Seizures after alendronate

Maclsaac, Richard J; Seeman, Ego; Jerums, George

doi:10.1258/jrsm.95.12.615

Cited by 25 publications

(4 citation statements)

References 11 publications

(11 reference statements)

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“…Another example of hypocalcemic seizures, and perhaps the most commonly seen, are drug-induced hypocalcemic seizures (Milman and Epstein, 2010). Biphosphonate may also induce hypocalcemic seizures due to a disturbance of calcium and phosphate metabolism (Maclsaac et al., 2002; Tsourdi et al., 2011). Finally, the anticonvulsant phenytoin may paradoxically exacerbate seizures when blood calcium is low (Ali et al., 2004).…”

Section: Introductionmentioning

confidence: 99%

Hypocalcemia-Induced Seizure

2015

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Calcium is essential for both neurotransmitter release and muscle contraction. Given these important physiological processes, it seems reasonable to assume that hypocalcemia may lead to reduced neuromuscular excitability. Counterintuitively, however, clinical observation has frequently documented hypocalcemia’s role in induction of seizures and general excitability processes such as tetany, Chvostek’s sign, and bronchospasm. The mechanism of this calcium paradox remains elusive, and very few pathophysiological studies have addressed this conundrum. Nevertheless, several studies primarily addressing other biophysical issues have provided some clues. In this review, we analyze the data of these studies and propose an integrative model to explain this hypocalcemic paradox.

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Section: Introductionmentioning

confidence: 99%

Hypocalcemia-Induced Seizure

2015

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“…In all three cases, the level of 25-(OH)-D has been described as low (<30 ng/ml). Importantly, there was no description about magnesium level.There are also another two cases of seizures reported in association with the administration of the above drugs, and in both reports, hypocalcemia was thought to represent the underlying mechanism [Navarro et al 2007;Maclsaac et al 2002]. However, if we go through these two reports, then the respective authors have described that it is the underlying vitamin D deficiency leading to hypocalcemia causing seizure rather than alendronate or zoledronic acid.…”

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confidence: 97%

“…There are also another two cases of seizures reported in association with the administration of the above drugs, and in both reports, hypocalcemia was thought to represent the underlying mechanism [Navarro et al . 2007; Maclsaac et al . 2002].…”

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confidence: 99%

Seizure associated with zoledronic acid therapy: side-effects or coincidental finding?

Das

2011

Therapeutic Advances in Endocrinology

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Bisphosphonates have been used in a wide range of malignancies and bone disorders. Recently, there have been a few reports of seizure associated with alendronate and zoledronic acid. We discuss them, along with our experience with use of zoledronic acid.In a recent series, the authors described three cases of seizures that developed after the administration of zoledronic acid [Tsourdi et al. 2011]. However, among these three cases, hypoglycemia (caused by prior gastric surgery leading to dumping syndrome) was the predisposing factor behind two cases. In the third case, the patient developed a febrile seizure on the second day of zoledronic acid administration. The authors proposed that zoledronic acid induced an acute phase reaction that had lead to lowering of the seizure threshold and resulting seizure. However, the requirement for vasopressor support and response to iv antibiotics suggest intracranial infection rather than simple febrile seizure, which the authors have not ruled out by cerebrospinal fluid (CSF) analysis. In all three cases, the level of 25-(OH)-D has been described as low (<30 ng/ml). Importantly, there was no description about magnesium level.There are also another two cases of seizures reported in association with the administration of the above drugs, and in both reports, hypocalcemia was thought to represent the underlying mechanism [Navarro et al. 2007;Maclsaac et al. 2002]. However, if we go through these two reports, then the respective authors have described that it is the underlying vitamin D deficiency leading to hypocalcemia causing seizure rather than alendronate or zoledronic acid. The authors of both of the reports propose that the patients might have subclinical hypocalcemia before starting the drugs (as a result of vitamin D deficiency) which was aggravated by the administration of zoledronic acid.The risk factors for zoledronic-acid-induced hypocalcemia include pre-existing vitamin D deficiency, hypoparathyroidism, hypomagnesemia, and previous thyroid or parathyroid surgery [Tanvetyanon and Stiff, 2006]. These conditions impair the normal release and activity of parathyroid hormone which acts to compensate for low serum calcium by increasing renal absorption of vitamin D and calcium. Pre-existing vitamin D deficiency in a population receiving a bisphosphonate has also been reported in up to 27% [Wang-Gillam et al. 2008]. The elderly and cancer patients are at particular risk of vitamin D insufficiency due to limited Sun exposure, reduced dietary intake and renal impairment. In our experience in children with osteogenesis imperfecta, we found no clinical problems due to hypocalcemia in any of the patients [Panigrahi et al. 2010].Rapid parenteral administration of bisphosphonates, might lead to hypocalcemia; however, it is infrequent and usually mild. So before initiating bisphosphonate therapy, any disturbances of mineral metabolism (calcium, magnesium) should be corrected. Following the approval and widespread use of bisphosphonates, a number of potential side effects have be...

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“…In a recent United States study of 1536 women receiving anti‐osteoporotic therapy, 52% had vitamin D deficiency 6 . Treatment with intravenous or (more rarely) oral bisphosphonates may also cause severe hypocalcaemia in people with severe vitamin D deficiency, 7 , 8 so it is prudent to screen for vitamin D deficiencies before initiating bisphosphonate therapy.…”

mentioning

confidence: 99%

Megadose therapy for vitamin D deficiency

Ebeling

2005

Medical Journal of Australia

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Seizures after alendronate

Cited by 25 publications

References 11 publications

Hypocalcemia-Induced Seizure

Hypocalcemia-Induced Seizure

Seizure associated with zoledronic acid therapy: side-effects or coincidental finding?

Megadose therapy for vitamin D deficiency

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