CORRESPONDENCE
Oral Bisphosphonates and Risk of
Wet Age-Related Macular
Degeneration
EDITOR:
ALENDRONATE IS A NITROGEN-CONTAINING BISPHOSPHO-
nate that has been widely used for the treatment of osteo-
porosis for more than 20 years with few side effects.
In vitro studies have shown that bisphosphonates have
antiangiogenic effects because they inhibit endothelial
cell adhesion, migration, and survival in human umbilical
vein endothelial cells. Recent in vitro studies exploring the
antiangiogenic activity of bisphosphonates showed novel
antiangiogenic effects suggesting they may be useful as
therapeutic agents for neovascular-related diseases.1,2 An
in vitro study in cultured retinal pigment epithelial cells
involving different concentrations of bisphosphonates
showed that higher doses had proinflammatory effects
(increasing interleukin activity) and lower doses had
mainly antiangiogenic effects (decreasing basic fibroblast
growth factor and vascular endothelial growth factor
activities).1
A recent study analyzing population databases of pre-
scription patterns in Canada3 has shown that long-term
use of oral alendronate was associated with increased risk
of use of intraocular antiangiogenics, a marker of wet mac-
ular degeneration. Although significant, the magnitude of
the effect was rather small. For example, in Table 3 of
the Canadian paper,3 the crude prevalence in subjects
with regular use of bisphosphonates for 1 year was 5.9%
in controls and 7.2% in users (only 1.3% difference).
And this difference was even smaller in irregular users.
More research is needed to confirm these findings.
Interestingly, daily low doses of oral alendronate (5 mg)
have been proposed as a treatment option for wet macular
degeneration owing to its antiangiogenic effects.4,5
Although there is limited evidence up to now, research
in this area is promising because alendronate is safe and
cheap, and could be an adjunct therapy for this disease. It
0002-9394/$36.00 © 2017 ELSEVIER INC. ALL
would be interesting to see whether the conjunct use of
low doses of oral alendronate plus intravitreal
antiangiogenics decreases the number of injections
needed to control neovascular macular degeneration.
ANDRZEJ GRZYBOWSKI
Olsztyn, Poland, and Poznan, Poland
RAFAEL IRIBARREN
GUILLERMO IRIBARREN
Buenos Aires, Argentina
SHIGERU HONDA
Kobe, Japan
FUNDING/SUPPORT: NO FUNDING OR GRANT SUPPORT.
Financial disclosures: The following authors have no financial disclosures:
Andrzej Grzybowski, Rafael Iribarren, Guillermo Iribarren, and Shigeru
Honda. All authors attest that they meet the current ICMJE criteria for
authorship.
REFERENCES
1. Or C, Cui J, Matsubara J, Forooghian F. Pro-inflammatory and
anti-angiogenic effects of bisphosphonates on human cultured
retinal pigment epithelial cells. Br J Ophthalmol 2013;97(8):
1074–1078.
2. Stresing V, Fournier PG, Bellahcène A, et al. Nitrogen-
containing bisphosphonates can inhibit angiogenesis in vivo
without the involvement of farnesyl pyrophosphate synthase.
Bone 2011;48(2):259–266.
3. Mammo Z, Guo M, Maberley D, Matsubara J, Etminan M. Oral
bisphosphonates and risk of wet age-related macular degener-
ation. Am J Ophthalmol 2016;168:62–67.
4. Honda S, Nagai T, Kondo N, et al. Therapeutic effect of oral
bisphosphonates on choroidal neovascularization in the
human eye. J Ophthalmol 2010;2010 http://dx.doi.org/10.
1155/2010/206837.
5. Miki A, Honda S, Nagai T, Tsukahara Y, Negi A. Effects of
oral bisphosphonates on myopic choroidal neovascularisation
over 2 years of follow-up: comparison with anti-VEGF therapy
and photodynamic therapy. A pilot study. Br J Ophthalmol
2013;97(6):770–774.
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