Children should have a baseline electrocardiogram before starting bisphosphonate therapy, senior author Dr. Agnes Linglart from Hopital Saint Vincent de Paul in Paris told Reuters Health by e-mail. Also, she said, “Risk factors for hypocalcemia (vitamin D deficiency, hypoparathyroidism) and for prolonged QT (hypomagnesemia, drugs) should be searched for and corrected before the initiation of therapy.”
Dr. Linglart and colleagues measured serum calcium levels and corrected QT intervals before and after three cycles (over the course of a year) of intravenous pamidronate infusions in 34 children with cerebral palsy and severe osteoporosis. Each cycle involved 2 days of infusions, for a total of 1.5 mg/kg per cycle.
None of the children had hypoparathyroidism or a family history of long QT syndrome.
Serum calcium levels declined in all children after pamidronate infusion, from a median 2.40 mM to 2.21 mM. Levels decreased after 92% of pamidronate infusions and fell below normal range after 65% of infusions.
Median QTc increased from 390 ms to 403 ms (with a median increase of 20 ms) after pamidronate infusion. The maximal increase was 80 ms, and the longest measured QTc was 460 ms.
In 3 children, the QTc interval increased to more than 440 ms, although these events did not correspond to the lowest postinfusion calcium levels.
“Even if the increase in QTc is small, incidents should be expected if larger numbers of children are exposed to IV pamidronate,” the researchers say. “This is of real concern because prolonged QTc can result in syncope, torsades de pointes, or sudden death, even if these complications are rare.”
Baseline QTc correlated significantly with postinfusion QTc, but neither the variation in calcium levels nor the dose of pamidronate was correlated with the lengthening of the QTc.
“The lengthening of the QT did not correlate with the decrease of the calcemia, but there was a tendency for it,” Dr. Linglart said. “It is likely that (a) prospective study on a large number of patients would unravel a correlation between QTc and calcemia.”
“Hypocalcemia by itself is known to prolong the QT,” she added. “It is therefore mandatory to check that patients do not have hypocalcemia or risk factors for hypocalcemia (like vitamin D deficiency) before the intravenous infusion of bisphosphonates.”
J Clin Endocrinol Metab 2010.