Introduction: There are few data regarding the clinical outcome of patients with parathyroid carcinoma (PC) and atypical adenoma (AA) after surgery. Aim of our study was to investigate disease recurrence and mortality rate as well as their predictors in a series of patients with PC or AA.Methods: Clinical and biochemical parameters, histological features, incidence of disease recurrence and mortality rate were retrospectively assessed in 39 patients (51% males, mean age 56.2 ± 17.2 years) diagnosed with PC (n=24) or AA (n=15) and followed up for 6.8 ± 5.0 years after surgery.Results: No differences in baseline characteristics were registered between the two groups, except for higher KI67 values in PC than AA (6.9 ± 3.9% vs 3.4 ± 2.1%, p<0.01). Eight patients (21%) experienced recurrence after a mean follow-up of 5.1 ± 2.7 years, with higher relapse rate in PC than AA (25% vs 13%), though this difference did not reach statistical significance. Mortality rate was 10% in the whole sample, without significant differences between PC and AA. Relapsing cases had been undergone the most extensive surgery more frequently and they had a higher mortality rate in comparison to non relapsing patients (38% vs 6% and 38% vs 3%, respectively, p<0.03 for both). In comparison to survivors, deceased patients were submitted to the most extensive surgery more frequently (50% vs 9%), they were older (74.8 ± 4.6 vs 53.2 ± 16.3 years), and they had higher KI67 values (11.7 ± 4.9 vs 4.8 ± 2.8, p<0.03 for all comparisons).Conclusions: During seven-year follow-up after surgery, no significant differences in recurrence and mortality rate were observed between PC and AA patients. Death was associated with disease relapse, older age and higher KI67 values. These findings suggest a similar and careful long-term follow-up in both parathyroid tumors, especially in older patients, and emphasize the need of further studies in large cohorts to throw light on this crucial clinical issue.

Purpose X-linked hypophosphatemia (XLH) is a rare hereditary skeletal disorder that may be very disabling and significantly impacting the quality of life throughout the lifespan. The aim of this document was to inform stakeholders about the lifelong impact, management, and treatment of individuals with XLH, especially focusing on the new therapeutic approach with burosumab. Methods From October 2023 to April 2024, a multidisciplinary working group of Italian experts on bone and mineral metabolism convened periodic online meetings. Statements were formulated identifying the most relevant studies, including randomized controlled trials, international guidelines based on GRADE criteria, and systematic reviews, and the experts’ opinions. Results The panel of experts provided "consensus statements" on the clinical management of individuals with XLH across lifespan. Five main issues were identified: (1) clinical and biochemical diagnosis of individuals with XLH and monitoring of the progression of the disease; (2) effects of conventional treatment with phosphate supplements and active vitamin D metabolites; (3) effects of the treatment with burosumab; (4) multidisciplinary approach and management of individuals with XLH; (5) consensus statement for transition from pediatric to adult care in individuals with XLH. Conclusion Individuals with XLH often experience unmet needs throughout life; a multidisciplinary approach involving different specialists, is recommended. The new treatment with burosumab can provide an effective and safety therapeutic option in reducing the burden of the disease in both children and adults. Therefore, awareness about the XLH disease should be increased among stakeholders. The criteria and reimbursement policies of burosumab should be revised.

Background: Conventional glucocorticoids (C-GC) replacement regimens have a detrimental effect on skeletal health in patients with adrenal insufficiency (AI), ultimately leading to an increased fracture risk. The novel dual-release hydrocortisone (DR-HC) formulations are characterized by a more favourable safety profile on various clinical endpoints. Data comparing the impact of C-GC and DR-HC on bone, however, are scarce.Methods: Twenty-seven patients with autoimmune primary AI (PAI; 13 treated with C-GC and 14 treated with DR-HC) were evaluated to compare bone-related parameters between the two treatment groups.Results: No significant differences between the two treatments groups were observed with respect to bone turnover markers. Patients treated with C-GC showed a lower bone mineral density (BMD) at lumbar spine (LS; 0.791 ± 0.195 vs. 0.942 ± 0.124 g/cm², p=0.025) and at femoral neck (FN; 0.633 ± 0.114 vs. 0.716 ± 0.088 g/cm², p=0.045). Moreover, they were characterized by a lower trabecular bone score (TBS; 1.236 ± 0.035 vs. 1.383 ± 0.030, p=0.004) and by a higher mean number of vertebral fractures per patient (0.75 vs. 0 fractures, p=0.002). TBS was the best predictor of fracture risk, with a pseudo-R² of 0.593; moreover, at mediation analysis, it was able to fully explain the observed detrimental effect of C-GC, compared to DR-HC, on fracture risk.Conclusions: These results suggest that DR-HC is associated with less bone-related complications compared to C-GC in patients with PAI. Moreover, TBS seems to play a pivotal role in the mediation of the relationship between glucocorticoid treatment regimens and fracture risk.

Despite the current debate on the best therapeutic approach, i.e. symptomatic vs intensive strategy, one zoledronate (Zol) infusion is effective in most patients with Paget’s disease of bone (PDB), whereas few need retreatment, whose predictors are not well established. We aimed to evaluate long-term efficacy of intensive Zol therapy and predictors of retreatment in PDB. Pagetic complications, clinical and biochemical response to Zol together with frequency of retreatment were retrospectively assessed in forty-seven PDB patients (age, mean ± SD: 72.5 ± 8.9 years, M/F: 24/23; symptomatic/asymptomatic: 16/31). Statistical analysis for retreatment prediction were based on Mann–Whitney U test, Pearson’s Χ2 and ROC curve analysis. During seven-year follow-up, all patients achieved pain relief and only one underwent arthroplasty. Bone alkaline phosphatase (BAP) detected three non-responder (6%) and six relapsing (13%) patients needing retreatment. Retreated patients had less old age (66.1 ± 11.2 vs 74.0 ± 7.7 years), higher frequency of polyostotic disease (78% vs 40%) and higher baseline (96.5 ± 24.8 vs 44.9 ± 27.7 mcg/l) and post-Zol nadir BAP levels (24.7 ± 24.1 vs 8.1 ± 4.1 mcg/l) than patients treated once (p < 0.05 for all comparisons). In multivariate analysis both serum baseline and post-Zol nadir BAP significantly predicted retreatment (OR 1.09, 95%CI 1.01–1.17 and 1.29, 1.03–1.62, respectively), with ROC curve analysis showing the greatest accuracies for threshold values of 75.6 and 9.9 mcg/l (sensitivity 88 and 90%, specificity 94 and 86%, AUC 0.92 and 0.93, respectively). Our data in mostly asymptomatic, metabolically active PDB patients treated with intensive Zol therapy show a negligible incidence of pagetic complications and long-term optimal disease control, with BAP being the best predictor of retreatment.