Diuretic initiation and the acute risk of hip fracture.
CONCLUSIONS
We found the risk of hip fracture was transiently elevated around twofold shortly after initiation of a loop or thiazide diuretic drug in a case-crossover and case-control study. No statistical association was found following the initiation of a comparator medication: ACE inhibitors. Awareness of these short-term risks may reduce hip fractures.


BACKGROUND
Little is known about the acute effects of initiating a diuretic drug on risk of fracture. We evaluated the relationship between initiating a diuretic drug and the occurrence of hip fracture.


METHODS
The study sample included 2,118,793 persons aged ≥50 years enrolled in The Health Improvement Network (THIN) between 1986 and 2010. The effect of a new start of a diuretic drug or comparator medication (ACE inhibitor) on risk of hip fracture was assessed using a case-crossover and case-control study during the 1-7, 8-14, 15-21, and 22-28 days following drug initiation.


RESULTS
Included were 28,703 individuals with an incident hip fracture over a mean of 7.9 years follow-up. In the case-crossover study, the risk of experiencing a hip fracture was increased during the first 7 days following loop diuretic drug initiation (OR = 1.8; 95 % CI, 1.2, 2.7). The elevated risk did not continue during the 8-14, 15-21, or 22-28 days following drug initiation. For thiazide diuretics, the risk of hip fracture was elevated 8-14 days after drug initiation (OR = 2.2; 95 % CI, 1.2, 3.9). No such association was observed in the 1-7, 15-21, or 22-28 days following thiazide drug initiation. ACE inhibitor initiation was not associated with a statistically significant increased risk of hip fracture. Similar results were observed using a case-control study.


CONCLUSIONS
The risk of hip fracture was transiently elevated around twofold shortly after the new start of a loop or thiazide diuretic drug. Awareness of these short-term risks may reduce hip fractures and other injurious falls in vulnerable adults.
Institute for Aging Research, Hebrew SeniorLife & Department of Medicine, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, MA, USA. sarahberry@hrca.harvard.edu
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D000058:Accidental Falls / Q000706:statistics & numerical data; D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects; D004232:Diuretics / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D004812:Epidemiologic Methods; D005260:Female; D006620:Hip Fractures / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D013997:Time Factors; D006113:United Kingdom / Q000453:epidemiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors