Treatment with beta-blockers, ACE inhibitors, and calcium-channel blockers is associated with a reduced fracture risk: a nationwide case-control study.
BACKGROUND
Cardiovascular diseases are associated with disturbances in calcium metabolism, including increased urinary calcium, vitamin D insufficiency, and decreased bone mineral density. Antihypertensive drugs may increase the risk of falling. However, risk of fracture in patients treated with non-diuretic cardiovascular drugs is largely unknown.


OBJECTIVE
We investigated associations between fracture risk and treatment with commonly used cardiovascular drugs: beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium-channel blockers.


METHODS
A population-based pharmaco-epidemiological case-control study with fracture in year 2000 as outcome and drug use during the previous 5 years as exposure. We used nationwide computerized registers to assess individual use of drugs and related these data to individual fracture records and information on socio-economic and health-related confounders.


RESULTS
We included 124,655 cases that sustained a fracture and 373,962 age and gender-matched controls. After adjustment for potential confounders, risk of any fracture was reduced by 9% [odds ratio (OR) 0.91; 95% confidence interval (CI), 0.88-0.93] in users of beta-blockers, by 6% (OR, 0.94; 95%CI, 0.91-0.96) in users of calcium-channel blockers, and by 7% (OR, 0.93; 95%CI, 0.90-0.96) in users of ACE inhibitors. Moreover, risk of hip fractures was reduced significantly by 7-14% in users of the three groups of drugs. No major differences were found between men and women or in subjects younger or older than 70 years of age. Sub-analyses indicated differences between groups of calcium-channel blockers, as use of non-dihydropyridine drugs was associated with a larger risk reduction than use of dihydropyridine drugs.


CONCLUSIONS
Treatment with beta-blockers, ACE inhibitors, and calcium-channel blockers is associated with a small but significantly reduced risk of fracture.
Department of Endocrinology and Metabolism, Aarhus University Hospital, Aarhus Sygehus, Aarhus, Denmark. rejnmark@post6.tele.dk
Lars
L
Rejnmark
Peter
P
Vestergaard
Leif
L
Mosekilde
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001842:Bone and Bones / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use*; D016022:Case-Control Studies; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D018570:Risk Assessment
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers