Effects of catecholamines on bone and mineral metabolism in patients with pheochromocytoma and paraganglioma

Pheochromocytomas and paragangliomas (PPGLs) are rare catecholamine-producing neuroendocrine tumors with significant systemic effects. While catecholamine-related cardiovascular manifestations are well-characterized as a prominent component of the clinical presentation, other systemic effects, particularly those on bone and mineral metabolism, remain much less characterized. Bone physiology and health in patients with PPGLs can be affected through catecholamine-mediated changes, skeletal metastases, or specific skeletal abnormalities associated with syndromic PPGL forms. The catecholamine effect on bone density was first noticed in experimental murine models, where β-adrenoceptor signaling was shown to increase bone resorption. These findings were further supported by epidemiological and translational studies indicating a protective role of β-adrenoceptor blockers in maintaining bone density. Both preclinical and clinical studies draw attention to the potential alterations of bone physiology in patients with PPGLs. To date, a few retrospective studies have evaluated bone turnover markers and bone mineral density (BMD) in these patients, consistently showing lower BMD and trabecular bone score, as well as elevated serum C-terminal telopeptides levels, compared to healthy controls with partial reversibility following surgical resection of the tumor. In this review, we summarize the available mechanistic and clinical literature on bone health in PPGLs, to raise awareness among clinicians, identify opportunities for primary prevention, and ensure a better quality of life.