Use of organic nitrates and the risk of hip fracture: a population-based case-control study.
BACKGROUND
Use of organic nitrates has been associated with increased bone mineral density. Moreover, a large Danish case-control study reported a decreased fracture risk. However, the association with duration of nitrate use, dose frequency, and impact of discontinuation has not been extensively studied.


OBJECTIVE
Our objective was to evaluate the association between organic nitrates and hip fracture risk.


METHODS
A case-control study was conducted using the Dutch PHARMO Record Linkage System (1991-2002, n = 6,763 hip fracture cases and 26,341 controls). Cases had their first admission for hip fracture, whereas controls had not sustained any fracture after enrollment. Current users of organic nitrates were patients who had received a prescription within 90 d before the index date. The analyses were adjusted for disease and drug history.


RESULTS
Current use of nitrates was not associated with a decreased risk of hip fracture [adjusted odds ratio (OR) = 0.93; 95% confidence interval (CI) = 0.83-1.04]. Those who used as-needed medication only had a lower risk of hip fracture (adjusted OR = 0.83; 95% CI = 0.63-1.08) compared with users of maintenance medication only (adjusted OR = 1.17; 95% CI = 0.97-1.40). No association was found between duration of nitrate use and fracture risk.


CONCLUSIONS
Our overall analyses showed that risk of a hip fracture was significantly lower among users of as-needed organic nitrates, when compared with users of maintenance medication. Our analyses of hip fracture risks with duration of use did not further support a beneficial effect of organic nitrates on hip fracture, although residual confounding may have masked beneficial effects.
Pouwels
Sander
S
Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacoepidemiology and Pharmacotherapy, University Utrecht, 3508 TB Utrecht, The Netherlands.
Lalmohamed
Arief
A
van Staa
Tjeerd
T
Cooper
Cyrus
C
Souverein
Patrick
P
Leufkens
Hubertus G
HG
Rejnmark
Lars
L
de Boer
Anthonius
A
Vestergaard
Peter
P
de Vries
Frank
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004812:Epidemiologic Methods; D005260:Female; D006620:Hip Fractures / Q000453:epidemiology* / Q000517:prevention & control*; D006801:Humans; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000008:administration & dosage / Q000627:therapeutic use*; D005996:Nitroglycerin / Q000627:therapeutic use; D016017:Odds Ratio; D011153:Population; D012306:Risk; D014665:Vasodilator Agents / Q000627:therapeutic use*; D055815:Young Adult
D009566:Nitrates; D014665:Vasodilator Agents; D005996:Nitroglycerin; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate