Is allopurinol use associated with an excess risk of osteoporotic fracture? A National Prescription Registry study.
Using a Danish Register cohort of 86,039 adult new allopurinol users and propensity score matched controls, we found that gout requiring allopurinol prescription was associated with an increased fracture risk.


OBJECTIVE
Gout, an acute inflammatory arthritis, is common and associated with elevated serum urate, obesity and high alcohol consumption. The mainstay of therapy is the urate-lowering agent, allopurinol. Here, we report the relationship between allopurinol prescription and fracture in a large registry population.


METHODS
We established a Danish Register cohort of 86,039 adult cases (new allopurinol users) and 86,039 age, sex and propensity score matched controls (not exposed to allopurinol or with a gout diagnosis), with no diagnosis of malignancy in the year prior.


RESULTS
We found a modest adjusted effect of allopurinol prescription on major osteoporotic fractures (hazard ratio (HR) 1.09, 95 % confidence interval (CI) 1.05-1.14, p = 0.04) and on hip fractures (HR 1.07, 95 % CI 1.11-1.14, p < 0.001), robust to adjustment for confounding factors (age, sex, comorbidity, medication use). Associations were stronger in men than women, and among incident allopurinol users whose gout diagnosis had been confirmed by at least one hospital contact. Prespecified subanalyses by filled dose of allopurinol (mg/day in first year of prescription) showed increased hip and major fracture risk in women in the highest allopurinol dose grouping only, while a less strong dose effect was evident for fracture rates in men.


CONCLUSIONS
Gouty arthritis requiring allopurinol is associated with an excess risk of major or hip fracture, with an allopurinol dose effect evident in women such that women taking the highest doses of allopurinol--suggestive of more severe disease--were at increased risk relative to women taking lower doses.
MRC Lifecourse Epidemiology Units, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. emd@mrc.soton.ac.uk.|Victoria University of Wellington, Wellington, New Zealand. emd@mrc.soton.ac.uk.|NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton, Southampton, UK. emd@mrc.soton.ac.uk.
Elaine M
EM
Dennison
Odense Patient data Explorative Network (OPEN), Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
Katrine Hass
KH
Rubin
Department of Medicine, Holbæk Hospital, Holbæk, Denmark.
Peter
P
Schwarz
MRC Lifecourse Epidemiology Units, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK.|NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton, Southampton, UK.
Nicholas C
NC
Harvey
MRC Lifecourse Epidemiology Units, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK.
Karen Walker
KW
Bone
MRC Lifecourse Epidemiology Units, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK.|NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton, Southampton, UK.|NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK.
Cyrus
C
Cooper
Odense Patient data Explorative Network (OPEN), Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.|Department of Medicine, Holbæk Hospital, Holbæk, Denmark.
Bo
B
Abrahamsen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000493:Allopurinol / Q000009:adverse effects*; D015897:Comorbidity; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006073:Gout / Q000188:drug therapy*; D006074:Gout Suppressants / Q000009:adverse effects*; D006620:Hip Fractures / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D058866:Osteoporotic Fractures / Q000139:chemically induced* / Q000453:epidemiology; D057216:Propensity Score; D016016:Proportional Hazards Models; D012042:Registries; D012307:Risk Factors; D014527:Uric Acid
D006074:Gout Suppressants; D014527:Uric Acid; D000493:Allopurinol
Allopurinol; Cohort; Fracture; Gout; Osteoporosis