Oral bisphosphonate use and age-related macular degeneration: retrospective cohort and nested case-control study

Cesar Garriga, Michael Pazianas, Samuel Hawley, Antonella Delmestri, Daniel Prieto-Alhambra, Cyrus Cooper, Andrew Judge

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Background: Hydroxyapatite (calcium and phosphate) spherules have been implicated in the initiation and establishment of age-related macular degeneration. Bisphosphonates could increase the dissolution of hydroxyapatite crystals and when they are used in elderly patients with osteoporosis they could reduce the risk of developing age-related macular degeneration.

Objective: To determine if oral bisphosphonate (BP) use is associated with the incidence of age-related macular degeneration in a large “real-world” population-based cohort of incident hip fracture patients.

Design: A cohort of 13,974 hip fracture patients (1999 to 2013) were used to conduct a: (a) propensity score matched cohort analysis and (b) nested case-control analysis.

Setting: A population-based study using electronic health records from UK primary care (Clinical Practice Research Datalink).

Participants: Hip fracture patients aged ≥50 years without age-related macular degeneration diagnosis prior to hip fracture date or in the first year of follow-up. Prior BP-users and those who died, transferred out or with last data collected before hip fracture were excluded.

Exposures: Incident BP use following hip fracture. BP use was further categorised according to medication possession ratio in quartiles.

Main outcome measures: Primary outcome was a diagnosis of age-related macular degeneration after the first year from index date. Propensity scores were used to match 1:1 BP-users to non-BP users. Covariates in the propensity score were index year, age, gender, body mass index, smoking, alcohol drinking, region, drug confounders and comorbidities. Subhazard ratios and their 95% confidence intervals were calculated including death as a competing risk. A nested 1:20 case-control analysis using conditional logistic regression provided risk estimates according to medication possession ratio.

Results: Among 6,208 matched patients and during 22,142 person-years of follow-up, 57 (1.8%) and 42 (1.4%) age-related macular degeneration cases occurred in BP-users and non-BP users, respectively. The survival analysis model did not provide significant evidence of a higher risk of AMD in BP-users (subhazard ratio: 1.60; CI: 0.95-2.72; P=0.08) although there was a significant increased risk among BP-users with high medication possession ratio (top quartile) relative to non-BP users (odds ratio: 5.08, 3.11-8.30; P
Original languageEnglish
Pages (from-to)34-46
Number of pages13
JournalAnnals of the New York Academy of Sciences
Issue number1
Early online date24 Jan 2018
Publication statusPublished - Aug 2018


  • Oral bisphosphonates
  • age-related macular degeneration
  • hip fracture
  • propensity score matching
  • nested case-control study

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