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J Bone Miner Metab. 2013 May;31(3):360-5. doi: 10.1007/s00774-012-0395-8. Epub 2012 Oct 18.

Symptomatic intracranial hypertension and prolonged hypocalcemia following treatment of Paget's disease of the skull with zoledronic acid.

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  • 1Unidade de Doenças Osteometabólicas, Serviço de Endocrinologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. bferrazd@gmail.com


Skull involvement in Paget's disease of bone can lead to neurological symptoms, prompting treatment. Intravenous zoledronic acid (ZA) has emerged as an effective and safe treatment option for patients with Paget's, leading to sustained remission and improved quality of life. A previously untreated 61-year-old female presented with 2-year history of facial asymmetry with progressive hearing impairment. Serum calcium levels were normal with upper normal levels of PTH and low 25OHD levels. Serum alkaline phosphatase was markedly increased and bone scan showed extensive pagetic involvement of the skull. Head CT and MRI revealed hydrocephalus with cerebellar tonsillar herniation, platybasia and basilar invagination. In the absence of clinical signs or symptoms of intracranial hypertension, she was treated with intravenous ZA after 15-day supplementation with calcium and vitamin D. Twelve hours after the infusion, the patient became confused, agitated and disoriented and developed urinary incontinence; cortical sulci became effaced on CT indicating increased intracranial pressure. Over the following days, she developed frank hypocalcemia requiring intravenous calcium infusion and calcitriol. Neurological status returned to normal within 24 h of onset, except for urinary incontinence. Nine months later she remained incontinent and still required calcitriol to maintain normocalcemia. Zoledronic acid is a first-line option for the treatment of Paget's disease, yet there can be complications in particular clinical scenarios such as pagetic hydrocephalus, as seen in this case. Plentiful supplementation of calcium and vitamin D before bisphosphonate therapy is paramount in order to minimize the risk of prolonged post-treatment hypocalcemia.

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