Particle disease: a unique cause of hypercalcemia

Hypercalcemia as a result of ectopic 1, 25-dihydroxyvitamin D (1,25-(OH)₂ D) production has been well-described in sarcoidosis and other granulomatous diseases. The 1-alpha-hydroxylase enzyme in activated macrophages is not subject to physiologic regulations, resulting in hypercalcemia with inappropriately normal or elevated 1,25-(OH) ₂ D. Particle disease is the local inflammatory response provoked by an overwhelming production of wear debris from a failed joint prosthesis. Enhanced focal bone resorption in particle disease has been described due to local production of inflammatory cytokines. However, this process previously has not been reported to cause hypercalcemia. We describe a patient with hypercalcemia, low parathyroid hormone levels, and elevated 1,25-(OH)₂ D whose failed prosthetic joint generated a large amount of inflammatory debris, forming a soft tissue mass with lymphadenopathy. Biopsy of the mass demonstrated activated macrophages and foreign body granuloma, resulting in unregulated production of 1,25-(OH)₂ D and hypercalcemia. We present the first case of hypercalcemia associated with elevated 1,25-(OH)₂ D in particle disease due to a failed prosthetic hip.