Yearly Zoledronic Acid in

Postmenopausal Osteoporosis

To the Editor: In their report on the Health Outcomes and Reduced Incidence with
Zoledronic Acid Once Yearly (HORIZON) Pivotal Fracture Trial, Black et al. (May 3
issue)1 conclude that a once-yearly infusion of zoledronic acid reduces the risk of
vertebral, hip, and other fractures. Although this is a well-designed and well-done
study, we are concerned about the increase in atrial fibrillation in patients treated
with zoledronic acid. Hypocalcemia as a cause was ruled out. There is no report of
hypokalemia during the study. Another electrolyte imbalance, hypomagnesemia, is
reported as a side effect of zoledronic acid2 and can cause cardiac arrhythmias.3,4
It would be interesting to know the incidence of hypomagnesemia during the
HORIZON study, mainly among the patients with atrial fibrillation.

Forty-nine patients in the zoledronic-acid group had transient hypocalcemia at days

9 to 11 after the infusion. There are several case reports describing hypocalcemia
during treatment with zoledronic acid, inducing a compensatory increase in
parathyroid hormone.5 In the study by Black et al., however, we are not informed
about the mean change in calcium and parathyroid hormone concentrations during
treatment.

Ron N.J. de Nijs, M.D., Ph.D.

Antonius A.A. Westgeest, M.D., Ph.D.
Mxima Medical Center
5631 BM Eindhoven, the Netherlands
r.denijs@mmc.nl

References

1. Black DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid for
treatment of postmenopausal osteoporosis. N Engl J Med 2007;356:1809-
1822. [Free Full Text]

2. Sorscher SM. Electrolyte abnormalities with zoledronic acid therapy. Cancer

J 2002;8:348-349. [Web of Science][Medline]

3. Abbott LG, Rude RK. Clinical manifestations of magnesium deficiency.

Miner Electrolyte Metab 1993;19:314-322. [Web of Science][Medline]
4. Whang R, Hampton EM, Whang DD. Magnesium homeostasis and clinical
disorders of magnesium deficiency. Ann Pharmacother 1994;28:220-
226. [Abstract]

5. Peter R, Mishra V, Fraser WD. Severe hypocalcaemia after being given

intravenous bisphosphonate. BMJ 2004;328:335-336. [Free Full Text]