Lower Bone Mass and Higher Bone Resorption in Pheochromocytoma: Importance of Sympathetic Activity on Human Bone

Context: Despite the apparent biological importance of sympathetic activity on bone metabolism in rodents, its role in humans remains questionable. Objective: To clarify the link between the sympathetic nervous system and the skeleton in humans. Design, Setting, and Patients: Among 620 consecutive subjects with newly diagnosed adrenal incidentaloma, 31 patients with histologically confirmed pheochromocytoma (a catecholamine-secreting neuroendocrine tumor) and 280 patients with nonfunctional adrenal incidentaloma were defined as cases and controls, respectively. Results: After adjustment for confounders, subjects with pheochromocytoma had 7.2% lower bone mass at the lumbar spine and 33.5% higher serum C-terminal telopeptide of type 1 collagen (CTX) than those without pheochromocytoma (P = 0.016 and 0.001, respectively), whereas there were no statistical differences between groups in bone mineral density (BMD) at the femur neck and total hip and in serum bone-specific alkaline phosphatase (BSALP) level. The odds ratio (OR) for lower BMD at the lumbar spine in the presence of pheochromocytoma was 3.31 (95% confidence interval, 1.23 to 8.56). However, the ORs for lower BMD at the femur neck and total hip did not differ according to the presence of pheochromocytoma. Serum CTX level decreased by 35.2% after adrenalectomy in patients with pheochromocytoma, whereas serum BSALP level did not change significantly. Conclusions: This study provides clinical evidence showing that sympathetic overstimulation in pheochromocytoma can contribute to adverse effects on human bone through the increase of bone loss (especially in trabecular bone), as well as bone resorption.