Severe hypocalcemia in a patient with extensive cranial Paget disease: a diagnostic challenge

Paget disease of bone (PDB) is a focal disorder of accelerated bone remodeling that typically presents with bone pain, deformity, or elevated alkaline phosphatase (ALP). Clinically significant hypocalcemia is uncommon and is usually associated with vitamin D deficiency and high bone turnover states. We report a 64-year-old woman who presented with altered mental status and severe hypocalcemia (total calcium 4.1 mg/dL [International System of Units (SI): 1.0 mmol/L]; reference range 8.5-10.1 mg/dL [SI: 2.1-2.5 mmol/L]) and markedly elevated ALP (1550 U/L; reference range 35-104 U/L). She had a history of progressive cranial enlargement and bilateral hearing loss. Laboratory evaluation revealed profound vitamin D deficiency. Skull radiography demonstrated extensive calvarial thickening with a classic “cotton wool” appearance, and bone scintigraphy showed intense tracer uptake throughout the cranial bones. 18F-sodium fluoride positron emission tomography/computed tomography confirmed diffuse osteoblastic activity confined to the calvarium without evidence of malignant skeletal lesions. Hypocalcemia resolved with calcium and vitamin D repletion, and intravenous zoledronic acid was administered for persistently active Paget disease. This case highlights that severe vitamin D deficiency is the primary driver of hypocalcemia, while high bone turnover may amplify its severity, underscoring the need for metabolic correction before antiresorptive therapy.