Decreased fracture risk in users of organic nitrates: a nationwide case-control study.
In a nationwide population-based pharmaco-epidemiological case-control study, including 124,655 subjects who had sustained a fracture during 2000 (cases) and 373,962 age- and sex-matched controls, we found an approximately 15% reduced risk of fractures in users of organic nitrates. Thus, organic nitrates may protect against osteoporosis.


BACKGROUND
Organic nitrates are widely used in the treatment of ischemic heart diseases. In addition, nitrates may affect bone. In vitro studies have shown that nitrates are able to inhibit bone resorption, and recent studies in humans have shown a positive effect on BMD and bone turnover.


METHODS
We studied the effect of organic nitrates on risk of fracture. We performed a population-based pharmaco-epidemiological case-control study with fracture in 2000 as outcome and use of nitrates (isosorbide mononitrate, isosorbide dinitrate, and nitroglycerin) during the previous 5 years as exposure variable. We used nationwide computerized registers to assess individual use of nitrates and related these data to individual fracture data and information on potential confounders. In the study, we included 124,655 subjects who had sustained a fracture during 2000 (cases) and 373,962 age- and sex-matched controls.


RESULTS
After confounder adjustment, use of nitrates was associated with an 11% reduced risk of any fracture (OR = 0.89; 95% CI, 0.86-0.92) and a 15% reduced risk of hip fracture (OR = 0.85; 95% CI, 0.79-0.92). Risk of any fracture was reduced in both men and women, but risk of hip fracture was only reduced in women. Hip fracture risk was reduced dose-dependently. Use of nitrates with a short duration of action was associated with lower risk estimates than use of slow release preparations.


CONCLUSIONS
Treatment with nitrates is associated with a decreased risk of fracture. Further studies should determine whether a causal relationship exists.
Rejnmark
Lars
L
Department of Endocrinology and Metabolism, Aarhus University Hospital, Aarhus Sygehus, Tage-Hansens Gade 2, Aarhus C, Denmark. rejunmark@post6@.tele.dk
Vestergaard
Peter
P
Mosekilde
Leif
L
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D016022:Case-Control Studies; D003718:Denmark; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology* / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000627:therapeutic use*; D016017:Odds Ratio; D012042:Registries; D012306:Risk; D012737:Sex Factors
D009566:Nitrates