Neuroendocrine neoplasia and bone (Review)

Abstract

This is a narrative review focusing on neuroendocrine neoplasia (NEN) and bone status, in terms of metastases and osteoporosis/fractures. One fifth of NEN have skeletal dissemination, this affinity being regulated by intrinsic tumor factors such as the C-X-C chemokine receptor 4 (CXCR4). Bone colonization impairs the patient quality of life, representing a surrogate of reduced survival. Patients with NEN without bone metastases may exhibit low bone mineral density, perhaps carcinoid-related osteoporosis, yet not a standardized cause of osteoporosis. Case-finding strategies to address bone health in NEN with a good prognosis are lacking. Contributors to fractures in NEN subjects may include: menopausal status and advanced age, different drugs, induced hypogonadism, malnutrition, malabsorption (due to intestinal resection, carcinoid syndrome), hypovitaminosis D, impaired glucose profile (due to excessive hormones such as glucagon, somatostatinoma or use of somatostatin analogues), various corticoid regimes, and high risk of fall due to sarcopenia. Pheocromocytoma/paraganglioma involve bone through malignant forms (bone is an elective site) and potential secondary osteoporosis due to excessive hormonal content and increased sympathetic activity which is a key player of bone microarchitecture/quality as reflected by low Trabecular Bone Score. Glucocorticoid osteoporosis is related to NEN-associated ectopic Cushing syndrome. Currently, there are a lack of studies to emphasis that excessive gut-derivate serotonin in NENs with carcinoid syndrome is a specific activator of bone loss thus a contributor to carcinoid-related osteoporosis.

Selected Parameters of Bone Turnover in Neuroendocrine Tumors—A Potential Clinical Use?

“…Statistical analysis was performed using Microsoft Excel v. 2108 (14332.20503) (Microsoft, Redmond, WA, USA) and Statistica v. 13.36.0 (StatSoft, Kraków, Poland). ROC analysis for osteocalcin, osteoprotegerin, and insulin-like growth factor binding protein 3 was performed with easyROC curve analysis web-tool version 1.3.1 [12] using default settings. In all tests, a value of p < 0.05 was considered statistically significant.…”

“…However, the continuous processes of bone formation and bone resorption can also be disturbed in cancer patients. Patients diagnosed with GEP-NETs have an increased risk of developing osteopenia and osteoporosis [11,12]. Hormones secreted by functioning GEP-NETs that may affect bone metabolism are serotonin, cortisol, and parathyroid hormone-related peptide.…”

“…Neuroendocrine tumors can be either hormonally functioning or non-functioning. The proposed mechanisms explaining osteoporosis in NENs (neuroendocrine neoplasms) include excessive secretion of cortisol (ectopic Cuhing's syndrome) and carcinoid syndrome associated with excess of serotonin secreted by NENs [11,12]. Other factors related to osteoporosis and the increased risk of fractures in patients with NENs include advanced age, malabsorption syndrome related to surgical treatment or treatment with somatostatin analogues, and the frequent presence of bone metastases [11,12].…”

“…The proposed mechanisms explaining osteoporosis in NENs (neuroendocrine neoplasms) include excessive secretion of cortisol (ectopic Cuhing's syndrome) and carcinoid syndrome associated with excess of serotonin secreted by NENs [11,12]. Other factors related to osteoporosis and the increased risk of fractures in patients with NENs include advanced age, malabsorption syndrome related to surgical treatment or treatment with somatostatin analogues, and the frequent presence of bone metastases [11,12]. Currently, there are no specific recommendations for assessing bone turnover in these patients, but such evaluations might improve the prevention of severe complications like bone fractures, ultimately enhancing the quality of life [11].…”

“…However, diagnostic markers specific to NETs are still being investigated. Patients diagnosed with GEP-NETs have an increased risk of developing osteopenia and osteoporosis [11,12]. The aim of this study was to assess bone metabolism using selected markers of bone turnover: OST, OPG, and IGFBP-3, in patients with NETs and in the control group.…”