures was documented. Results: Across all age groups, calcium intake was consistently higher in males (898.40 ± 312.87 mg/day) than in females (821.95 ± 351.3 mg/day); the prevalence of subjects in the lowest tertile of calcium intake was significantly higher among females than males (31.4% vs. 14.5% p < 0.05). Moreover, dietary calcium intake showed an inverse relationship with body fat mass in women (p < 0.05) and a positive association with lean mass in men (p < 0.05). Two hundred twenty-eight (24.3%) women and forty-eight (27.8%) men had a history of one or more fractures, and in both sexes, subjects with prevalent fractures had significantly lower dietary calcium intake values than those without fractures. Conclusions: This study indicates that inadequate calcium intake remains widespread in the Italian population, especially among subjects with low BMD and a history of fractures. Furthermore, this study confirms that dietary calcium intake significantly affects body composition.

Gonococcus, a bacterium resistant to most antibiotics, causes more than 80 million cases of gonorrhea annually and is considered a high-priority pathogen by the World Health Organization. Recently, vaccine development prospects were boosted by reports that licensed meningococcus serogroup B (MenB) vaccines provided partial protection against gonococcal infection. To determine antigens responsible for cross-protection, memory B cells isolated from 4CMenB-vaccinated volunteers were single cell–sorted to identify antibodies that kill gonococcus in a bactericidal assay. Nine different antibodies, all deriving from the IGHV4-34 germline and carrying an unusually long heavy-chain complementarity-determining region 3, recognized the PorB protein; four others recognized the lipooligosaccharide; and another four had unknown specificity. One of the PorB-specific antibodies provided protection in a mouse model of gonococcus infection. The identification of PorB and lipooligosaccharide as key antigens of gonococcal and meningococcal immunity provides a mechanistic explanation of the cross-protection observed in the clinic and shows that isolating human monoclonal antibodies from vaccinees can be instrumental for bacterial antigen discovery.

Background: The condition of vitamin D (25OHD) deficiency represents an important public health problem. In Europe, hypovitaminosis is common not only in the elderly population but also between 50 and 70 years, both in males and females. Data regarding vitamin D intake in the Italian population are very limited. In a recent paper, reporting data collected by a specific Frequency Food Questionnaire (FFQ), we observed in a small group of healthy subjects that the dietary consumption of vitamin D, both in females and males, was far below the average. Methods: With the aim of expanding our preliminary data, we conducted a survey on a large cohort of subjects from different areas of Northern, Central, and Southern Italy. The FFQ contained 11 different questions regarding the amount and type of intake of foods containing ergocalciferol and cholecalciferol. It was submitted to 870 subjects, 627 females and 243 males, with an age range from 40 to 80 years; 31.6% of the studied population was apparently in good health, while 68.4% were affected by different pathologies. Results: The present data confirm previous observations: the global quantity of vitamin D intake in 14 days was 70.8 μg (±1.8 SE, ±54.4 SD) in females and 87.5 μg (±1.9 SE, ±57.1 SD) in males; the mean daily intake of vitamin D in females and males was 5.05 μg (±0.5 SE, ±3.8 SD) and 6.25 μg (±0.21 SE, ±4.1 SD), respectively. In healthy subjects, a gradual decrease was observed in the overall intake of vitamin D in both females and males according to an increase in age bracket, ranging from 74.5 μg and 103.8 μg in the 40–50 age group to 54.5 μg and 87.8 μg in the 71–80 age group, respectively. Conclusions: In conclusion, the present data, collected in a large Italian cohort, underscore that the daily intake of vitamin D is far below the recommended daily average, thereby contributing to the development of potential hypovitaminosis.

There is currently a growing awareness that nutritional factors have major impacts on the risk of age-associated chronic non-communicable diseases and mortality