title: Inflammatory eye reactions with bisphosphonates and other osteoporosis medications: what are the risks?
abstract: Inflammatory eye reactions (IERs) are rare but have been associated with medications to treat osteoporosis. The aim of this review is to summarize the current literature on the association between IERs and specific medications to treat osteoporosis (bisphosphonates, selective estrogen receptor modulators, strontium, denosumab and teriparatide). We cover the known epidemiology, potential pathogenic mechanisms and a resume of unanswered questions. Briefly, this review highlights that none of the existing randomized clinical trials were powered to identify these rare adverse events, and the majority of the information available is from spontaneous case reports and case series reporting associations between bisphosphonates and IERs. No case reports describe IERs after other anti-osteoporosis medications. Importantly, some case reports describe recurrence of the IER after affected patients were rechallenged with the same or another bisphosphonate, and that no reported cases resolved without discontinuation of the bisphosphonate. However, three large population-based cohort studies have shown conflicting results between osteoporosis treatments and IERs, but overall these studies suggest that IERs may actually be part of underlying inflammatory disease processes that also cause osteoporosis, rather than due to the medications used to treat osteoporosis themselves. There are no clear pathogenic mechanisms for how bisphosphonates could potentially cause IERs. However, the drug is secreted into the tears by the lacrimal gland and could cause irritation to the mucous membranes with subsequent release of inflammatory mediators, similar to the systemic response typically seen after infusion of bisphosphonates. However, in summary it is still not known whether there is a true causal association between bisphosphonates or other anti-osteoporosis medications and IERs, or whether it is confounding by indication and is actually due to underlying inflammatory diseases that cause both osteoporosis and IERs.
authors: Academic Rheumatology, Musculoskeletal Research Unit, University of Bristol, Learning and Research Building, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, UK.
authors: Emma M
authors: EM
authors: Clark
authors: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Darshana
authors: D
authors: Durup
keywords: adverse events; anti-osteoporosis medications; bisphosphonates; inflammatory eye reactions; osteoporosis; pathogenesis
references: Ophthalmology. 2004 Jul;111(7):1275-9
references: 15234126
references: Retina. 2008 Jun;28(6):889-93
references: 18536608
references: Adv Ther. 2008 Dec;25(12):1235-56
references: 19066755
references: Drug Saf. 1999 Nov;21(5):389-406
references: 10554053
references: Reumatol Clin. 2013 Jan-Feb;9(1):42-52
references: 22947600
references: Basic Clin Pharmacol Toxicol. 2004 Jun;94(6):260-70
references: 15228497
references: Biochem Biophys Res Commun. 2002 Jan 18;290(2):869-73
references: 11785983
references: Lancet. 1989 Jul 1;2(8653):42-3
references: 2567810
references: Orbit. 2012 Apr;31(2):119-23
references: 22489855
references: Cochrane Database Syst Rev. 2008 Jan 23;(1):CD004523
references: 18254053
references: Medicina (B Aires). 1997;57 Suppl 1:93-100
references: 9567361
references: Calcif Tissue Int. 1997 Nov;61(5):386-92
references: 9351880
references: Biochem Biophys Res Commun. 1999 Oct 14;264(1):108-11
references: 10527849
references: Calcif Tissue Int. 1987 Dec;41(6):326-31
references: 3124942
references: Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8175-9
references: 8058775
references: CMAJ. 2012 May 15;184(8):E431-4
references: 22470169
references: J Bone Miner Res. 2013 Mar;28(3):455-63
references: 23044864
references: Menopause. 2008 Jul-Aug;15(4 Suppl):790-6
references: 18596600
references: Gynecol Endocrinol. 2013 Dec;29(12):1005-14
references: 24063695
references: Nature. 1995 May 11;375(6527):155-8
references: 7753173
references: Blood. 2000 Jul 15;96(2):384-92
references: 10887096
references: N Engl J Med. 1999 Mar 4;340(9):737-8
references: 10068336
references: Curr Rheumatol Rep. 2001 Oct;3(5):453-8
references: 11564378
references: Bone. 1996 Feb;18(2):133-9
references: 8833207