Hungry Bone Syndrome After Parathyroidectomy for Secondary Hyperparathyroidism: Pathogenesis and Contemporary Clinical Considerations
Adina Coman, Cristi Tarţa, Marco Marian, D Popa, Sorin Olariu, Mihai Rosu, Diana Uţu, Florina Buleu, Anca-Monica Macovei-Oprescu, Dorin Novacescu, Flavia Baderca, Marius-Sorin Murariu
Abstract
Secondary hyperparathyroidism (SHPT) in chronic kidney disease often necessitates parathyroidectomy (PTX), but this definitive treatment can precipitate hungry bone syndrome (HBS)-a profound, prolonged hypocalcemia caused by the rapid skeletal uptake of minerals after surgery. HBS results from the abrupt cessation of parathyroid hormone (PTH)-driven bone resorption while bone formation continues, leading to intensive mineral deposition (mainly calcium) into chronically demineralized bone. Clinically, HBS ranges from asymptomatic biochemical disturbances to life-threatening hypocalcemia with tetany, seizures, and/or cardiac arrhythmias. This illustrative review synthesizes current knowledge of HBS pathogenesis and management in the context of SHPT. We detail how the high-turnover bone remodeling state of SHPT (osteitis fibrosa cystica) creates an expansive unmineralized osteoid pool that avidly mineralizes post-PTX. We also explore molecular mechanisms (e.g., RANKL/OPG dysregulation, Wnt/β-catenin activation, osteocyte-driven signals, and calcium-sensing receptor effects) that underpin this process. Key preoperative risk factors for HBS include very elevated PTH and alkaline phosphatase levels, large skeletal calcium deficits, younger patient age, and total PTX. We outline the typical postoperative course of HBS, phased from immediate acute hypocalcemia to a nadir and gradual recovery. Prevention and management strategies are emphasized, centered on vigilant monitoring and aggressive calcium and calcitriol supplementation, with preoperative optimization (e.g., vitamin D loading, calcimimetics) to mitigate severity. By enhancing risk stratification and perioperative care, clinicians can improve outcomes and safely navigate patients through this challenging complication of endocrine surgery.