Increased prevalence of morphometric vertebral fractures in patients with hypercalcitoninemia due to medullary thyroid carcinoma

Context: Calcitonin is a well-established biomarker of medullary thyroid cancer (MTC) but it is also known to exert distinct effects on bone metabolism. Previous studies evaluating calcitonin actions on skeletal health have yielded inconsistent results regarding its protective or deleterious role. To date, the impact of chronic hypercalcitoninemia, typically observed in patients with MTC, on skeletal fragility complications, particularly vertebral fractures (VFs), has not been investigated. Design: We included patients with MTC and baseline calcitonin levels >50 pg/mL, matched 1:2 for demographics and comorbidities with patients affected by papillary thyroid carcinoma (PTC). VFs were assessed through morphometric analysis of preoperative lateral chest X-rays. Results: 99 patients were included (33 MTC, 66 PTC; median age 57 years; 27% male). No differences were observed in sex, age, or comorbidities between groups. VF prevalence was significantly higher in MTC patients than in PTC patients (24% vs. 7.6%, p = 0.029). Median calcitonin levels were higher in patients with VFs compared to those without (1267 vs. 501 pg/mL, p = 0.005). In multivariate analysis, MTC diagnosis was the only independent predictor of VFs (OR 4.3, p = 0.028). ROC curve analysis confirmed a significant predictive value of calcitonin levels for the presence of VFs (p = 0.006). Conclusions: This is the first study to demonstrate an increased prevalence of thoracic VFs in patients with MTC and hypercalcitoninemia compared with a matched population affected by another form of thyroid cancer. These findings expand the clinical spectrum of calcitonin-related effects, suggesting a potential role of excessive calcitonin levels in skeletal fragility risk.