Fragility fractures in well-differentiated gastroenteropancreatic neuroendocrine tumors: Results from a multicentered retrospective study

Abstract

Patients with gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) may present skeletal fragility that might be related to multiple factors, including bone metastases, vitamin D deficiency, hormone secretion, and disease treatments. This study examines the prevalence and determinants of fragility fractures in low grading (G1-G2) GEP-NETs. This retrospective study included 291 patients with G1-G2 GEP-NETs (154 men and 137 women). A longitudinal examination was available for 247 patients, with a median follow-up of 49 months (range 24-83). Information regarding disease course, osteo-metabolic profile, and clinical fractures were collected from electronic medical records. Opportunistic chest-abdomen computed tomography or magnetic resonance imaging scans were retrospectively examined to investigate morphometric vertebral fractures. Fracture prevalence in men over 50 and post-menopausal women (n = 200) was compared to an age-matched control sample of 1010 subjects (146 men and 864 women). Forty-five patients with GEP-NETs (15.5%) had fragility fractures at diagnosis of disease. Fractures were significantly associated with age, body mass index, comorbidities, and severe vitamin D deficiency (25(OH)vitamin D < 10 ng/mL) at univariate analysis, and to severe vitamin D deficiency (p = .03) and age (p = .01) at multivariate analysis. When compared to the control group, GEP-NETs patients were found to be independently associated with fractures (OR 2.0 IC95% [1.1-3.6], p = .02). At longitudinal evaluation, 10% of GEP-NETs experienced new fractures in relation to pre-existing fractures and surgical treatment of the tumor. This study provides first evidence that GEP-NETs may have a high risk of fragility fractures at the diagnosis of the disease. A proper and early assessment of bone health is therefore advisable in these patients.

Keywords: fractures; neuroendocrine tumors; osteoporosis; parathyroid hormone; vitamin D.

FIGURE 1

Distribution of clinical fragility fractures in the GEP‐NET group. The picture displays both the absolute number of fractures for each site and the prevalence in the whole group (n = 291).