Fracture risk in patients treated with loop diuretics


L. Rejnmark, Department of Endocrinology and Metabolism C, Aarhus University Hospital, Aarhus Sygehus, Tage-Hansens Gade 2, DK-8000 Aarhus C, Denmark.
(fax: +45 8949 7684; e-mail:


Background.  Loop diuretics (LD) increase renal calcium excretion. Discrepant results on associations between LD and fracture risk have been reported.

Objective.  To assess the fracture risk in users of LD.

Design and subjects.  A population-based pharmaco-epidemiological case–control design with fracture in year 2000 as outcome and use of LD during the previous 5 years as exposure variable. We used nationwide computerized registers to assess individual use of LD and related these data to individual fracture data and information on potential confounders. We compared 64 699 cases aged 40 years or more who sustained a fracture during year 2000 with 194 111 age- and gender-matched controls.

Results.  A total of 44 001 subjects used LD. Ever use of LD was associated with a crude 51% (OR 1.51; 95% CI 1.48–1.55) increased risk of any fracture and a 72% (OR 1.72; 95% CI 1.64–1.81) increased risk of hip fracture. The risk estimates were reduced after confounder adjustment, i.e. adjusted risk of any fracture was increased by 4% (OR 1.04; 95% CI 1.01–1.07) and risk of hip fracture by 16% (OR 1.16; 95% CI 1.10–1.23). In current users, a tendency towards a decreased fracture risk with increased dose was observed, whereas in former users risk of fracture increased with increased dose. Use of furosemide was associated with higher risk estimates than use of bumetanide.

Conclusion.  Treatment with LD affects fracture risk. Special attention should be paid to patients in whom treatment with LD is initiated or stopped, as they may be at an increased risk of fracture.