Nancy A. Melville

October 17, 2012

MINNEAPOLIS, Minnesota — Antihypertensive drugs, particularly angiotensin II–converting enzyme (ACE) inhibitors and beta-adrenergic blockers, are associated with an increased risk for falls and hip fracture among the elderly during the initiation of drug therapy, researchers reported here at the American Society for Bone and Mineral Research (ASBMR) 2012 Annual Meeting.

Researchers from the University of Toronto, in Canada, analyzed a database of more than 1.6 million elderly residents in Ontario to assess the association of newly initiated hypertensive therapy with risk for falls and hip fractures. They found that among 301,591 individuals who initiated antihypertensive medications, 1463 had hip fractures within the first 45 days of starting the medication.

The risk for hip fracture during the first 45 days of therapy was 43% greater than the risk during the control periods before and after treatment initiation, which spanned a 450-day observation period (incidence rate ratio [IRR], 1.43; 95% confidence interval [CI], 1.19 - 1.72).

The risk estimates were consistent among the 5 different classes of antihypertensive drugs that were evaluated, including thiazide diuretics, ACE inhibitors, angiotensin II–receptor blockers, calcium channel blockers, and beta-adrenergic blockers,

However, when the association was examined for individual drug classes, it only reached statistical significance for ACE inhibitors (IRR, 1.53; 95% CI, 1.12 - 2.10) and beta-adrenergic blockers (IRR, 1.58; 95% CI, 1.01 - 2.48).

Whereas antihypertensive drugs have previously been associated with an increased risk for falls among the elderly, research on immediate risk for fracture has been lacking or inconsistent, said lead author Debra Butt, MD, of the University of Toronto.

"There are studies supporting the immediate risk of falls during initiation of antihypertensive therapy; however, the underlying mechanism is thought to be orthostatic hypertension," she said.

"There is also conflicting evidence regarding the association between antihypertensive drugs and fractures, where the majority of literature looks at long exposure periods of months to years, and the underlying mechanism is thought to be related to bone mass."

The new research is the first to show an elevated risk in the immediate period following drug initiation.

"This is the first large, population-based study to demonstrate that antihypertensive drug use was associated with an immediate risk of hip fracture during the initiation of therapy in community-dwelling elderly," Dr. Butt said.

"This is a new finding, and based on this finding, caution is advised when initiating any kind of antihypertensive drugs in the elderly."

Due to the high risk for falls and the frequent use of antihypertensive drugs in this population, the risk issue is particularly important, she added.

"About one third to a half of people age 65 years and older fall each year," Dr. Butt noted. "About 1% of falls result in hip fracture, and about a third of those may die within the first year."

"Meanwhile, 50% of all Canadians age 65 years and older have hypertension, and more than 70% of newly diagnosed hypertensive elderly take antihypertensive drugs, so this is an issue that affects many people."

According to Daniel Solomon, MD, MPH, the study's clinical implications are difficult to determine because the absolute risk for fractures associated with antihypertensive medications remains unknown.

"The research is interesting and methodologically sophisticated; however, the self-control design is difficult to interpret, because one cannot easily calculate the absolute risk of the outcome, hip fractures in this example," said Dr. Solomon, a professor of medicine at Harvard Medical School and chief of the Section of Clinical Sciences at Brigham and Women's Hospital's Division of Pharmacoepidemiology in Boston, Massachusetts.

"Thus, while I believe that the investigators report an association that is likely causal, its public health implications are not clear," he said.

"Treating hypertension prevents cardiovascular events, but it may hasten hip fractures," he continued. "Without knowing the absolute risk of hip fractures associated with initiation of these medications, it is difficult to use this information."

Dr. Butt and Dr. Solomon have disclosed no relevant financial relationships.

American Society for Bone and Mineral Research (ASBMR) 2012 Annual Meeting. Abstract 1055. Presented October 13, 2012.